COLLECTED REPRINTS 
OF 
Medical Communications 
BY 
WILLIAM SYDNEY THAYER, M. D. 
Series III. 1905-1911 
BALTIMORE, MD. 
191 I CONTENTS. 
LXIX. Cotton Mather's Rules of Health. 
Johns Hopkins Hosp. Bull., Balt., 1905. xvi, 293. 
LXX. Gonorrhoeal Septicaemia and Endocarditis. 
Am. J M. Sc., Phila., 1005. cxxx, 751. 
LXXI. On Some Public Duties of the Physician. 
Maryland M. J., Bali., 1905, xlviii, 431. 
LXXII. Observations on Several Cases of Acute Pancreatitis. 
Johns Hopkins Hosp. Bull., Balt., 1905, xvi, 355. 
LXXIII. Address to the Graduating Class of the Training School for 
Nurses of the Union Protestant Infirmary. 
fifty-first Annual Report of the Union Protestant Infirmary 
of the City of Baltimore, 1905. 
LXXIV. On the Prophylaxis of Typhoid Fever. 
Maryland M. J , Balt., 1906, xlix, 327. 
LXXV. Second Report of the Tuberculosis Commission of Maryland. 
1906. 
LXXVI. An Analysis of Eight Hundred and Eight Cases of Chorea, 
with Special Reference to the Cardio-Vascular Manifesta- 
tions. 
J. Am. M. Ass., Chicago, 1906, xlvii, 1352-1354. 
LXXVII. Lines Read at the Dinner, given in Honour of Doctor Robert 
Fletcher at Maison Rauscher, Washington, Jan. 11, 1906. 
Johns Hopkins Hosp., Bull , Balt., 1906, Xzui, 179. 
LXXVIII. The Paravertebral Triangle of Dulness in Pleural Effusion 
(Grocco's Sign). W. S. Thayer and Marshal Fabyan. 
Am. J. M. Sc., Phila., 1907, cxxxiii, 14. 
LXXIX. Calcification of the Breast Following a Typhoid Abscess. 
W. S. Thayer and H. H. Hazen. 
> J. Exfer. M., N. Y., 1907, ix, 1. 
LXXX. Malarial Fever. 
System of Medicine, Albutt and Rolleston, Bond., 1907, ii, Pt. 2, 241. LXXXI. Experimental Studies of Cardiac Murmurs. W. S. Thayer 
ami W G. Mac Callum. 
Ain. J. M. Sc., Phila., 1907, cxxxiii, 249. 
• 
yXXXII On thi Impirtauce of the Simple Physical and Psychical 
Methods of Treatment 
N. Oi l. M & S. J , 19)7, lx, 278, and Johns Hopkins 
Hosp. Bull., Balt., 1907, xviii, 425. 
LXXXIII. Observations on the Teaching of Clinical Medicine. 
M. Louis 71. Rev. 1907, Ivi (n. s. /), 37; also, Proc. Asso- 
ciation <f American Medical Colleges, 1907, xvii, 101. 
LXXXIV. A Hitherto Undescribed Disease Characterized Anatomically 
by Deposits of Fat and Fatty Acids in the Intestinal and 
Mesenteric Lymphatic Tissues. W. S. Thayer and G. H. 
W hippie. 
Johns Hopkins Hosp. Bull., Balt., 1907, xviii, 382. 
LXXXV. Studies on Arterio-sclerosis, with Special Reference to the 
Radial Artery. W. S. Thayer and Marshal Fabyan. 
Am. J. M. Sc., Phila., 1907, cxxxiv, 811; also Tr. Ass. 
Am. Physicians, Phila., 1907, xxii, 694. 
LXXXVI. Remarks made at a Meeting Held in Commemoration of 
Major James Carroll, M. D., U. S. A. 
Johns Hopkins Hosp. Bull., Balt., 1908, xix, 7. 
LXXXVII. On the Early Diastolic Heart Sound (the So-called Third 
Heart Sound). 
Boston M. & S.J., 1908, clviii, 713; also, Medical Papers 
Dedicated to Reginald Heber Fitz, 8, Boston, 1908. 
LXXXVII I. On Some Relations of the Physician to the Public. Duties 
and Opportunities. 
J. Am. M. Ass., Chicago, 1908, I, 1877. 
LXXXIX. John Dutton Steele, 1868-1908. Minute adopted at the 
Annual Meeting of the Interurban Clinical Club, April, 
1909. 
XC. The Necessity of Post-Graduate Study. 
Post-Graduate, N. Y., 1909, xxiv, 389. 
XCI. Note on Pellagra in Maryland. 
Johns Hopkins Hosp. Bull., Balt., 1909, xx, 1. 
XCII. Further Observations on the Third Heart Sound. 
Arch. Int. Med., Chicago, 1909, iv, 297-305; also, Trans. 
Ass. Am. Phys., Phila., 1909, xxiv, 71-80. XCIII. Remarks on the Occasion of the Dedication of the New Hall of 
the College of Physicians of Philadelphia. 
The Johns Hopkins Hosp. Bull., Balt., 1910, xxi, 11-12, 
XCIV. On the Third Heart Sound. 
Compt. rend, xvi, Cong. int. de Med., Budapest, 1910, Sect, 
vt, med. int., 390. 
XCV. Quelques remarques sur le troisieme bruit du coeur. 
Arch. d. mal. du coeur {etc J, Par., 1910, Ui, 145-152. 
XCVI. On the Commoner Types of Functional Cardiac Murmurs. 
The Canadian Practitioner and Review, Toronto, 1910, 
xxxvy 481, also Tr. Ass. Am. Phys., Phila., 1910, 
xxv, 75. 
XCVII. On Two Cases of Intra-Thoracic Tumor. 
Old Dominion J. M. & S., Richmond, 1910-11, xl, 2. 
XCVIII. Address Delivered before the Graduating Class in the U. S. 
Medical School, May, 1909. 
Old Dominion J. M, & S., Richmond, 1910-11, xi, 313. 
XCIX. The Amoeboid Activity of Megaloblasts. 
Arch. Int. Med., Chicago, 1911, vii, 223. 
C. Two Cases of Congenital Haemolytic Jaundice with Splenomegaly; 
Observations on Haemolytic Jaundice. W. S. Thayer 
and Roger S. Morris. 
Johns Hopkins Hosp. Bull., 1911, xxii, 85-96. 
CI. A Study of Two Cases of Adams-Stokes Syndrome with Heart 
Block. W. S. Thayer and F. W. Peabody. 
Arch. Int. Med. Chicago, 1911, vii, 289- 
CH. On Haemolytic Jaundice. 
Illinois Med. Journal, February, 1911. 
CIII. On the Presence of a Venous Hum in the Epigastrium in Cirrho- 
sis of the Liver. 
Am. J. M. Sc. Phila., 1911, cxli, 313. 
CIV. Clinical Notes. (1) Intermittent Fever in Influenza, Simulating 
Malarial Fever. (2) Grave Malarial Fever with Few Par- 
asites in the Peripheral Circulation. Dangers of the 
Intravenous Injection of Quinine. 
Johns Plopkins Hosp. Bull., Balt., 1911, xxii, 241. 
CV. On Disseminated Caseating Tuberculosis of the Liver. 
Johns Hopkins Hosp. Bull., Balt., 1911, xxix, 242. COTTON MATHER'S RULES OF HEALTH. 
By William Sydney Thayer, M. D., 
Professor of Clinical Medicine, The Johns Hopkins 
University. [From The Johns Hopkins Hospital Bulletin, Vol. XVI, No. 174, 
September, 1905.] 
COTTON MATHER'S RULES OF HEALTH.* 
By William Sydney Thayer, M. D., 
Professor of Clinical Medicine, The Johns Hopkins 
University. 
Most men take pleasure in the manifestation of a certain 
playful irreverence toward the worthies of the past. With a 
perennial naivete we are fond of patronizing our great grand- 
fathers in a kindly sort of way. We smile at their quaint- 
ness and seriousness and ponderousness, while tacitly 
recognizing our own superior powers of perception and our 
more delicate sense of humor; and we rejoice in what always 
seems a deliciously original and somewhat temerarious 
fancy-that they may have possessed many of our commoner 
frailties behind that cloak of austerity with which respectful 
tradition, orthodoxical painters, and fickle fashion have 
helped to clothe them. And, as a rule, whatever our inten- 
tions, we are wont to weigh their lives and actions with 
scales built of our own contemporary criteria and with little 
real appreciation of the truth of the observation of the Gallic 
philosopher that " nothing seems so immoral (to-day) as to- 
morrow's code of morals," 1 and the converse. 
But after all, it is probably well that it should be so. How 
much of the spice of life we should miss, what a real mis- 
fortune it would be if one day, we should find ourselves able 
to enter wholly into the state of mind of those whose lives 
as it is, afford us so much occasion for beneficent reflection and 
[293] 
* Read before the Johns Hopkins Hospital Historical Club on 
March 13, 1905. 
1 " Rien ne semble plus immorale que la morale future." 
Anatole France, La vie litt^raire, 8°, Paris, 1895, III, 74. 
1 [293] 
speculation. The aspiration of Mr. Dinkelspiel who recently 
gave utterance to the profound thought that " Der vorld vould 
be much nicer if ve could see udders as ve see ourselfs," would, 
if realized, result in a very flat world. Moreover, we should 
not be half as amusing to our descendants. The posses- 
sion of truth in all things is doubtless precious, but we may, 
perhaps, be profanely thankful that with our human limita- 
tions there is little immediate prospect of being deprived of 
the greatest of life's privileges, the ever-present opportunity 
for its pursuit, while posterity is likely, for some time to 
come, to enjoy the pleasures of complacent contemplation of 
our inconsequent and entertaining wanderings. It is, perhaps, 
the part of the wise man in a study of the past, to rejoice 
in that which is fine, to smile at those contrasts which seem 
to him quaint and droll and unaccountable, but to hesitate to 
criticise or condemn. 
The reverend Cotton Mather has suffered much from too 
serious historians who have judged him freely from a nine- 
teenth century point of view. He was born in Boston in 
1663. His father, Increase Mather, the leading citizen of 
New England, was for some years president of Harvard Col- 
lege, while his mother was the daughter of John Cotton, one 
of the prominent men of Boston. From early youth he 
was regarded as a remarkable character. He entered Har- 
vard College at the age of eleven and a half, at which time 
he had already read Cicero, Terence, Ovid and Virgil and 
could write Latin with ease. He had also read through his 
Greek testament and had begun Homer, Isocrates, and the 
Hebrew grammar. In college he mastered Hebrew and com- 
posed treatises on logic and physics. He graduated at the 
age of fifteen and was ushered into independent life with a 
rather fulsome eulogy uttered by President Oakes as he pre- 
sented him with his degree; these remarks concluded with the 
following words: ^.Cottonus atque Matherus tam re quam 
nomine coalescant et reviviscant." 
It is not generally known that in Colonial days the names 
of the members of the graduating classes at Harvard were re- 
corded neither alphabetically nor according to scholarship 
[294] 
2 but in the order of their social standing.2 In the Quin- 
quennial Catalogue of Harvard University-that sacred vol- 
ume to which the late Professor Lane used to refer facetiously, 
as " the peerage," Cotton Mather's name stands second in the 
list of the class of 1678, preceded only by that of his cousin, 
John Cotton. It should, however, be mentioned that the 
class consisted of but four members. 
Suffering from an impediment of speech which it was 
feared at first might prevent his entering the ministry, he is 
said to have spent a part of his first two years in the study 
of medicine, but conquering this infirmity, he began his career 
as a minister at the age of eighteen. These were days when 
a young man of ambition started out in life with a firm re- 
solve to excel in many and diverse branches of .scienee-, and 
it may sometimes have happened, if he was endowed with a 
sufficient measure of self-assurance, that he thought he had 
mastered them all. Cotton Mather was a man of amazing 
general information. At the age of twenty-five he is said to 
have been able to write (sic) seven languages, including Iro- 
quois; and of his superior learning and ability there was, 
apparently, a serene consciousness which the irreverent of 
to-day might style as knowing it all. His main goal in life 
appears to have been the presidency of Harvard College, and 
his failure to attain this was a bitter and nourished disap- 
pointment. Conscious of his remarkable attainments and 
exceptional erudition, Mather appears to have been rather 
impatient with the rest of the world for a lack of what he 
deemed due respect and appreciation for his qualities-and he 
made his fair share of enemies. 
Born in an age of implicit and general belief in the pow- 
ers of Heaven and, especially, of Hell in all its forms, Cot- 
ton Mather preserved throughout his life an unshaken faith 
in the immediate presence of a God who noticed and so forth 
rewarded every good action, and of a Devil whose malign 
hand was ever to be detected ready to seize and hold with 
tightening grasp whosoever was guilty of the slightest lapse 
[294] 
2 Quinquennial Catalogue of Harvard University, 1900, p. 83. 
3 [294] 
from grace. He so trained himself that every common inci- 
dent of life was, so to speak, a mnemonic for a special prayer 
or pious ejaculation, and for days together, he subjected him- 
self to fasts and self-mortification such as might compel the 
admiration of the cloister. To the omnipresent Devil he 
was a mighty and militant enemy, and no one was so quick 
as he to detect and frustrate the malicious and insinuating 
schemes of his subtle adversary. When twenty-five years of 
age his attention was first directed to the evident manifes- 
tations of Satan in the bewitching of the child of a certain 
Mr. Goodwin of Charlestown by an agent of the infernal 
regions in the shape of a sharp-tongued old washerwoman 
who was duly executed for her hellish practices. And his 
preaching and publications concerning this case doubtless had 
their effect in spurring on the public to the decisive battle 
which was waged four years later at Salem against the powers 
of the invisible world. In this warfare Cotton Mather took 
an active part. But while tradition has, for nearly a century, 
pictured him as a relentless inciter of widespread executions, 
a study of the records appears to show that, active as he was 
in warfare against his infernal enemies, his voice was usually 
on the side of cautiousness and humanity, ever raised against 
the admission of " spectral evidence," and urging a recogni- 
tion of the possibility that the Devil might manifest himself 
in the form of an innocent individual. And if, when, in 
later years, witnesses, jury, and even magistrates were tor- 
tured by doubt and self-distrust and remorse, the stern old 
warrior remained unmoved and defended to his dying day 
the good fight which he had waged and won against the 
legions of Hell, it was not so much, as his enemies would have 
it, an evidence of vanity and cruelty, as that his moderate 
and humane counsel left him little to regret. 
Mather, although he failed to obtain the coveted presidency 
of Harvard College, was a great power in temporal as well 
as in spiritual affairs. He had, always, a lively interest in 
matters medical and was replete with advice and counsel, 
much of which was good. At the age of fifty-eight, he read, 
in the Philosophical Transactions of the Royal Society, a 
4 paper by Timonius on a " New Method of Introducing 
Small-pox by Transmission," in which was described the 
method of inoculation then in vogue in Turkey.3 
Impressed by the probable benefits which the introduction 
of this practice might bring to a city in which small-pox was 
spreading, Mather urged William Douglas, the leading physi- 
cian of the town of Boston to put the method into practice. 
Douglas refused, as did all other physicians excepting a mod- 
est young man, Zabdiel Boylston of Brookline, who, on June 
27, 1721, inoculated his son aged 13, a negro, and a little 
colored boy. This was only about six weeks after the intro- 
duction of the practice in London at the instigation of Lady 
Mary Wortley Montagu. 
These proceedings caused great public excitement. Al- 
most all the medical profession and many of the clergy vio- 
lently assailed these two courageous men. Insult and vitu- 
peration were poured upon them by pulpit and press, while 
angry mobs threatened their very lives in the streets. On one 
occasion, while Mather was harboring, at his own dwelling, a 
[294] 
[295] 
'The following passage from the Angel of Bethesda would 
seem to indicate that Mather had already learned of this practice 
from other sources. " There has been a Wonderful practice lately 
used in Several parts of the World, which indeed is not yet become 
common in our Nation. 
I was first instructed in it by a Guaramantee servant of my own, 
Long before I knew, that any Europeans or Asiaticks had the 
least acquaintance with it; and some years before I was enriched 
with the communications of the Learned Foreigners, whose ac- 
counts I found agreeing with that I received of my servant, when 
he shewed me the scar of the wound made for the Operation; and 
said, That no person ever died of the Small-pox in their country 
that had the courage to use it. 
I have since met with a considerable number of Africans, who 
all agree in One Story, That in their country grandy-many dy 
of the Small-pox: But now they Learn This way-: people take 
juice of small-pox, and cutty-skin, and putt in a Drop; then by'nd 
by a little sicky sicky: then very few little things like small-pox; 
and no body dy of it, and no body have Small-pox any more. Thus 
in Africa, where the poor creatures dy of the Small-pox like Rotten 
Sheep, a merciful God has taught them an Infallible preservative. 
Tis a common practice, and is attended with a constant success." 
[294] 
5 [295] 
convalescent from the operation, a mob attacked the house 
and threw a lighted bomb into the room occupied by the 
patient. Happily the fuse became detached and the bomb 
failed to explode. Attached to the bomb in such a manner 
that it might possibly have escaped destruction in the event 
of an explosion, was the following courteous message: " Cot- 
ton Mather I was once of your meeting, but the cursed lye 
you told of You know who, made me leave you, 
you Dog. And Damn you, I will enoculate you with this, 
with a pox to you." 
Threats of personal violence continued and Mather sin- 
cerely believed that his life was in grave danger. Though his 
fears may have been exaggerated, yet the following entry 
made in his journal a few days after the throwing of the 
" granado " is rather touching evidence of the state of mental 
exaltation under which he then laboured:4 
" 19/9(/" (Nov. 1721) "Now, I am so far from my Mel- 
ancholy Fear on this occasion, that I am filled with unut- 
terable Joy at the prospect of my approaching Martyrdom. 
I know not what is the Meaning of it; I find my mouth 
strangely stopp'd, my Heart strangely cold, if I go to ask for 
a Deliverance from it. But, when I think on my Suffering 
Death for saving the Lives of Dying people, it even ravishes 
me with a joy inexpressible & full of Glory. I cannot help 
Longing for the Hour, when it will be accomplished. I am 
even afraid almost of doing anything for my preservation. 
I have a Crown before me; and I now know by Feeling, what 
I formerly knew only by Reading, of the Divine Consolations 
with which ye minds of Martyrs have been sometimes irrad- 
iated. I had much rather Dy by such Hands, as now threaten 
my life, than by a Feaver, and much rather Dy for my con- 
forming to the Blessed JESUS in Essays to save the Lives of 
Men from the Destroyer, than for some Truths, tho' precious 
ones, to which many Martyrs testified formerly in the Flames 
of Smithfield" 
4 The privilege of consulting the manuscript diary of Cotton 
Mather for the year 1721, which is in the possession of the Massa- 
chusetts Historical Society, I owe to the courtesy of Dr. Samuel A. 
Green, librarian. 
6 But the old parson and the young physician pursued the 
even tenor of their way, and gradually gained adherents. In 
a year Boylston with two other colleagues had inoculated 
two hundred and eighty-six persons with but six deaths, three 
of which may have been due to previous contraction of the 
disease from other sources, while among 5579 uninoculated 
who took the disease during the same period, 840, or more 
than one in seven, died. These results ere long, won the 
day, bringing lasting fame to both at home and honorable 
recognition in the mother country to the brave physician, 
Zabdiel Boylston. 
Cotton Mather was a most prolific author, publishing dur- 
ing his life 382 works. His most famous publications are: 
" Magnalia Christi "-an ecclesiastical history of New Eng- 
land, which contains a mass of entertaining and valuable in- 
formation about the early days of the colony, and his "Won- 
ders of the Invisible World. Being an Account of the Tryals 
of Several Witches Lately Executed in New England," an 
amazing exposition of the strategy and machinations of the 
devil and of the tactics which the servants of the Lord should 
employ to resist them. Mather was a vigorous writer. He 
belonged rather to the class described by an author of his own 
time,5 who, " with a Supercilious Gravity, have magisterially 
inveigh'd against the Vices of Mankind" than to the others 
who " by the nipping Strokes of a Side-wind Satyr, have 
endeavored to tickle Men out of their Follies." Perhaps 
there may be some who would class him among what the same 
author calls the " Sowr Pulpit-Orators." 
His invectives against the Vices of Mankind were of no mean 
force, as the title of his well-known Execution Sermon may 
suggest. " TREMENDA-The dreadful sound with which 
the wicked are to be thunderstruck. In a sermon delivered 
unto a great assembly, in which was present, a miserable Afri- 
can (Joseph Hanno) just going to be executed, for a most 
inhumane and uncommon murder, at Boston May 25th, 
1721" 
[295] 
'The English Theophrastus. 8°. London, W. Turner et al., 
1702, Preface. 
7 [295] 
One can fancy the terror of a superstitious negro on listen- 
ing to this highly colored discourse, wherein he is apostro- 
phized as " 0 forlorn Ethiopian," while his crime is referred 
to as of Ethiopian hue. 
Mather's style was most remarkable, consisting, often, of a 
jungle of strange capitals and italics and Latin quotations 
interlaced with an exuberant undergrowth of punctuation 
marks, while in the recesses lurked the furtive anagram and, 
all too frequently, the Bandar-logian pun. But in the tangled 
underbrush there is a store of hidden treasure, and in many 
a passage of his writings there is fine dramatic force and 
vigor. 
Cotton Mather was honored abroad as well as at home. He 
was made a Doctor of Divinity by the University of Glasgow 
in 1710 and became a Fellow of the Royal Society in 1713. 
He died on the 13th of February, 1728, and was accorded a 
public funeral no less impressive than that of his father in 
which he had taken a great pride. 
Among his unpublished manuscripts he left a work en- 
titled : 
The Angel of Bethesda. 
' An ESSAY upon the Common Maladies of Mankind. 
' Offering, first, The Sentiments of PIETY, where to the 
' Invalids are to be awakened in & from their Bodily Maladies 
' And then, A Rich Collection of plain but potent and 
' Approved REMEDIES for the Maladies. 
' Accompanied with many very practicable Directions, for 
' The PRESERVATION OF HEALTH, to such as enjoy a 
good 
' Measure of so great a Blessing. 
' And many other curious, & grateful & useful Entertain- 
ments, 
' occasionally intermixed. 
' The whole being A Family-physician, which every Family 
' of any capacity may find their Account on being supplied 
' Withal. 
The manuscript of this remarkable work I have recently 
[296] 
8 had the privilege of inspecting, through the courtesy of the 
American Antiquarian Society. 
In the first chapter the author quotes from a former trea- 
tise entitled, "MENS SANA IN CORPORE SANO": 
" Lett us look upon Sin as the Cause of Sickness. There 
are, it may be, Two thousand Sicknesses: And indeed, any 
one of them able to crush us! But what is the cause of all? 
Bear in mind, that sin was that which first brought Sickness 
upon a Sinful World, and which yett continues to sicken the 
world, with a world of Diseases: & Sickness is in short, 
Flagellum Dei pro peccatis Mundi." 
'Twill be impossible to enter into anything like a full de- 
scription of this most interesting treatise. A few notes must 
suffice. 
In chapter V, which is entitled " Nishmath Chajim "8- 
the breath of life-there are some striking passages. " It is 
well known that if one Third of our Diseases, be those which 
we call, Chronical, more than one Half of this Third, will 
be those, which in Men go under the Name of Splenetic, and 
in Women go under the Name of Hysteric; tho' the Spleen 
and the Womb are often enough unjustly accused in these 
Denominations. It is marvellous to see, in how many Forms 
we undergo Splenetic and Hysteric maladies; The very Tooth- 
ache it self often belongs unto them: And Marvellous will 
be the Success, Marvellous the Esteem, of the Physician that 
can Discover 'em & Encounter 'em " . . . " These Maladies 
have many Symptoms, which may serve as Diagnosticks for 
them: Especially these TWO: That the Urine is Clear, Lim- 
pid, and Copious. And, That the Patient is Chiefly affected 
with his Indispositions, when he has just had his Mind under 
some Disturbance and Affliction." 
He advises rest and encouragement, and recommends ri- 
ding especially, but concludes: "UPON the Whole; OF all 
[296] 
8 This chapter has been published in book form. " Nishmath 
Chajim. The Probable SEAT of all Diseases, and a General 
CURE for them, further Discovered. More particularly, for 
Splenetic & Hysteric Maladies, which make so great a part of our 
Distempers." New London, 1722. 
9 [296] 
the Remedies under Heaven, for the Conquering of Distem- 
pers, & for the Preservation of Health & Prolongation of 
Life, There will now be found none, like serious PIETY." 
. . . . and "LET this be Remembered; Moderate Abstinence, 
& Convenient Exercise; and some Guard against Injurious 
Changes of the Weather, with an HOLY & EASY MIND, 
will go as far, in Carrying us with Undecay'd Garments thro' 
the Wilderness, to the Promis'd and Pleasant Land, which 
we are Bound unto, as all the Prescriptions with which all 
the Physicians under Heaven, have ever yet obliged us." 
There is an excellent chapter on "The Gymnastick or an 
Exercitation upon EXERCISE," which contains much wis- 
dom. Of riding, which he commends especially, he says: 
" If a man knew, and would keep to himself, any Remedy 
equal to that of a Course of Riding, Opes ille exinde amplis- 
simas facile accumulare posset, he might soon come to keep 
a coach and know ye English of Doct Galenus' opes. 
" I hope the Rider in the meantime, won't be unmindful of 
Darby Dawn's caution, 
But Lett the Rider take a care; 
Lest from a stumbling Horse or Mare 
He don't take Earth instead of Air. 
Chapter VII is in some respects, the most interesting of 
the work; it is entitled: " Conjectural]'a or, Some Touches 
upon, A Neto Theory of many Diseases." Quoting various 
authorities, he expresses the belief that a large number of dis- 
eases, among which are Small-pox, Plague, Consumption, 
Lues, bad colds and the itch, are due to infection with minute 
parasites which may be transmitted by the air or, under some 
circumstances, by contact with the patient. He refers to these 
parasites which, he says, may be too small to be visible by the 
best microscope, as "insects" or sometimes as "worms"; 
the chapter ends with the following paragraph: " But, 0 
ye Sons of erudition, and ye wise men of Enquiry; Lett this 
Enquiry come into a due Consideration with you; How far 
a potent ivorm-killer, that may be safely administered, would 
go further than any Remedy, yett found out, for the cure of 
many Diseases." 
10 In chapter XII he refers to the Gout as " Dominus Mor- 
borum; But especially, Morbus Dominorum," and offers the 
following consoling advice to the gouty: " Now, lett ye 
gouty People that are chastened with Pain on their Bed, and 
the multitude of their Bones with strong pain, fall into 
serious and awful Meditations, on ye pain, which will be ye 
portion of them, on whom an All-powerful God will make 
known the power of His Anger!" 
Chapter XIII is on " The Gout's Younger Brother or, 
The Rheumatism, and Sciatica." 
In chapter XX, on Small-pox, the interesting story of the 
introduction of inoculation is told. 
In the section on diseases of the eye he waxes eloquent: 
" SPECTACLES I Mankind is prodigiously inexcusable, in 
that the Name of ye First Inventor is entirely lost. That 
statues of Corinthian Brass have not Immortalized it." 
Chapter XLII is entitled: "The Main Wheel Scoured £ 
oiled or, Help for the Stomach depraved." 
The peritonitis which, in most cases doubtless represented 
appendicitis, is described unwittingly, in a manner which 
would have delighted the author had he realized what he was 
doing, in an appendix to the chapter on Cholic, in the follow- 
ing words: " A grievous and fearful Disease, an Appendix 
to the Cholic, is now broke in upon a miserable world; called, 
The Dry-Belly-Ache." . . . 
" Under the Torments of this horrible Disease, we may 
recommend unto the patient such sentiments of PIETY as 
we found the Cholic leading to." . . . 
" In so Difficult a case, and where so wise a Conduct is re- 
quired I dare not offer any prescription, but, A Wise Physi- 
cian. Consult such an one and follow his Directions, rely- 
ing wholly on ye Blessing of God." 
The small volume which I have this evening, is entitled 
" Manuductio ad Ministerium or DIRECTIONS for a Can- 
didate of the MINSTRY. Wherein, FIRST Right FOUN- 
DATION is laid for his Future Improvement; And, THEN, 
[296] 
[297] 
11 [297] 
RULES are Offered for such a Management of his Acade- 
mical and Preparatory STUDIES; And thereupon, For such 
a CONDUCT after his APPEARANCE in the World; as 
may Render him a SKILFUL and USEFUL minister of the 
Gospel." This work was published in Boston, " Printed for 
Thomas Hancock, and sold at his shop in Ann-Street near 
the Draw-Bridge " in 1726. It is dedicated, in Latin, to 
the studious youth of the academies especially in Glasgow and 
in New England as well as to any young non-conformists in 
England compelled to work in private. 
After a learned Latin introduction, he holds forth to his 
readers in twenty chapters upon various subjects, such as: 
§1. DEATH Realized. 
§2. The True End of Life Answered. 
§3. Conversion to Piety accomplished &c. 
The last chapters are RULES OF HEALTH and RULES 
OF PRUDENCE. There is so much that is wise and quaint 
and entertaining in these pages that I shall read the whole 
chapter, entitled: RULES OF HEALTH and a few ex- 
tracts from his even more admirable RULES OF PRU- 
DENCE: 
" §19. I have yet more to do; I may not leave you, till I 
leave a few RULES OF HEALTH with you; which I shall 
do with the utmost Brevity. 
" Having first encouraged you to cultivate an intimate Ac- 
quaintance with some Wise and Good Physician, who may 
have the continual Inspection of your Health, in your Friend- 
ly Conversation with him, I will defend you with the ensuing 
Admonitions. 
"I. The most Acute Physicians, find themselves compelled, 
with our Cheyne, unto this General Direction. The Grand- 
Secret and Sole Method for Long Life, and so for the Health 
which will befriend and sweeten it, is, To keep the Blood and 
Juices in a State of due Fluidity. And nothing will do this, 
but keeping much to a Spare, Lean, Fluid sort of a Diet. All 
who live long, and without much Pain, and after such a Life 
at length Die easily, are such as Live Abstemiously. 
" II. Borellus has a Remark on many Students falling into 
12 a Consumption, That it often proceeds, A Fumo candelarum 
hausto in Musaeis undiq; Clausis. 
"You will undergo the less of this Hazard, if you mind 
the Report of Manlius; Ego multos Periculosos Morbos el 
Miserias hujus Corpusculi mei Vito, hac unica Ratione, quod 
semper utor Diligentia, cito eundi cubitum. 
" III. The Medicina Gymnastica has done Miraculous 
Things. Bodily Exercise profits; But no Exercise compar- 
able to that of moderate Riding; whereof, the Reason why we 
find no more in the Prescriptions of the Ancients, (tho' 
Galen has a Chapter about it) for the Recovery of the 
Feeble, is because they were so simple as to Ride without 
Stirrups. The Saddle is the Seat of Health. As for the 
Games, which Exercise the Spirit and not the Body, particu- 
larly, the Noble and Ancient Game of Chess; These are by 
no Means proper for a Student. 
" IV. 'Tis an Observation of that Great Man, the Lord 
Verulam, Nihil magis conducit ad Sanitatem et Longaevita- 
tem, quam Crebrae et Domesticae Purgationes. A Family- 
Purge now and then taken, may be of Service to you. Pillu- 
lae Ruffi, especially when Chalybeated with adding about a 
third part of Sal Martis: Or else; A Bottle of Anniseed 
Water, with a Dram or two of Rhubarb steeped in it; These 
you may conveniently have always at hand for this Purpose. 
" V. Vander Heidan, has not related an hundredth part of 
the Vertues, in Cold Water. I tender you the Advice which 
the Aged Servant of GOD gave to his Valued Son, Drink not 
only Water; but use a little Wine for thy Stomach's sake. 
And yet I would say, upon Drinking a Glass of Generous 
Wine, often take a Glass of Water. And if the Beer they 
bring you, be too Strong, dilute it with putting a sufficient 
Quantity of Water into it. But never take Water, or any 
thing else, Cold, when you are Hot with Labour. There is 
Death in the Pot. 
" When you have run the hazard of disturbing your Stom- 
ach, with Ingurgitations from a Full Table, a Draught of 
Cold Water, will do Good like a Medicine. 
" Going to Bed, and Sweating from a large Draught of Cold 
[297] 
13 [297] 
Water, not only stops and cures a Cold, but also often extin- 
guishes a Fever at the Beginning. 
" Daily to wash your Head and Mouth with Cold Water, 
is a Practice that cannot be too much commended; If it were 
only for saving you from the Toothache. 
" For a Frequency in the Use of the Liquors, which they 
call Spirits, be as afraid of it, as you would be of a Familiar- 
ity with Evil Spirits. 
" VI. When you go to Infectious Places, one of the best 
Things you can do, is to hold and chew a bit of Myrrh in 
your Mouth. 
" VII. To feed much on Salt-Meats, won't be for your 
Safety. Indeed, if less Flesh were eaten, and more of the 
Vegetable and Farinaceous Food were used, it were better. 
The Milk-Diet is for the most part some of the wholesomest 
in the World! And not the less wholesome, for the Cocoa- 
Nutt giving a little Tincture to it. 
"VIII. Shall 1 smoke Tobacco? Answer; Be sure Not, if 
I can help it. Or let Alsted answer for me. Maximus Ta- 
baci Abusus est, quotidiano ejus usu, semetipsos, et bonas 
Horas perdere, et ex cerebro, mentis nobilissima sede, cami- 
num et cloacam efficere. In the Dutchy of Berguen, People 
may not Smoke, without purchasing a License for it. If you 
were to purchase of me a License for it, I know not how high 
Terms I should hold you to. If you want an Hydragogue, 
there is one preferrible in chewing some such Thing as a bit 
of Mastich; which would also whiten your Teeth, and 
sweeten your Breath, which Tobacco poisons. If once you 
get into the way of Smoking, there will be extreme hazard, 
of your becoming a Slave to the Pipe; and ever Insatiably 
craving for it. People may think what they will; But such a 
Slavery, is much below the Dignity of a Rational Creature; 
and much more of a Gracious Christian. I am sure, what 
the Great Voetius writes upon it, is very true; Minime con- 
venit viris honestis et gravibus; nominatim Ministris et Min- 
isterii Candidatis. There can be no Apologij for your taking 
up the slovenly Practice, and the Pains that must be taken 
to conquer the Poison, if you are not well advised and assured, 
[298] 
14 That your Health requires it. But I shall only recite what 
you will find in Two very considerable Writers, that you may 
form the better Judgment upon it. The One of these Writers 
is Magnenus, who tho' he be a mighty Friend to the Use of 
Tobacco, yet acknowledges, ' That it is not easy to relate, 
' what are the Damages, which the Inordinate and Immoder- 
'ate Use of this Fume does bring with it; for besides the in- 
satiable and greedy Lust of taking it, by its daily Use, the 
'Memory is impaired, the Stomach violated, the Brain exic- 
' cated, and the Life shortened; and the Offspring damnified. 
Yea, he lays this down as an undoubted Assertion; That the 
frequent and familiar Use of it, can be good for no Man. 
The Other is our Gale, who from his own Experience taxes the 
Smoke of Tobacco with very Noxious Qualities: He says, 
* He found it ma de more Humours than it brought away; 
' and tho' it opened his Body for the present, it proved in that 
'very thing a Prejudice afterwards; and Nature was but the 
'more Sluggish and Feeble anon, for the Force in this way 
'put upon it. He says, At last I came under a fixed Resolu- 
tion to deliver my self from this Vassalage; And this I ac- 
count not the least Deliverance of my Life. And yet, after 
all, I am not so Inflexibly sett, as utterly to deny you the 
Use of Tobacco, if you are sure of any Benefit from it. Only 
I insist upon it, That you be, (If I may use a Phrase, that if 
it may seem to trespass upon Good sense, it shall yet have as 
much as the Thing I write against) Excessively Moderate in 
it. And if you are growing so Wise as to Retrench and Re- 
form any Intemperance in it, which you may have been una- 
wares drawn into, do it not at Once, but by Degrees, lest by 
too quick a stop to an usual Discharge, your Health may be 
endangered. But, upon the whole; If you have hitherto es- 
caped this Epidemical Contagion, and are not yet a settled 
Inhabitant of the Terra del Fuogo, I cannot advise you in 
better Terms than those; It is Good for you to abide even as 
you are; And, If you may be kept free, chuse it rather. Yea, 
My Son, If Smokers entice thee, consent thou not. It is 
good Advice; and if you take it, you will one Day Thank him 
that gave it. 
[298] 
15 [299] 
ber, In multiloquio Stultiloquium; And Least said soonest 
mended. 
"It is a very prudent Remark; If one observes these Three 
small Imperatives, Audi, Cerne, Tace, he will need no other 
Passport for Travelling over the World. You will have a 
good Note of Wisdom, with two Satcllits to it, in my reciting 
to you the Observations of a very Discrete Man, who said; 
He had often got hurt by eating too much; rarely, by eating 
too little; Often got hurt by wearing too few Cloaths; rarely, 
by wearing too many; Often got hurt by Speaking; rarely, by 
holding his Tongue 
" VII. Let it be as a Law of the Medes and Persians with 
you, That you will never sacrifice any Hours of a short Life, 
in Contentions: Especially in Personal Contentions, and 
Quarrels and Squabbles, and Vitilitigations. Abundance of 
Sin will be unavoidably committed in them; And, The Game 
will not pay for the Candle 
" IX. Don't Use your Pen, and Lose your Time, in Eris- 
tic Writings, any more than unquestionable Duty and Pru- 
dence makes to be absolutely Necessary. Writing upon a 
Point, and in the Way and Strain of Controversy, will not 
only have a Tendency to discompose the Peace of your Mind, 
but miserably Divert the Studies of a short Pilgrimage, from 
such things as would be much more Profitable for your self 
and others. Anon, the Grand Point of the Controversy will 
be, only Who has most Wit or Grace of the Two, you, or your 
Antagonist. A mighty Business! If Jerom were pleased in 
an Hectoring way to forewarn his Opponents, that he was, 
Cornuta Bestia; I hope you won't be so. 
" X. If Calumnious Quills have publickly scratched you,- 
An Respondendum semper Calumniis?-No. Look as far 
back as Two Thousand Years ago, and you will find even a 
Plato giving a Pattern to a Christian, in his declining to take 
any Notice of the Invectives which a Xenophon had used 
upon him.-It may be, the Scribblers, are sorry Scoundrels, 
and such vile Children of Sheth, as it is beneath you to let 
them know that you have so much as read their Follies.-Or 
be they what they will', for the most part, the best way will 
16 be to. Shine on, Regardless of what the Batts and Owls may 
mutter against you. Or, if that Metaphor be too Sublime, 
let me say, At least As the Moon among the lesser Fires, keep 
a steddy Pace, Walking in your Brightness, notwithstanding 
the unregardable Allatrations of your Adversaries. If they 
persecute you with Libels, His a notable Hint, that Le Clerc 
has given you. Instead of answering them, write such learned 
and useful Books, as will be of perpetual Service to Mankind. 
These will procure such a casting and lasting Testimony for 
you, that there will need no more to make a Man ill tho't 
of, than this; That he was a Thersites to you, and one that 
wrote against you. These Books will be durable Monuments 
of your Valuable and Honourable Character, when the Libels 
of these poor Animalculicuncles will perish among the Wast- 
Paper, which the Haberdashers of small Wares have occasion 
for. 
" And if any Preacher should be so impertinent as to have 
any Girds at you in the Pulpit, remember the Advice of the 
sweet-spirited Melancthon to Vitus Theodorus, when the hot- 
spirited Osiander had preached against him; I charge you, 
Don't Answer the Man; Hold your Peace; Go on in your 
Ministry as if you had heard nothing!-The Gentleman soon 
found his Account in hearkening to his Candid Adviser. 
" That what I am driving may stick, you shall have it in 
the Form of two old Rusty Nails; The One, Magnum Contu- 
meliae Remedium Negligentia; The other, Site, et funestam 
dedisti Plagam. 
11 As wicked a Fellow as ever polluted a Pen, yet has this 
Passage worth transcribing from him, while his Name is not 
worth mentioning. ' The Malice of III Tongues cast upon 
' a Good Man, is only like a Mouthful of Smoke, blown upon 
' a Diamond, which tho' it clouds its Beauty for the present, 
'yet it is easily rubb'd off, and the Gem restored with little 
' Trouble to its Genuine Lustre. But an Honester Pagan than 
he, has told you, Perditi Hominis profligatique Maledictis, 
nullius Gloria dignitasq; Violatur. Old Cicero tells you 
so. . . . 
[299] 
17 [299] 
" XII. While you are yet in your Younger Years, be always 
furnished with a Stock of Weighty and Useful Questions. By 
wisely and humbly offering These, and with the Modesty of 
One desiring to be Instructed, you may commonly lead the 
Conversation, even with your Superiours, & almost necessi- 
tate a Profitable Conversation. You may be, as R. Jeremy 
was called, The Master of the Questions. A Discretion in 
this point, is a distinguishing Thing. But whenever you are 
Arguing, ordinarily propose every Thing rather Socratically 
than Dogmatically. Be not Positive; much less Clamorous; 
least of all Furious. But keep up an Air of Modesty, and 
carry on your Discourse, in the form of proper Questions; 
and as one willing to be instructed by him whom you are 
disputing with. 'Tis an Excellent Wisdom, this; To Argue 
Handsomely. . . . 
" XVII. If you have laid up an Inexhaustible Store of 
Stories, accommodated unto all the Purposes of the Profitable 
and the Agreeable, and have the Skill of telling them Hand- 
somely, and with a Deliberate, Expressive, Unstumbling 
Brevity, and produce them on many occasions, you may not 
only Ingratiate yourself wherever you make your Appear- 
ance, but also obtain almost any Request that you shall make 
one of them a witty Introduction to. The Precious Stones 
that every one sets a Value on, are called Pleasant Stones. 
But let not your Pleasancy, degenerate into any unbecoming 
Levity. Forever so Regulate it, and so Moderate it, that it 
may Gracefully Terminate in the most Serious Discourse, 
and if it may be, in the Inculcation and Insinuation of some 
serious Maxim, which may be Good for the Use of Edify- 
ing. . . . 
" XIX. It may not be amiss for you to have Two Heaps. 
An Heap of UNINTELLIGIBLES; and an Heap of IN- 
CURABLES. Ever now and then you will meet with some- 
thing or other, that may pretty much distress your Thoughts; 
But the shortest Way with the Vexations will be, To throw 
them into the Heap they belong to, and be no more distress'd 
about them. 
[300] 
" You will meet with some Unaccountable and Incompre- 
18 hensible Things; particularly, in the Conduct of many 
People. Throw them into your Heap of Unintelligibles ; leave 
them there. Trouble your Mind no further; Hope the Best, 
or Think no more about them. 
"You will meet with some Unperswadeable People; No 
Counsel, no Reason will do any Thing upon the Obstinates: 
Especially, as to the making of due Submissions upon Of- 
fences. Throw them into the Heap of Incureables. Leave 
them there. And so do you go on to do as well as you can, 
what you have to do. Let not the Crooked Things that can't 
be made str eight, encumber you. 
" XX. 'Tis a Trespass on the Bules of Prudence, never to 
know, when to have done. Wherefore, I have done!" 
[300] 
19 Gonorrhoeal Septicemia and Endocarditis. 
BY 
W. S. THAYER, M.D., 
OF BALTIMORE. 
FROM THE 
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 
November, 1905. Extracted from the American Journal of the Medical Sciences, November, 1905 
ON GONORRHOEAL SEPTICAEMIA AND 
ENDOCARDITIS. 
BY 
W. S. THAYER, M.D., 
OF BALTIMORE. 
The comparative frequency of gonorrhoeal septicaemia and 
endocarditis may be regarded as generally recognized, and, since 
the positive results obtained by Blumer,2 Lazear,3 and the writer,4 
abundant proof of the specific nature of the infection in many 
of these cases has been accumulated. At the same time the 
observations of many students have shown that a demonstrable 
septicaemia may exist in connection with various complications 
other than endocarditis. 
While the communication of Gurvich5 has made evident the 
fact that gonorrhoea may be followed by mild forms of valvular 
disease, those cases which have particularly attracted the attention 
of clinicians have been instances of grave malignant endocarditis. 
The clinical picture of these cases differs in no essential particular 
from that associated with ulcerative endocarditis from other 
causes. 
The development of symptoms suggestive of septicaemia with 
fatal results, consecutive to gonorrhoea, without evidence intra 
vitam of any focal complication, is also an occurrence of no great 
rarity. In most of these instances, however, necropsy reveals 
some local focus of infection outside of the urethra. Dr. Osler, 
1 Read before the Association of American Physicians, May, 1905. 
2 Thayer and Blumer. Endocardite ulc^reuse blennorrhagique. Septicemie d'origine 
blennorrhagique. Arch, de mdd exper. et d'anat. pathol., 1895, vol. vii., p. 701; also, Johns 
Hopkins Hosp. Bull., Baltimore, 1896, vol. vii., p. 57. 
3 Thayer and Lazear. A second case of gonorrhceal septicaemia and ulcerative endocarditis 
with observations upon the cardiac complications of gonorrhoea. Jour. Exper. Med., New 
York, 1899, vol. iv., p. 81. 
4 Thayer. Gonorrhceal endocarditis and septicaemia. Compt. rend. cong. internal, de m6d. 
1897, Mose., 1899, vol. iii., p. 5, sec. 350-367. 
5 Russk. Arch. Patol. klin. Med. i. Bakt., 1897, vol. iii., p. 329. 2 
THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
for instance, tells me of a case of lethal septicaemia consecutive to 
gonorrhoea, which presented, during life, no localizing symptoms, 
where, at necropsy, the only focal lesion to be found was a pros- 
tatic abscess no larger than the end of the thumb. A similar case 
was under my care thirteen years ago, in which, however, no 
necropsy was obtained. A young man of twenty-two developed, 
in connection with an acute urethritis, an intermittent fever of 
extreme severity. Observed for several weeks in the hospital, the 
heart sounds were perfectly clear, and no evidence of any localiza- 
tion of the infection was to be detected beyond the history of a 
very slight arthritis, which had entirely cleared up. The patient 
died several weeks after leaving the hospital. 
Padula,1 in 1892, described a form of mild continued or inter- 
mittent fever which he had observed in a number of instances of 
gonorrhoea, sometimes in simple cases, but more particularly in 
those with complications. After running a course of several 
weeks' duration the fever disappeared. 
From our present knowledge of the biological characteristics 
of the gonococcus it is natural to regard these cases, both mild 
and severe, as instances of true septicaemia. While this is well 
known to be the case in the more severe cases, the proof of the 
existence of septicaemia has not as yet been afforded in the milder 
instances. 
It was, however, our good fortune last summer to observe an 
instance of continued fever of about seven weeks' duration 
occurring in a case of acute gonorrhoea, without apparent com- 
plications, in which the existence of a septicaemia was established 
by cultures from the blood. The case will be described later in 
this communication. 
Our experience with gonorrhoeal endocarditis and septicaemia in 
the Johns Hopkins Hospital has been rather interesting. Apart 
from the eight cases reported by Blumer,2 Lazear,3 Harris and 
Dabney,4 Johnston,5 and myself,6 there have occurred two recent 
instances of ulcerative endocarditis of gonorrhoeal origin, to which 
I shall refer later, making in all six cases in which gonococci 
were positively identified by cultures from the blood intra vitam 
(Thayer and Blumer), from the local lesions at necropsy (Harris 
and Dabney, Case I.; Thayer, Case II. of this communication), 
or by both methods (Thayer and Lazear, Harris and Johnson, 
and Thayer, Case III. of this communication). 
1 Febbre infettiva da virus blennorrhagico. Roma, 8vo., 1892. 
2 Op. oit. 8 Op. cit. 
4 Report upon a case of gonorrhoeal endocarditis, etc. Johns Hopkins Hosp. Bull., Balti- 
more, 1901, vol. xii., p. 68. 
6 Harris and Johnston. Gonorrhoeal endocarditis, with cultivation of the specific organism 
from the blood during life. Johns Hopkins Hosp. Bull., Baltimore, 1902, vol. xiii., p. 236. 
• Op. cit. THAYER: GONORRHCEAL SEPTKLEMIA AND ENDOCARDITIS 
3 
In one case (Harris and Dabney, Case IL) the presence of 
characteristic organisms at necropsy, taken in connection with 
the absence of growths on ordinary media, afforded almost posi- 
tive proof of the specific nature of the infection. 
In three cases (Thayer and Lazear, Case XXXII. of the table, 
and Harris and Dabney, Cases HI. and IV.), with an evident 
mixed infection, organisms were found at necropsy microscopically 
and tinctorially characteristic of gonococci. In one of these (Har- 
ris and Dabney, Case III.) diplococci, morphologically and tincto- 
rially characteristic, were found in the pericardium, while cultures 
from the same source were negative. In the other two cases, 
although the cultures from the valves showed other organisms, 
the infection clearly followed an acute gonorrhoea without other 
apparent cause. 
In addition to these instances I have, in the past six years, seen 
in consultation four cases in which an ulcerative endocarditis has 
followed gonorrhoea. In only one of these instances were cul- 
tures taken intra vitam, and here streptococci were obtained. In 
one other, in which the necropsy revealed an ulcerative mitral 
endocarditis, an unidentified bacillus was cultivated. In all of 
these cases, however, the connection of the urethritis with the 
development of the symptoms, was such as to make it probable 
that the acute infection had served as the portal of entry. Such 
an experience as this is sufficient to emphasize the fact that an 
acute urethritis is by no means infrequently followed by an endo- 
carditis, either of specific gonorrhoeal nature or due to secondary 
or mixed infections which have found their portal of entry in 
the urethritis or have settled later upon the primarily infected 
valves. 
The last two hospital cases, which will be reported at the end of 
this communication, presented the usual features of ulcerative 
endocarditis-irregular, intermittent fever, chills, progressive 
anaemia, and nephritis-developing on the one hand in a case 
of acute gonorrhoea with arthritis about five weeks after onset, 
and in the other during a demonstrable urethritis, which the 
patient, a colored man, denied. It is interesting that in both of 
these cases, with a pure aortic lesion, there was a well marked, 
presystolic, rumbling (Flint) murmur, suggestive of mitral in- 
volvement. In one of the cases, indeed, a diagnosis of mitral 
diseasewas made. Cultures from the blood during life were posi- 
tive in one, negative in the other. In both cases pure cultures 
of the gonococcus were obtained at necropsy from the affected 
valves. 
The remaining case, which is regarded as of especial impor- 
tance, is an instance of gonorrhoeal septicaemia, with continued 
fever of seven weeks' duration. 4 
THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
Case I.-Male, aged twenty-eight years; gonorrhoea; posterior urethritis; 
continued fever of seven weeks' duration suggestive of typhoid; gonococci obtained 
in pure culture from, the circulating blood; recovery. 
Hospital No. 47,439; Medical No. 17,342. X., aged twenty-eight years, was 
admitted to the Johns Hopkins Hospital on 17th July, 1904, complaining of 
headache, fever, and a general "run-down" condition. 
Family History. Mother, living and well. One brother has some trouble 
with his stomach. One brother and one sister died in infancy. Family 
history, otherwise good. 
Previous History. Has always been strong and well. As a child, had 
scarlet fever, chicken pox; thinks that he had typhoid fever at the age of six 
or seven. Eight years ago he had two sores on his penis which were said to 
be chancres. He was treated constitutionally and had no secondary symptoms. 
Later, he has been assured by physicians that the lesions were chancroidal. 
Four years ago he had an attack of gonorrhoea with posterior urethritis. Three 
months ago, had a second attack, which has continued active to the present 
time. Has been a moderate drinker until eighteen months ago, since when 
he has been abstemious. 
Present Illness. On 10th July, on the first day of a vacation, while in the 
country, he was seized with a severe headache and fever; no chills. On the 
following day he was seen by Dr. S. Sydney Kellum, of Bellhaven, Virginia, 
who found that he had a temperature of 103.5° and was restless, complaining 
of severe pains in his head and back. He complained of having felt "weak 
and bad" for a week or so. The tongue was coated; the pulse about 90. The 
patient was given a laxative. On the following morning the temperature was 
'99.8°. He was up and about. R-Quin, sulph., gr. iv, every four hours. In 
the afternoon, however, his temperature was 102.6°. On the three following 
days the condition was about the same. On the evening of the 15th of July the 
temperature was 103.6°. The splenic dulness was slightly increased and there 
was some tenderness on pressure. On entering the hospital the patient had 
complained only of severe headache, fever and constipation. His mind was 
much taken up with the fear that he had lues. 
18th July, 1904. Red blood corpuscles, 5,024,000 to the cubic millimetre; 
leucocytes, 9000 to the cubic millimetre; haemoglobin, 92 per cent. Smears 
from the urethral discharge, which was fairly profuse, showed large numbers 
of gonococci. 
1 Oth July. On this date Dr. Cole noted that the patient was well nourished; 
face flushed; mental condition quite clear and bright. He moved himself in 
bed readily and did not appear very ill. The tongue had a thick yellow coat; 
pupils widely dilated. The chest was well formed; expansion good and equal; 
everywhere resonant. Auscultation, clear throughout. 
Heart. Point of maximum impulse was seen and felt in the fourth inter- 
space just inside the mammillary line. The dulness extended just to this point. 
There was no dulness to the right of the sternum. The heart sounds were 
everywhere clear and regular. Pulse regular, 23 to the quarter, of good force 
and volume; no dicrotism. The vessel wall was not thickened. The abdomen 
was full, though not distended. There was no abdominal pain; no tenderness. 
The edge of the spleen was felt about a finger's breadth below the costal 
margin, hard and not tender. Over the entire body, especially on the chest 
and thighs and also on the face, forearms and hands there was a diffuse 
slight mottling of the skin. At places these small bodies are slightly raised, 
particularly on the forearms; no characteristic rose spots. There was a slight 
urethral discharge. 
20th July. On this date I saw the patient, noting that the spleen was dis- 
tinctly palpable, well below the costal margin. 
23d July. Leucocytes, 8900. The temperature had ranged daily between 
99° and 103° with regular morning remissions. The blood was negative for THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
5 
malarial parasites. On the evening of the 23d the temperature reached 103.8°^ 
being affected little by sponging. After an ice sponge at 10 o'clock at night, 
however, the temperature fell to 98.4°, rising, however, soon afterward to 102° 
at 4 a.m. There was a slight chill on the afternoon of the 23d. 
24i/t July. Dr. Cole noted that the lungs were clear throughout. 
Heart. Impulse not seen or felt. Sounds best heard in the fourth and 
fifth spaces just inside the mammillary line; clear. Pulse, 27 to the quarter, 
of moderate volume and tension, a trifle irregular. 
25th July. The temperature remained elevated, being 101.2° at eight in the 
morning. Fresh and stained blood was negative for malarial parasites. On 
this date Dr. Thayer noted that the patient was in good condition. The 
tongue had a pasty coat; the abdomen was natural. 
Heart Apex impulse is not sharply defined; it is, however, felt just outside 
the mammillary line, in the fifth space, 12.5 cm. from the midsternal line. The 
dulness extends 0.5 cm. outside of this and 4.5 cm. to the right, the greatest 
diagonal dulness being 15 cm. The sounds, loudest at the point of maximum 
impulse, are clear excepting for a slight reduplication of the first sound which 
is rather better heard over the right ventricle. In the pulmonic area the 
second sound is sharp and clear, no reduplication. The sounds are also clear 
in the aortic and tricuspid areas. 
On the 26th, the patient complained slightly of a sore throat, the pharynx 
being a little injected. The right tonsil was slightly swollen with two small 
white follicular plugs. The pulse was about 25 to the quarter, of good quality, 
regular, nothing new on examination of the heart. There were a few rather 
suspicious papules on the abdomen suggestive of rose spots although not 
wholly typical. There was no tenderness and no distention of the abdomen. 
Widal tests, made on the 21st and on this date, were entirely negative. A 
rectal examination showed that the prostate was small, soft and rather tender. 
There were no nodules in the seminal vesicles. There was a marked right 
varicocele, while the left epididymis appeared to be somewhat indurated near 
the globus minor. The temperature, which had been above 104° on the two 
preceding days, fell lower in the morning, rising only to 103.6° at night. On 
the 27th the general range was a little lower. The leucocytes were 9000 to 
the cubic millimetre. 
28th July. It was noted by Dr. Thayer that the heart sounds were clear at 
the apex and base and in the tricuspid area. At the end of inspiration the 
first sound in the pulmonic area was a little prolonged. 
The diagnosis throughout had been regarded as lying between a gonorrhoeal 
septicaemia associated with an endocarditis, or typhoid fever. Despite the 
slight increase in leucocytes we had been growing more inclined to regard 
the case as one of typhoid fever. It was deemed wise, however, on this date, 
to take cultures from the circulating blood. These were accordingly made 
by Dr. Brush. 1.5 c.c. of blood were therefore withdrawn in the usual manner 
from the median basilic vein, from which two agar plates were made. The 
vein was then cut down upon and about 7.7 c.c. obtained from which one 
agar plate was made. 
At 8 p.m. on this day the patient complained of pain in the lower prsecordium, 
and to the right of the sternum. No friction rub, however, was heard. 
2^th July. The temperature still remained elevated, ranging between 99.6° 
and 102.8°. The spleen was readily palpable. The heart sounds were quite 
clear. There were several suspicious rose spots. Pulse, 22 to the quarter, 
regular, not dicrotic. During the next several days there was little change 
in the condition of the patient. 
Results of cultures taken on 28th July. In twenty-four hours there was a 
diffuse growth of minute grayish colonies on the first two plates, those in 
which the smaller quantity of blood was used. In the third plate there were 
a very large number of colonies of bacillus subtilis, a contamination. 6 
THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
Subcultures on blood agar from the first two plates yielded a faint growth 
of discrete, pin-point, almost translucent colonies composed of a diplococcus, 
which was almost entirely decolorized by Gram. Transferred to agar there 
were, in twenty-four hours at 37°, many pin-point, discrete grayish colonies 
unchanged in forty-eight hours and twelve days. On the plain agar slant 
there were very delicate, pin-point, slightly elevated, translucent islands along 
the smear. No change in forty-eight hours or twelve days. There was no 
growth on glucose agar, potato, bouillon, or litmus milk. The colonies consisted 
of biscuit-shaped diplococci growing in pairs, tetrads and short chains. They 
were immobile and decolorized by Gram's method. The cultural as well as 
the morphological and tinctorial characteristics justified the diagnosis of gono- 
coccus. 
From this time on there was a gradual fall in temperature. On 3d August, 
the temperature at eight in the morning, was 100.5°; leucocytes 12,000 to the 
cubic millimetre. The patient had been fairly comfortable, though there was 
a regular evening exacerbation of . the fever and often slight chilly sensations. 
There was some little headache. The urethral discharge had disappeared. 
4th August. On this date, Dr. Cole noted that the pulse was of good 
quality, 24 to the quarter; the tongue was still coated; the spleen readily 
palpable; the heart sounds clear. During the 6th, 7th and 8th the temperature 
gradually fell. On the 9th the highest point reached was 99.6°. On this date 
Dr. Cole noted that the patient's general condition was excellent; the tongue 
was clean; the heart sounds were clear. For the two preceding days the 
patient had complained of slight pain in the lower abdomen, but there was 
little or no tenderness and no distention. Leucocytes, 10,000 to the cubic 
millimetre. From this time on the temperature remained below 100°, excepting 
for a slight exacerbation to 100.8° on the 19th and to 100.4° on the 24th. 
On 28th August it was noted that the point of maximum cardiac impulse 
was in the fourth interspace, 9.25 cm. from the midsternal line, the dulness 
Teaching about to that point and 3.5 cm. to the right at the fourth rib. There 
was a slight cardio-respiratory souffle at the apex and a very slight scratchy 
murmur along the left sternal margin and in the pulmonic area. Pulse, 26 
to the quarter, frequently a little irregular. 
From this time on the patient steadily improved. There remained, however, 
a slight urethral discharge. 
16th September. On this date, the day before his discharge, it was noted 
that the patient's convalescence was uninterrupted; he was gaining rapidly 
in weight and strength. His color was good. There was slight dyspnoea on 
walking. The patient was, however, very nervous. 
Heart Point of maximum impulse not clearly seen or felt. Sounds best 
heard in the fourth interspace 9.5 cm. to the left of the median line. Relative 
cardiac dulness extends just to this point and 6 cm. to the left in the third 
interspace. To the right the dulness extends 5 cm. at the fourth rib. The 
sounds are well heard, clear and of normal relative intensity at the apex and 
base. In the pulmonic area there is still a short, rather slight systolic murmur 
heard over an area a little larger than the bell of the stethoscope and not 
transmitted. The pulmonic second is well heard, not accentuated. 
17th September. The patient left the hospital in excellent general condition. 
The urine, repeatedly examined during the patient's stay in the hospital, 
showed nothing remarkable, excepting a sediment containing at first much 
pus, which, however, disappeared in great part later. On several occasions 
there was a slight trace of albumin. 
In response to a letter the patient called to see me on 11th February, 1905. 
He stated that he had been perfectly well since discharge excepting for the 
fact that he was still under Dr. Young's treatment for his posterior urethritis. 
He looked perfectly well. The pulse at the beginning of examination was 
22 to the quarter, of fair size and duration, not remarkable in quality. The THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
7 
maximum blood pressure by the Cook instrument with the broad band was 
124; minimum about 108. 
Case I.-Gonorrhoeal septicaemia. 
Fig. 1 
August 
July 8 
THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
Heart. Point of maximum impulse, in the fifth space, a trifle inside 
the mammillary line. Relative dulness at the third rib; extends 2.7 cm. to the 
right of the midsternum and just outside the point of maximum impulse. 
Maximum diagonal dulness about 14.5 cm. The first sound at the apex is 
perfectly clear; second sound, clear. The sounds were also clear at the tricuspid 
pulmonic and aortic areas excepting for a very soft systolic souffle heard only 
at the base, louder in the pulmonic area, and an occasional reduplication of 
the second sound with inspiration, which was more marked on deep breathing. 
The heart's action is perfectly regular. There is no evidence of any cardiac 
lesion. 
Here, then, was a patient with vague, general symptoms of 
headache, backache, and general malaise, continued fever, a 
thickly coated tongue, a palpable spleen, and suspicious rose 
spots. These general symptoms, which lasted seven weeks, were 
not unsuggestive of typhoid fever. In view, however, of the cul- 
tures and the course of the case the condition was clearly due to 
gonorrhoeal septicaemia. Our suspicion throughout was that there 
might be an endocarditis, but at the subsequent examination, five 
months after his discharge, there was no evidence of cardiac 
involvement. If an endocarditis was present it must have been of 
so slight a degree as to leave no appreciable permanent damage. 
The main points of interest in these observations would seem 
to be: 
1. The demonstration of the fact that the mild, continued fever 
sometimes seen in connection with gonorrhoea without apparent 
complications is, in some instances at least, evidence of a true 
gonorrhoeal septicaemia. 
2. A true gonorrhoeal septicaemia in cases in which there is no 
evidence of local complications may run a course not dissimilar 
to that of typhoid fever. 
3. In doubtful cases of continued fever associated with gonor- 
rhoea the possibility of a gonorrhoeal septicaemia should always be 
borne in mind. 
CASES OF ULCERATIVE ENDOCARDITIS FOLLOWING GONORRHOEA. 
A. Two Instances of Pure Gonorrhoeal Endocarditis with Autopsy. 
Case IL-Male, aged twenty-one years; gonorrhoea; septicaemia; ulcerative 
endocarditis of the aortic valve with Flint murmur; death; autopsy. 
Hospital No. 48,901; Medical No. 17,794. C. L., colored, male, aged twenty- 
one years, cart driver, entered the Johns Hopkins Hospital on 14th November, 
1904, complaining of a cold, shortness of breath and cough. 
Family History. Parents living and well. One brother and one sister, 
living and well. No family history of tuberculosis. 
Previous History. Patient has always been strong and well. Denies acute 
infections including venereal disease. Neither drinks nor smokes. Has 
always done manual labor. Has been married sixteen months; wife is well. THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
9 
Present Illness. Three weeks prior to entry he was exposed to a rain storm, 
working all day in his wet clothes and suffering from chilly sensations. On 
the following day he had a "cold" and a slight hacking cough for which he 
took medicine for two weeks without benefit. By the end of the second week 
(6th November) he noticed shortness of breath after coughing and on exertion, 
particularly on walking fast or going up stairs. There was considerable 
expectoration of "phlegm." On the morning of admission he noticed, for the 
first time, oedema of his feet and legs. There has been nausea and vomiting 
on several occasions. On the day of entry the following note was made by 
the house physician, Dr. Giffen: "The patient is a very well developed young 
man. Pupils are equal; tongue slightly coated; mucous membranes of good 
color. Superficial glands of the neck are palpable but not markedly enlarged. 
There is marked sclerosis of the veins of the arm. 
"The thorax is well formed; angle wide; expansion equal. Vocal fremitus 
diminished over the left upper lobe; percussion clear throughout. Crackling 
rales are heard just above and below the right clavicle, as well as a few in the 
upper part of the right interscapular space and at both apices. 
"Heart. Point of maximum impulse in the sixth interspace, 8 cm. from the 
midsternal line. Relative dulness extends 10 cm. to the left at the apex, 4 cm. 
to the right of the median line. Pulsation in the temporal artery is visible; 
presystolic venous wave in the neck; slight precordial pulsation. On palpation 
there is an impulse with both systole and diastole. The pulse is definitely 
collapsing, of small volume and pressure, 28 to the quarter. The vessel wall 
is sclerotic. On auscultation at the apex there is a resonant, rumbling diastolic 
murmur followed by a sharp first sound. The second sound is indistinct. At 
the base there is a rough diastolic, heard in the second right interspace, loudest 
in the third left interspace. The two sounds are very sharp and snapping, 
the pulmonic much accentuated. A diastolic murmur is heard over the body 
of the heart. 
"The abdomen is slightly full. Relative hepatic dulness begins at the sixth 
right rib and extends three fingers' breadth below the costal margin in the 
mammillary line. The spleen is not palpable. There is oedema of the feet and 
slight oedema of the legs; genitalia normal." 
Blood. Red blood corpuscles, 4,480,000 to the cubic millimetre; colorless 
corpuscles, 9700 to the cubic millimetre; hsemoglobin, 90 per cent. 
The temperature, which, on entrance, was 98.6° fell by 8 p.m. to 98.2° and 
to 95.6° at 8 the following morning. At noon on 16th November it was 96.2°. 
16th November. At 9 o'clock the following note was made by Dr. Thayer: 
"The patient is propped up in bed. There is well marked throbbing of the 
carotids. The tongue has a white coat. The pulse is regular, 27 to the 
quarter, of moderate size, abrupt, suggestive of a Corrigan pulse, though by 
no means typical." 
"Thorax, symmetrical; costal angle of about 90°; precordial region a little 
fuller than on the right side. Point of maximum impulse visible in the sixth 
interspace 9.7 cm. from the midsternal line. Impulse, not particularly strong. 
Relative dulness extends just beyond the point of maximum impulse and 
3.8 cm. to the right of the midsternal line. The maximum diameter of the 
area of dulness is 15.5 cm. At the apex there is a distinct thrill felt best in 
the sixth interspace inside the point of maximum impulse and leading up to 
the impulse. At the apex a rumbling, presystolic murmur is heard ending in 
the first sound which, though feeble, is abrupt. The second sound is replaced 
by a soft, distinct, diastolic murmur. Immediately above and outside the 
impulse the diastolic murmur becomes more audible, and in the axilla, where 
the presystolic murmur has wholly disappeared, a dull humming first sound 
and a loud diastolic murmur are clearly heard. Passing inward in the sixth 
space the first sound becomes louder and the rumble is distinct; the diastolic 
murmur is feeble. Above the sixth rib, within the parasternal line, the pre- 10 
THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
systolic murmur disappears and there is heard a fairly sharp first sound and 
a distinct second sound with a loud aortic diastolic murmur. In the second 
and third left interspaces the first sound is dull and humming, the second 
sound intensely accentuated. In the second right interspace there is a famt 
systolic and a distinct diastolic murmur. An element of the second sound is, 
however, heard. The diastolic murmur is best heard in the fourth left inter- 
space. In the carotids there is a faint systolic hum; in the femorals, a distinct, 
short systolic tone.1 
" Lungs. There are still a few rales at both apices and an explosion of fine 
rales on slight cough at the right apex. When propped up in bed the liver is 
not palpable. By percussion, it extends apparently just below the costal 
margin in the mammillary line." 
Examination of the fresh blood shows no malarial parasites. Leucocytes, 
24,000 to the cubic millimetre. 
18th November. The temperature which was normal on the morning of the 
16th, rose in the afternoon to 102° and fell again to a subnormal point by the 
following noon, rising, however, again in the afternoon. On the morning of the 
18th it was 95.7°; by noon, 102.2°. A note made shortly after this by Dr. Cole, 
states that the patient was very ill; respirations 10 to the quarter; pulse 28 to 
the quarter, forcible, of large volume-a typical Corrigan pulse. The cardiac 
impulse was 10 cm. from the midsternal line. There was a slight presystolic 
thrill. The shock of both sounds was well felt. The first sound at the apex 
was loud and snapping and followed by a very short systolic murmur. It was 
preceded by a very loud rumble heard throughout almost the whole of diastole 
and running into the first sound. This disappeared as one passed outward, 
and a soft, blowing, diastolic murmur was heard throughout the whole period. 
Over the body of the heart both sounds were loud and booming. A soft 
to-and-fro murmur was heard along the left sternal margin, the diastolic being 
louder than the systolic. Along the right sternal margin, at the base of the 
heart, these murmurs were superficial, and over the sternum at the level of 
the second intercostal space, there was a scratching sound almost suggestive 
of friction. In the first and second right and left interspaces and over the 
subclavians there was a rather coarse systolic murmur differing in quality 
from that heard elsewhere. Leucocytes, 22,500 to the cubic millimetre. 
19th November. The intermittent fever still continued. The following note 
was made by Dr. Thayer: "The patient looks very ill, the face is puffy, the 
pulse larger than formerly, 21 to the quarter, definitely collapsing; there is no 
great change in the position of the apex impulse. 
'"Heart. The first sound is fairly sharp, and the diastolic murmur is suc- 
ceeded by a long rumble followed by a slight first sound. As one passes above 
the fourth rib there is a slight systolic and diastolic murmur associated with 
an intensely accentuated second sound, most marked in the third left space. 
The diastolic murmur is loudest at the fourth cartilage. In the aortic area 
there is a short to-and-fro murmur. The dulness extends 4 cm. to the right 
of the midsternal line." 
The irregular temperature still continued and two days later, on the 21st, 
it was noted by Dr. Thayer that the pulse seemed larger than formerly. "A 
little inside the nipple the first sound is rather abrupt and loud and the mid- 
diastolic rumble particularly intense. At the parasternal line the mid-diastolic 
rumble becomes feeble, the second sound sharper, and the soft early diastolic 
more audible. The accentuation of the second pulmonic sound is extra- 
ordinary." A tracing from the radial pulse was suggestive of aortic insuf- 
ficiency, the pulse at this time being 36 to the minute and the maximum 
pressure (Riva-Rocci, narrow band) 103 mm. 
Irregular, intermittent fever still continued, the temperature ranging between 
1 Ventricular systole. THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
11 
97° and 103°. On the 23d the following note was made by Dr. Thayer: 
"The pulse is much larger than formerly and definitely collapsing. The point 
of maximum impulse is in the sixth space, 10.8 cm. from the midsternal 
line. There is a well marked thrill at the apex which is associated with the 
impulse, whether diastolic or systolic, it is difficult to tell by palpation. The 
rumble is clearly presystolic. The first sound is very feeble. Inside the apex 
there is a rumble leading up to a fairly sharp first sound. As one passes inward 
a soft systolic murmur becomes audible in addition to the diastolic. There is 
a to-and-fro murmur in the aortic area and along the left sternal border. The 
vessels of the neck pulsate markedly. The patient was distinctly losing ground." 
On examination of the urethra a purulent discharge was discovered, the 
smears showing many pus cells and a moderate number of intracellular 
diplococci decolorizing by the method of Gram. 
On the following day Dr. Cole noted that the patient was much worse. 
The respirations were 64, gasping; pulse 30 to the quarter, of Corrigan quality; 
marked throbbing of the vessels of the neck. The resonance over the 
left front was impaired, numerous medium and coarse rales being audible, 
while at the apex, the breath sounds were harsh with many fine crackling 
Fig. 2 
Case II.-Radial pulse, 21st November, 1904. 
rales and prolonged expiration. High up in the axilla the breath sounds were 
tubular, and numerous coarse rales were heard in both backs. There was no 
great change in the cardiac signs. During the day the patient became very 
noisy and the pulse was extremely rapid. In the evening stupor came on, 
Followed by death at half-past 1 in the morning of 25th November. 
The urine was free from albumin throughout, the specific gravity varying 
from 1012 to 1025. There were, however, occasional hyaline and granular 
casts and a varying number of leucocytes in the sediment. 
The blood pressure, taken by the Riva-Rocci apparatus with the old, narrow 
band, was extremely low, the records ranging from 110 to 96 on the day of 
death. 
On 18th and 21st November cultures were taken from the circulating blood. 
On the first occasion, 7 c.c. of blood were distributed upon one plate and two 
flasks. On the second occasion 20 c.c. of blood were distributed among three 
plates and three flasks. The cultures were negative. 
In view of the discovery of the urethritis the diagnosis was gonorrhoeal endo- 
carditis. The remarkable accentuation of the second pulmonic sound, together 
with the loud, rumbling presystolic murmur and the rather abrupt first sound 
led us to a diagnosis of a combined mitral and aortic lesion. The necropsy,, 
however, revealed a pure aortic endocarditis. 
Necropsy (No. 2424) by Dr. MacCallum, nine hours after death. 
Anatomical diagnosis: Acute vegetative and ulcerative endocarditis; broncho- 
pneumonia; oedema of the lungs; parenchymatous degeneration of the kidneys; 
infarctions in the kidneys and papillary muscles of the heart; cardiac hyper- 12 
THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
trophy and dilatation; epicardial fibroid nodules; beginning arteriosclerosis; 
ecchymoses in the mucosa of the bladder. 
The heart is greatly enlarged; the enlargement of the left ventricle being 
especially prominent. The arteries are covered with complete chains of 
epicardial nodules. There is a thick, irregular, tendinous patch over the 
front of the right ventricle. The surface of the heart is, in general, smooth 
except for the epicardial nodules. The fat over the heart is gelatinous and 
■dark yellow. The apex of the left ventricle projects at least 3 cm. beyond that 
of the right and constitutes the point of the heart. The right auricle is dis- 
tended with post mortem clot. Its lining is smooth. The auricular appendage 
also contains a post mortem clot. The tricuspid and pulmonic valves are 
normal in appearance. The blood clot is very firm and makes a perfectly 
distinct mould of the valve. The mitral valve is normal in appearance. The 
chordae tendineae are delicate. The papillary muscles of the anterior leaflet 
show, however, an opaque patch of yellowish color bounded by a zone of dark 
red. On section this appears to be a necrotic, coagulated area surrounded by 
a zone of hemorrhage. On opening the aorta it is found that the edges of the 
valves are all delicate. The right coronary segment and the middle segment 
are normal throughout. The left coronary segment, however, has suffered 
a great change. The edge of the valve throughout is quite delicate. The base 
of the valve, however, is covered with large vegetations, and an extensive 
erosion of the tissue has taken place, so that the whole floor of the sinus of 
Valsalva is destroyed and the scissors can be passed from the left ventricle 
into the aorta through the open floor of the left coronary sinus of Valsalva. 
The valve thus remains as a bridge across the aorta from the lower edge of 
which there hang large irregular vegetations. The sinus is covered everywhere 
by rough vegetations. The remains of its floor project outward and are 
roughened in the same way. The sinus has been extended by ulceration into 
the wall of the left ventricle, especially anteriorly and toward the left where 
a cavity has been hollowed out in the upper portion of the wall of the left 
ventricle just behind the anterior mitral segment. The chief mass of vegetation 
which hangs in the blood stream and is covered with blood clot, measures 
about 18 mm. in length. It is soft and friable and has a folded, irregular, 
jellow surface. The post mortem clot may be pulled off from it like a glove 
finger leaving it quite clean and uniformly grayish yellow. The apices of all 
•of the mitral papillary muscles are crowned by areas of necrosis. The heart 
muscle is fairly firm and the wall of the left ventricle measures about 2 cm. 
in thickness. On tangential section the muscle is very opaque and much 
mottled with pale grayish and dark red areas. The coronary arteries show 
no marked sclerosis. There is a uniform roughening of the intima, especially 
in those areas where the epicardial nodules have developed. The endocardium 
is elsewhere smooth. That of the left ventricle has spots of opacity shining 
through. The right ventricle measures about 4.5 mm. in thickness and about 
8.5 cm. in length. The left ventricle measures 9.5 cm. in length. The aorta 
shows streaks of sclerosis not very far advanced. 
Lungs. There is a small amount of fluid in the left pleura. On removing 
the left lung it is found to be non-adherent. The surface of the lung is slightly 
roughened by a few tags representing old adhesions. The pleural surface is 
everywhere smooth and glistening, but very opaque and grayish as if the pleura 
were greatly thickened. The apical portion of the lung is inflated and soft. 
The remainder of the upper lobe and the whole of the lower lobe are very 
heavy and firm to the touch. Along the edges of the lobes, particularly along 
the edge of the lower lobe there are numerous small pin-head sized nodules, 
which are grayish and somewhat translucent. These seem to be solid masses, 
and not merely air bubbles. The lymph glands at the hilum are somewhat 
enlarged. They are soft, reddened and very oedematous. The bronchi contain 
a certain quantity of frothy fluid and their walls are smooth. On section the THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
13 
lung is very firm. The upper portion of the upper lobe is evidently air-contain- 
ing. The lower portion of the upper lobe is quite smooth on section, of a 
grayish red color with abundant areas of darker gray or black pigmentation, 
and the tissue is relatively airless. The same condition is found throughout 
the lower lobe but not quite so uniformly, there being patches of air-containing 
lung scattered here and there. The consolidation involves, irregularly, the 
whole lower portion of the upper lobe and the whole of the lower lobe with 
the exception of the small scattered air-containing spaces or areas described. 
The right lung is quite densely adherent over the upper lobe; it is rather 
smaller than the left and is very much roughened over the upper and middle 
lobes by adhesions. There is a deep scar causing a depression in the upper 
lobe. The middle lobe is densely adherent to the upper lobe and also to the 
lower. The anterior portions of the lung are air-containing and crepitant. 
The posterior and lower portions of the middle lobe feel solid. The whole 
posterior portions of both the upper and lower lobes feel firm. The bronchi 
contain a blackish, frothy fluid. On section, the same type of smooth elastic 
consolidation is seen throughout the upper and lower lobes as described in 
the left lung. Between the upper and middle lobe there is a mass of dense 
white scar tissue which occludes the bronchi and vessels. The posterior part 
of the lung is very oedematous and very elastic and firm, dark, reddish gray in 
color and almost entirely airless. The cut surface is quite smooth. A bit of 
the lung just floats in water. 
The spleen measures 14 x 9 x 6 cm.; weight, 200 gm. The capsule is 
roughened by old adhesions. On section the splenic pulp is somewhat swollen. 
The Malpighian bodies are very large and prominent, opaque, grayish white 
in color. The stomach and duodenum and pancreas are not remarkable. The 
liver measures 29 x 19 x 13 cm. and weighs 2450 gm. Its capsule is smooth 
and uniform in appearance. On section the lobulation of the liver is very 
distinct. The lobules are extremely large and have a yellowish-gray periphery 
and a reddish centre. The red portion is very sharply marked off from the 
grayer portion and frequently shows central points of orange yellow. 
Kidneys. The left kidney is firm and not enlarged, measuring 11 x 6 x 5 cm. 
The capsule splits in peeling off and leaves a rather smooth surface which is 
of a grayish red color. On the surface in the middle line there appears a 
small opaque area surrounded by a dark red area. On section this opacity 
extends 4 mm. into the substance of the kidney and is surrounded completely 
by a zone of haemorrhage. The cortex of the kidney is thick, measuring 12 mm. 
The striations are straight. The glomeruli are prominent. The epithelial 
portions of the cortex are rather opaque and gray. The right kidney presents 
no opacities on the surface. The capsule strips off smoothly. On section it 
presents the same general appearance as the left, the cortex being swollen 
and the glomeruli particularly prominent. The kidneys weigh 450 gm. 
together. The adrenals are apparently normal. The cervical lymph glands 
are much enlarged, very oedematous and dark red. The thyroids and oesophagus 
are not remarkable. 
Bladder. The mucosa of the bladder is smooth. There are some ecchy- 
moses at the fundus. The urethra is quite normal in appearance. The testicles 
and epididymes are normal in appearance. 
Bacteriological Report byW. W. Waite. Cover-slip preparations were made 
from vegetations on the aortic valve and from the urethra. Plate cultures on 
ordinary media were made from the pericardial cavity, heart's blood, vege- 
tations on the aortic valve, gall-bladder, liver, spleen and kidney. Rabbit's 
blood agar tubes were made from vegetations on the aortic valve. 
Cover-slip preparations from the urethra stained with methylene blue 
showed several kinds of organisms. That present in greatest numbers was a 
diplococcus of a distinct biscuit-shape, which was inside and about pus cells. 
The cover-slip preparations from the vegetations showed in any single field 14 
THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
numbers of organisms which were all cocci arranged singly and in pairs. The 
paired organisms had their long axes parallel and were distinctly biscuit- 
shaped. None of the organisms held their stain when treated by Gram's 
method. 
On the rabbit's blood agar tubes from the vegetations there were numerous 
small translucent colonies which appeared to be all of one kind. A gentian 
violet stain showed but one type of organism which was a diplococcus arranged 
singly and in pairs, which decolorized completely by Gram's method. Transfers 
were made to blood serum, plain slant agar and hydrocele agar. The blood 
serum and agar showed no growth. The hydrocele agar, however, contained 
many small clear translucent colonies on the surface of the medium. A 
culture allowed to grow twenty-four hours in the incubator at 36° C. and then 
kept at room temperature lived only two days. 
Diagnosis: micrococcus gonorrhoea!. 
The plates on ordinary media contained a few colonies of micrococcus 
roseus and micrococcus cereus. These were probably air contaminations or 
end infections. The heart plates contained a few colonies, the pericardium, 
1; vegetations, 2; gall-bladder, 4; liver, 6; spleen, 22. 
Case III.-Male; aged jorty-two years; gonorrhoea; arthritis; septicaemia; 
ulcerative aortic endocarditis; death. 
Hospital No. 49,214; Medical No. 17,889. R. W., aged forty-two years, 
married, a dyer by trade, was admitted to the Johns Hopkins Hospital on 
12th December, 1904. 
Family History. Father, living and well. Mother, died at fifty-two of 
typhoid fever. Two brothers, living and well. Three brothers died in infancy. 
One sister, living and well; two died of unknown cause. Family history, 
otherwise good. 
Previous History. Has always been a healthy man. Had a severe attack 
of scarlet fever at five, since when he has been bald. Measles at seventeen; 
whooping-cough at seventeen. No other serious illnesses. Seven years ago 
he suffered from "indigestion" for six months, but has had no trouble since 
then. Denies lues. 
Habits. Drinks an occasional glass of beer; smokes one package of tobacco 
a week. Average weight, 148 pounds. 
Present Illness. Four weeks ago developed an acute gonorrhoeal urethritis. 
Two weeks ago noticed that his right wrist was tender and lame, so much so 
that he was obliged to stop work on the following day; it has been gradually 
growing stiffer and more painful. Three days ago his right shoulder became 
lame and for two days his right eye has been a little sore early in the morning. 
There has been no trouble with vision. Has not slept well for the last four 
nights, and for the last two nights there has been profuse sweating. There 
has been no cough; no expectoration. 
On entrance it was noted that the patient was well nourished; tongue fairly 
clean; mucous membranes of good color. Slight conjunctivitis of the right 
eye. The pupils were unequal, the left the larger. Both reacted to light and 
accommodation. There was marked pulsation of the vessels of the neck and 
of the brachials. The skin was hot and dry. The lungs were clear through- 
out. 
Heart. Point of maximum impulse in the fifth interspace 9.5 cm. to the 
left of the median line. Relative cardiac dulness begins at the upper border 
of the third rib, extending, in the fourth interspace, 2.5 cm. to the right and 
9.5 cm. to the left. All over the heart is heard a soft, systolic bruit. Sounds 
otherwise clear. The second pulmonic is not accentuated, though there is a 
reduplication of the second sound in this area. Pulse, 21 to the quarter, 
regular in force and rhythm, volume good, tension good, vessel wall not felt. 
Blood pressure (Riva-Rocci, broad band), 125 mm. Abdomen natural, no 
tenderness. Neither spleen nor liver palpable. THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
15 
Genitalia. Slight oedema with glairiness of the meatus. There was a small 
accessory meatus with a slightly glairy discharge as well. Gonococci were 
demonstrated in the discharge. No swelling of the epididymis. 
Joints. Right wrist thickened, hotter than the other wrist, not especially 
painful nor tender, slightly reddened. Motion limited in all directions. Pain 
and limitation of motion in the carpo-metacarpal joints of the thumb. Other 
joints appear to be free. 
Examination of the blood showed that the red corpuscles were regular in 
outline, of good shape and size. There was a slight leucocytosis but no 
parasites. 
Blood Count. Red blood corpuscles, 4,960,000 to the cubic millimetre; 
colorless corpuscles, 10,600 to the cubic millimetre; haemoglobin (Gowers), 
98 per cent. 
13tA December. The temperature, 99° on admission, fell to 98° at 8 p.M. and 
was normal on the following morning. Note by Dr. Cole: "Slight injection of 
the conjunctiva; no purulent discharge; no opacity of the cornea; pupils equal; 
no glandular enlargement excepting for tw'o glands about as large as peas in 
the left axilla, and the right epitrochlear gland, which is about the size of a pea. 
The left epitrochlear is just felt. Chest, well formed; lungs everywhere hyper- 
resonant on percussion. Breath sounds distinct. A few piping rales. 
''Heart. Point of maximum impulse not well seen nor felt. No absolute 
cardiac dulness. Relative cardiac dulness extends 8.5 cm. to the left; above 
to the third rib. Slight reduplication of the second sound at the apex. Soft 
systolic murmur in the pulmonic area. Aortic and pulmonic seconds of 
normal intensity. Spleen not palpable. 
"Joints. Complains of tenderness in the right shoulder. There is no 
swelling, no heat. The right wrist is swollen for the most part on its inner 
surface; temperature, elevated; moderate tenderness and swelling being most 
marked on the radial side of the dorsum of the wrist and about the head of 
the radius; do not extend up the sheaths of the tendons. No other joints 
affected." 
1 6th December. The temperature remains normal. No great change in the 
symptoms. Dr. Osler noted on this date that there was a well marked systolic 
murmur. 
18/A. December. Dr. Cole observed on this date that the right wrist was 
swollen, especially over the inner portion, the skin red and hot. The patient 
complained of throbbing pain in the joint, worse at night. The pain was 
sufficient to awaken him. There was no restriction of motion in the right 
shoulder; no tenderness. There was an appearance of atrophy of the inter- 
ossei on the dorsum of the right hand. The motion of the wrist was restricted. 
There was oedema about the joint, which extended about one-third of the 
distance up the arm. 
"19t/i December. Red blood corpuscles, 5,122,000 to the cubic millimetre; 
colorless corpuscles, 10,400 to the cubic millimetre; haemoglobin (Gowers), 97 
per cent. 
"Urethral discharge still shows diplococci, which decolorize by Gram. 
The pain in the wrist continues. The swelling now extends half way up the 
arm, the redness and tenderness being most marked about two and one-half 
inches above the wrist, where there is a brawny oedema, the skin being red 
and hot. The wrist is stiff but not extremely tender. The heart sounds are 
quite clear (Cole)." 
3d January, 1905. The patient has been in the hospital since 12th December 
and has had at intervals a small amount of fever reaching above 100°. For 
the past five days the temperature has been lower than usual. Yesterday 
morning it rose to 99.5°. The patient was out of bed at this time and com- 
plained only of a slight headache. This morning he arose as usual, feeling 
well, but was not especially hungry. zAt 8 a.m. the temperature was found to 16 
THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
be 100.5° and the patient was at once put to bed. The temperature steadily 
rose to 103.8° at 4 p.m. On examination, the tongue was found to be dry 
and red, but not coated. The pulse was 120; the lungs were clear throughout 
on auscultation and percussion. There was a soft, blowing systolic murmur 
heard, especially, along the left sternal border. The abdomen showed nothing 
remarkable. The spleen was not palpable. The patient complained of feeling 
drowsy and sleepy. Colorless corpuscles, 16,500. 
On the succeeding day (4th January) Dr. Cole made the following note: 
"With a sudden rise of temperature which occurred yesterday there have been 
no symptoms excepting that the patient has complained of slight chilly sensa- 
tions. The face is a little flushed, the tongue moderately coated and dry. 
The pharynx is red and injected though the patient complains of no soreness. 
Scattered over the abdomen, back, lower chest and also, to a lesser extent, on 
the arms, are small elevated red spots which disappear on pressure, and 
resemble somewhat rose spots except for their size which is 5 to 6 mm. in 
diameter. They are a little more elevated and surrounded by a zone of slight 
hypersemia. The patient thinks that he has previously noticed such an eruption 
over the body. Respiration, quiet and slow; lungs, quite clear throughout on 
percussion and auscultation. 
"Heart. Point of maximum impulse not seen nor felt. Relative cardiac 
dulness difficult to outline; extends apparently 9 cm. to the left at the fifth 
rib, to the upper border of the third rib above, and 2.5 cm. to the right at the 
fourth interspace. No impulse is to be felt anywhere over the cardiac area. 
At the ;ipex both sounds are well heard, the second almost as loudly as the 
first, while the systolic and diastolic pauses are of almost equal length. The 
heart's action is not rapid and is regular. No murmur can be heard at the 
apex or over the body of the heart. Both second sounds at the base are snap- 
ping, the aortic second being louder than the pulmonic. Over the sternum 
and in the second and third left interspaces near the costal margin, the second 
sound is a little prolonged and, though no definite murmur can be made out,, 
it may be that a faint diastolic souffle is present. The abdomen is full; neither 
tender nor distended. The spleen cannot be felt. The edge of the liver is 
palpable one finger's breadth below the costal margin in the mammillary line. 
The right wrist is still stiff. The patient also complains of tenderness in the 
left wrist, though no swelling or redness is to be seen." Cultures were taken 
on this date from the blood. 20 c.c. of blood were distributed on two plates 
of hydrocele fluid agar; four plates of plain agar; one flask of bouillon; one 
flask of litmus milk. 
On the following day the colorless corpuscles were 8000 to the cubic milli- 
metre. Blood pressure, 116 mm. The temperature was lower-not above 100°. 
6th January. The sputum, small in amount, mucopurulent and tenacious, 
showed microscopically leucocytes and epithelial cells; it was negative for 
tubercle bacilli. The blood pressure at 5.50 p.m. was 135 mm. 
There was no growth in the cultures made on 4th January. 
7th January. The temperature on the 6th ranged between 100.2° and 
102.5°. On the 7th it fell gradually to 99.6° at 8 p.m. Colorless corpuscles, 
18,900 to the cubic millimetre. 
9th January. On this date, Dr. Cole noted that the patient's temperature 
was lower; pulse 23 to the quarter, regular. There was pain and tenderness 
over the left side of the larynx; no swelling or redness. The eruption of 
reddish papules over the body had disappeared to a certain extent. The 
spleen could not be felt. The oedema and tenderness of the right w'rist had 
almost entirely disappeared, but there was still some stiffness. The patient 
complained of a slight aching in his ankles. 
Blood Count. Red blood corpuscles, 5,252,000 to the cubic millimetre; 
colorless corpuscles, 11,360 to the cubic millimetre; haemoglobin (Gowers), 
82 per cent. THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
17 
On the following day (10th January) Dr. Cole noted that the papular 
eruption was disappearing; pulse, 26 to the quarter, regular, of rather large 
volume with a forcible quick impulse and a slightly collapsing quality. 
The impulse of the heart was neither seen nor felt. Sounds, best heard in 
the fifth space 8.5 cm. from the midsternal line, to which point the relative 
cardiac dulness extended; to the right it reached 4 cm. in the fourth interspace, 
and above to the upper margin of the third rib. There was no shock to be 
Chart showing area over which the diastolic murmur was heard on 10th January, 1905. 
(Dr. Cole.) 
felt at the apex or base. At the apex the heart sounds were quite clear, both 
being well heard. The second was rather loud. Passing upward and inward 
in the fourth interspace, a soft, prolonged, blowing diastolic murmur became 
audible; this was heard over rather a wide area as shown in the diagram. Its 
maximum intensity was over the middle of the sternum, opposite the fourth 
interspace. The pulmonic second sound was not accentuated but was loud 
and well heard. The aortic second was also well heard but was not as- 
loud as the pulmonic. There was no systolic murmur at the base. 
Fig. 4 
Case III.-Radial pulse, 10th January, 1905. 
11th January. Yesterday evening the patient began to complain of sharp 
abdominal pain which could not be definitely localized and was relieved by 
movements of the bowels. Colorless corpuscles, 15,400 to the cubic millimetre. 
Cultures were again taken from the blood; 20 c.c. of blood were taken from 
the median basilic vein under antiseptic precautions and divided among six 
plates of agar, one plate of litmus milk and one flask of bouillon. 18 
THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
13th January. At the morning visit Dr. Osler made the following note: 
"The patient looks pale, the tongue is red and fissured; pulse is full, soft, 
dicrotic. The skin is clear; no petechise. 
"Heart. Apex beat not visible; no marked pulsation in the vessels of the 
neck. There is a wavy impulse in the veins of the arm. In addition to the 
distinct pulsation there is a filling of the vein with expiration and the partial 
emptying with inspiration. There is no shock of either sound at apex or base; 
no forcible impulse; no especial impulse in the cardiac area. On auscultation, 
at the apex both sounds are heard. There is a soft murmur with the first 
sound. Toward the base and along the left sternal border there is a diastolic 
murmur which increases in intensity and is at its maximum in the second left 
space; it is well heard also at the second right costal cartilage and over the 
manubrium; well heard down the sternum. The pulse has become of a 
collapsing quality." 
On the following day (14th January) Dr. Osler noted that the apex beat 
was faintly visible in the fifth left interspace inside the mammillary line; not 
palpable. The shock of neither sound was palpable. No thrill at the base. 
A wavy impulse in the neck but not of the character of aortic insufficiency. 
"Visible pulsation in the upper arm is quite marked. Radial pulse has become 
collapsing. At the apex both sounds distinct, somewhat increasing in intensity 
toward the sternum. No systolic heard at the apex. Sounds quite loud at 
the lower sternum. On approaching the third rib there is a diastolic murmur 
of great intensity, which, to-day, has definitely changed in quality. It is not 
only more intense but has a decidedly musical sound. It is heard well also 
at the aortic cartilage." 
Results of cultures taken on 11th January On the plates containing equal 
quantities of agar and blood there was in twenty-four hours, at 37° C., a 
growth of faint grayish translucent colonies, deep in the medium; all flat and 
round-not oval. On blood agar, surface smears, there was a good, discrete 
growth of fine grayish translucent colonies. On hydrocele agar there was a 
growth of discrete, grayish, translucent colonies. 
These colonies all consisted of a biscuit-shaped diplococcus without 
motility, staining readily and evenly and decolorizing by Gram's method. 
After forty-eight hours there was no growth on the surface of the plates of 
blood and agar. The colonies already present were 1 to 2 mm. in diameter- 
no subsequent increase in size. On the blood agar surface smears the colonies 
in forty-eight hours were not over 2 mm. in diameter. On blood serum in 
forty-eight hours there were faint discrete colonies. On hydrocele agar, in 
forty-eight hours, the colonies were slightly larger-some fusing of the colonies. 
There was no growth on plain agar slant, on hydrocele fluid and bouillon or 
on litmus milk. 
Diagnosis: Gonococcus. 
On the following day (16th January) Dr. Cole noted that the area of cardiac 
dulness reached 2.5 cm. to the left of the midsternal line and 4 cm. to the right 
in the fourth interspace. The spleen was not to be felt. 
17th January. Blood Count. Red blood corpuscles, 4,640,000 to the cubic 
millimetre; colorless corpuscles, 14,800 to the cubic millimetre; haemoglobin, 
82 per cent. 
The patient steadily lost ground. On the 18th he complained of epigastric 
pain and had several attacks of nausea and vomiting. On this date the 
following note was made by Dr. Thayer: The patient looks rather pale and 
ill, the tongue is very red and beefy; pulse, regular, of large size, short duration, 
ill sustained, 25 to the quarter. There is moderate heaving in the precordial 
area. Apex impulse, not clearly defined. The cardiac dulness begins above 
at the upper border of the third rib and extends about 4 cm. to the right of 
the midsternal line and, over the fifth rib, about 8 cm. to the left. The greatest 
diagonal dulness from left to right measures a trifle over 13 cm. The sounds THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
19 
are best heard in the fifth interspace just inside the outermost dulness. At 
the apex the first sound is clear, the second followed by a soft, blowing diastolic 
murmur which is prolonged through the greater part of diastole and, in the 
fourth space at about the parasternal line, becomes louder and more accent- 
uated in the latter part of diastole, taking on the features of a mitral pre- 
systolic murmur. Along the left border of the sternum the first sound is clear 
Fig. 5 
Case III.-Radial pulse. 16th January, 1905. 
the second, replaced by a well-marked diastolic murmur which is heard loudly 
in both aortic and pulmonic areas. The element of the second sound is 
louder in the pulmonic than in the aortic area. The murmur is well heard 
over the manubrium. In the carotids there is only a rather faint systolic 
tone; slight tone in the femorals. It is rather striking that the presystolic 
murmur is so well heard inside the parasternal line, as well as in the tricuspid 
area. 
Fig. 6 
4 cm. from midsternum 
■8 cm, from midsternum 
Case III.-Showing cardiac dulness on 18th January, 1905. 
The nausea and vomiting continued. On the 20th Dr. Osler noted that the 
murmur had increased greatly in volume and intensity. No systolic murmur 
was audible. 
On the 21st I saw the patient again, noting that the pulse was markedly 
dicrotic, ill-sustained, though not of a particularly large size nor of a char- 
acteristic aortic character. "At the apex but two sounds are heard; a long 
and rather rumbling murmur with a short sound of moderate intensity. The 
short sound is the first sound. The long rumbling murmur occupies, appar- 20 
THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
ently, all diastole. Passing inward, the diastolic murmur becomes greatly- 
increased in intensity, loudest at the sternal end of the fourth left interspace,, 
where the first sound is barely audible, the loud roaring murmur being almost 
the only sound. In the second left interspace the second sound is fairly sharp 
and the murmur is of less intensity. In the aortic area there is a to-and-fro 
murmur of moderate intensity. An element of the second sound is heard. 
It is interesting that, at the apex, the murmur, though feebler than near the 
sternum, runs directly into the first sound. Near the sternum it reaches its 
climax and comes to an end a little earlier. The right side is much enlarged, 
reaching, on percussion, as much as 6 cm. to the right of the midsternal line. 
The dulness on the left reaches about 9.2 cm. outward over the fifth rib. 
There is a slight femoral tone. The liver flatness reaches 7 cm. below the tip 
of the ensiform and 4 cm. below the costal margin in the mammillary line." 
On 23d January, Dr. Osler noted a distinct, slight vibratory thrill, and on 
the following day Dr. Cole described a well marked thrill. 
Blood Count. Red blood corpuscles, 4,108,000 to the cubic millimetre; 
colorless corpuscles, 13,200 to the cubic millimetre; haemoglobin, 72 per cent. 
The temperature was very irregular, intermittent and remittent. Febrile 
paroxysms frequently accompanied with chills, occurred sometimes as often 
as three times in twenty-four hours. 
On the 27th Dr. Thayer noted that the pulse was 30 to the quarter at the 
time of the visit; the right side of the heart extended on percussion about 
5.8 cm. from the median line; on the left only about to the mammillary line 
or 10 cm. from the median line. The first sound was heard best in the fifth 
space a little inside the point of outermost dulness; it was not loud but was 
rather sharp; the second sound was immediately followed by a diastolic 
murmur which ran all the way up to the first sound, having, toward the end 
of diastole, something of a rumbling quality. In the fourth left interspace 
the murmur was louder and more like a mitral diastolic. It became still louder 
as one passed inward and was loudest a little outside of the left sternal border 
in the fourth space. The heart's action was so rapid that it was difficult to 
place the sound exactly, but at the point of greatest intensity of the diastolic 
murmur at the sternal and of the fourth space, the rumbling, loudest part of 
the murmur seemed to be late rather than early in diastole. At this point 
the first sound was very slight and the second barely audible, marking the 
beginning of the murmur. In the pulmonic area, in the second left interspace, 
there was a soft to-and-fro murmur in association with the two sounds, the 
second, sharply accentuated. The same is true in the aortic area, the murmurs, 
however, being rather louder. The second aortic sound is sharp. There is no 
sharp tone in the aorta; a tone in the crurals of moderate intensity. "The 
striking features of this case are an extremely large right side with auscultatory 
signs which would point to a pure aortic lesion. On the other hand, the first 
sound at the apex has a rather short and abrupt character which might suggest 
mitral disease. The position of greatest intensity of the late diastolic murmur 
in the tricuspid area is again remarkable. Over the right side of the chest 
and the dull area to the right of the sternum the heart sounds are well heard, 
each followed by a soft murmur. At the end of the third left interspace the 
diastolic murmur is limited to early diastole, while over the whole of the rest 
of the left precordial area there is a late diastolic accentuation. The pulse is- 
collapsing and of aortic qualjty." 
The patient steadily lost ground; there was intermittent fever with frequent 
chills. Examination of the fresh blood on January 29th showed that the red 
blood corpuscles were of normal size; a little pale; no malarial parasites. There 
was a moderate leucocytosis with a moderate increase in polymorphonuclears. 
30tA January. Dr. Osler observed on this date, that "the most interesting 
change that has occurred is the rough diastolic over the body of the heart. 
Over the aortic area and along the left border of the sternum the murmur is THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
21 
•soft, the maximum intensity being in the tricuspid area. There is a good 
deal of pulsation in the neck. 
31 st January. Blood Count. Red blood corpuscles, 3,164,000 to the cubic 
millimetre; colorless corpuscles, 25,000 to the cubic millimetre; hiemoglobin 
(Gowers), 60 per cent. 
The patient steadily lost ground. On 2d February Dr. Cole noted that 
there had been no special change in the heart sounds excepting that the 
Fig. 7 
Case III.-Pulse tracing. 30th January, 1905. 
rumbling murmur in the fourth and fifth interspaces inside the parasternal 
line had become more marked and more typically presystolic in time, of 
entirely different quality from the diastolic murmur heard over the sternum 
and along the left sternal margin. 
On 3d February Dr. Thayer noted that the patient looked puffy and doughy. 
There were a number of perfectly fresh petechial spots on the trunk and 
Fig. 8 
r Area of maximum intensity 
\ of churning mid-diastolic 
' and presystolic murmur. 
•6.2 cm. to right of midsternal 
line. 
Sounds heard best. 
Chart made by Dr, Thayer on 3d February, 1905. 
extremities. The pulse was 29 to the quarter, soft and of rather good size; 
of short duration; collapsing quality marked on raising the wrist. The pulsa- 
tion of the carotids was fairly well marked. The apex impulse was not sharply 
localizable. Slight impulse just behind the left nipple. There was epigastric 
pulsation. On percussion the dulness extended 6.2 cm. to the right of the 
median line in the fourth space, and 5 cm. in the third. In the apex region 
the sounds were best heard in the fifth space, about 7.5 cm. out. There was 22 
THAYER: GONORRlItEAL SEPTICEMIA 'AND । ENDOCARDITIS 
a gallop rhythm dependent upon a reduplication 6f' the first sound or a very 
slight presystolic murmur, it was difficult to say ^hich, as well as a very 
slight systolic murmur. The sounds were very soft and1 masked by loud 
stertorous breathing. The second sound ri^hich was audible was1 followed 
by a very slight diastolic murmur. Passing inward a murmur became heard 
in diastole leading up to the first sound and beginning, apparently, imme- 
diately after the second sound. In the fourth space, inside the parasternal 
line, this became suddenly very loud and near the ear; Of an echoing, vibratory 
quality and was almost the only sound heard. Listening very carefully a 
slight soft whiff of a different character might be heard at the beginning of 
diastole. Immediately above this the rumbling murmur disappeared and the 
first and second sounds were heard, followed by a soft diastolic murmur 
limited to the early part Of diastole and of ordinary aortic quality. The 
second sound in the second left interspace was sharp arid associated with 
this same diastolic murmur. In the second right interspace was heard a short 
systolic souffle and a fairly sharp second sound followed by a diastolic murmur. 
The churning mid-diastolic and presystolic murmur was heard with maximum 
intensity in the limited area marked on the chart in the third and fourth 
left interspaces. To the right of the sternum, in the dull area, the heart sounds 
were well heard-with a well marked to-and-fro systolic and diastolic murmur. 
Fig. 9 
Case III.-i-Radial pulse, 3d February, 1905. 
These were especially loud in the third right space. There was a distinct 
pulsation in the dull area on the right. 
The patient, who had been failing rapidly for a week arid constantly com- 
plaining of feeling "awful sick," became weaker and more restless and died 
at 7.10 on the morning of 4th February. 
The necropsy (No. 2463) was performed byl Dr. MacCallum three and a 
half hours after death. 
Anatomical Diagnosis: Acute aortic endocarditis with ulceration of the 
valves; acute splenic tumor with anaemic infarction; acute diffuse nephritis; 
myocardial degeneration; atelectasis and oedema of the lungs; slight cirrhosis 
of the liver; chronic adhesive pleuritis; diphtheritic cystitis. 
"Thorax. The pleural cavity of the left side isTree from adhesions but 
contains about 600 c.c. of turbid fluid, and the right pleural cavity is almost 
obliterated by thin veil-like adhesions. The pericardial cavity contains a 
little thick fluid. The surfaces are smooth and glistening. The heart is 
somewhat enlarged. The right ventricle is extremely flabby, and as the heart 
lies in the pericardium, a solid opaque mass can1 be felt through the walls of 
the right ventricle, projecting so as to be easily seen. 1 It is apparently attached 
to the wall Of the ventricle which cannot1 be lifted awayt from it. 
"Heart. The heart is smooth externally arid there is a small hsemorfhage 
over the anterior portion of the back of the ventricle. There is a similar small. THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
23 
haemorrhage on the posterior surface near the apex. The tricuspid valve, 
viewed from the auricle, show's no abnormality. The mass described above 
proves to be a papillary muscle. The tricuspid and pulmonic valves are quite 
normal. The mitral orifice measures about 3 cm. in transverse diameter. 
Viewed from the auricle no definite vegetations are seen. The valve is thick- 
ened throughout its whole edge except for a small portion of the posterior 
valve. The posterior valve is much shortened. The thickening is most 
marked in the anterior leaflet, where it extends for a width of perhaps 7 mm. 
back from the edge. The chordae tendinese are practically normal. The 
aortic valves are covered on the ventricular side with a vegetation which 
involves the right and left coronary segments. The vegetations are large and 
rounded, measuring perhaps 1.5 cm. in diameter. They spring from the 
central portion of each of the valves and bind the two valves together so that 
the left coronary segment is much distorted and pulled over toward the right. 
A probe can be easily passed through the valves where the vegetations lie upon 
them, and thus into the ventricle. 
"When the fresh clot is removed the vegetations are found to be very rough 
and irregular and covered with ridges. The holes in the valves are at least 
6 mm. across. The valves are obviously eroded when viewed from the sinus 
of Valsalva, the eroded portion being roughened and covered with red clot. 
The left coronary artery shows some yellow plaques of sclerosis, but it is 
patent and wide. The right coronary artery is much smoother and shows no 
extensive plaques of sclerosis. The back of the mitral valve shows some 
yellow patches. The aorta is fairly smooth, there being some sclerosis and 
a thickening just above the valves. The myocardium of the right ventricle 
is excessively flabby. The wall of the ventricle measures 3 mm. in thickness. 
The myocardium of the left ventricle measures about 15 mm. in thickness; 
it is rather opaque and dull gray in appearance. 
"The spleen measures 16 x 14 x 6 cm. and weighs 550 grams; it is very 
much enlarged. Its capsule is tense and dark grayish-red in color. The upper 
surface of the spleen shows two patches of dense, firm tissue which are slightly 
elevated above the surrounding surface and are grayish yellow in color with 
a margin of blackish red. Both of these areas are covered with a fibrinous 
exudate. On section they extend into the substance of the spleen and are 
opaque, grayish yellow in color. The larger is distinctly softened in the centre. 
The spleen is very much swollen and on section is rather grayish looking and 
opaque. The Malpighian bodies stand out sharply as opaque gray dots in 
an excessively hypertrophied splenic pulp. 
"The bladder is distended with urine. In the posterior wall just below the 
fundus there are numerous red areas somewhat raised, dull on the surface, 
pale in appearance and surrounded by a margin of deep red spots. The 
mucosa of the bladder elsewhere is fairly normal, somewhat dull and granular 
at the trigone. 
"The prostate is not enlarged but the prostatic veins contain, here and there, 
thrombi. The seminal vesicles are normal in appearance and contain a clear 
fluid. The testicles and epididymes are apparently normal." 
Microscopically, the urethral mucosa was slightly infiltrated with leucocytes, 
while the mucosa of the bladder showed a typical diphtheritic inflammation. 
Microscopical examination of the vegetations on the aortic valve showed a 
large number of diplococci of distinct biscuit-shape, most of which were intra- 
cellular. Some cells were packed full of cocci. The organisms decolorized 
by Gram's method. 
Cultures on ordinary media from the heart and kidney were sterile. Those 
from the spleen showed one small colony of streptococcus pyogenes; from the 
abdominal cavity, one colony of streptococcus pyogenes and one of micrococcus 
albus. From the bladder which had been opened and somewhat exposed, a 
small bit of tissue was excised after singeing the surface, and put into the culture 24 
THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
medium. Colonies of the pseudodiphtheria bacillus and bacillus alcaligines 
were obtained. Ascitic agar tubes were made from the vegetations on the 
aortic valve. On these there developed in pure culture, small, white colonies 
of biscuit-shaped diplococci arranged in tetrads and pairs which decolorized 
by Gram. No growth in milk. Diagnosis: Micrococcus gonorrhoeas. 
At the same time Dr. Boggs made cultures from the heart's blood and from 
the vegetations on the aortic valve-smears on hydrocele agar. Those from 
the heart's blood were negative; those from the vegetations showed a pure 
culture of micrococcus gonorrhoeas. 
This case was particularly interesting from the point of view of 
the physical signs. The remarkable presystolic accentuation of 
the diastolic murmur, the intensity of the presystolic rumble, the 
area in which it was heard, and the great extent of the dulness 
to the right would seem to have quite justified the suspicions 
which we had intra vitam of the existence of a combined aortic 
and tricuspid lesion. From the anatomical lesions, however, it 
would seem that this murmur must have been due to the disturb- 
ance caused by the regurgitation of a large mass of blood directly 
upon the anterior mitral curtain at the time of entry of the blood 
from the left auricle. 
B. Four Cases of Ulcerative Endocarditis following Gonorrhoea. 
Case IV.-Male, aged twenty-one years; gonorrhoea; arthritis; ulcerative 
endocarditis of the mitral valve; embolism of the anterior tibial artery; death; 
no necropsy. 
X., aged twenty-one years, a commercial traveler, was seen with Dr. Slemons, 
of Salisbury, Maryland, on March 18, 1899. 
His family history was good. He had always been a healthy boy; had never 
had rheumatism or serious illnesses of any nature. 
Present Illness. In the latter part of December the patient contracted 
gonorrhoea. Early in January, he began to have chills at irregular intervals 
followed by fever and sweating. After the first several chills the discharge 
disappeared. He kept about at work despite the fact that he felt ill. In 
February the right knee and ankle became somewhat swollen arid painful 
and he had to give up work for several days. In a severe storm early in Feb- 
ruary he was subjected to great exposure, and on the 20th the chills and 
fever, which had continued, had so far exhausted him that he was obliged 
to give up work and go home. Since this time he had been in bed suffering 
from fever which, at times, had been more or less continuous, at other times 
intermittent and associated with excessively severe rigors. The duration of 
fever, during these paroxysms was often surprisingly short, the patient having 
sometimes as many as three attacks in twenty-four hours, the temperature 
falling with great rapidity in association with profuse, drenching sweats. He 
had become feeble and anaemic. The febrile paroxysms were often accom- 
panied by vomiting. Several days before my visit, during a paroxysm, the 
patient suddenly felt a numb, tingling sensation in the right leg. Since then 
the leg below the knee had felt as if it were asleep; it wras cold and he had 
been unable to move it as freely as the other, while the foot and calf had been 
somewhat tender. 
At the time of examination the patient was in bed, on his back; well formed 
man; somewhat emaciated. The face was pale and sallow; the lips and THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
25 
mucous membranes, pale. There was marked pulsation of the vessels of the 
neck. The pupils were widely dilated; the respirations rapid and rather 
shallow. The patient looked very ill and was so weak that he was unable to 
tell a connected story of his illness, the effort to speak being very considerable. 
The tongue showed a black coat (peptomangan). The pulse was regular, 
of low tension, 33 to the quarter. The lungs were clear throughout. 
Heart. Well marked pulsation in the fifth space just inside the nipple. 
On palpation there was a marked systolic thrill in the pulsating area. Dulness 
began at the second space above and did not reach the right parasternal line. 
No marked evidence of right-sided enlargement. On auscultation there was 
a very loud, blowing, systolic murmur which almost replaced the first sound 
at the apex and was heard throughout the axilla and back. The murmur 
diminished markedly as one passed inward and upward, but a soft systolic 
murmur, probably the mitral murmur transmitted, was heard all over the 
cardiac area. The second pulmonic sound was accentuated; the second 
aortic feeble but clear. In the tricuspid area the first sound was well heard 
in association with the murmur. The spleen was not palpable, though the 
area of dulness was markedly increased. Liver not remarkable. No ascites. 
In a rather poor light no petechise were visible. 
The right leg below the knee was pale and distinctly cold as compared 
with the left. The posterior tibial artery was not palpable on either side. 
The pulsation of the anterior tibial was felt on the left but not on the right. 
Urine (only one ounce obtained), high color; trace of albumin; sediment, 
on centrifugalization: Decolorized red blood corpuscles; leucocytes in con- 
siderable number; hyaline and finely granular casts with red blood cells and 
fatty degenerated epithelial cells adherent. Occasional free, fatty degenerated 
epithelial cells. 
Blood. Fresh specimen. The corpuscles are pale; difference in size, more 
than normal; slight poikilocytosis; great increase in the number of leucocytes. 
A differential count of a thousand leucocytes stained by Ehrlich's triple 
stain, showed small mononuclear leucocytes, 4 per cent.; large mononuclear 
and transitional forms, 5.6 per cent.; polymorphonuclear (neutrophiles and 
two or three mast cells), 90.1 per cent.; eosinophiles, 0.3 per cent. 
No nucleated red blood corpuscles were seen. No cultures from the blood 
could be taken. The patient steadily lost ground and died within a week 
after the visit. There was no necropsy. 
In this instance the direct association between the acute gonor- 
rhoea and the development of the ulcerative endocarditis would 
make it in every way probable that the case was one of true 
gonorrhoeal septicaemia. 
Case V.-Male, aged thirty-five years; gonorrhoea; ulcerative endocarditis of 
the mitral valve; death; an unidentified bacillus obtained in cultures from the 
valves. 
X., male, aged thirty-two years, a lawyer, was seen in consultation with Dr. 
H. B. Deale, of Washington, on 2d June, 1899. 
The patient had had the usual diseases of childhood. Four years ago, 
severe attack of typhoid fever lasting five weeks. Has been under treatment 
for several years for some throat affection. 
On 1st April, after a hard winter, he began to feel very tired and thinks 
that he had an irregular fever coming on particularly in the afternoon, 
and lasting from three to five hours, followed by profuse sweating. The fever 
was occasionally preceded by a slight chill lasting from fifteen to forty-five 
minutes. There have been frequent headaches; loss of appetite; moderate 
diarrhoea. On further inquiry it was found that the patient had had 
gonorrhoea at about the time of the onset of his symptoms. 26 
THAYER: GONORRHCEAL SEPTICEMIA AND ENDOCARDITIS 
The patient was first seen by Dr. Deale on 13th May, 1899. The tempera- 
ture was 103°, pulse 88. There was nothing abnormal about the heart sounds 
or quality of the pulse. The blood showed no malarial parasites. The fever 
ranged from 99° to 103°, the pulse from 76 to 104 during the first week. 
On 18th May a loud systolic murmur was heard at the apex, transmitted to 
the axilla. About 27th May the temperature became higher and the pulse 
much more rapid with periods of marked irregularity. Widal tests on 20th 
and 24th May were negative. 
2d June. The patient was an emaciated, anaemic-looking man, somewhat 
cyanotic; respirations rapid and rather shallow; vessels of the neck pulsating 
markedly. Pulse 34 to the quarter, partly from excitement, of rather low ten- 
sion. Heart. The apex impulse was palpable about in the mammillary line. 
There was a loud systolic murmur which almost replaced the first sound, and 
was heard well through the axilla and back. The murmur was barely audible 
at the base; the second pulmonic sound sharply accentuated. At the tricuspid 
area and over the greater part of the right ventricle the second sound was 
somewhat reduplicated, having a sticky character; slight suggestion of a diastolic 
murmur. The second aortic was feeble but clear. The lungs were clear on 
percussion. On auscultation, fine, sticky rales were heard at both apices and 
bases, and, to a certain extent, along the anterior borders of the lungs, while 
the respiration over the middle of the right back was rather feeble. The 
spleen was not palpable, although the area of dulness appeared to be 
increased. The diagnosis was ulcerative endocarditis of the mitral valve, 
probably gonorrhoeal. 
The patient, died on 3d June. 
The necropsy by Dr. Carroll showed that the heart was much enlarged; 
the left ventricle markedly hypertrophied. The walls of both ventricles were 
thickened. The aortic valves were competent with the water test and quite 
normal. " Both flaps of the mitral valve support large, irregularly shaped, 
pendulous masses of new formation which project from one-fourth inch 
at the margin, to about three-fourths inch at the centre, into the cavity 
of the ventricle. The leaflets of the tricuspid valve showed a slight nodular 
thickening along their margins. Cultures from the heart's blood, vegetations 
and from the liver on plain agar, human serum agar, Loeffler's blood serum 
mixture, blood agar mixture and bouillon revealed small, slowly developing, 
circumscribed colonies of small, slender bacilli often in pairs. These failed 
to grow on any transplantations. They were decolorized when treated by 
Gram's method. One of the Loeffler tubes from the heart's blood and one 
blood agar mixture showed these organisms in pure culture. The sam 
organism was found in cultures from the vegetations in connection with a 
staphylococcus." 
The close association of the onset of symptoms in this case 
with an attack of gonorrhoea justifies the suspicion that the 
urethritis may have served as the portal of entry to the infection, 
although evidence of its primary gonorrhoeal nature is wanting. 
Case VI.-Man, aged thirty-one years; gonorrhoea; prostatitis; arthritis; 
ulcerative endocarditis (mitral insufficiency'); death; no necropsy. 
H. G., male, aged thirty-one years; clerk. Family history good. Had 
always been a strong, robust man, rather given to athletics. Had never had 
any serious illness or previous venereal disease. Consulted Dr. S. Likes on 
7th July, 1902, with a gonorrhoea of eight weeks' duration, which had been 
treated by internal and local medication. Examination showed no discharge 
from the meatus. The urine was very cloudy by the test of the three glasses. 
The prostate was uniformly enlarged and the secretion following massage 
was very purulent and contained gonococci. The patient was put under THAYER: GONORRHCEAL SEPTICAEMIA AND ENDOCARDITIS 
27 
treatment-daily massage of the gland, followed by mild permanganate 
irrigations. He began to improve until the prostatic secretion was almost 
normal and the urine clear. 
On 24th July he had a chill followed by pain and swelling in both knee- 
joints. The chills recurred at irregular intervals, though the rheumatic 
symptoms soon began to abate, disappearing completely within a week. No 
local lesion could be found to account for the symptoms. 
On 12th August I saw the patient in consultation with Dr. Likes. He 
was a healthy looking man, though the complexion was a little dull and sallow. 
The lung and heart sounds were clear. The spleen was palpable. The 
urine was free from albumin. 
The chills and irregular fever continued and the patient was seen again 
■two days later. At that time a soft systolic murmur was audible all over the 
cardiac area, rather harsher, perhaps, in the aortic area. The two sounds 
were of normal relative intensity. 
Ten days later the patient was seen again. Irregular fever and chills had 
continued, although the patient felt quite well between attacks. The patient 
began to look somewhat anaemic and was clearly losing weight. The pulse 
was large and soft. The systolic murmur was audible, loudest at the apex, 
clearly heard as far outward as the anterior axillary line. The second pulmonic 
was accentuated; the apex impulse was 11.5 cm. from the median line. A 
specimen of urine was of normal color, acid, 1015, showing a slight trace 
of albumin. 
From this time on the patient steadily lost ground. I saw him again on 
10th October, at which time he had become more emaciated and anaemic. 
A systolic murmur similar to that before described was still audible. From 
this time the patient's condition grew gradually worse, chills recurring once 
or twice in twenty-four hours, although at one time there was a period of 
four days of normal temperature. From time to time Dr. Likes states there 
were attacks of violent coughing lasting about twenty-five minutes-about six 
of these attacks in all. There was marked and progressive anaemia with 
enlargement of the spleen and local tenderness. At no time was there any 
pain over the cardiac area. The patient gradually lost ground and died on 
November 9th, one hundred days after the onset of the condition. Dr. Likes 
states that the cardiac murmur became louder in the latter days of the illness. 
No necropsy was allowed. 
In this instance no cultures were taken from the blood, but the 
onset and course of the case were strongly suggestive of a true 
gonorrhoeal endocarditis. 
Case VIL-Man, aged twenty-one years; urethritis; epididymitis; inter- 
mittent fever; ulcerative aortic and pulmonic (?) endocarditis; arthritis; cerebral 
embolism; streptococcus pyogenes obtained from the peripheral circulation; 
death; no necropsy. 
Y., aged twenty-one years, seen in consultation with Dr. Y. on 27th 
October, 1903. Family history unimportant. Has been a healthy boy. Has 
never had rheumatism. In January the patient had an attack of urethritis 
followed later by an epididymitis from which, in the course of several months, 
he apparently entirely recovered. He has not, however, been well since this 
time. During the summer, especially in the latter part, he has had slight 
recurrent febrile attacks. 
On 6th September he came home from Chicago and was put to bed by his 
father, who is a physician. The temperature ranged from 97° to 99° in the 
morning to 102° to 103° at night. There was considerable sweating. The 
heart was enlarged and tumultuous in its action; pulse, 90 to 110; respiration, [Reprinted from Maryland Medical Journal, November, 1905.] 
ON SOME PUBLIC DUTIES OE THE PHYSICIAN 
By W. S. Thayer, 
Professor if Clinical Medicine, Jolins Hopkins University. 
ADDRESS DELIVERED BEFORE THE MEDICAL AND CHIRURGICAL FACULTY OF MARYLAND 
AT DEER PARK, SEPTEMBER 22, 1905. 
Most of us are familiar with the oft-expressed regret for the 
passing of the day when the family physician was the sole coun- 
sellor with regard to all fleshly and many spiritual ills of his 
patient, and it must be acknowledged that, along with the many 
advantages which spring from the modern tendency toward con- 
centration and limitation of one's field pf action, there are some 
drawbacks. The patient, passing from one adviser to another, 
with whom there is, perhaps, but a formal acquaintance, is too 
likely to miss the support arising from the old confidence and faith 
in the familiar and trusted friend; while, on the other hand, it is 
doubtless true that this old confidence and faith, this friendship 
and reliance, inevitably broadened the physician and developed in 
him a capacity for beneficent personal influence which often sur- 
passed even that of his brother of the clergy. This personal influ- 
ence the urban practitioner of today is unquestionably losing to a 
certain extent. He no longer occupies in the family quite the same 
place that he formerly filled. And the same change is taking place, 
little by little, even in the life of the country doctor, for with mod- 
ern methods of transportation the advantages and disadvantages 
of the increased tendency toward specialism are offered freely to 
the rural population. It is not uncommon for those of us who 
practice in town to be visited by the patients of our country breth- 
ren, who, too often with a false conception of the superior powers 
of the city physician, seek his advice without consulting him who 
is their safest guide and counsellor, in much the same manner as 
the patient in the city consults, upon the advice of friends or on his 
own fancy, this or that "specialist"-a misty and magical name 2 
today-of the limits qf wnose domain they have, alas, a sadly hazy 
idea. But although time has doubtless taken something from the 
peculiarly charming personal relations which have often existed 
between doctor and patient, yet it has brought abundant compensa- 
tion both to the public and to the medical profession. On the one 
hand, division of energy and concentration of forces have given to 
the physician an insight into the nature and cause of disease which 
has put into his hands powers of which in days past he had little 
fancy; and this very fact, on the other hand, affords the public an 
ever-increasing assurance of protection from many of its most 
dreaded enemies. The physician may have lost some of his per- 
sonal influence, but he has gained invaluable capacity for practical 
public service. But a capacity for public service and knowledge 
of certain means which may prevent the spread of disease and save 
human life are not gains which can be enjoyed at leisure. The 
possession of such knowledge, of such capacity, of such opportuni- 
ties implies the duty to make use of all. Of some of those 
duties which have grown upon us in late years I would speak 
briefly today. 
It is, after all, but a relatively short time since microscopical, 
bacteriological and chemical methods of investigation first took 
a regular place in the practice of medicine. When many of us who 
are here today entered upon the exercise of our profession the use 
of most of these methods of study was limited to a few special 
workers in the laboratories of universities or schools. Today they 
are invaluable for the accurate diagnosis of many of the most im- 
portant maladies with which we have to deal. With the increasing 
demands for more complicated and finer methods of diagnostic 
investigation the curriculum of our medical schools has broadened, 
the time required for medical training has lengthened, the advan- 
tages offered to the student have greatly increased. But if the 
practitioner enters upon his work today with a broader basis of 
information and experience than was true of the graduate of 20 
years ago, it is nevertheless often difficult or impossible for him to 
utilize many desirable or, indeed, one may in some instances say, 
necessary diagnostic procedures, inasmuch as the old-time demands 
of practice have in no way diminished, while the new methods of 
investigation impose upon him more work than one man can 
accomplish in 24 hours. And although to the city practitioner the 
laboratories of hospitals and special students are of considerable 
assistance, yet the expense associated with the relegation of this 
work to private investigators is beyond the means of a great part 
of the urban public, while distance and the lack of special arrange- 
ments deprive the majority of rural residents of all these advan- 
tages. Here, however, our State and local boards of health are 
rapidly offering to the busy practitioner the necessary assistance. 
Today, for any physician in the State of Maryland, the Board of 
Health undertakes, gratuitously, examinations of the blood to 
assist in the diagnosis of typhoid fever or malaria, of cultures from 
the throat in cases of suspected diphtheria, of the sputa whenever 3 
there is a question of tuberculosis. In the city of Baltimore the 
same assistance is offered by the local board. Thus the country 
practitioner stands upon the same level with his city brother as 
regards these necessary diagnostic measures. Such opportunities 
he should not neglect to utilize. 
In any suspected epidemic of cholera, of yellow fever, of plague, 
of typhoid fever, of cerebro-spinal meningitis the State Board of 
Health is ever ready to furnish the necessary expert investigators 
and to offer every assistance. 
What have been the first results of the advances of late years in 
our knowledge of the nature, especially, of the infectious diseases, 
and of the discovery of improved diagnostic methods? The an- 
swer is obvious. The knowledge of the nature of an infectious 
disease, and of the manner in which the poisonous agent enters the 
body, have been followed in many instances by the discovery of 
methods of destroying these agents or preventing their entry into 
and their dissemination in the organism, while early diagnosis, 
with the recognition of the first cases, has given us the key to suc- 
cessful prophylaxis. We possess today, for instance, knowledge 
which should enable us in an ideally-governed State to recognize 
at the outbreak and largely prevent the spread. of diphtheria, 
typhoid fever, malarial fever, yellow fever, cholera, plague, tuber- 
culosis. Moreover, with regard to one of the most terrible of the 
scourges of mankind, diphtheria, we have at hand an almost cer- 
tain means of cure if the disease but be recognized at a sufficiently 
early period. Why, then, does tuberculosis exist widespread? 
Why does typhoid fever carry off every year hundreds of the 
flower of our country ? Why does malaria in some localities wear 
out, debilitate, and render incapable for work and a prey to disease 
valuable members of the community? 
Is this the fault of our governors and legislators? Not at all. 
Jt is because we live in a state of society which is still far from 
ideal-in a community in which everyone is, to a greater or less ex- 
tent, working for himself, with little intelligent responsibility for 
the general good. It is because we still lack a large measure of the 
attributes of true civilization. With the barbarous and untutored 
savage in the African jungle every word and every act are deter- 
mined by the impulse of the moment, by that familiar instinct 
which impels us all to follow the path of least resistance. His 
simple mind is incapable of grasping the idea of the practical ad- 
vantages of truth and loyalty and justice, much less of any re- 
ligious or moral obligation. And in his more or less guileless 
desire to make his own pathway smooth by obliging his civilized 
neighbor when it is convenient, and knocking him in the head when 
that seems the simplest way to comfort, he inevitably entangles 
himself in a snare which brings about his own destruction. The 
idea of the necessity of the practice of truth and justice with our 
neighbor, of charitable and loyal co-operation with our fellows, 
as the basis on which we may assure for ourselves the safest and 
happiest form of government is an idea which is acquired only by 4 
many centuries of bitter experience. And while the more intelli- 
gent part of most Christian communities of today, either through 
faith or reason, or both, profess to accept these principles with 
regard to the conduct of life and society, the philosopher from 
another planet would, I fear, be amazed should he attempt to com- 
pare individual profession with collective practice. 
The degree to which a community is capable of disinterested 
co-operation for the promotion of the general welfare is a good 
measure of its grade of civilization. Should one, however, apply 
such a test to the manner in which the medical profession and the 
general public in this country deal with affairs of public health 
I fear that his first sentiment might not be one of encouragement. 
When we meet in our practice with a suspected case of diph- 
theria our first thought is too apt to be, "What a nuisance! If 
this case be reported, the house will be posted; there will be no 
end of trouble for the family"-who are at the same time urging 
us to say nothing for the present, and will take it sorely amiss if 
we notify the Board of Health. What a temptation, if the symp- 
toms be mild, to take every precaution and let it pass, or, if there 
be doubt, to take no measures at the moment, and not to alarm the 
family until we are perfectly sure of the nature of the case; and in 
either instance delay may mean, through the ignorance or careless- 
ness of the family, the beginning of an epidemic. 
If, again, it be a case of typhoid fever, how often do we begin 
the necessary precautions at the very onset, at the time when we 
nervous; if we insist upon the proper precautions, she will imme- 
diately understand what is in our mind. She "will die if she sus- 
pects it is typhoid fever." The business of the hotel will be ruined 
if anyone fancies this possibility. The neighborhood will be dis- 
credited. There is a good chance, after all, that it may amount to 
nothing. One waits, therefore, until, after a week or two, a posi- 
tive Widal test or the natural course of circumstances determines 
the diagnosis, and during this week or two the mother has, per- 
haps, acquired the disease by direct contagion, or contamination 
of food or water supply may have started an epidemic in the house 
or neighborhood. 
In a Southern city, in the summer, a few cases of fever occur of 
a puzzling or uncertain nature. Are they perhaps dengue? What 
if they should be yellow fever? But, no; that is not likely. We 
have had no serious yellow fever for years, and the condition of 
the city is now so much better than it was. Might it not be safer 
to notify the Health Department at once of these uncertain and 
slightly suspicious cases and adopt all precautions? Of course, if 
one were but sure. But, then, think of the results if the cases be 
innocent, after all, and yet our suspicions become public-a shot- 
gun quarantine, the business of the city at a standstill, and with its 
gradual resumption a certain inevitable permanent loss to the ad- 
vantage of the rival community. Suppose, even, that time should 
show it to be yellow fever; it would be early enough to take action 
then. Five or six years ago there were a few cases which the 5 
Health Department said were yellow fever, and yet there was no 
general epidemic. And then, to be sure, there were many among 
us who believed and stated with assurance that these cases were 
not yellow fever at all, but only estivo-autumnal malaria. After all, 
that suspicion was born only of over-conscientiousness. It would 
be folly to upset the whole State on such mere fancy. And from 
two to three weeks later there is a sudden outburst of new cases, 
some of which are fatal, and but too clearly the dreaded enemy- 
but it is already too late, and, despite intelligent and vigorous 
action by local and national authorities, there is an epidemic of 
thousands of cases, with the loss of hundreds of valuable lives. 
The only daughter of the family is brought .to you with evident 
tuberculosis. The parents realize that there is no hope; they can 
ill afford to take her away, and they know it is useless; but "Above 
all, Doctor, don't tell her what it is. She does not suspect it, and 
it will kill her if she has any idea of it." But it is of importance 
to her to know the truth that she may follow that course of life 
which is best for herself and safest for those about her. "No, no," 
you are assured, "you don't know her sensitive nature. To tell her 
will be to put an end to all hope. The family understand; they 
will take all precautions, they will teach them to her in such a way 
that she may not suspect," and the delicate, sensitive girl sits shiv- 
ering by the stove and takes patent medicines, and slowly dies, and 
the precautions are not carried out, and next year her only brother, 
the hope of the family, follows close on her heels. 
There is no danger to others; tuberculosis is not contagious; 
these cases have not been reported, and perhaps the final cause of 
death was "pneumonia." And a year later the infected house 
poisons another innocent and unsuspecting family. 
This is the path of least resistance, this is the natural course 
followed by our ingenuous savage, the way along which we find 
ourselves ever inclined to follow, and the result is, in the end, the 
same-calamity. 
But little by little, laboriously through ages, humanity is learn- 
ing the value and necessity of co-operation, of social and political 
regulation and restraint, of the necessity of the sacrifice of many 
individual liberties for the welfare of the whole; and while, as a 
rule, experience-cruel, personal experience-alone teaches the 
masses, yet it is perhaps true that today the public is as intelligent 
and as capable of profiting by the experience of others and by the 
researches and advice of the competent student as it ever has been 
in times past. The thoughtful element of the medical profession, 
and happily many of the public, have come to realize that dissi- 
pated individual effort cannot suffice to protect the community as 
it should be protected, that such protection can only be afforded 
by the labors of properly constituted boards of health, supported 
by the united efforts of the medical profession. And this is, I sin- 
cerely believe, our most important public duty as physicians: 
thorough, cordial, intelligent support of and co-operation with our 
central boards of health. 6 
What does such co-operation imply ? 
i. We should use our influence in every way to bring it about 
that the board itself should consist of disinterested men who are 
trained to or specially fitted for the essentially scientific duties of 
such a body. In times past there have been many men whose train- 
ing has not particularly fitted them for such positions-busy gen- 
eral practitioners, who have yet developed into faithful and effi- 
cient health officers. There are many such in the country today. 
All honor to them! But with modern educational opportunities 
there should be no difficulty in the State and in ouc larger cities 
in finding men whose training especially qualifies them for this 
work. What boards of health have been in the past and still are 
in many localities where the appointments are made as rewards for 
political service or as gifts to friends it is needless to point out. 
And how extraordinary it is to think that individuals, a part of 
whom at least, are gifted with some powers of reason, should place 
the protection of the public health in the hands of men who have 
no more training in and no more idea of those measures of sanitary 
science which insure the safety of the public than an able seaman 
might have of the government of the engines of an ocean steamer. 
A few days ago, in a French journal, I came across the follow- 
ing words, attributed to Socrates: "It is a remarkable fact that 
those who wish to become skilled on the lyre or on the flute, in 
riding or in any such exercise, work ceaselessly and undergo 
fatigue and suffering to learn their trade, while our great politi- 
cians who wish to govern us, fancy that they become suddenly 
capable of everything as it were by instinct, without study or prep- 
aration." The quotation is inexact, but the observation is singu- 
larly applicable to modern conditions. 
But if the Athenian held that the art of politics could not be 
taught, it was not so with regard to the other arts or sciences. 
"When we are met together," says Socrates, "in the assembly, and 
the matter in hand relates to building, the builders are summoned 
as advisers; when a question of shipbuilding, then the shipbuilders, 
and the like of other arts which they think capable of being taught 
and learned. And if some person offers to give them advice who 
is not supposed by them to have any skill in the art, even though 
he be good-looking and rich and noble, they do not listen to him, 
but laugh at him and hoot him until he is either clamored down 
and retires of himself, or, if he persist, he is dragged away or put 
out by the constables at the command of the prytanes. This is 
their way of behaving about the arts which have professors."* 
The medical profession should be the first to realize the fact that 
the members of boards of health should be chosen with all the care 
and discrimination that would be exercised in the selection of a 
professor in a university. That such appointments should be 
allowed to fall into the slough of party politics, that members of 
*Plato, Protagoras: "The Dialogues of Plato," translated by Jowett, 
Oxford, 8vo, 1871, I, 124. 7 
the medical profession, without any of the necessary special train- 
ing, should put themselves forward as applicants for such offices, 
should be abhorrent to our whole body. 
This State is fortunate in possessing a Board of Health which 
may well be an object of pride to all. It is a competent, disinter- 
ested, eminently efficient body. It is a board in which we may 
trust and confide, to support which loyally we owe it to ourselves 
and patients. 
2. The first and most essential evidence of confidence in a 
board of health is the faithful and immediate reporting of all cases 
of communicable disease. The only way to protect the public and 
ourselves, is to record all contagious diseases, not only when we 
positively recognize them, but when we suspect their existence; 
to take cultures from every case suggesting diphtheria; to have 
examinations of the sputa made whenever we fear the presence of 
tuberculosis; to send to the department specimens of blood wher- 
ever there is a question of typhoid or malarial fever, to notify or 
confer with the Health Board concerning every case in which one 
suspects measles, whooping-cough, scarlet fever, chicken-pox or 
smallpox, yellow fever or plague. 
We should remember that it is the first doubtful case that counts, 
that nearly every epidemic can be nipped in the bud, while it takes 
often but a fearfully short time to gain a growth which over- 
whelms us. 
3. We should assist our boards of health in every way in carry- 
ing out proper methods of prophylaxis. What this means in yellow 
fever where the methods of protection are so simple and efficacious, 
need not be emphasized. It would have been simple enough at the 
outset to prevent the present epidemic by that intelligent co-opera- 
tion between physician and board of health which is of such vital 
importance to our welfare. 
One of the most serious problems with which we have to deal 
is in connection with typhoid fever. Here, indeed, a great field 
lies before us. If every instance of this omnipresent reproach to 
civilization were promptly recognized or suspected and reported 
to the authorities, the excreta carefully and systematically disin- 
fected, and proper precautions taken by the nurses and attendants, 
the disease might be eradicated from our midst. Every case of 
typhoid fever in which the dejecta and urine are not disinfected is 
a menace to the community. Boards of health should distribute 
among the medical profession careful directions as to the proper 
measures of protection, and these should be carried out in every 
suspicious case. But more than this, we should ourselves, in our 
dealings with the public, use our influence constantly to bring 
about improvement in the sanitary conditions, in the measures 
which should be adopted against flies, in the proper construction 
and protection of outhouses, in the control of the water supply. 
These are questions in which boards of health may be of the 
greatest assistance, but where much of the burden falls upon us 
individually. No one of us can tell what neglected case of typhoid 8 
fever may be the source of an epidemic. What may be accom- 
plished by co-operation and well-directed effort is shown by the 
records of several German experimental stations, where simply by 
instruction of the public and the carrying out of efficient measures 
of early diagnosis and disinfection the disease has been wiped out 
in various localities. 
Again, nothing can be more impressive than that which has been 
accomplished by the Italian Society for the Study of Malaria and 
the various campaigns of Koch in Africa and Italy. 
To report every case of tuberculosis is becoming daily of greater 
importance. It is but too clear that the infected house is the hotbed 
of the disease; that it is of vital importance for the protection of 
the public that the patient should be instructed as to his manner 
of life; that proper methods of cleaning and disinfection should 
be carried out, and that after the death or removal of a sufferer 
from tuberculosis, fitting instructions should be given to the 
family or to the owner or occupant of the house or room in which 
he has lived. Our State has an admirable and far-reaching law 
on this subject, formulated by the Board of Health. Every phy- 
sician on reporting a case of tuberculosis, is furnished with a set 
of instructions as to measures required by the State-measures 
which are only such as we should all carry out in our practice, 
while all necessary implements and disinfectants are furnished 
gratuitously by the State. For the time and trouble required to 
fill out the reports which are demanded the State furnishes a 
slight compensation, or will, at the request of the physician, under- 
take these measures through the agency of the Board of Health. 
No breach of professional secrecy is involved in these reports, and 
the necessary prophylactic measures imply no unpleasant publicity. 
The State Board of Health is bound to accept this information as 
confidential, and has always done so. The information which is 
given in such reports is, after all. no more than that which we give 
every day on sending specimens of sputa for examination. 
These few examples must suffice. The State Board of Health 
should be a vital organ which mav supply to the physician 
throughout the State nourishment in the shape of the latest infor- 
mation. while it puts into his hands the power to perform invalu- 
able services to the public and to his patients in the way of 
prophylaxis. 
The dav is sure to come when the functions of otir boards of 
health will be much broader than they are now, when stations will 
be established throughout the country whose duty it will be to 
supply to the local practitioners the means required for earlier 
diagnosis, more thorough and intelligent prophylaxis, and, let us 
hope, ere long, for the specific treatment of many acute infections. 
To us, as practical physicians, the Board of Health is a right arm. 9 
Failure to recognize this fact and to work in harmony with the 
Board, an attitude of suspicion towards it, a tendency to avoid the 
new duties which have come upon us-these are but the outcrop- 
ping of our innate tendency to seek the path of least resistance, 
that tendency which we share with our above-mentioned amiable 
savage. If we follow this path of least resistance, we cut off our 
main source of strength and fall, inevitably, into impotence and 
danger. 
These are a few of the public duties which have grown upon us 
in late years. They are grave duties, but they are also privileges. 
In this age of division of labor no one of us can do all. The remote 
country practitioner, by careful observation and report to the cen- 
tral body, may prove the means of the most important and far- 
reaching discovery. After all, who knows which one of us may 
supply the vital link to the chain. Let us remember that we are 
all members of one organism, and to accomplish our duty to the 
community and to ourselves we must work together as one organ- 
ism ; that if, at first, it may seem that we are losing some precious 
individual privileges, we shall, on second thought, realize that by 
system and order, each working in his own field and co-operating 
with his neighbor in furthering the progress of the profession, we 
have acquired powers as a body which are of infinitely greater 
value to the community at large as well as to each separate member. 
Thanks to the continued and faithful labors of a few of our 
number, and especially of that dear friend who, in his Anglican 
retirement, is, let us hope, adding to that inexhaustible store of 
youth for which he has always been pre-eminent that he may be 
born again at the end of his sixtieth year, we meet here today an 
unusually strong and harmonious and united body. There has 
never been a time when the members of this Faculty have had 
greater right to pride than today-pride in the character of our 
members, in the character of the work which we are doing as an or- 
ganization, and, above all, in the harmony and good fellowship 
which prevail. But,after all, we are but beginning, and the message 
which I would give you today is merely to urge that individually 
among ourselves and among our fellows we should endeavor to 
cultivate yet further the spirit of unselfish co-operation for the 
general good which has, more than anything else, brought us the 
advantages which we enjoy today. 
Let us make full and conscientious use of the diagnostic as- 
sistance which is offered us by the public laboratories. 
Let us realize the necessity of co-operation with our State 
and local health departments in reporting all cases of communi- 
cable diseases and in carrying out strictly the necessary prophy- 
lactic measures. 
Let us use all our personal influence to bring about improve- 10 
ment not only in the general public sanitation, but also in the 
conditions as we meet them in our own dwellings and in the houses 
of our patients. 
And, above all, let us remember that our great strength lies 
in co-operation-co-operation in our work for the advancement 
of the medical profession; co-operation in support of the char- 
acter of our central boards of health, by insisting, in so far as the 
power in us lies, in the separation of these bodies from politics; 
co-operation in maintaining the honor and usefulness and strength 
of this old association, through which we can accomplish the 
greatest good for the community and for ourselves. OBSERVATIONS ON SEVERAL CASES OE ACUTE 
PANCREATITIS. 
By William Sydney Thayer, M. D., 
'Professor of Clinical Medicine in the Johns Hopkins 
University. [From The Johns Hopkins Hospital Bulletin, Vol. XVI, No. 176, 
November, 1905.] 
OBSERVATIONS ON SEVERAL CASES OF ACUTE 
PANCREATITIS. 
William Sydney Thayer, M. D., 
Professor of Clinical Medicine in the Johns Hopkins 
University. 
The following cases, four of which come under the head 
of suppurative, and one of gangrenous pancreatitis, are 
deemed worthy of report, as well from a diagnostic stand- 
point as from the fact that their course and outcome empha- 
size the importance of early recognition and prompt surgical 
interference under similar circumstances. The first of these 
cases was seen a few months ago in consultation with Dr. J. C. 
Pound. The other four are from the wards of the Johns Hop- 
kins Hospital. Three of these I have had the good fortune to 
see myself; one was under the care of Dr. Futcher. 
Case I. Woman; 51. Previous attacks of biliary colic. 
Onset of present illness with an attack of biliary colic and 
jaundice followed by fever, nausea, vomiting, and pain on the 
left side of the abdomen. Deep tumor mass occupying the 
epigastrium and left side of the abdomen, extending well out- 
ivard and backward into the flank. Operation, thirty-seven 
days after onset, revealed parapancreatic abscess with dissemi- 
nated fat necrosis. Recovery. 
Mrs. W., married, 51 years of age, was seen in consultation with 
Dr. J. C. Pound on 31 October, 1904. The family history was 
negative. She had had typhoid fever in childhood but had other- 
wise been a healthy woman. Married; no children. Passed the 
menopause a year ago. Ten years ago had a few attacks of sharp 
[355] 
[356] 
1 [356] 
pain in the epigastrium and right hypochondrium seldom asso- 
ciated with nausea or vomiting. 
Present Illness.-In June she had had a sharp attack of pain 
in the epigastrium and right hypochondrium lasting several 
days; this was associated with jaundice which lasted a week. 
The stools, for several days, resembled putty. Four weeks ago 
to-morrow the patient had another attack of pain in the epi- 
gastrium of not very marked severity, though it was enough to 
require an hypodermic of morphia. This was followed by 
jaundice which lasted four or five days. There was also fever 
and nausea and vomiting which, at first, were rather severe. 
There was what she calls a " sore pain " in the epigastrium, par- 
ticularly on the left side. The nausea and vomiting, worse in the 
afternoon, have continued off and on ever since. There has been 
intermittent fever associated with considerable sweating at times, 
especially at night. The main complaint has been of a " sore 
pain " throughout the left side of the abdomen. 
On physical examination the patient was found to be a well- 
nourished woman of a rather sallow, yellowish appearance, sug- 
gesting suppuration; temperature 102.8°. The thorax was clear 
throughout, the lungs descending behind to an equal level on both 
sides. The heart sounds were clear; the apex in normal position. 
The abdomen was rather full, slightly more prominent on the 
left side, especially a little above the crest of the ileum. On 
palpation there was to be felt a deep mass extending somewhat 
across the epigastrium to the right but especially filling up the 
left side of the epigastrium, and extending downward to a point 
as low as the level of the anterior superior spine of the ileum. 
On the left it reached to a point about as far out as the mid- 
axillary line. It was deeply situated below the gut. The 
border of the liver was not clearly felt and on the right did 
not, apparently, descend below the costal margin. The mass 
suggested to Dr. Pound and myself a deep parapancreatic abscess, 
although the situation was much further to the left than is 
common in such cases. The relation of the symptoms to the 
attack of biliary colic was, however, suggestive. 
1 November. Examination of the blood showed: red blood 
corpuscles, 3,964,000 to the cu. mm.; colorless corpuscles, 16,800 
to the cu. mm.; hemoglobin (Dare) 61%. 
A differential count of 500 leucocytes stained by Ehrlich's 
method showed: small mononuclears, 8.6%; large mononuclears 
and transitionals, 6.6%; polymorphonuclear neutrophiles, 84.4%; 
eosinophiles, 0.4%; mast cells, 0.4%. 
The red cells were normal in size and form. There were no 
irregularities in contour; no nucleated red corpuscles were ob- 
served. 
(2) Urine.-Normal, amber color, clear, acid 1009, no albumin, no 
sugar. Microscopically, few squamous epithelial cells; an oc- 
casional leucocyte; no casts; no crystals. 
An exploratory operation was suggested, but the family de- 
murred. 
7 November. On this date the patient was again seen in con- 
sultation with Dr. Pound. During the past week the condition 
has not essentially changed. Examination to-day, however, shows 
some slight modification in the character of the mass which 
extends, perhaps, a little lower, while it is not as prominent in 
[356] 
Position of deep mass in Case I. 
the epigastrium. There is, also, flatness in the left back, reaching 
to a point as high as the angle of the scapula. The upper limit 
of dulness is higher in the scapular line than at the spine. 
In front, however, the lower level of the lung is about at the 
same point as on the right. Below the line of flatness, vocal 
fremitus is absent, while the respiration is rather indistinct, of a 
tubular quality, with nasal voice sounds, somewhat suggestive 
of segophony, especially toward the upper part. 
9 November. The patient who had been urged to consent to 
operation, agreed to see Dr. Finney to-day. On examination a 
decided change was noticed in the outline of the deep mass, in 
(3) [356] 
that it projected much more in the flank, reached further outward 
and began to show distinct evidence of fluctuation. There was 
also slight oedema of the subcutaneous tissue just above the crest 
of the ileum. 
The patient was removed to the Union Protestant Infirmary 
Where Dr. Finney operated on the following day. 
The abscess was opened in the left flank where it appeared to 
be pointing. This opening led into a very large cavity which 
extended upwards into the epigastrium in the region of the 
pancreas, downwards toward the pelvis and backwards into the 
para-renal region. Escaping with the pus were masses of necrotic 
fat and shreds of necrotic tissue. 
The patient bore the operation well, but the fever, ranging from 
normal in the morning to 100° and 101° at night, continued. 
There were frequent attacks of nausea and vomiting; little food 
could be retained. On 20 November, I saw the patient who was 
much emaciated, extremely feeble and delirious. The pulse was 
140. The condition was such that it was feared she might not live 
through the night. From this time on, however, she steadily 
improved. The vomiting ceased, the appetite returned and the 
delirium disappeared. 
On 22 December, the patient had so far improved that she was 
able to go home, although the evening temperature was still a 
little above 99° while a sinus persisted. 
The urine was free from sugar throughout. 
In the discharge from the wound large masses of necrotic 
tissue appeared on various occasions. On 20 November, for 
instance, a piece measuring 6 x 6.5 cm. escaped, while on 29 No- 
vember, a piece was discharged as large as the palm of the hand. 
Several of these masses suggested bits of true pancreatic 
tissue. 
A specimen was sent to Dr. Bloodgood who made the following 
report: 
Pathological No. 5897. Mrs. W., patient of Dr. Finney, U. P. I. 
" Clinical Diagnosis, Pancreatic Abscess.-Necrotic and haem- 
orrhagic tissue shows no evidence of remains of pancreatic gland. 
Gross Description.-The specimen consists of a mass of tissue 
which is so friable and mushy that it cannot be handled without 
falling to pieces. It is of a greyish pink color and seems to be 
somewhat loosely bound together by fibrous shreds; in one area 
there is a blackish mass, quite friable, which has the appearance 
of a blood clot 
Microscopical Description.-Section 1, marked ' blood clot,' 
shows areas of disorganized blood in a granular tissue taking 
[357] 
(4) the eosin stain in which I can recognize no stained nuclei. The 
architecture of the necrotic tissue suggests fat. 
Section 2, marked ' tissue ' has the same appearance as section 
1, no nuclei taking the stain. There is no tissue suggesting the 
architecture of fat and no positive evidence of pancreatic tissue. 
Remarks.-Clinically, the case was considered by Dr. Thayer to 
be one of pancreatic disease. The tissue sent to the laboratory 
was of necrotic haemorrhagic fat which came from the abscess 
cavity." 
Case II.1 Man; 34- For a year and a half attacks of 
cramp-like epigastric pain; present attack: severe epigastric 
pain; vomiting; fever; epigastric tumor; diagnosis of acute 
pancreatitis with parapancreatic ahscess; operation twelve days 
after onset; recovery. 
Hosp. No. 10,210; Surg. No. 3190. W. E. D.; aged -34; married; 
a piano polisher, was admitted to the Johns Hopkins Hospital 
on 25 June, 1905. Family history, negative. Previous History.- 
As a child had had chicken pox and pneumonia, the latter at the 
age of six. Had been married thirteen years; no children. For 
years had been a regular drinker of beer and whiskey though not 
to great excess. Smoked and chewed tobacco. Five years before 
entry had been overcome by heat. Was in bed at this time for a 
week. For two years had been subject to attacks of nausea in the 
morning with occasional attacks of vomiting, the vomitus con- 
sisting of a greenish, slimy substance. 
For a year and a half the patient had been subject to attacks 
of severe cramp-like pain in the abdomen. The pains were local- 
ized in the median line across the epigastrium and about the 
umbilicus. The first attack came on at night and was very severe, 
so much so that relief was obtained only by large doses of mor- 
phia. With each attack the patient had been compelled to remain 
at home for from several days to a week. There was often 
vomiting; probably fever; never jaundice. 
P. I.-Ten days before entry the patient came home from work 
on account of a slight sensation of heaviness in the epigastrium 
and a feeling of anxiety similar to that which had preceded his 
other attacks of pain. The same evening vomiting came on. 
The pain was intense and continuous, and a swelling appeared 
just above the umbilicus at the area of greatest tenderness. 
There was constipation. During the next week the patient was 
[357] 
1 Published previously in the Am. J. M. Sc., Phila, 1895, CX, 396. 
(5) [357] 
obliged to remain in bed. There was continuous fever, and delir- 
ium. A diagnosis of abscess of the liver was made by his physi- 
cian. On 25 June, he was admitted to the Johns Hopkins 
Hospital. I saw the patient shortly after entry and made the 
following note: 
" On physical examination the patient is a well-formed man, 
quite corpulent; lips and mucous membranes of good color. The 
tongue is coated, the temperature elevated; the mental condition 
dull; the patient is a little confused. Examination of the thorax 
is negative. On inspection the abdomen is full, showing a rather 
Position of the palpable mass in Case II. 
undue prominence in the median line across the epigastrium. 
Hepatic flatness begins at the sixth rib in the mamillary line, 
while in the same line the lower border of the liver can, appar- 
ently, be felt about on a level with the umbilicus; it is not, 
however, very distinct, owing to the tension of the abdominal 
muscles. Liver-flatness is coextensive with this area. Passing 
toward the median line the resonance becomes tympanitic. Just 
below the xyphoid cartilage the resonance is loudly tympanitic, 
and from the sensation conveyed by palpation there is evidently 
an air-containing organ (stomach?) just below the skin. Below, 
between this and the umbilicus, at the point of maximum prom- 
(6) inence, is to be felt a deeply seated mass, over which there is 
well marked tympany. The outline of the mass is indistinct. 
It is not tender on ordinary palpation. To the right this mass is 
not to be sharply separated from what would appear to be the 
liver; to the left it reaches about to the costal region. Pressure 
over the lower left ribs does not cause pain. In the knee-elbow 
position nothing further is to be made out. Splenic dulness is 
about normal in area, and does not pass the costo-articular line. 
There are no glandular enlargements." The appended chart, 
made at the time of this examination, shows the position of the 
deep mass, of the hepatic dulness, and the epigastric tympany. 
The urine was free from albumin or sugar. 
The blood showed a leucocytosis. 
A diagnosis of acute pancreatitis with disseminated fat necrosis 
and, possibly, sequestration of the pancreas was made, and an 
exploratory operation was advised. This was performed by 
Dr. Finney on 27 June. 
In the median line, adjoining the liver and stomach, a mass of 
adherent fatty tissue was found which was filled with numerous 
fat necroses. This mass of tissue was adherent to the stomach 
and liver. The transverse colon passed over the lower part 
of the opening and was involved in the adhesions. The general 
abdominal cavity was packed off with gauze and an opening into 
the mass was made later. From this opening a large quantity 
of brownish pus with large masses and shreds of necrotic fat 
escaped. The finger passed far backward at the bottom of the 
wound into what appeared to be a cavity in the pancreas. The 
main excavation represented evidently the lesser peritoneal cavity. 
The material discharged from the opening showed pus, bacteria, 
numerous fatty acid crystals and large and small masses of 
necrotic fat. Cultures were unfortunately not made, as the 
opening occurred unexpectedly. No tissue that could be definitely 
identified as pancreatic was found in the discharge. The patient 
made a perfect recovery and has been well ever since. His pres- 
ent good health may be inferred from his appearance, for he has 
kindly consented to come before us this evening. 
Case III.2 Man, 47; six months before attack, jaundice 
with biliary colic; present illness: sudden intense cramp-like 
abdominal pain; nausea; vomiting; collapse; abdominal dis- 
[357] 
[358] 
2 This case has been reported by Dr. Opie in Am. J. M. Sc., 
1901, CXXI, 27. 
(7) [358] 
tension; constipation; tender, painful tumor in the right 
half of epigastrium and hypochondrium; diagnosis by Dr. 
Bloodgood of pancreatitis; operation on 21st day; death; 
necropsy; necrosis of pancreas; suppurative parapancreatitis; 
stone lodged in diverticulum of Vater. 
Hosp. No. 30,996; Med. No. 11,482. J. T. H.; 47; married; 
physician; entered the hospital on 26 June, 1900, complaining of 
abdominal pain, distension and fever. 
The family history was negative. Previous History.-Has had 
scarlet fever and measles. Chews tobacco; does not smoke or 
drink; is not a heavy eater. Has complained frequently of pain 
and distension after eating; rarely, nausea and vomiting. 
Six months ago, had an attack of jaundice accompanied by 
slight pain in the abdomen; the jaundice lasted for several weeks. 
During this period the stools were but slightly clay-colored. 
His sister is inclined to believe that this attack was not dissimilar 
to his present illness. There was some nausea and a good deal 
of abdominal pain; moderate fever. He was obliged to stay in 
bed for some time, but by the end of three weeks had recovered 
entirely. 
Present Illness.-Eighteen days ago, at nine o'clock at night, 
there was a sudden attack of nausea and vomiting with intense 
cramp-like abdominal pains which could not be localized. The 
patient was collapsed, the abdomen distended, and the pain rather 
general; no change in the condition for four or five days. 
On the third day the patient was found to have a temperature of 
about 101.5°. After the first night the vomiting became less 
frequent though it has occurred off and on ever since. The 
bowels were constipated, possibly due to the morphia which was 
given; the skin, cold and clammy. The respirations were not 
accelerated. On about the seventh day a tender area was noticed 
in the right hypochondrium which was a little fuller than any 
other part of the abdomen, though at no time during the illness 
were the muscles of the right side more rigid than those of the 
left. The physician believes that the abdominal respiratory 
movements were practically normal. On the fifth day the bowels 
were opened by purgatives. The faeces were normal in color and 
have been essentially natural since then, although laxatives have 
had to be used twice. The last movement occurred four days 
ago. For eleven days there has been an irregular fever ranging 
between 101° and 103°; there have been four or five chills. 
Nausea and vomiting have been slight and the abdominal pain 
has not been severe. But little morphia has been given. The 
(8) area of tenderness in the right hypochondrium has, however, 
persisted, while the abdominal distension has steadily increased. 
There have been no cerebral symptoms, and the mind has been 
perfectly clear throughout. There has been no jaundice. The 
patient has lain on his right side during most of the time, with 
the thighs flexed on the abdomen. The pulse has ranged from 
100-120; at times, dicrotic. 
26 July, 1900. On entrance, the patient was seen by Dr. Futcher 
who made the following note: "The patient is a man of large 
frame; complexion, a trifle sallow; mucous membranes, somewhat 
[358] 
Position of palpable mass in Case III. 
anaemic; tongue, a little coated; very slight yellowish cast to the 
conjunctivae. He lies upon his right side with the knees flexed. 
The pulse is of fairly good volume and tension, regular in force 
and rhythm, vessel wall not thickened. Lungs, clear throughout 
on percussion and auscultation. Heart.-Point of maximum im- 
pulse not seen or felt. Sounds best heard in the fourth inter- 
space, 9 cm. from the midsternal line; sounds enfeebled at 
apex and base. Abdomen.-The right costal groove is partially 
obliterated; the right lumbar region slightly fuller than the left. 
There is a distinct, visible prominence in the right hypochon- 
drium and the right half of the epigastrium, extending into 
the upper right quadrant of the umbilical region. Distinct pul- 
(9) [358] 
sation is visible in the upper epigastrium. Respiratory move- 
ments are less marked on the right than on the left. On palpa- 
tion there is a distinct resistance in the area above noted. The 
lower margin of this area of definite resistance corresponds with 
the line indicated in the chart extending a little to the right 
of the umbilicus to a point about on a level with the anterior 
superior spine, passing up through the umbilicus, the left border 
of the umbilical region and around again through the epigastrium 
to the right. To the right the outline of the mass is not so 
easily felt. The margin is rather round and extends to a point 
10.5 cm. below the costal margin in the mamillary line and to 
the level of the umbilicus in the median line. 
The surface is firm, a little irregular. The lower margin 
descends on inspiration. In the median line the fingers can 
be pressed in above the resisting mass. There is dull tympany 
over the tumor and the dulness is continuous above the costal 
margin with the hepatic flatness which extends to the middle 
of the sixth interspace. . . . The border of the spleen is not 
definitely felt. There is nothing to be made out in the right 
iliac fossa." Leucocytes 18,300. 
27 June, 1900. The stool passed last night was soft, unformed, 
golden in color throughout, rather resembling gold dust and 
having a definite glistening appearance. There was nothing 
remarkable save for the large number of fatty acid crystals. 
Following inflation of the stomach with tartaric acid and 
bicarbonate of soda, the epigastrium and upper part of the 
umbilical region became decidedly more prominent. There was 
no peristalsis. The upper border of the stomach tympany began 
over the middle of the sixth interspace in the parasternal line 
and reached a point 5.5 cm. above the level of the umbilicus in 
the median line. The stomach, after inflation, measured only 
21 x 11 cm. The mass in the right hypochondrium and right 
half of the umbilical region did not appear to be connected with 
the stomach. The glands in the left axilla were slightly enlarged. 
Leucocytes, at 11 a. m., 19,300. The condition was about the 
same. There was some nausea and vomiting early in the 
morning. The vomitus was green in color, acid to litmus. Free 
hydrochloric acid was present, the acidity amounting to 27; total 
acidity, 50. 
Urine.-High; clear; acid; 1017; no sugar; trace of albumin. 
Microscopically: mucous cylindroids; one granular cast seen. 
28 June, 1900. Leucocytes, at 4 p. m., 19,500. There has been 
no change in patient's condition. He takes his nourishment well 
and has not vomited since yesterday. The temperature, since 
admission, has ranged between 99.2° and 101.8° and but once has 
[359] 
(10) been above 100.4°. He has complained of no pain and there is 
but little sensitiveness on palpation over the mass. The patient 
has, at times, been somewhat irrational and very drowsy. The 
right lateral decubitus and the flexion of the knees and thighs 
continues. There is no muscle spasm. The pulse has varied 
from 108-124, and has, at times, been irregular and intermittent. 
The respirations since admission have been from 20-28 to the 
minute. A fresh specimen of blood shows nothing abnormal 
save a leucocytosis, chiefly polymorphonuclear. 
29 June. 6 a. m., leucocytes, 18,500. Last night the patient 
was decidedly irrational; the pulse, irregular and rapid. There 
was marked restlessness, the patient endeavoring to get out of 
bed. The temperature rose during the night reaching 104° at 
six this morning. Stool, obtained by rectal tube, showed no 
amcebae; no red blood corpuscles; no pus. Color, light yellow; 
a few fatty acid crystals. The stool early this morning was 
liquid, of a yellow ochre color; no amcebae; no blood corpuscles; 
no pus. There was a large quantity of fatty acid crystals; no 
fat globules. 
Dr. Futcher made the following note: " The mass in the right 
hypochondrium and epigastrium has not apparently changed in 
size. There is no tenderness on palpation." The temperature 
rose at six p. m. to 104°. The urine, throughout, was free from 
sugar. 
The patient was seen on this date, by Dr. Bloodgood, who made 
a diagnosis of suppurative pancreatitis and advised operation 
which was performed on the following day. On opening the 
peritoneal cavity numerous areas of fat necrosis were visible. 
The omentum was matted together. On making an opening 
through the omentum a large amount of dark, brownish black 
fluid escaped. The patient's condition was so bad that a drainage 
tube was inserted and the wound closed without further investi- 
gation. The general weakness, however, increased and at 8 p. m. 
the patient died. 
Necropsy.-Anatomical diagnosis; cholelithiasis; calculus 
lodged in the common duct near its orifice; slight jaundice; old 
haemorrhage within and about the pancreas: localized necrosis 
of pancreas; chronic interstitial pancreatitis; necrosis of fat of 
pancreas; greater and lesser omentum, mesentery and subperit- 
oneal tissue of the abdominal wall; parapancreatic abscess limited 
by lesser peritoneal cavity; laparotomy wound. 
A partial necropsy was made by Dr. Opie through the incision 
three hours after death. " The body is that of a large-framed, 
muscular man with abundant subcutaneous fat. Peritoneal 
Cavity.-The omentum, which contains a large quantity of fat, is 
adherent in the neighborhood of the operation wound to the 
[359] 
(11) [359] 
anterior abdominal wall by light, fibrinous adhesions. Its surface 
is thickly studded with conspicuous, opaque, white areas, varying 
in size and shape, but usually round and about 3 mm. in diameter, 
extending about 1.5 mm. below the surface. On section similar 
foci are found embedded in the fat. Opaque, white areas are 
present in the fat of the mesentery, where they are most 
abundant near its intestinal margin, in the subperitoneal fat of 
the anterior abdominal wall, over the bladder, over the kidneys, 
and about the colon. Abscess cavity.-The drainage-tube inserted 
into the abdominal wound passes through a small, incised opening 
in the great omentum and enters an immense abscess cavity which 
occupies approximately the site of the lesser peritoneal cavity. 
The foramen of Winslow is closed. The stomach is pushed up- 
ward and forward, and its anterior surface is adherent to the 
lower surface of the liver to the left of the gall-bladder. The 
spleen, partially surrounded by fat containing many opaque, 
white areas, is bound by fibrous adhesions to the diaphragm. 
The walls of the cavity are very irregular and ragged, and have 
a necrotic appearance, in general opaque and gray, occasionally 
black. This blackish-gray appearance extends only a short dis- 
tance below the surface, and where the wall is formed by fat, 
give place to numerous foci of opaque, white color. The retro- 
peritoneal fat in front of the left kidney and psoas muscle has 
been eroded, and an extension of the cavity passes behind the 
jejunum near its junction with the duodenum. To the left of 
the descending portion of the duodenum, occupying the position 
of the pancreas and projecting forward into the abscess cavity, 
is a great mass of black material, necrotic in appearance, extend- 
ing to the left as far as the spleen. This material is reddish- 
black on section, somewhat spongy in texture, soft, dry, and 
friable. The cavity contains a large quantity-at least 500 cc.- 
of fluid, reddish gray material, containing fat droplets and black, 
necrotic particles The bile ducts are slightly dilated and 
contain thin yellow bile. The gall bladder is bound by numerous 
adhesions to the duodenum and stomach. Its walls are thick- 
ened and it is much distended, containing viscid yellow bile and 
a large number-over one hundred-of brown facetted calculi 
varying in diameter from 0.5 to 1 cm. The hepatic, cystic and 
common ducts are much dilated. On opening the duodenum a 
stone is felt below the mucous membrane situated in the common 
bile duct, about 1.5 cm. from the orifice of the diverticulum of 
Vater. It is 7 mm. in diameter and resembles those present in the 
gall bladder. 
Pancreas.-The pancreatic duct unites with the common bile 
duct at a point 7 mm. from the duodenal orifice. For a distance 
of 1.5 cm. the two ducts are separated by a thin septum only, 
(12) and in contact with this septum is lodged the gall stone previously 
mentioned. The pancreatic duct is not distended. The pancreas 
occupies the posterior wall of the lesser peritoneal abscess cavity, 
and is covered by the mass of reddish black, friable material, 
changed, coagulated blood, above described. The organ is of 
large size, and the glandular tissue is in great part firm, yellow- 
ish-white, and well preserved. The interstitial tissue has a dull, 
reddish, in places hemorrhagic appearance, and contains con- 
spicuous, opaque, areas of irregular shape. Where the anterior 
surface of the head and body is in contact with the overlying 
material there is a superficial zone of soft, grayish, necrotic 
appearance. 
The other organs-heart, lungs, spleen, stomach, intestines, 
and kidneys-present no noteworthy alteration. ..." 
The complete histological examination may be found in Dr. 
Opie's article above referred to. 
Bacteriologically, cultures from the heart's blood, lungs and 
liver showed bacillus coli. A plate culture from the material 
covering the pancreas and forming part of the abscess wall con- 
tained the B. coli and the B. lactis aerogenes and the B. proteus. 
Case IV. Woman; 49. Previous attacks of biliary colic; 
sudden severe epigastric pain relieved by morphia; persistent 
dull epigastric pain with nausea and vomiting; tender tumor 
in the right umbilical, epigastric and lateral abdominal re- 
gions; diagnosis by Dr. Halsted of pancreatitis; operation; 
recovery. 
Hosp. No. 39,822; Med. No. 14,390; Surg. No. 13,415. V. C. B.; 
single; 49; housekeeper; a patient of Dr. J. T. Strickland of 
Roanoke, Va., was admitted on 20 May, 1902, complaining of 
" stomach trouble." 
Family history.-Negative. Previous history.-Patient has had 
measles, chicken pox, and whooping cough and, fifteen years ago, 
typhoid fever. Passed menopause five years ago. Has been sub- 
ject to severe headaches; has never suffered from digestive dis- 
turbances until four years ago when she was suddenly seized with 
an agonizing pain in the pit of her stomach; the pain did not 
radiate; it continued until relieved by morphia. There was no 
nausea or vomiting but she felt cold and sweated profusely; no 
jaundice. From that time she has had occasional similar attacks 
but they have not increased in frequency in the past year, and 
she has always recovered on the following day. 
Present illness.-Five weeks ago the patient had a sense of dis- 
[359] 
[360] 
(13) [360] 
comfort in the epigastrium after eating supper; this distress 
became gradually worse, and, in about four hours, had developed 
into an agonizing pain in the pit of the stomach. The pain did 
not radiate into the back. She was cold; there was a drenching 
sweat but no nausea or vomiting; no jaundice. Hot applications 
gave no relief, which was afforded only by an hypodermic in- 
jection of morphia. The attack was similar to those which she 
had had previously, but more severe. Ever since this time she 
has felt very ill. There has been constant dull pain in the 
epigastrium; attacks of vomiting, persistent and protracted, have 
recurred every two or three days, the vomitus being thick and 
dark green in color. She has been able to take only very light 
food. At the onset there was obstinate constipation for about a 
week; thinks she has had a little fever every now and then toward 
night. There have been no chills; no sweating at night. There 
has been no attack of sharp pain since the onset. About three 
weeks ago she noticed a hard tender mass in the abdomen which 
has not disappeared. She has never been jaundiced; has been 
extremely nervous and has not slept well. 
On the day of entry the blood count showed: red blood cor- 
puscles, 4,120,000 to the cu. mm.; colorless corpuscles, 8250 to the 
cu. mm.; haemoglobin, 68%. 
On the same day the following note was made by Dr. Thayer: 
" The patient is sparely nourished; lips and mucous membranes 
of good color; the skin is slightly yellow; the sclera pure white. 
The temperature last night was 100.5°, this morning 99.2°. 
Pulse 31 to the quarter, of moderate size, fairly good tension; 
vessel wall, not palpable. 
Thorax symmetrical; costal angle about 90. Expansion equal. 
Resonance clear in fronts and axillae. Heart.-Apex impulse 
in the fifth space in normal position; sounds clear, of normal 
relative intensity. 
The abdomen looks a trifle fuller in the right epigastric and 
umbilical regions than on the left. No observable peristalsis. 
On palpation, there is to be felt a firm, very tender mass which 
lies in the epigastric and right umbilical regions extending over 
into the right lateral abdominal region. This descends to a point 
slightly below the level of the umbilicus and moves downward 
slightly with inspiration. It has, so far as can be made out, no 
sharp border. To the right the outline is indistinctly to be felt 
passing a little beyond the vertical line extending through the 
anterior superior spine of the ileum. To the left it reaches ap- 
parently about 3-4 cm. beyond the umbilicus. The hepatic flat- 
ness passes directly into the dulness over the mass but the 
dulness is not absolute. Even on light percussion there is slight 
tympany over the tender area. The spleen is not palpable though 
(14) there is dulness to the costal margin as indicated on the chart. 
The border of the mass has not the sharp edge of the ordinary 
hepatic border though it does feel rather firm. There is no appar- 
ent fluctuation. Below this area the abdomen is negative. There 
is no prominence in the right lumbar region. The tumor mass is 
not to be felt with the posterior hand over the lower ribs. 
Without dilatation it is impossible to differentiate the stomach 
from the other air-containing organs. As the patient changes 
position the tumor is practically immobile, falling but little 
toward the dependent side." 
[360] 
Position of tumor in Case IV. 
The urine was of normal color; acid; 1017; no sugar; trace of 
albumin. Sediment, flocculent containing a few hyaline casts, 
mucous cylindroids and epithelial cells. No Diazo reaction. The 
Widal test was negative. 
The temperature during the two days that she was on the 
medical side, ranged between 99.2° and 100.2°. Nothing remark- 
able was noted about the character of the fceces, no entry being 
made in the history. 
On the following day the patient was seen by Dr. Halsted who 
regarded the case as one of pancreatitis and advised operation, 
which was performed by him on 23 April. An incision was 
(15) [360] 
made over the mass in the right hypochondrium, through the 
rectus muscle and separating the fibers. When the peritoneum 
was reached there were some oedema and evidence of inflamma- 
tion. The peritoneum was divided and the abscess cavity was im- 
mediately encountered, from which about an ounce of thick, yel- 
low material was evacuated. This was odorless and contained 
numerous small masses resembling fat. The opening was en- 
larged a little and the cavity explored. It ran downward for a 
distance of about 7 cm. and backwards perhaps 10 cm. It appeared 
to be lined on the sides by bowel and posteriorly by a hard mass, 
the exact position of which could not be determined. The abscess 
cavity contained masses of necrotic looking tissue which Dr. Opie 
regarded as necrotic omental fat. A considerable quantity of this 
necrotic stringy material was evacuated and the abscess cavity 
was wiped out and packed with iodoform gauze. . . . The abdom- 
inal cavity was not opened and no exploration was made to 
determine the presence or absence of gall stones. The patient 
made an uninterrupted recovery and was discharged from the 
hospital on 24 June well. 
Case V. Man; 37. Seven months before entry, intense 
epigastric pain; vomiting and purging ; gradual recovery in 
two months; three weeks before entry, epigastric pain; vomit- 
ing; persistence of symptoms in a milder degree; diagnosis of 
pancreatitis; operation; death from hemorrhage into cavity; 
necropsy: gangrenous pancreatitis; perforation of stomach 
and duodenum. 
Hosp. No. 43,308; Med. No. 15,860; Surg. No. 14,924. S. T. H., 
married, 37 years old, mechanic, patient of Dr. Jones of New- 
bern, N. C., was admitted on 7 July, 1903, complaining of pain m 
the stomach, nausea and occasional vomiting. 
The family history was negative. Personal history.-The pa- 
tient had chicken pox at 9, measles and whooping cough at 10; 
malarial fever at 24; occasional attacks of "kidney colic." He 
was married at 31. His wife had had no children and no mis- 
carriages. Had been a hard worker, his occupation keeping him 
indoors most of the time. Had not been a heavy drinker but 
occasionally drank apple brandy. Had been a hearty eater; a 
slight smoker; had chewed a good deal of tobacco; denied venereal 
disease. 
Present illness.-Seven months before entry he was seized 
at night with a sudden severe pain in his stomach associated 
with vomiting. The pain which had improved, returned in the 
[361] 
(16) morning and continued most of the day associated with moderate 
purging. The vomitus contained no blood. The pain lasted off 
and on for two months but finally entirely disappeared. His 
health remained fair up to three weeks ago, when he had another 
attack of pain in the stomach associated with sweating and 
moderate vomiting. There was no jaundice; he was somewhat con- 
stipated. The bowels were moved by purgatives. He had weighed 
185 pounds, but lost much with his first attack after which, 
however, his weight returned to 172 pounds. It now is about 
160. During the last three weeks he has grown much weaker. 
At one time a tumor is said to have appeared in the gall bladder 
region which was lifted by the heart beat and pulsated. It has, 
since then, disappeared entirely. On the day of entry the follow- 
ing note was made by Dr. Thayer: "Complexion very sallow, 
conjunctivae clear, slightly, if at all, yellow. Tongue, dry with 
a yellowish coat; clear and pale on the edges. Complexion, very 
dark. Patient looks ill; the eyes are sunken; pulse 29 to the 
quarter at the beginning of examination; size moderate, rather 
compressible. 
Thorax.-Symmetrical; costal angle, 90. Note over the right 
lung seems slightly more tympanitic than over the left. Flatness 
begins on the right side at the sixth rib in the mamillary line; 
on the left at the lower border of the seventh. Respiration is 
clear in the left front and axilla; also in the right front. The 
lower border of the left lung behind is a trifle lower than that of 
the right. Back is clear on auscultation. 
Heart.-Negative. Abdomen.-Natural. Well marked epi- 
gastric pulsation. The left side of the epigastrium is slightly 
fuller than the right. On palpation there is to be felt a distinct 
muscular resistance in the epigastrium more particularly on the 
right side. The liver is rather indistinctly felt. It descends on 
deep inspiration, from under the ribs, in the anterior axillary 
line. Under the superior belly of the right rectus there seems 
to be something which descends with inspiration but the tense- 
ness of the muscle prevents accurate palpation. In the median 
line also there is a distinct tenderness but nothing very definite 
is to be felt. The gastric resonance is easily made out extending 
rather far to the right and lying rather transversely. The spleen 
is not distinctly palpable though the dulness just passes the costo- 
articular line. In the median line the liver dulness reaches one 
and a half finger's breadths below the tip of the ensiform. 
A little later Dr. Cole observed that the patient looked very ill 
and was in a rather collapsed condition. The abdomen was a 
little full, especially in the upper half, more so on the left side 
of the epigastrium than on the right. Well marked epigastric 
[361] 
(17) [361] 
pulsation. On the right movements are fairly good. " On palpa- 
tion, below the umbilicus, the walls are not held firmly, and fairly 
deep palpation may be made without much resistance. No masses 
are palpable. There is a marked increase in resistance above 
the umbilicus and in the epigastrium. Here there is very distinct 
tenderness though it is not exquisite, and the walls are held 
quite firmly, the patient resisting voluntarily; there is no definite 
muscle spasm. On deep inspiration one can make out an in- 
definite mass in the epigastrium, the lower border of which is 
felt extending across the median line' about midway between the 
umbilicus and the tip of the ensiform and reaching upwards to 
the left costal margin. This ridge feels somewhat irregular 
though it cannot be definitely determined. The percussion note 
over this mass is tympanitic; it lies apparently behind the 
stomach. No mass is felt in the right hypochondrium. The edge 
of the liver is not palpable." 
The temperature was normal, ranging during the few hours 
that he was on the medical side, between 97.6° and 98.6°. 
A blood count showed: red blood corpuscles, 5,140,000 to the cu. 
mm.; colorless corpuscles, 33,700 to the cu. mm..; haemoglobin, 
82%. 
An approximate hasty differential count showed in one hundred 
cells: small mononuclears, 6; large mononuclears, 5; polymorpho- 
nuclears, 89; eosinophiles, none. 
The gastric contents, after an Ewald test meal, amounted to 
22 cc. of a fluid of a bright green color with flaky particles. 
The supernatant fluid is opalescent, the odor characteristic; total 
acidity, 33; hydrochloric acid, 19; no lactic acid. Microscopically: 
Bacilli of various kinds, no Oppler-Boas bacilli; many cells, for 
the most part leucocytes; few epithelial cells and yeasts. 
Urine.-Yellowish brown; slightly turbid; 1022; strongly acid; 
no sugar; no albumin; urea 0.33 per cc.; no bile pigment; sedi- 
ment: uric acid; two doubtful hyaline casts in centrifugalized 
specimen. 
A diagnosis of acute pancreatitis was made and the patient 
was transferred to the surgical side, Dr. Finney performing an 
exploratory laparotomy on the same day. The peritoneal cavity 
contained no free fluid. The omentum seemed rather hard and 
indurated; no fat necrosis. The gall bladder was found to be 
rather thick but no stones were palpable. The tip of the omen- 
tum was adherent far down on the right side just below the gall 
bladder, and at this point there were two areas which looked like 
spots of fat necrosis. A number of similar points about one or 
two cm. in diameter were also found in the mesentery of the 
ascending colon. There was some general thickening of the 
pancreas which was most marked at the tail where there was a 
(18) good sized mass. The spleen was large and surrounded by 
adhesions. The liver seemed small. The case was considered 
to be one of acute pancreatitis or possibly carcinoma of the tail 
of the pancreas and it was deemed inadvisable to explore further. 
9 July, 1903. The patient's condition after operation was fairly 
good. In the evening the temperature was 104°, falling the next 
morning to 101.8°, the pulse improving correspondingly. To-day, 
however, the pulse has been weak, about 120, and strychnine and 
digitalin have been continued. In the afternoon the temperature 
rose to 102.3°. The patient began to wheeze, cough, and ex- 
pectorate, and in the left side of the chest, both in front and 
behind, loud moist rales were heard; no tubular breathing. 
11 December. The patient's condition grew steadily worse. 
There "was frequent vomiting which was not relieved by washing 
the stomach. The pulse was weak and rapid. The abdomen was 
not distended. The temperature on the 10th ranged from 100.8° 
to 102.6°. On the afternoon of the 11th there were three profuse 
discharges of fresh bright blood from the bowels, death following 
soon afterwards, at 4 p. m. 
Necropsy (No. 2135). Anatomical diagnosis.-Acute gangren- 
ous pancreatitis with necrosis of the greater part of the pan- 
creas; formation of fat necroses and perforation of stomach, 
duodenum and transverse colon; erosion of splenic artery with 
hcemorrhage into the pancreas and transverse colon; cholelithi- 
asis; arteriosclerosis of coronaries. 
A partial necropsy was performed through the incision which 
was slightly enlarged. The peritoneum in the region of the in- 
cision showed a few ecchymotic areas. The great omentum was 
well developed and was slightly adherent to the hepatic flexure 
of the colon. The ccecum, ascending and descending colon were 
of a deep red color. . . . The spleen was adherent to the dia- 
phragm and a mass could be felt in the region of the tail of the 
pancreas. On dissection between the stomach and transverse 
colon in the median line, a cavity was opened containing a dark 
red mass of semi-fluid blood clot mixed with a number of opaque, 
white, firm, friable masses. These masses possessed no definite 
structure but it was possible to see that at one time they probably 
had had an alveolar arrangement. There was a fsecal odor. The 
abdominal organs were removed entire and on cutting through 
the oesophagus a few small blood clots escaped. In tearing through 
the adhesions between the spleen and the diaphragm another cav- 
ity containing similar material was opened; this proved to be 
continuous with that which was first described. On careful exam- 
ination of the transverse colon an opening was found in its su- 
perior surface 1.5 cm. in diameter with fairly smooth edges. This 
was situated about 5 cm. to the right of the middle line. The 
[3611 
[362] 
(19) 1362]' 
mucosa of the colon in this region was deeply blood-stained as 
well as the surrounding tissue in the cavity wall. The stomach 
was now opened along the greater curvature; a small quantity of 
slightly reddish fluid escaping with a few of the opaque white 
masses previously mentioned; the latter were most numerous near 
the pyloric orifice. About 9 cm. from the cardiac orifice on the 
greater curvature, and 3 cm. posterior to the attachment of the 
gastro-colic omentum on the posterior wall of the stomach, were 
two openings, both communicating with the cavity above men- 
tioned. The larger and posterior was 9 cm. in diameter; the 
smaller, anterior, 2 mm. in diameter. The gastric mucosa except- 
ing for these openings wras normal and of the usual pale pink 
color with practically no evidence of blood staining. The edges 
of the ulceration as seen from within the stomach were smooth 
and fairly regular in outline. There was no evidence of thicken- 
ing. The opening into the stomach was now continued into the 
duodenum along its right side. About 3 mm. below the pylorus on 
the left side of the duodenum, adjoining the pancreas was another 
large irregular opening, 1.5 cm. in diameter; the edges were 
smooth, the outline showing a few indentations. This communi- 
cated directly with the cavity previously mentioned. On continu- 
ing the opening into the duodenum a second opening was found 
just internal to the papilla of Vater, about 2 cm. in diameter. This 
resembled the first opening described in the duodenum in possess- 
ing smooth edges and an irregular outline and in communicating 
with the cavity above described. 
The gall bladder was opened and found to contain nine small, 
angular, facetted, reddish-colored gall stones, the largest measur- 
ing 5 mm. in diameter. The cystic duct contained no gall stones 
and was patent. The common bile duct was patent and contained 
no stones. Its opening was situated just externally to and to the 
right of the second opening into the duodenum. The duct of 
Wirsung could not be found in the papilla, but on carefully pass- 
ing a probe through the common duct, at the base of the perfora- 
tion just internal to the papilla it could, by slightly altering its 
course, be passed through the papilla. The duct of Santorini 
could not be found. 
On making a section through the head of the pancreas, a por- 
tion of normal pancreatic tissue corresponding to the head and 
measuring 1.5 cm. in transverse thickness and 3 cm. in antero- 
posterior diameter, could be distinctly seen. The left part of this 
normal tissue with the duodenum formed the right of the cavity 
which was bounded above by the stomach and passed outward 
between the stomach and the spleen, extending upwards to the 
left from a point about 4 cm. to the left of the middle line. An- 
other arm passed below and behind the spleen and occupied the 
(20) region of the tail and the left part of the body of the pancreas. 
The main cavity lay between the colon and stomach and occupied 
the position of the body and greater part of the head of the pan- 
creas. The inferior boundary was formed by the folds of the 
slightly developed transverse meso-colon. The whole cavity con- 
tained the substance previously mentioned. There was a marked 
faecal odor. No trace of normal pancreatic tissue was found with 
the exception of the small portion of the head previously men- 
tioned. The source of the haemorrhages was from the splenic 
artery as far as could be observed in the short time allowed for 
the examination. 
Examination of the pancreas with the exception of the portion 
of the head previously described showed that it was replaced by 
masses of firm, whitish, friable, opaque material with a faecal 
odor. Some semblance of the alveolar structure of the pancreas 
could be made out in places. This was mixed with recent blood 
clot, semi-fluid and apparently only a few hours old, suggesting 
that the haemorrhage was a secondary and probably terminal 
event. The dissection of the head of the pancreas showed that 
the common bile duct and the duct of Wirsung united at least 
1 cm. below the orifice of the papilla of Vater. 
[362] 
Since the renewal of interest in diseases of the pancreas 
which followed, especially, the notable work of Fitz 3 we have 
gained much knowledge concerning the nature, frequency, 
and symptoms of acute pancreatitis. 
The experimental observations of Hildebrand,4 Koerte/ 
Dettmer,6 Hlava,7 Williams,8 Flexner,9 and others, demon- 
strated that acute pancreatitis might be produced by various 
mechanical and chemical injuries to the organ. 
The direct relation between the escape of pancreatic juice 
into the surrounding tissues and the development of dissemi- 
3 Boston M. & S. J., 1889, CXX, 181, 205, 229. 
4 Centralbl. f. Chir., 1895, XXII, 297. 
5 Berliner Klinik, 1896, No. 102. 
6 Inaug. Diss., Goettingen, 1895. 
7 Bulletin international de l'academie des sciences de Boheme, 
1897. 
8 Boston M. & S. J., 1897, CXXXVI, 345. 
9 Johns Hopkins Hosp. Rep., Balto., 1900, IX, 743. 
(21) [362] 
nated fat necrosis, first suggested by Langerhans,10 may be 
regarded as proven since the demonstration of a fat-splitting 
ferment in the necrotic foci by Flexner,11 and the investiga- 
tions of Opie.12 
The notable observations of Halsted13 and Opieu would 
seem to indicate that one of the most important causes of 
acute pancreatitis is the retrojection of bile into the pan- 
creatic duct, such as may occur in connection with the pas- 
sage of a stone or its lodgment in the diverticulum of Vater, 
in cases where the opening of the duct of Wirsung occurs at a 
point sufficiently far from the outlet of the common duct to 
admit of its patency at the time of obstruction of the latter. 
Repeated experiments have shown the possibility of producing 
pancreatitis in this manner. Apart from Opie's and Hal- 
sted's observations a study of the literature reveals the strik- 
ing frequency of the sequence of acute pancreatitis upon 
cholelithiasis. In my first case of pancreatitis the onset of 
an acute haemorrhagic inflammation followed immediately the 
passage of a stone which was found, at necropsy, in the com- 
mon duct.10 
Peiser16 has recently called attention to a suggestive relation 
between acute pancreatitis and parturition. Eight out of 
121 cases collected by him occurred during the puerperium. 
He accordingly suggests that the changes which give rise to 
this process may be similar to those occurring in the liver and 
other organs in eclampsia, and due possibly to like toxic sub- 
1363] 
[362 
10 Arch. f. path. Anat, (etc.), Berl. 1890, CXXII, 252, and 
Festschr. Rudolf Virchow, 80, Berlin, 1891. 
11 J. Exper. M., N. Y„ 1897, II, 413. 
12 Contributions to the Science of Medicine, dedicated to Wil- 
liam H. Welch, Johns Hopkins Hosp. Rep., 1900, IX, 859. 
13 Johns Hopkins Hosp. Bull., Balto., 1901, XII, 179. 
14 Johns Hopkins Hosp. Bull., Balto., 1901, XII, 182; also Am. 
J. Med. Sc., 1901, CXXI, 27. 
15 Boston M. & S. J., 1889, CXXI, 506. 
10 Deutsche Zeitschr. f. Chir. LXV, quoted by Miinzer, Cen- 
tralbl. f. d. Grenzgeb. d. Med. u. Chir., Jena, 1903, VI, 490, 529, 573, 
619, 664. 
[363] 
(22) stances. Miinzer,17 on the other hand, calls attention to the 
possibility that the primary necrosis may follow embolism of 
small vessels in the pancreas with giant cells from the pla- 
centa. 
Those cases of acute pancreatitis which go on to suppura- 
tion, the " subacute " form of Robson and Moynihan, have 
especial interest in that they alone are amenable to surgical 
treatment. In most of these cases the onset is as acute as in 
the haemorrhagic form, but the symptoms are, as a rule, less 
aggravated and the changes are not at first of sufficient extent 
and gravity to cause the death of the patient. Subsequently 
the necrosis and secondary infections result in the formation 
of more or less extensive abscesses with the characteristic con- 
tents, in which may lie larger or smaller portions of the 
sequestrated necrotic pancreas. In view of the satisfactory 
results of prompt surgical interference, the question of early 
diagnosis in these cases is extremely important. As has 
been said the symptoms are more or less characteristic. The 
onset, sometimes ushered in by an attack of biliary colic, is 
usually characterized by sudden, intense, abdominal pain, 
localized, as a rule, in the epigastrium but often more or less 
general and associated with obstinate vomiting and collapse. 
The fever is not, as a rule, excessive. In some instances the 
attack may be followed by or associated with jaundice. 
In the course of a few days the acute symptoms subside, 
but there remains epigastric tenderness with fever, pos- 
sibly chills, sweating and evidence of deep abscess. Vom- 
iting is often obstinate. Not infrequently a deep mass may be 
felt. This mass, as is strikingly emphasized by our cases, may 
extend on either side into regions considerably distant from 
the normal limits of the pancreas. It may occupy a situation 
such as to suggest a paracholecystitis (Case IV) or a parane- 
phritic abscess (Case I). It may be confounded with the 
results of perforation of the stomach, intestine, or gall- 
bladder. The cases reported emphasize, especially, this varia- 
[363] 
1TMiinzer, Centralbl. f. d. Grenzgeb. d. Med. u. Chir., Jena, 1903. 
VI, 490, 529, 573, 619, 664. 
(23) [363] 
bility in the position of the tumor mass; in two, the tumor ex- 
tended to the right of the median line; in one, to the left; 
in two, it lay about in the median line. A deeply-seated in- 
flammatory mass in the upper abdomen, when perforation of 
the stomach, intestine, or gall-bladder is improbable, should 
always suggest a suppurative pancreatitis, especially if the 
onset has followed shortly after attacks of biliary colic. 
In cases of this nature careful study of the excreta may be 
of a certain help. The gross observation of fatty stools is 
not of very great clinical importance, although Ury and 
Alexander18 assert that a discharge of large quantities of 
liquid fat after the passage of solid, formed faeces is almost 
diagnostic of extensive pancreatic affection. The determi- 
nation of the relation of neutral fat in the stools to the fatty 
acids and soaps may be of assistance. In extensive pancreatic 
disease there is an interference with the normal fat splitting 
in the intestine-amounting, ordinarily, to from 70 to 80 per 
cent of the fat. Before passing judgment upon either of 
these questions it is, of course, important that the patient 
should be subjected to careful experimental feeding. Ac- 
cording to Ury and Alexander there are three possibilities 
with regard to abnormalities in the fat content of the faeces 
in pancreatic disease: 
(1) There may be an increased quantity of fat with a 
diminished fat splitting. 
(2) There may be an increased quantity of fat with nor- 
mal fat splitting. 
(3) There may be a normal quantity of fat with dimin- 
ished fat splitting. 
Unfortunately, the careful feeding necessary for thoroughly 
satisfactory observations of this sort, is usually impossible in 
acute pancreatitis. 
Interference with the digestion of fat is often associated 
with deficiency in the proteid digestion. The mere discovery 
of muscle fibres cannot, however, be regarded as an abnor- 
mality, and, apart from the quantity of meat taken, it may de- 
18 Deutsche med. Wchnschr., 1904, XXX, 1311, 1345. 
(24) pend upon various other conditions disturbing the movements, 
secretion, and absorptive powers of the small intestine. Oser 19 
lays some stress upon the importance of the evacuation of 
quantities of solid faeces which are unduly large relatively to 
the diet taken. 
Glycosuria is rare and of little diagnostic importance. One 
would expect it to follow only most extensive pancreatic 
destruction; we know nothing of any selective influence of 
acute inflammatory processes in the islands of Langerhans. 
A test which may prove of considerable importance, is that 
suggested by Opie who, in one case of acute haemorrhagic pan- 
creatitis was able to demonstrate the probable presence of a 
fat-splitting ferment in the urine; Opie20 pointed out that 
there was a reasonable possibility that in acute pancreatitis 
traces of lipase might be demonstrable. 
The recent observations of Hewlett21 upon this question are of 
considerable importance. This observer has determined that 
lipase appears in the urine after a variety of insults to the 
pancreas of dogs; it is found in greatest amount as a result of 
experimental acute haemorrhagic pancreatitis. The procedure 
adopted by Hewlett for determining lipase in the urine is a 
modification of the Kastle-Loevenhart method depending upon the 
hydrolytic cleavage of ethyl butyrate in a solution containing 
lipase, into butyric acid and alcohol. The urine is then extracted 
with ether and the amount of butyric acid determined by titra- 
tion. The following is the method in detail: "Five cubic centi- 
meters of urine are placed in each of three flasks. The urine in 
the second flask is then boiled. To the urine in the third flask 
are added three drops of a one per cent solution of phenolphthalein 
and N/10 sodium hydrate solution is allowed to run in from a 
burette until a faint pink color appears. The amount of sodium 
hydrate solution used is read off and a like amount is added to 
the first and second flasks. To each of these two flasks, the first 
of unboiled urine, the second of boiled urine, is then added 
twenty-five hundredths cubic centimeter of ethyl butyrate and 
one-tenth cubic centimeter toluene, and they are placed in a 
thermostat at 39° C. for about twenty hours. The toluene is 
[863] 
[364] 
19 Die pathognostischen Symptome der Pancreaserkrankungen, 
Die deutsche Klinik, etc., Berlin, 1901, 151. 
20 Johns Hopkins Hosp. Bull., 1902, XIII, 117. 
21 J. Med. Research, Bost., 1904, XI, n. s. VI, 377. 
[363] 
[364] 
(25) {364] 
added in order to prevent the growth of bacteria. At the end 
of this time each flask is taken out and sufficient N/10 hydro- 
chloric acid is added to more than neutralize the alkali previously 
added by five-tenths cubic centimeter. Each specimen is then 
shaken in a separating funnel with fifty cubic centimeters of re- 
distilled ether, and the ether is separated. After adding three 
drops of a one per cent solution of phenolphthalein to twenty-five 
cubic centimeters of pure alcohol, the latter is brought to the 
neutral point. The ether extract from the separating funnel is 
now added to the neutralized alcohol and its acidity is determined 
by titrating with N/20 potassium hydrate solution. Any decided 
difference between the acidity of the ethereal extracts of the boiled 
and of the unboiled urine is due to the butyric acid formed by 
the cleavage of the ethyl butyrate; and where the difference in 
acidity is at all great the odor of this butyric acid can be easily 
recognized." 
It is greatly to be regretted that this test was not made in 
the first case. Directions had been left to carry it out which 
were interfered with by an unfortunate accident. 
It is- an interesting fact that in three of these cases the 
presence of gall stones was proven. In two they were found 
at autopsy. In a third, our last case, the gall bladder was not 
explored but repeated attacks of characteristic biliary colic 
had occurred, one at the onset of the pancreatic symptoms. 
In the other two instances the gall bladder was not examined 
although in Case IV the history was decidedly suggestive of 
cholelithiasis. 
Consideration of these cases also tends to impress one with 
the feeling that pancreatic disease ought to be more commonly 
recognized than is the case. The complex of symptoms is, 
in many instances, characteristic. In all of these cases a 
diagnosis was made. In the four cases which fell under our 
observation a positive diagnosis was made in two instances, 
and in one, pancreatitis was suggested as the strongest pos- 
sibility. In Case IV the correct diagnosis was made by Pro- 
fessor Halsted. In Case III, which I did not see, Dr. Blood- 
good recognized the condition. 
The most important point brought out by the review 
of these cases seems to me to be the favorable result of early 
operation. Of the four instances of suppurative pancreatitis 
(26) which were operated upon, three recovered. In Case II, in 
which there was a fatal result, the patient had been in a 
miserable condition for three weeks before operation. 
The fourth instance was clearly a case of gangrenous pan- 
creatitis. 
Final considerations: 
(1) A consideration of these five cases would seem, in the 
first place, to emphasize the importance of the relation be- 
tween cholelithiasis and pancreatitis. 
(2) It should further call attention to the importance of an 
early diagnosis. Relief can be expected only from early oper- 
ation and drainage, and while it may be truly said that a posi- 
tive diagnosis is often difficult, yet there are few conditions 
with which suppurative pancreatitis is likely to be confounded, 
in which exploration is not the proper and conservative 
course. 
[364] 
27 17 
After Books Were Closed. 
1904. 
Name. 
Through Whom. 
Amount. 
Nov. 
1 
Mr. John Black 
$ 5 00 
Nov. 
1 
Miss M. P. Ould 
5 00 
Nov. 
1 
Mr. Joshua Levering 
Miss Ould 
5 00 
Nov. 
7 
Mrs. Chas. Slagle 
5 00 
Nov. 
7 
Miss Grace Parker 
5 00 
Nov. 
7 
Acker, Merrill & Condit 
.... Miss Ould 
10 00 
Nov. 
7 
Mrs. Chas. Keyser 
5 00 
Nov. 
7 
Mr. and Mrs. William Buckler 
10 00 
Nov. 
14 
Miss Clara Tyler 
5 00 
Nov. 
14 
Mrs. Eugene Levering 
5 00 
Jan. 
23 
Mr. Eugene Levering, Sr 
5 00 
Feb. 
5 
Mr. Eugene Levering, Jr 
5 00 
Feb. 
27 
Miss Butler 
Miss Weston.. 
5 00 
Donations for Year Ending October 28, 1905. 
Jan. 13 Lecture at Anniversary in Church $ 65 57 
Jan. 28 From Report Advertisements 5 00 
Feb. 35 Donations from Printing Report Mrs. Levering ... 105 00 
Oct. 17 Donation from Madison Avenue M. E. Church 80 00 
Oct. 23 Donation Mr. Gustavus Ober 30 00 18 
Address to the Graduating Class of the Training School 
for Nurses of the Union Protestant Infirmary.* 
By William Sydney Thayer, 
Professor of Clinical Medicine in Johns Hopkins University. 
The position of a graduate on an occasion such as this is enviable in 
more than one way. After several years of hospital life, involving 
submission to a discipline which, while possibly wholesome, is unques- 
tionably rigid, there is, I know, a feeling of relief when one realizes 
that this is the last time that one is bound to listen silently, without 
the right of reply, to the solemnly-delivered precepts of a teacher or 
adviser. From to-day one is free and independent, and that you feel 
this sense of approaching deliverance is again a blessing to him who 
must address this advice, inasmuch as the lightness of heart incident 
to your happy position assures him a more charitable consideration 
than might otherwise fall to his lot. 
I need not express my appreciation of the honor which your Super- 
intendent has done me in asking me to deliver this address at the first 
public exercises which have been held on the occasion of the gradua- 
tion of a class of nurses from this training school. It is with a double 
sense of satisfaction that I have accepted the invitation, associated as 
I am, not only with this Institution, but also with that which is, in a 
sense, its mother. 
When one looks upon the group of women who form this graduating 
class, and when one considers the nature of the gathering, he cannot 
but be impressed with the difference between the character and con- 
dition of the nurse of to-day and that of the nurse as she was when 
many of us who have barely passed the age of comparative usefulness 
were children. Not many years ago the individual sought for as a 
nurse was a healthy woman who could stand hard, continued work; 
who was physically strong and willing to do the unpleasant and often 
unsesthetic duties which devolve upon one who cares for the sick. 
The duty was regarded as menial-the class which undertook such 
work was often what might have been expected. 
The condition of affairs to-day is, indeed, radically different. What 
has brought about this transformation? 'Tis, after all, but a part of 
the great change which has come over medicine itself in the course of 
the last century. A hundred years ago, in most countries, the every- 
day practitioner of medicine and surgery occupied a very different 
position in society from that which he fills to-day. He, too, was often 
'April 27, 1905. 19 
regarded rather as a menial. He entered by the servant's door, and 
he belonged to a relatively humble order of society, and, although 
there were many and great exceptions, his social qualities were com- 
monly enough, not such as entitled him to further distinction. 
But the great advances in our knowledge in all branches of the 
natural sciences, and their increasing application to medical and surg- 
ical problems, have rendered it necessary for the properly-equipped 
physician to be a man of a general education, while the enormous field 
for investigation and research is drawing daily to these branches of 
learning men of higher and higher mental calibre, so that to-day, even 
in the most conservative of European countries, the name physician is 
no longer a social stigma, while the character of medical men has 
radically changed. 
In the old days, as has been said, physical strength, natural apti- 
tude, and a certain degree of experience in handling the patient were 
practically all that was required of a nurse. How different is the 
condition to-day! Think for a minute of the demands of antiseptic 
surgery. The technique required of an assistant at operations-the 
preparation of dressings-the subsequent care of the patient, demands 
a highly-trained individual, who must understand the reasons for the 
necessary precautions. These things cannot be left to an uneducated 
or irresponsible person. On the other hand, in medicine the taking 
and recording of observations of the pulse, the temperature, the res- 
piration, the excreta of the patient, the watchfulness which must be 
exercised to detect the onset of a multitude of dangerous complica- 
tions upon which the very life of the patient may depend, these things 
again demand education, training, experience,^£nd both in surgery and 
in medicine this training is beyond the grasp of one who has not had 
from the beginning the advantages of a more or less liberal education. 
Thus it is that it has come to pass that the modern nurse has arisen, 
and that the requirements necessary to entitle her to practice are 
daily increasing. With the necessity for the more highly-educated 
nurse has come the institution for her preparation-the modern train- 
ing school for nurses. 
But as the functions gnd duties and opportunities of the nurse have 
increased steadily, so to^has the field of the training school broadened. 
As has been said already, the nurse must have more than mere expe- 
rience in watching and caring for the sick; she must know something 
of the conditions which she is nursing-she must have a certain knowl- 
edge, not only of the anatomy and physiology of the body, but also of 
the character and the course of the symptoms, the incidents and the 
dangers of the main diseases which she may be called upon to nurse, 
as well as a comprehension of the significance of the usual methods of 
treatment. The . surgical nurse must know the nature and causes of 
the accidents which may follow lapses in antiseptic technique. The 
omission of proper precautions by the nurse, or by other attendants, 20 
in the sterilization and disposition of the excreta in cases, for instance, 
of typhoid fever or cholera may be the exciting cause of a deadly epi- 
demic. That these precautions be carried out it is all important that 
the nurse should thoroughly comprehend the conditions which make 
these measures necessary and the rationale of the required antiseptic 
precautions. Much will depend upon her ability to properly explain 
these things to the family and friends of the patient. If informed 
they may be easily induced to take every pain to protect themselves 
and others; ignorant, they will have small regard for all your prophy- 
lactic measures. All this instruction requires lectures, and classes, 
and study, which, in addition to the all-important practical experi- 
ence, is continually extending and lengthening the required course of 
training. Thus the modern training school for nurses has come to be 
an educational institution of no mean scope. 
The properly-conducted training school has various more or less 
distinct functions- 
(1) To train young women impelled by choice or necessity to adopt 
the career of a nurse. 
(2) To provide immediate care for the sick in the institutions with 
which they are connected. 
(3) To offer education, and resource, and inspiration to many a 
worthy woman whose surroundings are such, as they often are, as to 
stifle and prevent her full development. This last function is by no 
means the least important. 
. The complaint is sometimes heard that in too many schools women 
are admitted whose condition in life is such that they need not nurse 
after graduation; that in many instances they do not nurse; that val- 
uable training is, therefore, thrown away upon a more favored class 
to the exclusion of those who must earn their living. In a well-con- 
ducted school this reproach is rarely justified. It is a mistake to ask 
the question, "Must you nurse?" or "Do you expect to nurse?" too 
closely if the applicant be a person of proper mental and general 
character and attainments. 
What does the education and experience in a modern training school 
give to the pupil? Apart from the mere instruction in the care of the 
sick and the general anatomical and physiological information- 
(a) It gives a worldly experience and a knowledge of human nature 
beyond that attainable in most other spheres of life. 
(b) It offers an invaluable training of the powers of observation. 
(c) It gives a woman a taste of an active, busy, systematic life-a 
life with an aim. ' 
And what is the result? How often does one hear the bitter complaint, 
"I have lost my daughter; she will never remain at home agiin." 
No, the thoughtful woman who has passed through a modern training 
school for nursesz will never remain at home jdle again. But is this a 
loss? An unhappy, oftentimes an ill, woman, the source of care and 21 
anxiety and worry to her friends, has become a self-sufficient active 
member of the community. She may practise nursing, she may 
teach, she may devote herself to some branch of charity which is 
beyond the reach of her less fortunate sister; she may not nurse, but 
she can never again be idle. There is one less dependent, one more 
independent member of society. Let us not forget this role of the 
training school. It is not a small part of its work, and the world owes 
it a full measure of gratitude. 
The woman who enters a training school for nurses should possess 
certain definite qualifications. 
She must, as I have said, have had the advantages of a more or less 
liberal education. 
She must be of average strength physically 
She must be, in a sense, mature. 
It often seems a hardship to a girl-say, of twenty-who must earn 
her living, to be refused admission to a training school because she is 
too young, but it is right that it should be so. Both during the course 
of her training and in her later career the nurse is exposed to an amount 
of admiration and adulation to resist which requires not only maturity, 
but real strength of mind. It is her almost inevitable fate, from the 
character of her associations and from the nature of her work, that the 
interest and sympathy and admonition which she inspires in student, phy- 
sician, and patient should, in a varying, but always considerable propor- 
tion of cases, reach a degree which must seriously interfere with the 
course of her career if she be not a more or less settled and self-suffi- 
cient person. The house physician always falls in love with a nurse, 
and it is a fact, fortunate or unfortunate, that even at two or three 
and twenty, the age commonly regarded as justifying admission to a 
training school, the feminine heart is not always as firmly fixed as 
might be desirable for the best interests of the institution. More- 
over, the responsibilities of nursing are such as demand a person with 
a degree of judgment and self-control which years and experience 
alone can bring, and it must be acknowledged that twenty-three is not 
an advanced age. 
She must be thoroughly in earnest, and she must realize that she 
will be obliged to submit to a discipline which, in many instances, 
may seem to her absurd and unnecessary, and, indeed, sometimes 
humiliating; but whatever the individual may feej, the women who 
have conducted the best and most creditable training schools have 
regarded such a discipline as necessary for the proper development 
and conduct of the institution. The pupil nurse must submit. As a 
graduate she may, perhaps, be able to found an institution where all 
these things are changed. 
She must realize that she may be exposed to dangers of contagion 
of different sorts. To be sure these dangers are not ordinarily great, 
but no one can tell what may befall the individual. She must be will- 22 
ing to take her chance like the physician, and if the occasion throw 
her into a position of real danger-such, for instance, as the nursing of 
typhus fever, she must not shrink from her duty. If, after entering 
the training school, she manifest fear or unwillingness in such posi- 
tions, it is the surest evidence of her unfitness for the life which she 
has chosen. 
She must be willing to do hard work, and often highly unpleasant 
work, but it is just as well to remember thet she will not be required 
to do more than a healthy woman of average strength can properly 
do. The average nurse graduates from a training school in better 
physical condition than was her's on entrance. 
Whatever the character or the intentions of the women who enter 
the training school, it will always be the case that the majority of 
those who graduate are destined to practice their profession actively. 
Of these the duties and responsibilities and cares will be great, the 
privileges greater. 
You will receive constantly the confidencejof the public; you will 
share with them the most intimate secrets of their lives; you will see 
much that will pain you, much that will shock you-the responsibili- 
ties will be heavy. On your tact and patience and charity may 
depend the future welfare, not only of your patient, but often of the 
whole family, and it will be your duty to bear with it all, to give what 
silent sympathy you can-to be still-and to forget. 
You will meet with much that is trying-with ill-bred and inconsid- 
erate people, and 'twill be your duty to preserve a cheerful, though 
difficult, equanimity. 
You will meet with physicians who will criticise you in a manner 
which may seem to you often hard and unjust, but 'twill be the part 
of wisdom to accept it without reply, for the surest way to confound 
your critic and to comfort your patient is by silence and industry. 
You will frequently have long hours and little rest, and it may often 
be that you will be conscious of the fact that you are yourself iller than 
your irritable and exacting patient, but you will feel it your duty to 
keep at work and hide your weariness with a cheerful mask. 
But the compensations far outweigh the burdens. The very fact 
that you have become the trusted confidante of the public, the respon- 
sibilities which this brings to the high-minded woman are immensely 
broadening, and day by day the beneficent influence which your mere 
silent presence will exert upon the sick, and the weak, and the unfor- 
tunate will increase. The little irritations incident to your association 
with inconsiderate and vulgar people will be trying at first, but 
remember, and you ought soon to learn to remember, that the impa- 
tience and ill-temper of others cannot injure you. 
Above all things, do not feel that you are obliged, by specific word 
or act, to attempt to vindicate or elevate the position of the trained 
nurse. Your position is as high as your character and conduct make 23 
it. No one can afford to look down upon you because of your position. 
If he does, it is he alone who belittles himself and renders himself 
ridiculous by so doing. The criticism of your inferiors can do you no 
harm. Aristotle's high-minded man is conscious that honor is due 
him, and accepts it, for 'tis the only thing that his fellow can offer 
him that is worth his acceptance; but he cares naught for honor, 
excepting in so far as he is conscious that it is due him. 'Tis not the 
part of the high-minded man or woman to seek for honor for honor's 
sake. I console myself often under circumstances such as these by 
reflecting on the words of the wise Frenchman*, who has said, "The 
more I consider human life, the more I am convinced that it is the 
part of wisdom to pass judgment upon it with irony and pity, as the 
Egyptians invoked for their dead the Goddess Isis and the Goddess 
Nephthys. Irony and pity are two good counsellors. The one, with 
her smile, makes life sweet; the other, with her tears, makes it 
sacred. The Irony that I invoke is not cruel; she rails neither at love 
nor at beauty. Her smile is sweet and benevolent, and she it is who 
teaches us to make light of the wicked and the foolish, who, but for 
her, we might be weak enough to hate." If you can accustom your- 
self to regard the petty carpers of life with pity and that benevolent 
irony to which the French author refers-an irony which is closely 
akin to our sense of humor-you will find, 'ere long, that your irrita- 
tion at the annoying incidents of your work will greatly diminish-that 
you will be stronger and more self-sufficient for having undergone the 
trials. If you can but learn to recognize and appreciate the humorous 
aspects of life, much that might otherwise be sorely trying will lose 
its sting. 
As I have said, you will meet with some physicians who will criti- 
cise you with what may seem to you unjust severity; you will meet 
with many physicians whose methods are different from those of the 
men among whom you have been trained-with some who may seem 
to you ignorant or negligent. Beware of judging them! There are 
weak and vacillating physicians as there are weak and vacillating 
nurses, or even weak and vacillating clergymen; but this I can tell 
you, the more you see of medical men, the more you will realize how 
rare it is to find one who is not honestly and faithfully doing his best; 
the more you see of medical men, the prouder you will be of the char- 
acter of your co-workers at the bedside of the sick. You cannot 
remember too well that it is ignorance, and isolation, and gossip that 
breed distrust. 
But although at first the misfortunes-the suffering -the evil with 
which you meet may tend to discourage you~-may, indeed, for a time 
shake your faith in your fellow-man-the more you see of human' 
nature the more you will come to feel that its ugly features are, in 
most cases, but skin deep, covering often fast-rooted capacity for 
'Anatole, France. Le Jardin d'Epicure. Paris: 1895, 121. 24 
gratitude, for affection, for devotion-nay, for true heroism. If your 
eyes are open for that which is beautiful in this world, you will find it 
wherever you look, hide though it may at times in the darkest and 
most obscure corners; and you will come to know the world as it is- 
a hard world often, a cruel world sometimes, an unfathomable world 
generally, but a great and good world in that it brings compensations 
to all who know how to live and deserve them, which represent^ the 
highest human ideals of happiness. Your life as a trained nurse, with 
all its hardships, should be a long lesson in optimism. 
There is one field in which the nurses who are going forth to-day 
may exercise an especially widespread influence for the public good. 
The discoveries of the last twenty-five years, revealing to us the cause 
of so many infectious diseases, have made clear to us also that we are 
our own worst enemies; that to our own ignorance, to our own care- 
lessness and uncleanly habits is due their prevalence; that by the 
private and public observance of certain precautions such diseases as 
typhoid fever, tuberculosis, and malarial fever can be largely pre- 
vented. All over the world efforts are being made to bring about this 
result-a result which can be accomplished only by long and patient 
efforts to educate and inform the public. As I have observed before, 
the part which you have to play in this campaign, which is one of the 
most important features of the life of to-day, is essential and vital. 
You will be called upon to instruct the public, not only as a district 
nurse and in hospitals, but wherever you are, in public or in private, 
you should seek the occasion to use your influence for the good of your 
fellow. 
And let me remind you of one more thing. Professional secrecy is 
as much the duty of the nurse as of the physician. Either who forgets 
this obligation ruins his career and, what is more, his character. 
'Tis an old and trite admonition, but none the less vital. Three Latin 
imperatives, quoted nearly two centuries ago by a wise old New Eng- 
land clergyman*, in a quaint volume of "Directions to Candidates for 
the Ministry," would make as good a motto for the trained nurse as 
can well be conceived, "Audi, cerne, tace," listen, watch, be silent. 
I have touched upon a few of the duties and opportunities of the 
nurse. Before I close let me testify how often, in my experience, the 
nurse has risen to meet them. Among the nurses with whom I have 
come into contact during an intimate and continuous association with 
hospitals and training schools for nearly seventeen years, have been 
some of the broadest minded, most charitable and best women that I 
have ever known, and I feel sure that it has been the very opportuni- 
ties and experiences which they have had, and which lie before you, 
that have made them what they are. 
*Cotton Mather. 25 
Donations from December, 1904, to November, 1905, 
Inclusive. 
December, 1904. 
Mrs. Georgiana Showers, 2024 
Mt. Royal Terrace Magazines. 
Needle Work Guild of America 
(Baltimore Branch) Five pairs towels, two bath towels, four 
sheets, eight pillow cases, nine under- 
shirts (women and children), four 
undershirts (men), two outing gowns 
(children), two kimonos, two night- 
shirts (children), six suits women's 
underwear. 
"Unknown" Six suits men's underwear. 
December, 1905. 
From Hospital Relief Associa- 
tion Nineteen boxes candy for wards. 
Jas. Carver, 1205 N. Calvert 
Street _ .....Magazines for children's ward.. 
Christmas, 1905. 
Allen Pitt, Roland Park, for 
Children's Ward Six books, one ball, four dolls, one train 
cars, two wagons, one fire engine, one 
dog, two watches. 
Mr. Davis, for Hospital Two barrels holly and evergreens. 
Mrs. Marshall Winchester Five dollars. 
Mrs. Benjamin Sadtler One dollar. 
Miss M. C. Conkling One dollar. 
Mrs. Winfield Henry One large pound cake for nurses. 
Miss M. P. Ould Two cakes for nurses. 
H. T. Arthur & Co. One large cake. 
Mrs. Wm. Rutherford One orange cake and one cocoanut cake. 
Mrs. Jas. H. Trainor One plain cake. 
For Children's Ward. 
Mrs. Boyd, York, Pa Fifteen stockings filled with toys. 
Miss Hickock Ten stockings filled with toys. 
Miss Page ....Toys, dolls, books. 
Mrs. Levering Toys and dolls. 
Miss Riach. Doll. 
Miss Rolando Eighteen pairs stockings, one dozen 
handkerchiefs, four dozen oranges. 
Through Mrs. Stran, from Chil- 
dren's Friend Circle Twenty-five pounds candy and nine baby 
dresses. 
Miss Gross, from friends Soap, books, ball, dolls, and toys. 
Dr. Fisher Five dollars. 
Mrs. Finney Five dollars. 
Mr. Chipchase Five dollars. 26 
Mrs. Henry Two dollars. 
Dr. Pancoast One dollar. 
Dr. Pancoast, for servants Two dollars. 
Miss Stewart One dollar and fifty cents. 
From "Friends" ... Two dollars. 
Mrs. Wm. Buckler, for nurses..Cake, candy, and books for library 
"N. H." 
Elizabeth and Eleanor May 
Jencks One scrapbook. 
Miss Virginia Ball Christmas tree. 
Mrs. Sims One doll, Christmas tree trimmings. 
For Hospital. 
Miss Montell One turkey. 
Mr. Plitt, Lexington Market - One turkey. 
Mrs. Henry One gallon oysters. 
Geo. Roeder & Sons, Lexing- 
ton Market Two beef tongues. 
Money given by Mrs. Winchester, Mrs. Sadtler, and Miss 
Conkling spent for turkeys and fruit for Christmas day. 
January, 1905. 
Mrs. William Buckler Sent in twice during the month cake for 
nurses, flowers for wards. 
February, 1905. 
"A Friend" Three nightshirts for Men's Ward, four 
dress shirts for Men's Ward. 
Mrs. Wm. Buckler Cake for Nurses' Home. 
Mrs. Buck, Bolton Street One bag of worn clothing. 
March, 1905. 
Mrs. Wm. Buckler Cake sent every two weeks for Nurses' 
Home. 
Miss Parker Three dresses for Children's Ward. 
"Unknown" Magazines for wards. 
April, 1905. 
Through Mrs. Thos P. Stran ...Seventy-two gingham dresses for the 
Children's Ward from the Children's 
Friend Circle. 
Mr. Blume, Pennsylvania Ave..One package magazines-"Collier's 
Weekly." 
Miss M. E. Griffith Flowers. 
Miss McGuire Two dozen table napkins, twelve gowns 
for Women's Ward. 
Miss Volck, The Arundell Thirty-four packages of books and peri- 
odicals. 
Mrs. Wm. Buckler Cake sent for Nurses' Home. 
Mrs. Charles Spence Flowers for Men's Ward. 
Mrs. Bruce One box clothes (boys' pants and waists) 
for Children's Ward. 
May, 1905. 
Mrs. Wm. Buckler Flowers for Nurses' Home, flowers for 
wards. 
"A Friend" Magazines and periodicals. [Reprinted from Maryland Medical Journal. September, 1906.] 
ON THE PROPHYLAXIS OF TYPHOID 
FEVER. 
By W. S. Thayer, M.D. 
REMARKS BEFORE THE MUNROE COUNTY MEDICAL SOCIETY, AT ROCHESTER N. Y., ON 
MAY 31, 1905. 
It is difficult to protect oneself from an enemy whose nature and 
whereabouts are unknown. If we reflect upon our position but a 
a few years ago, with regard to most of the infectious diseases, we 
must realize that this was practically the situation. Great changes, 
however, have taken place within the last 20 years. To take but 
a few examples, how far have cholera and plague and yellow' fever 
lost their terrors! Once the presence of one of these diseases is 
recognized, we possess, now, knowledge which gives us the means 
to prevent its further spread. The ever-present danger lies in the 
existence of foci in which the infection prevails as an endemic, 
where, owing to the ignorance or shiftlessness or prejudices of the 
inhabitants, no attempt has as yet been made to overcome the 
danger at its source. Thus it is that, with regard to cholera and 
plague, India and China, and, with regard to yellow fever, certain 
parts of the West Indies and Central and South America are a 
constant menace to the civilized world. The last 25 years have 
witnessed a great awakening. This is the day of preventive medi- 
cine, and it has already become recognized that the responsibilities 
in this matter are not confined to medical men alone; the general 
public, too, must play its part, and its part is no small one. The 
results of the widespread, popular campaign against tuberculosis 
which has been initiated in the last few years throughout the world 
are already apparent. 
We have, however, among us another disease which is endemic 
throughout our country districts north, south, east and west, and 
from these endemic foci there arise yearly epidemics varying in 
size from those which affect a score or two of people in the country 
to such as cause thousands of cases and hundreds of deaths in large 
cities, as, for example, those which for some years have afflicted 2 
Pittsburg and Philadelphia. In the Spanish War there were 
20,738 cases of typhoid fever among our troops. Practically one- 
fifth of the soldiers encamped in this country during the war ac- 
quired the disease, and 1580 died. 
Fulton1 has demonstrated the fact that typhoid fever is essen- 
tially a country disease; that it is in the rural districts that it is 
permanently endemic; that the proportion of deaths from typhoid 
in the country is considerably higher than that in the city, and that 
it is the country which infects and gives rise in great part to the 
epidemics which occur in the cities. I do not know that our rural 
morbidity from typhoid fever varies materially from that in other 
countries, but certain it is that the figures in our cities are far from 
creditable. In the first number of the Public Health Reports for 
19042 there was published a most instructive table of the mortality 
from typhoid fever in those cities of the United States with a popu- 
lation of above 70,000, the rate varying from 9.7 per 100,000 popu- 
lation for Savannah to 124.7 f°r Pittsburg. This mortality in 
Pittsburg is simply appalling-an average of one and one-quarter 
deaths for every 1000 inhabitants; at the very lowest possible esti- 
mate one case for every 100 inhabitants. The figures for Balti- 
more in 1903 were somewhat over 30-for 1904, 43 per 100,000. 
Now, what do we know of this disease? Are there no measures 
of protection which we can adopt to combat this appalling mor- 
tality? What is typhoid fever? Twenty-five years ago we were 
ignorant as to its cause and nature. Today we are well aware that 
typhoid fever is brought about by the entrance into the organism 
of a specific bacterium-bacillus typhosus. We know that in the 
great majority of instances the infectious agent gains entrance 
through the mouth with food or drink, although there is some 
reason to believe that it may at times enter through the air pas- 
sages by means of inhaled dust. It soon finds its way into the 
blood, in which it multiplies, and is distributed to various organs 
of the body. Through the agency of a specific poison or poisons 
intimately connected with the bodies of these bacteria there de- 
velops a characteristic intoxication which we know as typhoid 
fever. As a result of certain more or less characteristic anatomical 
changes, especially in the intestine, there arise in some cases vari- 
ous local manifestations. But these local manifestations are not 
the main features of the disease. Essentially, typhoid fever is a 
septicemia, and in the great majority of instances typhoid bacilli 
may be cultivated by proper methods during life from the circu- 
lating blood. At necropsy they are to be found in all the internal 
organs, while in about one-third of the cases they may be cultivated 
from the intestinal tract and from the urine. 
Now, in order to combat the disease we must know, in addition, 
(1) the sources of infection, the means by which the infecting 
typhoid Fever : Some Unconsidered Hindrances in Its Prophylaxis. Journal of 
the American Medical Association, Chicago, 1904, XLII, 73. 
2Puhlic Health Reports. Washington (Government Printing Office), 1904, XIX, 
Pt. I, 5. 3 
organism is usually conveyed into the body, and (2) the habitat 
of the organism outside of the body-where it comes from. 
(1) Sources of Infection.-It is now well known that infection 
takes place usually through the gastro-intestinal tract, possibly at 
times by inhaled dust. 
How do the typhoid bacilli enter into the food and drink ? 
(a) Water.-The role of water has been and is, probably, largely 
overestimated by the general public, mainly owing to the fact that 
the common water supply, if infected, may, and not infrequently 
does, give rise to larger and more striking epidemics than can arise 
in any other way. An infected general water supply, however, is 
directly of relatively little importance in the ever-prevailing coun- 
try epidemics which are responsible for so many deaths each year. 
In an enormous number of cases occurring in the encampments of 
our army during the Spanish War the effect of water as a conveyer 
of infection was slight and unimportant. Indirectly, however, in 
both country and city, water often plays an important part. A 
slightly contaminated supply, of which, perhaps, many individuals 
might drink without serious effect, may well serve now and then 
to convey the infection to some substance such as milk, which is 
an excellent culture medium for the organism. If one bacillus 
were, for instance, left in a milk can which was rinsed with in- 
fected water, there would develop in a few hours in milk enough 
bacilli to affect many people. And epidemics of typhoid fever due 
to infected milk are of common occurrence in urban as well as in 
rural populations. 
(b) Ice.-The role of ice has been much discussed. It must be 
said that there is yet little evidence to show its great importance. 
It has, however, been proven that typhoid bacilli may retain their 
vitality for over four months at least in ice,-3 while the most casual 
inspection of the sources from which our ice supply is often ob- 
tained will serve to convince us of the possibilities of contamination. 
(c) Uncooked Vegetables.-There can be little doubt that in 
some instances green vegetables, such as lettuce and celery, which 
are eaten raw, may serve as conveyers of infection. Human 
dejecta are often used as manure for gardens in which these sub- 
stances are grown, and colon bacilli have been more than once 
demonstrated upon these articles of diet, while Laveran reports an 
instance in which the eggs of tenia were discovered upon lettuce 
supplied for a garrison of French troops. 
(d) Dust.-It was the opinion of Drs. Reed, Vaughan, and 
Shakespeare4 that dust was to be regarded as a possible source for 
the spread of contamination in connection with the epidemics in 
our army during the Spanish War both through direct inhalation 
and through the dissemination of bacteria not yet dead upon un- 
'Park: Duration of Life of Typhoid Bacilli, Derived from Twenty Different 
Sources. In Ice. Journal Boston Society Medical Science, 1900-1901, V, 37*1. 
4Reed, Vaughan, and Shakespeare : Report on the Origin and Spread of Typhoid 
Fever in United States Military Camps During the Spanish War of 1898. Washing- 
ton (Government Printing Office), 1904, 667, 4°. 4 
protected food capable of serving as a culture medium. It may 
easily be seen how this might occur in badly-infected localities. 
(e) Flies.-The observations of many students, especially those 
of Reed, Vaughan, and Shakespeare, during the Spanish War, 
and the recent important studies of Dr. Alice Hamilton5 of Chi- 
cago, have shown that the common housefly is a grave source of 
danger in typhoid fever. The way in which the disease spreads 
through a household is familiar to everyone. The manner in which 
flies in the army encampments pass from the infected pits to the 
mess table and kitchen was graphically described in the valuable 
report to which I have so frequently referred, while more posi- 
tive and striking proof of the agency of flies is afforded by Dr. 
Hamilton's studies. In an epidemic of typhoid fever in the city of 
Chicago, which arose in all probability from a contaminated gen- 
eral water supply, it was noted that, in certain circumscribed locali- 
ties, the disease was so much more prevalent than in the city at 
large that there could be no question but that some other cause than 
the general contamination of the supply was at work. An investi- 
gation of these regions showed that they were localities in which 
the sewerage was of a most primitive sort. There was often no 
sewerage system at all-simply country outhouses, which, in many 
instances, had overflowed, sometimes filling the yard, sometimes 
the cellars of the houses. The people of these localities were poor 
and for the most part ignorant of necessary precautions. In a 
number of instances whole families, one after another, came down 
with the disease. Flies in enormous numbers were demonstrated 
in and outside of the affected houses, often swarming over food 
which might well have served as a culture medium for the bacilli. 
Typhoid bacilli were on various occasions cultivated from flies 
captured in and outside these infected houses. Contamination of 
food by flies may probably be regarded as one of the main sources 
of the spread of the disease in our rural districts. When one 
reflects upon the ordinary sanitary arrangements of the simple 
country-house he must feel that it would be strange if this were 
not so. 
(f) There is another source of the spread of typhoid fever 
which has been by no means sufficiently recognized, namely, that 
of a direct contact either with the patient or with fomites. Typhoid 
bacilli are frequently present, not only in the stools and urine of the 
patient, but also in his sputa, and those who attend him must be 
constantly exposed to the danger of soiling their hands with in- 
fected material. I met last summer with a most interesting case, 
in which the patient, a child, infected two nurses and the attending 
physician. All other sources of contamination could be easily 
ruled out. The experience of Koch and his pupils in several recent 
epidemics in the country districts in Germany6 go far to show that 
6HamiIton : Journal of the American Medical Association, 1903, XL, 596. 
8Drigalski: Ueber Ergebnisse bei der Bekampfung des Typhus nach Robert 
Koch. Oentralbl. f. Bakt., Jena. 1904, orig,, XXXV1, 776. 5 
the spread of the disease by flies and by contact plays a more im- 
portant part than has been previously realized. 
It should be remembered that convalescents from typhoid may 
carry the bacilli in their system and spread about in their excreta 
for considerable periods of time.7 
Experiments have shown that when a pure culture of typhoid 
bacilli is poured upon clothes the organisms retain their vitality 
for from two to three months, and it is highly probable that in the 
rolls of blankets such as are carried by the soldier they may live 
for a longer period of time.8 
In cities which are properly drained many of these dangers are 
much diminished and in general the condition of the inhabitants is 
much better, with the one exception that in most American towns 
there is the ever present danger of a general poisoning of the 
water supply. 
(2) Habitat.-Where does the typhoid bacillus come from? It 
cannot be too much emphasized that every case of typhoid fever 
comes from another; that the typhoid bacillus gets into the ex- 
ternal medium only from a case of human typhoid fever, and that 
it escapes from the human being by means of the feces, of the 
urine, of the sputa, of the bath water, of the soiled clothes. The 
experiments of many observers go to show that the urine in 
typhoid fever contains bacilli in about one-third of the cases during 
the height of the disease. Generally the organisms disappear with 
convalescence. Sometimes, however, they may be present for 
long periods afterwards, even for months. It is fair to say that in 
most of these instances there is evidence of their presence in a 
visible cloudiness of the urine or the presence of a slight cystitis 
or pyelitis, but not always. In the feces, again, the bacilli are to 
be found, according to the observations of Von Drigalski, in about 
33 per cent, of the cases between the eleventh and twentieth days, 
while they may remain present for long periods after convales- 
cence, though this is exceptional. A considerable number of ob- 
servers have demonstrated typhoid bacillus in the sputa of patients 
with this disease, while their presence in the bath water, in view 
of the not infrequent involuntary dejections which occur during 
the baths, is, of course, self-evident. Experience, especially during 
the Spanish War, has emphasized the probable importance of 
infected clothes. Experimentally, it has been shown that typhoid 
bacilli may live under ground for as much as a year, but there is 
little to suggest that the prolonged existence of the typhoid bacilli 
in the soil often plays a role of great importance. 
Ought not this knowledge to give us a fair measure of power to 
prevent the disease and to protect the public ? The answer is self- 
evident. What steps should be taken ? 
Prophylactic Measures.-The prophylactic measures which we 
should adopt against typhoid fever may be divided into two gen- 
eral classes: 
7Ueber chronische Typhusbazillentriiger. Klinisches Jahrbuch, Jena, 1905, XIV, 476. 
8Reed, Vaughan, and Shakespeare. Op. cit. 6 
(i) The prevention of the entrance of typhoid bacilli into the 
subject, or as a substitute, where this is impossible, the production 
of an active immunity in exposed individuals. 
(2) The prevention of their escape from the patient. 
(1) The Prevention of the Entrance of the Bacteria Into the 
Subject.-These measures are, in a general way, familiar to all 
and need little comment in this communication. 
(a) Protection of the Water Supply.-In towns the relation of 
the well to the house and to other structures should, of course, be 
carefully considered. In the city the surroundings of the source 
of the supply should be carefully cleared up, while the eventual 
installation of proper filtration plants-filtration plants which have 
been tested and passed upon by disinterested scientific experts- 
is an unquestioned necessity for all of our large municipalities if 
we wish to protect our citizens and to keep pace with the progress 
of the world. The water supply has an undoubted relation to the 
urban prevalence of typhoid fever. It is somewhat humiliating to 
compare our urban typhoid mortality with that of the larger Euro- 
pean cities. As a matter of interest, a few months ago I ran over 
the records in the Public Health Reports of a few European cities, 
which I compared with those of the city of Baltimore, which occu- 
pies a position not far from the middle of the list of American cities 
with a population of above 70,000. The figures are striking. 
Against a mortality of somewhat over 30 per 100,000 for Balti- 
more, we find a mortality of slightly over 12 for Paris, of 12 for 
London, of but little over 6 for Berlin, while in Hamburg, a town 
of about the size of Baltimore, which, before the introduction of a 
filtration plant in 1891, had a mortality of 24.7, the death-rate from 
typhoid fever 10 years later, in 1901, was but 5.1 as against 25 and 
a fraction for Baltimore in the same year-and 43 in 1004! 
The necessity of conscientious and general boiling of water, if 
the supply be suspicious, is familiar enough to all. 
(b) Care with regard to the eating of all contaminable foods 
need not be insisted upon. It should, however, be observed that 
the habit, widely prevalent in this country, of drinking unsterilized 
milk from uncertain sources plays probably a very large part in 
spreading typhoid fever in our midst. 
(c) Proper Precautions With Regard to Plies.-The more gen- 
eral use of mosquito netting as a sanitary measure should be 
encouraged. Special measures should be adopted to keep flies 
away from food in kitchens, pantries, and on the table. 
(d) The Construction of Sanitary Water-closets or Outhouses.- 
This is a most difficult matter in the country, but one, as may be 
readily seen, of grave importance. Every measure should be taken 
to preserve the dejecta from exposure to flies. Tight spring doors 
should be provided, and all windows and openings should be netted. 
(e) Personal Cleanliness.-It is of the utmost importance to 
remember that typhoid fever is a contagious disease. He who 
comes in any way in contact with the patient cannot be too careful. 
Dirty hands are too often the agents of infection, not only of the 
individual, but of food, and may serve to spread the disease abroad. 7 
(f) Preventive Inoculations.-That a certain degree of active 
immunity against typhoid fever may be conferred by subcutaneous 
inoculations with dead cultures of the bacillus has been clearly 
shown, especially by the observations of Pfeiffer and Kolle9 and 
Wright.10 The results of inoculations on a large scale carried out 
in the British army in South Africa show unquestionably not only 
that the inoculated are less prone to infection, but that the course 
of the disease when acquired is milder. In time of epidemic in 
armies or among attendants in fever wards such vaccinations 
should be carried out. 
(2) Prevention of the Escape of the Infectious Agent From the 
Patient.-The point of greatest importance, however, especially in 
the public, prophylaxis against typhoid fever,consists in the preven- 
tion of the escape of the bacillus from the human being into1 the exter- 
nal medium. The problem is in no way different from that in cholera, 
in yellow fever, in plague, in tuberculosis. As Cole11 has pointed 
out, it is only because the rate of mortality is so much less than it 
is in cholera or in some of these more malignant infections, and 
because, alas, we have become so familiar with the prevalence of 
the disease in our midst, that we neglect so many vital precautions. 
To prevent the escape of typhoid bacilli from the infected indi- 
vidual demands the concerted effort not only of the individual phy- 
sician, but of local, State, and national departments of health. To 
carry out thorough and complete measures would involve the 
establishment of hygienic stations throughout the country, sys- 
tematic examination of the dejecta, stools, and blood of suspicious 
cases, and more than this, of healthy individuals in the immediate 
neighborhood. It would involve keeping the typhoid patient under 
supervision for a long period of time after his convalescence, as is 
now done in the case of diphtheria. It will, I fear, be a long time 
before such ideal conditions can be brought about. But there is 
an immense amount that we can do ourselves. We know that 
while there are exceptions, the typhoid patient ceases in the great 
majority of cases, to be a danger to the community at the end of 
his convalescence, and if we, as physicians, were to insist upon the 
proper sterilization of everything which may be contaminated by 
the patient, if we were to treat every suspicious case as if it were 
typhoid fever, we should be able to save thousands of lives yearly 
and we should make rapid steps toward the eradication of the 
disease. 
Now, the measures which we should carry out are not difficult. 
They have been admirably summarized by Cole.12 
(a) Protection of the Patient From Flies.-This is an extremely 
important point. It brings up with it the question of the advisa- 
bility of the isolation of the typhoid patient. As Cole observes, it 
would doubtless be far better if our typhoid patients were isolated 
in separate rooms or wards, not only on account of the danger of 
•Deutsch, med. Wochenschr., 1896, XXII, 735. 
10A Short Treatise on Antityphoid Inoculation, 8°, Westminster (Constable), 1904. 
"The Prevention of Typhoid Fever. Journal of the American Medical Associa- 
tion. 1904. XLII, 1399. 
12Op. cit. 8 
transmission of the infectious agent by means of flies, but because 
of the influence which it would have on the attendants in stimu- 
lating them to carry out the necessary rules of precaution better 
than is now commonly done. It would be well if the medical and 
general public realized more generally that typhoid fever is a con- 
tagious disease. The ward or the room should be thoroughly pro- 
tected by fly screens. If this be impossible, the patient should be 
kept continually covered by a netting during the season in which 
flies are about. 
(b) Sterilization of the Urine.-The simplest and best method 
of sterilizing the urine is to place about 200 c. c. of a solution of 
1 to 1000 bichloride of mercury in a large jar, which should always 
be kept covered. The urine should be poured directly into this jar. 
This amount of bichloride would be sufficient to sterilize 3000 c. c. 
of urine. The amount should be left standing until two hours after 
the last urine has been added. Another vessel should be provided 
containing 1 to 1000 bichloride of mercury or a sufficient quantity 
of 1 to 20 carbolic acid, in which the urinal may be immersed dur- 
ing the period when it is not in use. A urinal which is used for a 
typhoid patient should not be used for others without previous 
sterilization. As Dr. Cole has pointed out, the infectiousness of 
the urine may be diminished in cases where typhoid bacilli have 
been found by the administration of urotropin. Urotropin does 
not sterilize the urine. It does, however, prevent the multiplication 
of bacilli in the urinary passages, and is an important help. This 
may be given in doses of about two grams (grs. xxx) per day, 
divided into three or four doses. 
(c) Sterilization of the Feces.-The most satisfactory method 
of sterilizing the feces is to add to the dejection about twice its vol- 
ume of 1 to 20 carbolic acid; stir this thoroughly and allow it to 
stand for at least two hours. The bed pan should be thoroughly 
washed out with carbolic acid and kept immersed between the 
periods of its use, unless it be sterilized by boiling or heat. The 
feces should be kept in this mixture for at least two hours. 
(d) Sterilization of the Bath Water.-This is best accomplished, 
according to Cole, by adding to each bathtub about half a pound 
of chloride of lime, which will thoroughly sterilize the water in 
half an hour. The chloride of lime may be bought in half-pound 
sealed packages, and should be opened immediately before using, 
as it readily deteriorates. 
(e) Sterilization of the Linen.-linen should be soaked in 
1 to 20 carbolic acid for two hours before sending to the laundry. 
If, however, it is put directly into the boiler, the same end may 
be served. 
(f) Sterilization of Dishes and Utensils.-All dishes should be 
sterilized thoroughly by boiling. 
(g) Supervision of the Patient Until His Excreta Are Free 
From Bacilli.-This is a demand impossible to meet without skilled 
laboratory assistance. In the absence of this we must continue all 
precautions till the discharge of the patient, warning him when he 
leaves our hands that unless he exercises care in the disposition of 9 
his excreta he may be a source of danger to those about him. Hap- 
pily, the great majority of cases are by this time free from bacilli. 
If these measures were carried out strictly in every case, typhoid 
fever could be eradicated from the community. There are, how- 
ever, various difficulties in the way, chiefly because of the facts that 
many cases of mild walking typhoid are unrecognized, and that in 
some others convalescents excrete typhoid bacilli in their urine and 
feces for months. Only by the establishment of extensive experi- 
ment stations, as has already been attempted in parts of Germany, 
can the best results be accomplished. But what can be accom- 
plished in this way is strikingly suggested by the report of the 
treatment of the epidemic at Trier by Koch. 
There is no doubt that careful antiseptic precautions in the care 
of the patient are the most important prophylactic measures in con- 
nection with typhoid fever. We should remember that every case 
of typhoid fever arises from another; that it is through the neglect 
and carelessness in occasional cases that the great destructive 
epidemics arise. What, then, is our duty? We must arouse the 
public, medical and general, to the necessity of these precautions, 
and the only way to do this is to practice them invariably ourselves, 
to impress upon our patients and colleagues the urgent necessity 
for such action, to take every step to educate the public. 
The day must come when our health departments, State and 
local, will supply us with proper means, not only for carrying out 
all necessary disinfection, but for the investigation of individual 
cases, just as is now done in so many States and cities with regard 
to diphtheria. The busy practitioner cannot make elaborate bacte- 
riological examinations, but that these should be carried out, and 
carried out by competent and conscientious individuals, is an 
urgent necessity. That all this will come I have no doubt. But 
the beginning lies with us. It may be urged that these measures 
are irksome and timetaking. To a certain extent they are, but are 
they nearly as irksome and nearly as timetaking as those antisep- 
tic precautions which the modern surgeon uses every day, the 
neglect of which would be regarded by the profession and public 
as a crime? I cannot but feel that in this respect our position as 
practitioners of internal medicine is hardly creditable when com- 
pared with that occupied by our brothers, the surgeons. There is 
just as much necessity for the employment of antiseptic precau- 
tions in the treatment of a patient with typhoid fever as there is in 
an operation, for instance, upon a cancer of the breast. Nay, there 
is far more, for in the latter instance there is danger to but one 
individual, while in the former our neglect may cost many lives, 
resulting not only in the development of further cases in the imme- 
diate household, but perhaps in a devastating epidemic. 
There is much to accomplish, and years may yet pass before 
public measures will be what they should be, but we must act today, 
and there is much for us to do. It is for us who know, to help to 
protect those who know not how to protect themselves, and the 
reward will come quickly, for in protecting them we are protecting 
ourselves. SECOND REPORT 
OF THE 
TUBERCULOSIS COMMISSION 
OF 
MARYLAND 
1906 Tuberculosis Commission of Maryland. 
1904=1906. 
W. S. Thayer, M. D., President. 
Lillian Welsh, M. D. 
H. Warren Buckler, M. D. 
Daniel W. Hopper. 
John M. Glenn, Secretary. SECOND REPORT 
OF THE 
TUBERCULOSIS COMMISSION 
OF 
MARYLAND 
1906 To His Excellency, HON. EDWIN WARFIELD, 
GOVERNOR OF MARYLAND, 
Sir: 
The Tuberculosis Commission has the 
honor to transmit to you herewith the results of its 
deliberations upon the questions for the consideration 
of which it was appointed. 
i 
Respectfully, 
W. S. THAYER, 
President. TABLE OF CONTENTS. 
PAGE 
I. General summary, 4 
IL Introduction and general recommendation, . 6 
III. A brief consideration of the history, character, 
functions, value and cost of hospitals for the 
treatment of incipient tuberculosis, with rec- 
ommendations and plans for an institution 
suitable for the State of Maryland, . . 10 
VI. Report of committee on tuberculosis in state penal 
institutions, 20 
V. Appendix, Laws of Maryland, . ... 27 I. GENERAL SUMMARY. 
(1) Tuberculosis is the most wide-spread and fatal 
OF INFECTIOUS DISEASES, CAUSING FROM ONE-FIFTH TO ONE- 
TENTH OF THE TOTAL MORTALITY OF THE WORLD. 
(2) There are at least 10,000 sufferers from tu- 
berculosis IN MARYLAND TODAY. 
(3) Tuberculosis prevails especially during early 
ADULT LIFE. 
(4) Over 2500 individuals, in great part at the 
PRIME OF LIFE AND DURING THE PERIOD OF GREATEST WAGE- 
EARNING CAPACITY, DIE EVERY YEAR IN THE STATE OF MARY- 
LAND FROM TUBERCULOSIS. 
(5) The loss of these lives means to the state an 
ANNUAL POTENTIAL LOSS OF AT LEAST 10,000,000 DOLLARS. 
(6) After insanity, tuberculosis is the condition 
WHICH REDUCES THE GREATEST NUMBER OF CITIZENS TO A 
STATE IN WHICH THEY BECOME DEPENDENT FOR ASSISTANCE 
OR SUPPORT UPON THE COMMUNITY IN WHICH THEY LIVE. 
(7) Tuberculosis is a disease caused by the en- 
trance INTO THE BODY AND THE GROWTH THERE OF A SPE- 
CIFIC MICRO-ORGANISM-THE TUBERCLE BACILLUS. 
(8) The micro-organism usually enters the economy 
THROUGH THE NOSE OR MOUTH BY RESPIRATION, THROUGH 
INFECTED FOOD OR THROUGH WOUNDS OF THE SKIN. 
(9) The bacilli are spread about chiefly by the 
SPRAY EMITTED BY PATIENTS SUFFERING WITH THE DISEASE 
IN COUGHING OR SPEAKING, AND BY THEIR EXPECTORATION. 
(10) The most important method of distribution 
OF THE TUBERCLE BACILLI IS PROBABLY PROMISCUOUS SPIT- 
TING. 
(11) Tuberculosis is a preventable and in many 
INSTANCES, A CURABLE DISEASE. 
(12) Efforts are now being made to control the 
DISEASE IN THIS STATE : 5 
(a) By carrying out the admirable regulations 
of the State Board of Health with regard to the 
REGISTRATION OF CASES OF TUBERCULOSIS, DISINFECTION 
AND THE INSTRUCTION OF THE PATIENTS AND THEIR FAMILIES 
THROUGH THE ATTENDING PHYSICIAN. 
(b) By the educational campaign conducted by 
the Maryland Association for the Prevention and Re- 
lief of Tuberculosis. 
(c) By the Phipps Dispensary in the City of 
Baltimore for the treatment of ambulatory cases of 
TUBERCULOSIS AND BY A SIMILAR INSTITUTION JUST ESTAB- 
LISHED at the University of Maryland. 
(d) By the admirable work of the visiting 
NURSES SUPPORTED BY THE INSTRUCTIVE VISITING NURSE 
Association and of nurses working in connection with 
WITH THE DISPENSARIES ALREADY MENTIONED. 
(e) By the efforts of the Eudowood Sanatorium 
FOR TUBERCULOSIS AND ITS BRANCH AT MOUNT AlRY. 
(13) It is highly advisable that there should be 
ESTABLISHED IN THE COUNTIES AND LARGE CENTRES OF 
POPULATION LOCAL HOSPITALS FOR CONSUMPTIVES FOR THE 
TREATMENT OF THE MORE ADVANCED CASES OF THE DISEASE 
AND THE PROTECTION OF THE FAMILIES OF THE SUFFERERS. 
There is at present but one institution in Maryland 
FOR THE TREATMENT OF SUCH PATIENTS. 
(14) The outlook for recovery from tuberculosis 
IS GOOD ONLY IN EARLY CASES. 
(15) The important elements of treatment are : 
(a) Rest. 
(b) Food. 
(c) Fresh Air. 
(16) Early cases of tuberculosis are treated with 
GREATEST SUCCESS IN PROPERLY CONDUCTED SANATORIA IN 
COUNTRY DISTRICTS. 
(17) Careful studies of the question have shown 
THAT THE ESTABLISHMENT OF SUCH SANATORIA BY THE STATE 
IS NOT ONLY A GREAT CHARITY, BUT ECONOMICALLY, A VALU- 
ABLE FINANCIAL INVESTMENT FOR THE COMMUNITY, RESULT- 
ING AS IT DOES IN THE ANNUAL SAVING OF A NUMBER OF 
VALUABLE LIVES. 6 
(18) Four states already support sanatoria for 
THE TREATMENT OF TUBERCULOSIS IN WHICH AN AVERAGE OF 
NEARLY 80% OF CASES YEARLY ARE SO FAR BENEFITED THAT 
THEY ARE ABLE TO RETURN TO WORK. 
(19) In seven other states bills providing for the 
ESTABLISHMENT OF SANATORIA ARE NOW UNDER CONSIDER- 
ATION. 
(20) It is urgently necessary that such a sana- 
torium FOR THE TREATMENT OF EARLY TUBERCULOSIS 
SHOULD BE ESTABLISHED BY THE STATE OF MARYLAND. 
(21) The commission cordially approves the bill 
PROVIDING FOR A STATE SANATORIUM INTRODUCED IN THE 
Maryland Senate in March, 1906. 
IL 
INTRODUCTION AND GENERAL 
RECOMMENDATIONS. 
(1) As pointed out in the Report of the previous Com- 
mission,* tuberculosis, especially in the form of pulmonary 
tuberculosis, is the most wide-spread and fatal of the infec- 
tious diseases, causing alone from one-fifth to one-tenth of 
the total mortality of the world. It is a disease which, pre- 
vailing especially in early adult life, carries away yearly 
thousands of individuals in their early prime at the period of 
greatest wage-earning capacity. More than this, with the 
exception of insanity, tuberculosis ranks first among all dis- 
eases in the proportion of its subjects who finally become de- 
pendent for assistance or support upon the state or community 
in which they live. Investigations have shown that there 
are at least 10,000 cases of tuberculosis in Maryland, over 
2,500 deaths occurring every year, while the total potential 
loss to the State entailed by deaths from tuberculosis cannot, 
at the lowest estimate, be less than 10,000,000 dollars a year. 
Tuberculosis is a preventable and in many instances, a 
curable disease. It is spread in great part by careless and un- 
cleanly habits of the infected individual. 
'Report of the Tuberculosis Commission of the State of Maryland, 1902-4. 7 
A general movement directed toward controlling and pre- 
venting this terrible scourge has been initiated throughout 
the civilized world. To this movement Maryland should con- 
tribute her share. Already excellent work in the education 
of the public is being done by the Maryland Association for 
the Prevention and Relief of Tuberculosis. In the City of 
Baltimore two dispensaries have been established for the 
treatment of patients, while a system of district nursing has 
been organized through these dispensaries and through the 
Instructive Visiting Nurse Association. 
The previous Commission pointed out the following 
measures as most important in the struggle to combat and 
control this disease. 
(a) Enforcement of anti-spitting ordinance. It was urg- 
ently recommended that an amendment be made to the exist- 
ing law forbidding spitting upon the floors, seats and plat- 
forms of railroad or railway passenger cars which would ex- 
tend this law so as to cover the decks of steamboats, the 
floors of all public conveyances and of state buildings, and 
would direct that notices forbidding spitting upon the floors 
and calling attention to this act be posted in all public con- 
veyances. 
(b) State Notification. It was advised that the act re- 
quiring notification to the State Board of Health of the exist- 
ence of certain infectious diseases be amended so as to include 
tuberculosis in all its forms. 
(c) Disinfection. It was recommended that the law re- 
quiring disinfection of premises after their occupation by 
persons suffering from certain infectious diseases be amended 
so as to include tuberculosis. 
(d) Sanatoria. The opinion was emphasized that the 
establishment of state sanatoria for the care and treatment 
of consumptives would be of lasting benefit to the state and 
to the community, and that whatever expense might attend 
the founding and maintenance of these plants would be ulti- 
mately more than repaid by the results of treatment. 
As a result of these recommendations the Legislature 
passed two excellent acts * : 
'See Appendix, pages 26-31. 8 
(1) Providing for the registration with the State Board 
of Health of all cases of tuberculosis. 
(2) Empowering the State Board of Health to carry out 
through its own agents and through the medical profession 
proper measures of disinfection. 
The Commission believes that it is justified in asserting 
that the State of Maryland has now upon its statute books 
the wisest and most far-reaching laws upon the question of 
tuberculosis that exist in any state in the Union. It also 
believes that upon the tactful and judicious administration 
of these laws, as supervised by our State Board of Health, 
results of incalculable value to the community will be accom- 
plished. 
The State, however, has not as yet, adopted any special 
measures providing for the treatment of tuberculosis. The 
Commission after due consideration, believes that it is desir- 
able for the State to encourage, and in part to direct, and sup- 
port a general scheme for the care of tuberculosis in Mary- 
land. The following plan is suggested. 
(1) Dispensaries. There should be in Baltimore and in 
the larger towns of Maryland a sufficient number of dispen- 
saries for the advice and treatment of ambulatory patients. 
Apart from the actual value of these institutions in the 
treatment of the sick they afford an excellent opportunity for 
the education of the public, while providing for the protect- 
ion of the patient's families and those about them. It has, 
moreover, been found that in the Phipps Dispensary an in- 
creased number of early cases of the disease have been 
brought to light-cases in which under proper out-of-door 
treatment there is reasonable ground for hope of permanent 
recovery. Such dispensaries afford a valuable means for 
selecting proper cases for treatment in sanatoria for incipient 
tuberculosis. 
(2) District Nurses. A proper system of district 
nursing for tuberculosis should be developed as well in con- 
nection with established dispensaries, as through the efforts 
of private associations, such as the Instructive Visiting Nurse 
Association of Baltimore. 
The work of assistance and instruction which can be 
done by tactful and well trained nurses at the homes of the 
sufferers is of the greatest value. 9 
(3) Hospitals for Consumptives. There is a crying 
want in the community for hospitals in or in the immediate 
neighborhood of the larger centres of population, to which 
sufferers from tuberculosis in any stage may be sent. That 
the establishment of adequate hospitals for consumptives 
will eventually be of great benefit to the community has been 
abundantly proven by the results already obtained in other 
countries, especially in England. The value of such institu- 
tions consists not only in the relief and sometimes in the cure 
which is afforded to the patients themselves, but also in 
their efficacy as a means of protection to the families of 
ignorant and careless advanced cases of the disease. Such 
institutions should be in cities or towns or at a convenient 
distance from the main centres of population. And event- 
ually, for the relief of the suffering poor as well as for the 
protection of their families and the public, ample accommo- 
dations for such patients should be afforded. In properly 
conducted institutions of this kind many patients in whom 
the outlook is at first regarded as unfavorable, are found to 
improve to such an extent that they may be transferred later 
to the hospitals for incipient cases, in which a permanent 
arrest of the disease may be brought about. 
The Commission believes that such institutions should be 
under the management of private corporations, counties or 
municipalities. Such hospitals should exist in every county. 
In the city of Baltimore there already exists a municipal 
hospital for consumptives at Bay View. 
The Commission recommend, as a beginning, that every 
general hospital receiving financial assistance from the 
State shall be required to devote a ward or building to the 
treatment of cases of tuberculosis, the number of beds to be 
proportionate to the subsidy given by the state. 
(4) Hospitals for Incipient Tuberculosis. The Com- 
mission believes that there is an urgent call for the estab- 
lishment of hospitals for the treatment of incipient tuber- 
culosis. 
Such institutions should be situated in high and dry rural 
districts. There is great need in Maryland today for the es- 
tablishment of a sanatorium in which cases of tuberculosis 
recognized at an early stage by their physicians, selected at 10 
other hospitals or treated at the dispensaries and regarded as 
proper subjects for thorough out-of-door treatment may be 
sent. There exist in the State of Maryland two such institu- 
tions, the Eudowood Sanitarium at Towson and its branch at 
Mt. Airy, which have already a fairly good equipment. These 
institutions have, with meagre and insufficient support, been 
doing faithful work in the treatment of tuberculosis. The 
Commission believes that an arrangement may easily be made 
by which these institutions may join forces with the state in 
carrying out its plan. Under such circumstances we are of 
the opinion that these institutions will prove a valuable 
adjunct to the further plans which are suggested. The 
Commission, therefore, would recommend that if satisfactory 
arrangements such as those above referred to, can be made, 
the state should give adequate support to this institution. 
The Commission, however, regards as immediately urgent 
the erection of a state sanatorium for the treatment of incipient 
tuberculosis. Such a plant can be built and conducted at a 
moderate expense. The main expense of construction is 
connected with the erection of a permanent administration 
building and kitchen. To this as will be set forth later, 
wards for the accomodation of patients can be added at a 
very moderate expense. 
In the succeeding sections of the report there are pre- 
sented a series of considerations upon the origin, efficiency 
and character of sanatoria for tuberculosis with detailed de- 
scriptions and plans of an institution such as we believe 
would be adapted for the State of Maryland. 
III. 
A BRIEF CONSIDERATION OF THE HISTORY, 
CHARACTER, FUNCTIONS, VALUE AND COST OF 
HOSPITALS FOR THE TREATMENT OF INCIPIENT 
TUBERCULOSIS, WITH RECOMMENDATIONS 
AND PLANS FOR AN INSTITUTION 
SUITABLE FOR THE STATE 
OF MARYLAND. 
(1) Duty of the State to establish sanatoria for the treat- 
ment of her poor consumptives. 11 
Every civilized community recognizes that it is the duty 
of the government to protect its citizens from communicable 
diseases that have been proven to be a menace to public 
health and to the safety of the individual. Maryland has 
enacted legislation that provides for the enforced isolation and 
care of persons suffering from certain diseases known to be 
dangerous to the public welfare. The State has seen fit to erect 
and support institutions for the care of the indigent insane, the 
feeble-minded, the epileptics, and for degenerates of various 
types. Generous appropriations are annually made to general 
hospitals throughout the State, which open their doors to the 
poor suffering from typhoid fever, pneumonia and numerous 
other acute and chronic diseases. Up to the present time, 
however, no adequate appropriation has been made by the 
State for the purpose of caring for the treatment of those 
suffering from consumption, the largest individual class of sick 
persons requiring assistance. 
Every hospital in the State known to your commission 
that receives state assistance and in return supports state 
beds for the sick poor, closes its doors to the unfortunate 
victim of pulmonary tuberculosis. Your Commission wishes 
to call your attention to the fact that, with the exception of 
the Baltimore City tuberculosis hospital and a small hospital 
in Baltimore County with a capacity of less than forty beds, 
there is no institution in this State where the hundreds of 
poor worthy consumptives can find a proper place for treat- 
ment, or a comfortable refuge in which to die. Left alone, 
deprived of the aid so readily bestowed upon other sick, and 
thrown upon their own too scanty resources, these poor 
sufferers go to crowd the over congested almshouses; or else 
they die in their own homes amid indescribable surroundings, 
forming until the day they breathe their last additional foci 
for the spread of the dreaded disease. 
Pulmonary tuberculosis or consumption is now regarded 
as a dangerous communicable disease. It causes more deaths 
in Maryland per annum than any other three of the most fatal 
diseases for which our government, as stated above, has 
made provision. Being communicable, tuberculosis is to a 
large extent preventable, and it would therefore seem fitting 
for the State to adopt proper measures for its restriction. 12 
According to the law passed by the last legislature, it is 
the duty of this Commission to report to you concerning the 
advisability of the establishment of a state sanatorium for 
consumptives, discussing the sort of locality suitable for such 
an institution and the probable cost for its erection, equip- 
ment and subsequent maintenance. 
(2) The origin of the treatment of consumption in sana- 
toria. The fresh air treatment of consumption was advocated 
as far back as the time of Hippocrates (B. C. 375), but the 
present so-called sanatorium method of treating pulmonary 
tuberculosis in a specially conducted institution, where a diet 
is supplied as nutritious and abundant as the patient is able 
to assimilate, with open air life day and night, was inaugu- 
rated by Dr. George Bodington, of Warwickshire, England, 
in 1835. In his work entitled "Essay on the Cure of Pul- 
monary Consumption on Principles Natural, Rational and 
Successful," he advocated a generous diet of milk, eggs and 
fresh meats, and insisted upon abundance of air day and 
night. Bodington recommended treatment under the sur- 
veillance of a medical superintendent in country houses 
situated in proper localities for all cases of pulmonary tuber- 
culosis. 
The second sanatorium for the successful treatment of 
tuberculosis was established by Hermann Brehmer in Gbrbers- 
dorf, Silesia in 1859, but not until 1884 when Edward L. 
Trudeau started the Adirondack Cottage Sanitarium at Sara- 
nac Lake, New York, was there an institution in this country 
for the exclusive care of this disease. 
Subsequently, at varying intervals, other institutions of 
a similar character, have been erected, the success of which 
has given a tremendous impetus to this method of treatment. 
There are at present, in this country, in 
Alabama, 2 institutions. Maine, 1 institutions. 
Arizona, 4 " Massachusetts, 12 " 
California, 6 " New Mexico, 8 " 
Connecticut, 2 " New York, 21 " 
Hawaii, 1 " North Carolina, 4 
Illinois, 3 " Pennsylvania, 14 " 
Indiana, 3 " Rhode Island, 4 
Iowa, 1 ' ' 13 
The United States government has three sanatoria : one 
for the United States army at Fort Baird, New Mexico; 
another established by the Marine Hospital Service at Fort 
Stanton, New Mexico; and a third at Pensacola, Florida, for 
the treatment of cases developing in the navy. 
The following states have already completed or are build- 
ing sanatoria for the care of their indigent consumptives. 
Massachusetts has a state sanatorium established at a cost of 
$200,000 at Rutland in 1898, additions practically doubling 
the size of the institution having been built since; New 
Jersey is building a state institution at Glen Gardner as a re- 
sult of an appropriation of $200,000; New York has a state 
hospital at Raybrook, Essex County, established in 1904 at a 
cost of $250;000; Rhode Island opened, in 1905, a state insti- 
tution at Pascoag at a cost approximating $200,000. The 
following states have at present bills before their respective 
legislatures for appropriations for similar institutions: Illinois, 
Maine, Montana, New Hampshire, Vermont, Virginia, Wis- 
consin. 
Connecticut contributes $25,000 a year towards the sup- 
port of the Gaylord Farm Sanatorium, which amounts, prac- 
tically, to a state institution; and Ohio, at her last legislative 
session, appropriated $35,000 towards the purchase of land 
and preparation of architect's plans for a proposed state 
hospital for consumptives. 
(3) Results accomplished at Sanatoria. The good ac- 
complished at the several sanatoria now in operation is proven 
beyond controversy by their annual reports, some of which 
cover a period of many years. So the permanency of the 
results of sanatorium treatment as far as the individual is 
concerned, is fully demonstrated. These statistics are far 
too voluminous to be included in this report, but your Com- 
mission feels justified in referring to a few of the more 
recently published results of treatment at sanatoria in this 
country 
The last report of the Massachusetts Sanatorium at Rut- 
land for the past five years, shows that the disease was 
arrested in 45% of the patients admitted for treatment, while 
39.6% were very much improved, so that a total of 85.1% of 
all patients received were able to return to work and again 
become wage earners. 14 
The report from the Adirondack Cottage Sanitarium con- 
cerning 1,200 cases shows 23% of complete recoveries, while 
the disease was arrested in 56%. In other words, 79% of the 
patients treated were able to return to work. The Loomis 
Sanatorium at Liberty, New York, in its last annual report, 
showed that 68% of the patients were able to return to work. 
Tuberculosis generally selects for its victims individuals 
between the ages of 20 and 40, oftentimes the breadwinners 
of the family. If such an individual when sick, be cared for 
until he is able to return to his work, he will again resume 
the responsibilities of his family. Let him die, and the burden 
of their support must fall upon the state. Each life has a 
certain economic value to the state, variously estimated at 
from $500 upwards. If a sanatorium in Maryland with a 
capacity for 75 patients should care for 150 patients a year, 
at the very lowest estimate 25% of these would recover their 
health permanently, and an additional 25% would be wage 
earners for at least one year. This would mean a saving of 
75 lives per annum. If the money value of a life be placed 
at $500 a year, these 75 lives would be worth annually $37,500 
or considerably more than the operating expenses of the insti- 
tution. With these figures for the first year it is obvious that 
in a few years a sanatorium would prove a financial invest- 
ment of the greatest value to the State. 
(4) Protective and Educational Value of Sanatoria. 
While the chief aim of the sanatoria is that of saving life, 
this is by no means the sole value of these institutions to the 
public. Every patient cared for removes a focus of infection, 
and diminishes the chances of the disease attacking other 
members of the family or community. This is a most import- 
ant factor from a prophylactic standpoint, and is one of the 
chief means at our disposal for the restriction of the spread 
of the disease, especially among those individuals who are 
too ignorant to realize that they are a source of danger to 
their friends and relatives. 
The second point to be considered, and one that is more 
far reaching than the first, is the educational value of sana- 
toria. The influence exerted by "discharged cures" upon 
the family and neighbors cannot be over-estimated. Each 
individual while in the sanatorium is obliged to adopt the 15 
rigid regime laid down in such institutions, which not only 
educates him in every particular necessary to prevent the 
infection of others, but thoroughly imbues him with the real- 
ization of the absolute necessity of fresh air, sunshine and a 
proper ventilation for the enjoyment of perfect health. 
Touching upon this point, Dr. S. A. Knopf in his work en- 
titled "Prophylaxis and Treatment of Pulmonary Tubercu- 
losis," says that sanatoria not only serve as educators of 
patients, but as educators of communities as well. In the 
villages where the two largest German sanatoria are situated, 
Gorbersdorf and Falkenstein, the mortality from tuberculosis 
among village people has annually decreased, being now one- 
third less than before the establishment of the sanatoria. 
(5) Location for State Sanatorium for Consumptives. 
One duty imposed upon your Commission by the resolution 
creating it, was to report upon a suitable location for a 
sanatorium for consumptives. While it is deemed inadvis- 
able for this Commission to report definitely upon any special 
site, it may be said with assurance that there are various 
localities in this state perfectly suitable for an institution 
such as the one contemplated, where pulmonary tuberculosis 
can be treated as successfully as in any state of the Union. 
In general your Commission would advise that the place 
selected should have an altitude of at least 1,000 feet above 
sea-level and should be situated on a southerly or south-easterly 
slope, protected by woodlands or hills on the north. The soil 
should be of a dry and porous character, capable of good 
drainage, and the atmosphere of the locality should be as free 
from moisture as possible. A considerable tract of land of 
at least 100 acres should be secured, with an unlimited 
supply of pure water, obtained either by the public water 
supply of the locality or by a complete system of its own. 
The location should also be in close proximity to rail road 
communication, not only for the convenience of patients and 
friends, but for the economical hauling of supplies, a separate 
and distinct station on the railroad being regarded as prefer- 
able. Another requirement for the proposed site, which 
your Commission deems to be most essential, is that it should 
be no further from the chief centre of population than the 
other conditions above mentioned necessitate. In many 16 
sections of this State there are such sites as that described 
which would be suitable for the location of a sanatorium for 
consumptives. 
(6) Construction and Cost of Equipment. Another re- 
quirement of the law under which this Commission is serv- 
ing is to report upon the cost of construction and equip- 
ment of a state hopital for consumptives. The Commission 
has called in consultation the well known architects, Messrs. 
Wyatt and Nolting of Baltimore City. The drawings here- 
with presented are of their design. 
After a careful study of plans of existing institutions, 
the Commission would recommend a type of building for the 
accommodation of patients which it believes promises the 
greatest economy of construction and at the same time secures 
the maximum amount of fresh air, sunlight and ventilation. 
The plan recommended comprises : 
(1) An administration building. 
(2) A dining hall with a capacity for 100 to 150 persons, 
situated in the rear of the main building and connected with 
it by a short gallery. 
(3) A kitchen building with sleeping rooms for the 
domestics on the floor above. 
(4) The patient's accommodations, which consist of 
separate pavilions, male and female, occupying the opposite 
sides of the main building, forming an east and west wing 
and thereby gaining southern exposure. 
In regard to the approximate cost of such a set of build- 
ings, our architects are unable to make a positive estimate 
without going into the details of construction and finish of 
the buildings as shown in the accompanying plan. They have, 
however, submitted a rough estimate, stating that the scheme 
of the first part proposed, namely the administration build- 
ing, one dining room and kitchen with two wings accommo- 
dating 64 patients, will amount, as a whole, to from $80,000 
to $85,000, the cost of the administration building being about 
$33,000, that of the dining room and kitchen $33,000, while 
the pavilion will cost about $14,000. 
A more complete description of an institution such as the 
Commission deems most fitting for the immediate wants of 
the state of Maryland accompanies the appended plan. 17 
(7) Cost of Maintenance. The amount which the State 
will be called upon to contribute toward the maintenance of 
such an institution would, of course, depend entirely upon the 
policy that may be adopted for the reception of patients. 
If the State should decide to accept all patients as presumably 
indigent, regardless of their true financial condition, and 
thereby assume the whole cost of their stay in the sanatorium, 
the expense of such a plan would be considerable, but if the 
State adopts a plan similar to that in use at the Massachusetts 
State Sanatorium, where a charge of a uniform rate of $4.00 
a week is made against every patient, the cost of mainte- 
nance, as may easily be seen, will be considerably reduced. It 
might be well to fix the charge later at a figure found to be 
one-half what it actually costs the institution per patient per 
week. In exceptional cases especially worthy or in unusually 
suitable cases, it might be well to provide that such individ- 
uals could be sent to the institution upon the order of the 
State Tuberculosis Commission or Board of Managers of the 
Sanatorium, wholly at the expense of the State, after a care- 
ful investigation had been made of their finances. 
The Commission has attempted to furnish some idea of 
the average cost per patient in institutions such as we have 
proposed to erect. The cost per patient per day at the Massa- 
chusetts State Sanatorium at Rutland has proven to be $1.42. 
The cost at the Adirondack Cottage Sanitarium at Saranac 
Lake is found to be about the same. The cost at the Eudo- 
wood Sanatorium, by the most careful and economical admin- 
istration, has been $1.10 per day. The Commission would 
advise that the average cost per patient per day would be 
approximately $1.25. Taking the total number of hospital 
days in an institution of the capacity that we have advo- 
cated, presumably running at full capacity, as 22,630, the 
total cost would be not over $30,000 per annum; or if the 
rule above suggested of charging each patient half rates 
should be adopted, $15,000. This, in all probability, is too 
conservative an estimate, as many extras will always develop 
in the management of such an institution which cannot be 
foreseen in a report of this kind. But your commission 
is of the opinion that the cost to the State should not exceed 
$25,000 per annum. This sum is not a large one, less than 18 
many of the annual appropriations now made for other objects, 
while the investment from every point of view would be a 
paying one, second to none other in which the State is in- 
terested. 
(8) Plans and Description of the Proposed Buildings. 
The plan adopted comprises: 
(a) An administration building, containing public re- 
ception rooms, doctors' and nurses' offices, examination 
rooms, a pharmacy and library. The basement of this build- 
ing contains general store-rooms, heating apparatus, cold- 
storage plant and mortuary. The second floor is given up to 
sleeping quarters for the superintendent and his staff, with 
proper toilet accommodations. The third floor of the main 
building is devoted entirely to an infirmary for febrile cases 
and those suffering from unforeseen complications or inter- 
current disorders, with quarters for nurses and attendants 
upon such cases. A large laboratory for clinical work and 
scientific research is also provided for on this floor. 
(b) In the rear of the administration building is the 
dining hall with a seating capacity for about 150 persons, 
and on the second floor of this building are quarters for the 
nurses and orderlies. The dining hall is connected with the 
patients' quarters and the administration building by two 
enclosed galleries, which enable the patients to go from their 
sleeping quarters to the dining hall in inclement weather 
without passing through the administration building. 
(c) In the rear of the dining hall is placed the kitchen 
building, with necessary serving rooms, etc., and sleeping 
rooms for domestics on the floor above. The whole scheme 
is so arranged and disposed that with this kitchen building 
as an approximately central point additional and similar 
pavilion and dining room accomodations may be arranged in 
the future, so that this domestic service building may be 
utilized for the whole. This will avoid the expense of erecting 
and maintaining new kitchen buildings. 
(d) The patients' accommodations consist of separate 
pavilions - male and female occupying opposite sides of 
the main building-forming east and west wings (marked 
A, B, C, D, E and F,) and thereby gaining southern exposure. 
Each wing is built upon the "pavilion" plan, being entirely 19 
open in front, with the sides and backs so arranged on hinges 
as to make it possible to open up three sides of the building, 
placing the patients practically in the open air. Each wing 
has a capacity for thirty-two patients, and may be subdivided 
into two smaller pavilions, with a capacity for sixteen each, 
thereby ensuring as great privacy as this type of building will 
allow. For each subdivision with accommodation for sixteen 
patients a recreation parlor or solarium is provided in which 
the patients may spend the time they are allowed to be in- 
doors. In the rear of these parlors is a large locker room, fitted 
with separate lockers for each individual, and in the end of 
this room are two smaller rooms containing necessary shower 
baths and toilet equipment. The recreation parlor and locker 
rooms are comfortably heated, but the main pavilions, in 
which the patients spend the greater part of their days and 
nights, are not heated at all. Canvas drop curtains in front 
protect the patients from wind and rain, and in the winter 
time sliding glass doors may be substituted for the canvas 
curtains, if the weather warrants. 
The choice of building material is not finally made. The 
architects have suggested that the administration building 
should be of brick or concrete; the same would be desirable 
for dining room and kitchen building, but it is not absolutely 
necessary if economy must be considered. In that case they, 
as well as the pavilions, may be of frame construction, but 
the latter are to be treated on the interior with some imper- 
vious, hard and smooth wall finish. In the estimate as given 
all buildings, except the administration building, are of frame 
construction. These plans are so arranged that additional 
pavilions, C. & D. as shown on the scheme, may be added 
at any time as the need arises. 
As stated in a previous section of the report, it is pro- 
posed that the buildings shall occupy the southern slope of a 
hill in such a manner that pavilions C. & D. may be upon a 
level sufficiently above pavilions A. & B. to allow a wholly 
open and unimpeded exposure. In view of the fact that a 
large percentage of the State's indigent consumptives belongs 
to the colored race, provision has been made in the scheme 
for a complete reduplication of the two main pavilions with 
separate dining hall to be built in the rear of the kitchen at 20 
a future date if such a measure be deemed desirable. None 
of these proposed additions, however, (comprising additional 
dining room and pavilions C., D., E. &F.) have been included 
in the estimate. 
As has been pointed out in the preliminary remarks, this 
plan provides for solid and permanent central quarters for 
which the main outlay will be required. About this central 
nucleus new pavilions of frame construction for the accom- 
modation of patients can be added at a limited expense. The 
Commission, however, would advise that the number of pa- 
tients to be provided for at a single institution should not 
exceed 250. 
IV. 
REPORT OF COMMITTEE ON 
TUBERCULOSIS IN STATE PENAL INSTITUTIONS 
It is a well recognized fact nowadays that tuberculosis 
is essentially a disease of house infection. The well known 
work of Flick and others has demonstrated conclusively 
that tubercle bacilli are bred, fostered and disseminated to a 
larger degree through the medium of infected dwellings than 
through any any other one means. Individuals leading in- 
door lives or closely confined by indoor occupations, are far 
more likely to contract tuberculosis than those whose calling 
constantly keeps them in the fresh air. It would seem, there- 
fore, that inmates of penal institutions, confined as they are 
of necessity, and spending the greater part of their time 
in close, poorly ventilated cells, should be especially prone to 
tuberculosis infection. 
In the dark corners of the average prison cell, rarely vis- 
ited by sunlight, the tubercle bacillus finds an ideal place to 
remain until it has the chance to propagate through the 
medium of the cell inmate. But it should be borne in mind 
that no matter how dark the cell, how poor the ventilation, 
how fit a subject for infection the inmate may be, tubercu- 
losis cannot be contracted unless the tubercle bacilli be pres- 
ent; and it should further be remembered that tubercle bacilli 
cannot be present unless the quarters have been occupied by 
a consumptive living in absolute violation of all the laws pre- 
scribed by sanitary authorities and his disease has remained 
unrecognized by the prison officials. 21 
With these ideas in mind, the Tuberculosis Commission 
of the State of Maryland and the Maryland Society for the 
Relief and Prevention of Tuberculosis, at a recent joint meet- 
ing, passed a resolution to investigate the penal institutions 
of the State, with special reference to the existence of pul- 
monary tuberculosis. A committee of physicians especially 
interested in the subject was appointed, and through the 
hearty co-operation of the Governor permission was soon 
obtained to study the conditions existing at the House of 
Correction. Through the courtesy of the superintendent, 
Colonel Jesse Moore, the committee were enabled to make 
not only a most exhaustive investigation of the institution 
from a general sanitary standpoint, but also an individual 
physical examination of each prisoner. 
The Maryland House of Correction, at Bridewell, Anne 
Arundell County, is used chiefly as a prison to relieve the 
congestion of the various county jails of the State. The pris- 
oners are chiefly short term convicts, the average duration of a 
sentence being, as seen in the tables below, 5 months, 23 
days. As most of the prisoners come from the country, a large 
percentage of them was previously engaged in outdoor work, 
as is shown by the tables below. The building consists of an 
administration building with two large wings on either side, 
extending to the north and to the south, the latter being a 
recent addition and not yet open for occupancy. Each wing 
contains a huge central cage built entirely of brick and cement 
with steel doors. This cage is four tiers high with approxi- 
mately fifty cells to the tier. Each cell measures 5 by 8 feet, 
is built entirely of cement, and contains separate water 
basins and toilet accommodations. The ventilation is obtained 
by a hole in the ceiling measuring five inches in diameter, which 
connects with a central air shaft running up the centre of the 
main cage from basement to roof. Each main wing is lighted 
and ventilated by a series of windows running the entire 
height of the building at intervals of four feet, and so arranged 
as to be automatically opened from top to bottom. The 
drainage from the water basins and closets passes into pipes, 
which run through the centre of the main cage to the end of 
each wing where they join the main drain pipe and flows 
into a small branch some one-half mile distant from the 
institution. 22 
Before beginning the actual examination of the prisoners 
the committee decided to ask each one the following ques- 
tions : 
(1) Have you ever had any cough ? (2) Have you had 
a cough since admission to the institution ? (3) Have you 
had any spittle since admission ? Have you ever spat up 
blood (a) before admission (b) since admission ? As a 
whole the prisoners were found to be an extremely healthy, 
robust and well nourished set of men and women, remarkably 
free from any pulmonary disease, especially when it is con- 
sidered that two-thirds of the prisoners are negroes. The 
resident physician, Dr. R. A. Hammond, was extremely 
courteous, and aided in the examinations in every way possi- 
ble. Dr. Hammond said that upon admission to the institu- 
tion prisoners were not subject to any medical examination 
whatever, so it was impossible to ascertain their physical 
condition on entry. Tuberculosis, therefore, might easily 
exist in an incipient form in a prisoner without being noted by 
the attendants until the disease had advanced to such a con- 
dition that it was self-evident what was the trouble with the 
prisoner. The committee made a careful investigation of the 
culinary department, and found everything, in a measure, 
clean and sanitary. In view of the recent theories that tuber- 
culosis is usually contracted by the ingestion of infected 
foods, special examination of all the attendants in the kitchen, 
bakery and serving rooms was made. They were found to be 
in a healthy condition. 
The results may be tabulated as follows : 
(1) Total examined 400 
(2) Color and sex- 
White males 116 or 29% 
White females 12 or 3% 
Black males 256 or 64% 
Black females 16 or 4% 
(3) Previous occupation- 
Indoor 75 or 18.75% 
Outdoor 325 or 81.25% 23 
(4) Past history as regards pulmonary disease- 
(a) Past cough 110 or 27.50% 
(b) Present cough 100 or 25.00% 
(c) Present expectoration 120 or 30.00% 
(d) Haemorrhage-before admission. 11 or 2.75% 
since admission .. 42 or 10.50% 
(e) Negative 17 or 4.25% 
(5) Physical examination- 
Positive evidence of tuberculosis 6 or 1.50% 
Suspicious signs of tuberculosis 22 or 5.50% 
Glandular tuberculosis 5 or 1.25% 
Bronchitis, non-tubercular 3 or 0.75% 
Negative (no pulmonary disease)... .364 or 91.00% 
Hospital accommodations. The committee wishes to call 
special attention to the extremely poor, antiquated and un- 
hygienic quarters connected with the institution for the 
housing of the sick. The main hospital for males consists of 
one large ward to which cases of all kinds are admitted. The 
room is well lighted and could be well ventilated, but the 
atmosphere was extremely close and odor disagreeable. The 
beds and bedding were dirty, and the patients in a very filthy, 
unkempt condition. The committee found twelve patients in 
the ward, four of whom were suffering with pulmonary tu- 
berculosis. These consumptive patients were sleeping in 
beds next to individuals with other diseases, and as far as 
could be learned, were observing no precautions to prevent 
contamination. 
The room set aside for sick females was of a similar 
character, though smaller, with no facilities for isolation or 
segregation of tuberculosis patients. No cases of consumption 
were in this ward at the time of the committee's visit, 
although the matron informed us that a poor consumptive 
had been in there for several months. 
Over-Crowding. With a few exceptions, each of the cells, 
as described above, contained two inmates, one of whom was 
compelled to sleep upon the floor. It will not be necessary 
to say more about this most objectionable over-crowding, 
because the opening of the new wing within the next few 24 
months will double the capacity of the institution, and do 
away entirely with this feature. 
Recommendations. We cannot close this report without 
making certain recommendations, which all agreed were 
essential to the proper care of the health of the prisoners. 
First and foremost, we urgently recommend the introduction 
into this institution of a systematic medical examination to be 
made upon the admission of the prisoner, and that the result 
be recorded upon a history card kept for the purpose and in- 
dexed. Secondly, in all suspicious cases, giving a history of 
cough and expectoration, (the tables show how frequently 
this occurs), specimens of sputum should be sent to the lab- 
oratory of the State Board of Health as long as the symptoms 
persist. Thirdly, the erection in a part of the building now 
devoted to general hospital uses of an isolated wing for the 
care and treatment of those patients suffering from pulmon- 
ary tuberculosis, so fitted up that they may obtain as much 
fresh air and sunshine as prison life will permit. If this 
addition be not practical in view of the fact that the State 
has recently expended several hundred thousand dollars upon 
the House of Correction, we strongly urge the transfer of all 
cases of pulmonary tuberculosis to the hospital of the Mary- 
land Penitentiary, where proper housing facilities have been 
erected for the special care of consumptives. 
Maryland Penitentiary. The committee next visited the 
Maryland Penitentiary and were most courteously received by 
the Warden, Mr. John Weyler. After the object of the visit 
was explained however, the Warden informed the committee 
that it would not be possible to make individual examinations 
of each inmate and that the records of the prison physician 
would show the amount of tuberculosis existing in the insti- 
tution. Mr. Weyler was most kind in conducting the com- 
mittee through the entire prison and adjoining workshops, and 
it is a pleasure to be able to repeat what is already generally 
known, that in the Maryland Penitentiary the State possesses 
a model prison. The housing facilities for the convicts could 
not be improved upon, the cells are clean, well kept, properly 
ventilated and as fresh in appearance as the day they were 
first occupied. The culinary department was a model of 
cleanliness, and the workshops, where the convicts spend their 25 
time when not confined to their cells, were as healthy as 
circumstances would permit. 
The committee was especially pleased with the hospital, 
which is as well equipped and managed as any modern up-to- 
date hospital in the city. The convicts suffering from tuber- 
culosis are isolated in a special ward, where they are given 
every possible chance to recover their health and strength. 
It was a novel sight to see the convict consumptives sitting in 
their steel cages well wrapped up with all the windows of the 
ward wide open, taking the cure as prescribed by the prison 
physician. Indeed, it is no exaggeration when the committee 
makes the statement that the convict consumptive is better 
cared for than his brother sufferer who has committed no 
wrong against the State. Yet the State makes no attempt 
to care for the latter. 
As stated above, the committee had no means of deter- 
mining the actual number of cases of tuberculosis in the pen- 
itentiary except by a study of the physician's report. Each 
prisoner, upon reception at the institution, is obliged to un- 
dergo a physical examination by the prison physician to de- 
termine the state of his health and the kind of work he is 
best fitted for. These examinations are of the greatest im- 
portance, indicating at the time of admission the existence 
of any communicable disease. They should be made with the 
utmost care, and the most careful records kept of the in- 
mates' physical condition. The committee regret that these 
records at the Maryland Penitentiary are very incomplete, 
and from a medical standpoint valueless. No record is kept, 
as far as the committee could ascertain, of the number of 
new cases of pulmonary tuberculosis admitted each year nor 
of their subsequent career while in the institution, both 
measures of the utmost necessity if a dangerous communi- 
cable disease like tuberculosis is to be stamped out of the 
prison. As stated in the beginning of the report, tuberculo- 
sis cannot develop without the presence of tubercle bacilli, 
and tubercle bacilli cannot be present unless cast off by some 
individual who is admitted suffering with the disease. In the 
annual report of the warden it is stated that sixteen cases 
were treated in the hospital during the past year. Many of 
these were doubtless infected after admission. 40.9% of the 26 
deaths were due to some form of tuberculosis. Three cases 
of miliary tuberculosis (which must have been of recent de- 
velopment) were admitted to the hospital. These reports do 
not compare favorably with some of the records of other 
prison hospitals, notably that of the Stillwater prison of the 
State of Minnesota, where no death has occurred from tuber- 
culosis for two years, or of Clinton prison, New York, where 
the death rate has been reduced from nearly 50% to below 
20% by the efforts of Dr. Ranson, the prison physician. 
From the experience of the committee at the House of 
Correction, where twenty suspicious cases and two positive 
cases were found among the prisoners at large, the committee 
has no doubt that there are quite a number of unrecognized 
cases of pulmonary tuberculosis at present among the con- 
victs of the Penitentiary. As a remedy to such possible ex- 
isting conditions, both at the Penitentiary and the House of 
Correction, the committee urge that a law be enacted making 
it mandatory upon the physicians of all jails and penal insti- 
tutions to examine every person upon reception, with a view 
to detecting every case of tuberculosis, no matter in what 
stage, and to fill out a proper certificate showing the condi- 
tion of each person examined. A copy of this certificate 
should in jail cases be submitted to the court of trial, in order 
to hasten the trial of the tuberculous victim. In case of 
committment to a penal institution, it should accompany the 
regular commitment papers (Ranson). Once identified as 
tuberculous, the prisoner should be either treated in the 
tuberculosis ward of the prison, if the disease be in an acute 
stage, or if it be quiescent, should be assigned to work that will 
permit of as much fresh air as prison life will allow. The case, 
however, should be under constant scrutiny, with a view to 
anticipating any signs of renewed activity of the disease. 
If such a system be adopted, the whole problem of penal 
tuberculosis becomes greatly simplified and the records of 
the Maryland institutions should soon become a source of 
pride to the prison officials, as those of Ranson of New 
York and Merrill of Minnesota must be already. 27 
V. 
APPENDIX. 
LAWS RELATING TO TUBERCULOSIS. 
Acts of 1904, Chapter 399. 
An act to protect citizens of Maryland from certain 
communicable diseases, especially tuberculosis of the lungs 
and larynx. 
Section 1. Be it enacted by the General Assembly of 
Maryland, that from and after the date of the passage of this 
Act, any person affected with any disease whose virus or 
infecting agent is contained in the sputum, saliva or other 
bodily secretion or excretion, who shall dispose of his sputum, 
saliva or other bodily secretion or excretion so as to cause 
offense or danger to any person or persons occupying the 
same room or apartment, house or part of a house, shall, on 
complaint of any person or persons subjected to such offense 
or danger be deemed guilty of a nuisance. And any person 
subjected to such a nuisance may make complaint in person 
or writing to the Commissioner of Health of Baltimore City 
or the local health officer of any city, town or county in the 
State of Maryland where the nuisance complained of arises or 
exists. And it shall be the duty of the Commissioner of 
Health or any local health officer receiving such complaint to 
investigate, and if it appears that the nuisance complained of 
is such as to cause offense or danger to any person occupying 
the same room, apartment, house or part of house, he shall 
serve a notice upon the person so complained of, reciting the 
alleged cause of offense or danger, and requiring him to dis- 
pose of his sputum, saliva or other bodily secretion or excre- 
tion in such a manner as to remove all reasonable cause of 
offense or danger. And any person failing or refusing to 
comply with orders or regulations of the Health Commissioner 
of Baltimore City or of the health officer of any city, town or 
county requiring such nuisance to be abated, shall be deemed 
guilty of a misdemeanor and on conviction thereof shall be 28 
fined ten dollars; provided, that the requirements of this 
section shall apply only to pulmonary and laryngeal tuber- 
culosis, pneumonia, influenza and such other diseases as the 
State Board of Health may from time to time determine to 
be communicable by means of sputum, saliva or other bodily 
secretion or excretion. 
Section 2. It shall be the duty of the physician attend- 
ing any case of pulmonary or laryngeal tuberculosis to pro- 
vide for the safety of all individuals occupying the same 
house or apartment, and if no physician be attending such 
patient this duty shall devolve upon the local health board, 
and all duties made incumbent upon the physician in the fol- 
lowing sections shall be performed by the local board of 
health in all cases of pulmonary or laryngeal tuberculosis not 
attended by a physician or when the physician is unwilling 
or unable to perform the duties specified. 
Section 3. It shall be the duty of the local board of 
health to transmit to the physician reporting any case of pul- 
monary or laryngeal tuberculosis a printed report, after the 
manner and form to be prepared and authorized by the State 
Board of Health, naming such procedures and precautions as 
in the opinion of the State Board of Health are necessary or 
desirable to be taken on the premises of the said tuberculosis 
case, and it shall be the duty of the State Board of Health 
to print and keep on hand a sufficient number of such report 
blanks and to furnish the same in sufficient numbers to any 
local board of health upon due requisition of the latter. Upon 
receipt of the blank report the physician shall fill, sign and 
date the same and return to the local board of health without 
delay ; provided, that if the attending physician is unwilling 
or unable to undertake the procedures and precautions speci- 
fied, he shall so state upon this report and the duties herein 
prescribed shall then devolve upon the local board of health. 
Upon receipt of this report the local board of health shall 
carefully examine the same, and if satisfied that the said 
attending physician shall have taken all necessary and desir- 
able precautions to insure the safety of all persons living in 
the house or apartments occupied by the consumptive, and to 
insure the safety of the people of the State of Maryland, the 
said local board of health shall issue an order on the State 29 
Board of Health in favor of the attending physician for the 
sum of one dollar and fifty cents, to be paid by the 
State Board of Health out of a fund hereinafter provided. If 
the precautions taken by the attending physician are, in the 
opinion of the local board of health, not such as will remove 
all reasonable danger or probability of danger to the persons 
occupying the said house or apartment, the local board of 
health shall return to the attending physician the report blank 
with a letter specifying the additional precautions which they 
shall require him to take ; and the said attending physician 
shall immediately take the additional precautions specified 
and shall record and return the same on the original report 
blank to the local board of health. It shall further be the 
duty of the local board of health to transmit to the physician 
reporting any case of pulmonary or laryngeal tuberculosis a 
printed requisition, which shall be prepared by the State Board 
of Health and issued in sufficient number to any local board 
of health upon due requisition of the latter. Upon this 
requisition blank shall be named the materials kept on hand 
by the local board of health for the prevention of the spread 
of the disease, and it shall be the duty of the State Board of 
Health to purchase such supplies as it may deem necessary 
from the fund hereinafter provided, and to supply them to any 
local board of health upon the requisition of the latter. Any 
physician may return a duly signed requisition to the local 
board of health for such of the specified materials and in such 
amount as he may deem necessary in preventing the spread 
of the disease, and all local boards of health shall honor, as 
far as possible, a requisition signed by the attending physician 
in such case. It shall be the duty of every local board of 
health to transmit to every physician reporting any case of 
pulmonary or laryngeal tuberculosis, or to the person reported 
as suffering from this disease, provided the latter has no 
attending physician, a circular of information prepared and 
printed by the State Board of Health and which shall be furn- 
ished in sufficient quantity to every local board of health on 
due requisition of the latter. This circular of information 
shall inform the consumptive of the best methods of cure of 
his disease and of the precautions necessary to avoid trans- 
mitting the disease to others. 30 
Section 4. Any physician or person practising as a 
physician who shall fail to execute the duties prescribed by 
this act, or who shall knowingly report as affected with pul- 
monary or laryngeal tuberculosis any person who is not so af- 
fected, or who shall wilfully make any false statement concern- 
ing the name, age, color, sex, address or occupation of any per- 
son reported as affected with pulmonary or laryngeal tuber- 
culosis, or who shall certify falsely as to any of the precautions 
taken to prevent the spread of infection, shall be deemed 
guilty of fraud, and on conviction thereof shall be subject to 
a fine of one hundred dollars, or to imprisonment not exceed- 
ing six months, or both fine and imprisonment, in the dis- 
cretion of the court. 
Section 5. The State Board of Health shall prepare 
and keep on hand all the circulars, blanks and printed matter 
required by the preceding section and all additional printed 
matter necessary in executing the provisions of this act, and 
shall issue the same in sufficient quantity to the local boards 
of health upon due requisition of the latter; and the said 
State Board of Health shall further purchase and issue upon 
due requisition to the local boards of health the supplies re- 
quired by the provisions of this act. For the purpose of 
defraying the expenses of printed matter and postage, for 
recompensing physicians for measures of prophylaxis, and for 
purchasing and issuing the supplies necessary in carrying out 
the provisions of this act, the sum of five thousand dollars 
annually or as much thereof as may be necessary is 
hereby appropriated, payable by the Treasurer of the State 
upon warrant of the Comptroller at such times and in such 
sums as may be authorized by the State Board of Health upon 
presentation of the proper voucher. 
Section 6. And be it enacted that this act shall take 
effect from the date of its passage. 
Approved April 8, 1904. 31 
Acts of 1904, Chapter 412. 
Registration and Disinfection. 
An act to add certain new sections to Article 43 of the 
Code of Public General Laws, title "Health", sub-title, 
"Infectious Diseases", to follow Section 34-F and to be known 
as Sections 34-G, 34-H, 34-1, 34-J and 34-K. 
Section I. Be it enacted by the General Assembly of 
Maryland that certain new sections be and the same are 
thereby added to Article 43 of the Code of Public General 
Laws, title "Health", sub-title, "Infectious Diseases", 
to follow Section 34-F and to be known as Sections 34-G, 
34-H, 34-1, 34-J, 34-K and to read as follows : 
Section 34-G. From and after the passage of this act 
the State Board of Health of Maryland shall keep a register of 
all persons in this State who are known to be afflicted with 
tuberculosis. The State Board of Health shall have sole and 
exclusive control of said register, and shall not permit in- 
spection thereof nor disclose any of its personal particulars 
except to officials authorized under the laws of Maryland to 
receive such information. 
Section 34-H. The superintendent or other person in 
charge or control of any hospital, dispensary, school, reform- 
atory or other institution deriving the whole or any part of 
its support from the public funds of the State of Maryland, or 
of any city, town or county in the State of Maryland, having in 
charge or under care or custody any person or persons suffer- 
ing with pulmonary or laryngeal tuberculosis, shall, within 
forty-eight hours after the recognition of such disease, make 
or cause to be made in the manner and form prescribed by the 
State Board of Health, a record of the name, age, sex, color, 
occupation, social condition and residence of the person or per- 
sons so affected, together with such other information as may 
seem necessary or important. And all such records shall be 
delivered, under seal, to the State Board of Health on Monday 
of the week immediately following that in which the records 
were made. Any superintendent or other person charged 
with a duty under this section, who shall fail or refuse to 
comply with the requirements of this section, shall be deemed 
guilty of a misdemeanor, and on conviction thereof shall be 
fined not more than twenty-five dollars. 32 
Section 34-1. Whenever any physician knows that any 
person under his professional care is afflicted with pulmonary 
or laryngeal tuberculosis, he shall transmit to the secretary 
of the State Board of Health, within seven days, and upon 
blanks provided by the State Board of Health for that pur- 
pose, the name, age, sex, color, occupation, social condition 
and residence of such person. And any physician failing or 
refusing to comply with the requirements of this section shall 
be deemed guilty of a misdemeanor and on conviction thereof 
shall be subject to a fine of ten dollars. 
Section 34-J. The apartments occupied by any con- 
sumptive shall be deemed infected, and when vacated by the 
death or removal of said consumptive occupant shall be dis- 
infected by the Board of Health of the city, town or county 
in which such apartments are situated. And it shall be the 
duty of the householder, physician or other person having 
knowledge of the facts, to notify the local Board of Health 
within forty-eight hours after the death or removal of a per- 
son affected with pulmonary or laryngeal tuberculosis. And 
any person failing to comply with the provisions of this sec- 
tion shall be deemed guilty of a misdemeanor, and on convic- 
tion thereof shall be subject to a fine of ten dollars. 
Section 34-K. Any person who lets for hire or causes 
or permits any one to occupy apartments previously occupied 
by a consumptive, before such apartments shall have been 
disinfected by a board of health, shall be guilty of a misde- 
meanor, and upon conviction thereof shall be fined twenty-five 
dollars. 
Section 2. And be it enacted that this act shall take 
effect from the date of its passage. 
Approved April 8th, 190^' An Analysis of Eight Hundred and 
Eight Cases of Chorea, with Special 
Reference to the Cardio-Vas- 
cular Manifestations. 
W. S. THAYER, M.D. 
Professor of Clinical Medicine in Johns Hopkins University. 
BALTIMORE. 
Reprinted from The Journal of the American Medical Association, 
October 27. 1903, vol. xlvii, pp. 1352-1354. 
CHICAGO: 
PRESS OF THE AMERICAN MEDICAL ASSOCIATION, 
ONE HUNDRED AND THREE DEARBORN AVENUE, 
1906. AN ANALYSIS OF EIGHT HUNDRED AND 
EIGHT CASES OF CHOREA, WITH SPECIAL 
REFERENCE TO THE CARDIO-VASCU- 
LAR MANIFESTATIONS.* 
W. S. THAYER, M.D. 
Professor of Clinical Medicine in Johns Hopkins University. 
BALTIMORE. 
Some time ago Dr. Thomas suggested to me that it 
might be of interest to analyze the records of the cases 
of chorea which had been treated in his department in 
the Johns Hopkins Hospital Dispensary with reference 
to the cardio-vascular manifestations. For the most part 
these cases have been rather carefully studied, each 
patient, as far as possible, having been sent to the med- 
ical department for special notes on the heart. Last fall, 
accordingly, I undertook this task, which was particu- 
larly interesting to me in view of the fact that many of 
the special notes had been made by myself. I have 
added to these cases those which have been treated in the 
hospital wards during the same period, the majority of 
which I have also been able to study. 
My plan wras somewhat similar to that which was 
adopted a few years ago in the study of the cardio-vas- 
cular complications and sequels of typhoid fever. It in- 
volved : 1. A study of the records of these cases while 
under treatment. 2. A study of the pathological ob- 
servations in the fatal cases. 3. An investigation into 
the present condition of all old patients with whom it 
was possible to enter into communication. 
The amount of time required to go over so large a 
number of cases made it impossible for me to finish this 
whole undertaking in time for this session. That which 
I present consists of a brief summary of the first part of 
the work, namely, a study of the records of 808 cases of 
* Read in the Section on Practice of Medicine of the American 
Medical Association, at the Fifty-seventh Annual Session, June, 1906. 2 
chorea treated in the Johns Hopkins Hospital and Dis- 
pensary, with special reference to the condition of heart 
and vessels. 
Number of Cases.-The material amounted to 808 
cases, of which 698 were treated in the dispensary and 
110 in the wards of the hospital. 
Race.-Of these cases, 783, or 96.9 per cent., were 
white; 25, or 3 per cent, only, were colored. As the 
proportion of colored patients treated for all diseases in 
the medical department of the hospital and dispensary 
amounts to about 12 per cent., it may be seen that these 
figures go to support the observations of Weir Mitchell 
and others that chorea is relatively rare in the negro. 
Sex.-Two hundred and thirty-tw'o, or 28.7 per cent., 
of these cases were in males; 576, or 71.2 per cent., were 
in females; about the usual proportion. 
Age.-The following table, arranged by hemi-decades, 
will show the incidence of chorea according to age: 
TABLE SHOWING INCIDENCE OF CHOREA ACCORDING TO AGE. 
YEARS. 
Cases. 
Percentage. 
1 to 5 
20 
2.5 
10 to 15 
369 
46.2 
15 to 20 
83 
10.4 
20 
2.5 
Uncertain 
10 
It may thus be seen that 84.5 per cent, of the cases 
were between the age of 5 and 15. 
• Number of Attacks.-The frequency of relapses and 
recurrent attacks of chorea is well recognized. In 799 of 
these 808 cases good records could be obtained as to the 
number of attacks. In 499, or 62.4 per cent., the patient 
was seen in the first attack alone. In 163, or 20.4 per 
cent., there was a history of two attacks. In 137, or 17.1 
per cent., there was a history of three or more attacks. 
Incidence of Rheumatism.-A point of special im- 
portance, particularly with regard to the occurrence of 
cardio-vascular manifestations, is the frequency with 
which rheumatism was observed, or distinctly noted in 
the history. The atypical and mild character of acute 
rheumatism in children is familiar. Considering the 
histories given by the patients or their parents, it was 
deemed wise for our present purposes, to classify 
arbitrarily, as acute rheumatism, all those cases in which 3 
there was a clear, definite history of pain and tenderness 
in joints. The patients and their parents and friends 
were always carefully questioned on this point. Out of 
789 cases in which there was a record as to the previous 
history of the patient, in 171, or 21.6 per cent., a his- 
tory of rheumatism was obtained.1 In 618, or 78.3 per 
cent., there was no history of rheumatism. 
Fever.-Observations on the temperature, important 
though they undoubtedly are, were unfortunately not 
made in many of the dispensary cases. A discussion of 
the temperature records in the hospital cases is reserved 
for the section treating of organic heart lesions. 
Heart.-In 118 cases in the dispensary, and in one 
case in the hospital no note on the heart was recorded. 
Of the remaining 689 cases, cardiac murmurs were de- 
tected in 235, or 40.5 per cent.; they were absent in 
345, or 59.4 per cent. In about one-quarter of the in- 
stances with abnormal heart sounds, the murmurs were 
soft systolic souffles, heard at the base alone, or over the 
whole cardiac area, and unassociated with other modifi- 
cations of the size or functions of the heart, such as 
might justify the diagnosis of organic lesion. 
In 175, or 25.4 per cent., of the cases in which an ex- 
amination of the heart was recorded, conditions justify- 
ing the diagnosis of organic cardiac disease were found. 
In 16 more instances the signs were sufficient to warrant 
a reasonable suspicion that such changes were present. 
Including these, the proportion of cases with possible 
organic change would be raised to 27.7 per cent. 
Character of the Cardiac Lesions.-The cases in which 
the diagnosis of organic cardiac disease was made have 
been divided into three classes, one in which the con- 
dition was certain; another in which the existence of 
organic change was regarded as probable; a third, which 
has been already mentioned, including 16 cases in which 
organic lesions were suspected. Taking into considera- 
tion those cases only in which organic lesions were 
deemed probable, 175 in number, there were: 
Cases of mitral insufficiency Ill 
Cases of mitral stenosis 7 
Cases of mitral stenosis and insufficiency 39 
Cases of mitral and aortic insufficiency 10 
Cases of mitral stenosis and aortic insufficiency 1 
Cases of double mitral disease and aortic insufficiency 1 
Cases of acute endocarditis, probably mitral in character 6 
1. In some of these cases rheumatic symptoms were observed 
while the patient was under treatment. 4 
In 20 instances with definitely recognized organic 
lesions an acute endocarditis was also present. There 
were 3 cases of acute pericarditis. In 2 instances a diag- 
nosis of adherent pericardium was made in a relapse. 
Fatal Cases.-1There were 4 fatal cases of chorea in- 
saniens, and one case in which the patient died during 
an attack of acute rheumatism which had been asso- 
ciated with a choreic attack. Of the 4 cases of chorea 
insaniens there were autopsies in two instances. Inbothof 
these cases the patient had had rheumatism, one in con- 
nection with the fatal attack. In both instances acute 
endocarditis was found; once, mitral; once, aortic and 
mitral. Of the two other cases, in one a well-marked 
endocarditis and pericarditis was recognized intra vitam, 
while in the second, a soft systolic murmur alone was 
audible over the cardiac area; at the same time, however, 
high fever and an extremely rapid, irregular pulse justi- 
fied the diagnosis of an endocarditis. In this case there 
was no history of rheumatism. In the fifth case, in 
which death occurred during an attack of acute rheu- 
matism which had followed chorea, there was subacute 
endocarditis of the mitral and aortic valves as well as 
an acute pericarditis. 
RELATION OF THE CASES WITH CARDIAC INVOLVEMENT 
TO RHEUMATISM, TO RECURRENT ATTACKS AND 
TO FEBRILE MANIFESTATIONS. 
Relation of Rheumatism to Cardiac Involvement.-It 
was deemed of interest to note the relation of those cases 
with cardiac involvement to rheumatic complications. 
The following table shows the proportion of instances in 
which acute rheumatism occurred among the cases, with 
and without cardiac involvement: 
No history 
Rheumatism. of rheumatism. 
Cases. Per cent. Cases. Per cent. 
Without cardiac involvement ... 105 16.9 513 83. 
With cardiac involvement 66 38.5 105 61.4 
TABLE SHOWING INCIDENCE OF RHEUMATISM. 
The relatively higher percentage of a history of acute 
rheumatism in those cases with cardiac involvement 
might, in part, be due to the fact that a large proportion 
of these cases were hospital patients whose histories were 
taken with greater care and accuracy. Looking at the 5 
question from another standpoint (Chart 1), however, 
it was found that: 
Of 171 cases with a history of rheumatism, 34.5 per cent, showed 
organic cardiac lesions. 
Of 618 cases with no history of rheumatism, 16.9 per cent, showed 
organic cardiac lesions. 
It is clear, therefore, that cardiac manifestations were 
more frequent in those patients who had suffered from 
acute polyarthritis. 
Relation of Relapses and Recurrent Attacks to Cardiac 
Involvement.-The following table bears on the question 
of the relative frequency of recurrent attacks in cases 
with and without cardiac lesions: 
TABLE ILLUSTRATING FREQUENCY OF RECURRENT ATTACKS IN CASES 
WITH AND WITHOUT CARDIAC LESIONS. 
Three or 
Single attack. Two attacks, more att'cks. 
Cases. Pr ct. Cases. Pr ct. Cases. Pr ct. 
Without cardiac Involvement.414 65.6 121 19.2 94 14.9 
With cardiac involvement .... 85 50. 42 24.7 43 25.2 
If, again, one divide the total number of cases into 
three groups, those in which there is a record of but one 
attack, those in which there is a record of two attacks, 
and those in which there is a record of three or more 
attacks, and study the percentage of cardiac lesions in 
each group (Chart 2), the following figures are ob- 
tained : 
PERCENTAGE OF CARDIAC LESIONS IN CASES WITH SINGLE AND MUL- 
TIPLE ATTACKS. 
Number 
of cases...., 
Single attack. 
Cases. Fr ct. 
499 
Three or 
Two attacks, more att'cks. 
Cases. Pr ct. Cases. Pr ct. 
163 137 
Cardiac 
lesions . 
85 17. 
42 25.7 43 31.3 
The histories of individual cases, moreover, show 
very clearly in a number of instances, the development 
of cardiac lesions with relapses and recurrent attacks. 
Relation of Fever to the Development of Cardiac Com- 
plications.-The temperature, as has been said, was 
regularly recorded only in hospital cases. In but 1 out 
of 110 instances was there a complete absence of fever 
during the att^bk. In 4 more of these cases It was 
noted that the temperature was normal during the 
greater part of the time, the elevations being slight and 
occasional. In the rest of these cases there were fre- 
quent elevations of the temperature above 99 degrees; 
in the majority, indeed, it remained somewhat above 
normal during the greater part of the acute attack. 6 
Of particular interest is a comparison of the temper- 
ature records of those patients with and without cardiac 
complications. The following table shows the temper- 
ature records in 48 cases without demonstrable cardiac 
involvement as compared with 59 cases in which organic 
lesions were detected: 
TABLE SHOWING PREVALENCE OF FEVER IN CASES WITH AND WITHOUT 
CARDIAC INVOLVEMENT.'. 
Temperature No fever. 99 to 100. 100 to 101. 101 or above. 
Cardiac Involvement. Cases Pr.ct. Cases Pr.ct. Cases Pr.ct. CasesPr.ct 
Absent 1 2 19 39.5 24 50 4 8.3 
Present 0 .. 9 15.2 19 32.2 31 52.5 
If we look now at the question from the standpoint of 
the percentage of cardiac lesions detected among these 
oX Z 3 OR HORE NO Rr-W llX)*-ia' 
Rheum Rheum attack attacks attacks fever 
!6.9/o QN.5/O 17% ZS.7% Sl.3% o% 3Z.I% W./Z 08.8% 
Chart. 1. 
Chart 2. 
Chart 3. 
Chart 1.-Percentage of cardiac lesions in cases with and without 
a history of rheumatism. 
Chart 2.-Percentage of cardiac lesions in relation to number of 
attacks. 
Chart 3.-Percentage of cardiac lesions in relation to the degree 
of fever. 
cases when arranged in groups according to the degree of 
fever present (Chart 3), we obtain the following sug- 
gestive table: 
2. In one of these cases without heart lesion the temperature 
was doubtless due to an abscess, while in two or three of the cases 
with cardiac Involvement the high temperature was due to com- 
plicating rheumatism. 7 
TABLE SHOWING PERCENTAGE OF CARDIAC LESIONS RELATIVELY TO THE 
PRESENCE AND DEGREE OF FEVER. 
Temperature .... No fever. 99 to 100. 100 to 101. 101 or above. 
Cases 1 28 43 35 
Cardiac lesions ....... 9 (32.1%) 19(44.1%) 31 (88.8%) 
From the clinical symptoms and the condition of 
patients returning to the hospital subsequently, there 
is considerable reason to believe that, in a large propor- 
tion of these febrile cases, acute endocardial complica- 
tions were present. In many patients in whom in one 
attack there was fever without evidence sufficient to 
justify a diagnosis of organic cardiac lesion, there was 
found, on later observation, definite valvular disease. 
CONCLUSIONS. 
A consideration of these cases would suggest that well 
marked febrile manifestations, without rheumatism, oc- 
curring during the course of chorea, especially if they 
be associated with undue rapidity or irregularity of the 
pulse, should be regarded as at least strongly suggestive 
evidence of acute endocarditis. It may of course be 
possible that such fever is but the index of an in- 
fection which lies at the bottom of the choreic man- 
ifestations as well as the associated endocarditis. Slight 
grades of fever were, it is true, observed in almost every 
case treated in the wards of the hospital. There is noth- 
ing, however, in these studies to justify conclusions with 
regard to the old question as to whether endocarditis in 
chorea represents a secondary infection or a special 
localization of an infectious agent which is responsible 
for the essential manifestations of the disease. 
The most important and interesting part of this in- 
vestigation remains to be carried out, namely, the study 
of the circulatory conditions in old patients, but it may 
not be amiss to call attention again to certain points of 
interest brought out by this preliminary analysis. 
1. Of 689 cases of chorea observed at the Johns Hop- 
kins Hospital or Dispensary during one or more at- 
tacks, 25.4 per cent, showed evidences of cardiac involve- 
ment; such evidence was present in over 50 per cent, of 
the patients studied in the wards of the hospital. 
2. Cardiac involvement occurred with somewhat 
greater frequency in those cases in which there was a 
history of acute polyarthritis than where such history 
was absent. 
3. Cardiac involvement was commoner in cases of 8 
chorea with frequent recurrences than in those in which 
there was a history of a single attack. 
4. In 110 cases of chorea treated in the wards of the 
hospital there was fever of a moderate extent in almost 
every instance. 
5. In a large majority of the cases in which high 
fever was present there was evidence of cardiac involve- 
ment. 
6. There is good reason to believe that the presence of 
fever in otherwise uncomplicated chorea is, in a large 
proportion of cases, associated with a complicating endo- 
carditis. Since 
Read at the Dinner Given in Honour of 
©ocfor (goBerf fflifctytt 
at Maison Rauscher, Washington 
January 11, 1906 Since 
Read at the Dinner Given in Honour of Doctor Robert Fletcher 
at Maison Rauscher, Washington, January 11, 1906. 
F age means but the sum of leaves 
Time's calendars unfold, 
Our honoured guest must recognize 
That he is rather old. 
If youth means elasticity, 
A ready wit and tongue, 
A mind alert, a spirit gay. 
He's eminently young. 
If age means stores of learning ranged 
On ordered shelves along, 
Still crescent 'neath the nurture of 
A guardian sage and strong, 
All centred in an index which 
Is hidden in the brain, 
Our friend has surely reached an age 
We may not see again. 
If youth betrays itself by vim, 
And broken bones, soon healed, 
A constant tendency to pry 
In every secret field; By always leading in the van 
Of life's long search for truth- 
Why then, despite his years, he's but 
The prototype of youth! 
So here's a glass to four score years, 
To ripe and wise old age, 
To all the gains which gen'rous time 
Scores on his record page; 
And here's a glass to fervid youth, 
To supple limbs and mind 
Wherein hope's rainbow arches o'er 
All doubts that lower behind; 
And here's a health to him in whom 
All these conditions meet, 
Old in all virtues born of days, 
Young where'er youth is sweet. 
Long may he live to taste alike 
Of age and youth the joys; 
Old, yes, in years, but in his heart 
A boy among the boys! 
-WILLIAM SYDNEY THAYER. (Reprinted from The Johns Hopkins Hospital Bulletin, 
Vol. XVII, No. 179, February, 1906.] The Paravertebral Triangle of Dulness in 
Pleural Effusion (Grocco s Sign). 
BY 
W. S. THAYER, M.D., 
PROFESSOR OF CLINICAL MEDICINE, JOHNS HOPKINS UNIVERSITY, BALTIMORE, MARYLAND, 
AND 
MARSHAL FABYAN, M.D., 
ASSISTANT PHYSICIAN, JOHNS HOPKINS HOSPITAL, BALTIMORE, MARYLAND. 
FROM THE 
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 
January, 1907. Extracted from the American Journal of the Medical Sciences, January, 1907. 
THE PARAVERTEBRAL TRIANGLE OF DULNESS IN PLEURAL 
EFFUSION (GROCCO'S SIGN). 
By W. S. Thayer, M.D., 
PROFESSOR OF CLINICAL MEDICINE, JOHNS HOPKINS UNIVERSITY, BALTIMORE, MARYLAND, 
AND 
Marshal Fabyan, M.D., 
ASSISTANT PHYSICIAN, JOHNS HOPKINS HOSPITAL, BALTIMORE, MARYLAND. 
In March, 1902, Grocco,1 of Florence, described, in the following 
words, a new physical sign which he had observed in pleural effu- 
sions: "Paravertebral triangle of the side opposite that of the pleural 
effusion. When, with a pleural effusion of sufficient size, one per- 
cusses from above downward, along the spinous processes of the 
vertebrae, with the patient in the sitting posture, there appears, at 
the level of the fluid, a dulness which, relative at first, becomes 
absolute as one passes downward, in association with a progressively 
increasing sense of resistance. In like manner, by percussing 
downward on the healthy side, along lines parallel to the spinous 
processes, there is noted, opposite the dulness in the median line, 
a paravertebral area of deficient resonance, of triangular shape. 
One side of this drill area is represented by the line of the spinous 
processes; another, by the lower border of the area of thoracic 
resonance for a short distance which varies in length from two to 
three or more centimeters; the outer side is represented by a line 
which, starting from the base, rises obliquely to unite at an acute 
angle with the median line at about the upper limit of dulness. In 
a right-sided effusion, other things being equal, the paravertebral 
triangle has seemed to me more marked. Although symptomatology 
abounds in methods for differential diagnosis between pleural 
effusion and pulmonary infiltration, there can be no doubt that the 
sign which I have mentioned may be of value in some cases, 
especially in right-sided and encapsulated exudates. I shall return 
to this subject later with a detailed description which may illustrate 
that which, if I be not mistaken, is a diagnostic sign of pleural 
effusions hitherto undescribed and worthy of consideration." 
1 Brevi note di semeiotica fisica. Riv. crit. di clin. med., Firenze, 1902, iii, 274-280. 2 
THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
Later in the same year, Grccco2 exhibited two radiegrams, one 
from a' living patient, and one from a cadaver in which the chest had 
been filled with a solution of acetate of lead, demonstrating the fact 
that the shadow extended past the median line to an extent sufficient 
to account for the symptoms observed. Koryani,3 in a study of 
auscultatory percussion published shortly after Grocco's communi- 
cation, noted that dulness in pleural effusions crosses the median 
line, extending over to the healthy side in such a manner as 
to agree essentially with the descriptions of Grocco. Following 
this, various clinical observers have given testimony to the diag- 
nostic value of this sign: Silvestrini,4 Maragliano,5 Flora," Pierac- 
cini,7 Bucco,8 Berghinz,8 Ferranini,10 Baduel and Siciliano,11 Cec- 
chini,12 Raucfuss,13 Kozlovsky,14 Kisel,15 Kernig,18 Gracheff,1' 
Plessi,18 and Ewart.19 Barbieri,20 on the other hand, on the basis 
of two cases in which he was unable to demonstrate the sign, and 
of several experiments on the cadaver in which he was unable, by 
intrapleural injections, to bring about marked displacement of the 
mediastinum, concludes that the sign can have no relation to the 
conditions on the diseased side. Ghelfi21 also considers the sign 
2 Triangolo paravertebrale opposto nella pleurite esbudativa. Lavori di Cong, di med. int. 
(1902), Roma, 1903, 190. 
3 Ein Beitrag zur differentialen Diagnostik pleuritischen Ergiisse. Wien. klin. Rundschau, 
1902, xvi, 300. • 
4 Discussion of Grocco's communication. Lavori di Cong, di med. int. (1902), Roma, 1903, 
190. 
6 Contribute alia semeiotica dei versamentipleurici. Boll. d. soc. Eustach., Camerino, 
1903, i, 18-27; Alcune forme di pleurite. Cron. d. clin. med. di Genova, 1903, ix, 145-149. 
6 Recenti noti semeiologiche sulle pleuriti. Riv. crit. d. clin. med., Firenze, 1902, iii, 407. 
7 Le polmonite massiva o pneumo-bronchite fibrinosa. Clin, mod., Pisa., 1903, ix, 5-8; 
Il suono retrosternale di Banti, ed il triangolo paravertebrale di Grocco. Clin, mod., Pisa, 1903, 
ix, 303-307. 
8 II sintoma di Grocco: il triangolo paravertebrale opposto nella pleurite essudativa. 
Cronica della clin. med. del Prof. De Renzi in Napoli., N. Riv. clin. terap., Napoli, 1903, vi. 
342. 
9 Sul triangolo paravertebrale di Grocco. Riv. crit. di clin. med., Firenze, 1904, v, 530. 
10 II triangolo paravertebrale opposto di Grocco nei versament ipleurici unilateral ilibri. 
Riforma, Palermo-Napoli, 1904, xx, 953-955. 
11 II traingolo paravertebrale di Grocco. Riv. crit. di clin. med., Firenze, 1904, v, 5;21; 37. 
12 Contributo allo studio del sintoma di Grocco. con speciale riguardo alia pleuriti sierosa 
o siero-fibrinosa destra. Riv. crit. di clin.-med., Firenze, 1904, v, 765-770. 
13 On paradoxical phenomena in percussion of the chest. Russky Vrach, S. Peterb., 1904. 
iii, 295-6; Die paravertebrale Diimpfung auf der gesunden Brustseite bei Pleuraergiissen 
Verhandl. d. Versamml. d. Gesellsch. f. Kinderk. Deutsch. Natur u. Aerzte, 1904, Wiesb., 
1905, xvi, 202-211, 1 pl. We have been unable to consult the original of this publication. 
14 Discussion of Rauchfuss' communication. Russky Vrach, 1904, iii, 296. 
15 Ibid. 
» Ibid. 
17 Paravertebral dulness in pleuritic effusions and percussion of the spine. Kazan med. 
J., 1903, v. 39-51. 
18 Sul triangolo paravertebrale opposto di Grocco. Riv. crit. di. clin. med., Firenze, 1905, 
vi, 411-414. 
19 The practical value of Grocco's paravertebral triangle. Lancet, 1905, ii, 216; A rapid 
method for the diagnosis and estimation of pleural effusion. Polyclin., Lond., 1906, x, 13-16. 
20 Sul triangolo paravertebrale: Rendic. d. Ass. med. chir. di Parma, Roma, 1903, iv, 60. 
24 Sul triangolo paravertebrale di Grocco (contributo clinico). Parma, 1904, A. Bartoli, 
16 p. 80. THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
3 
uncertain and of obscure origin; he observed it in six cases only, out 
of thirteen. Rodrigues Alves22 concludes that the sign is of no 
value, as modifications in the percussion sound of any sort in one- 
half of the back may cause a certain amount of change of the same 
character on the healthy side, in a strip along the spine which he 
considers somewhat analogous to the paravertebral triangle. This 
he finds especially true in pneumonia. His plates, however, seem 
to indicate that he has failed to grasp the essential character of this 
sign. Gracheff finds paravertebral dulness on the healthy side a 
constant and valuable diagnostic sign. In some instances, however, 
he finds that the area is not triangular, but of a hemiovoid shape, 
the transverse measurement being greatest toward the upper part. 
He insists, especially, as does Signorelli,23 on the importance of per- 
cussion of the spine. The paravertebral dulness, he thinks, may 
be simulated at times by changes at the base of the lung on the 
opposite side, particularly in pneumonia, but -flatness over the spine 
is distinctive of effusion. 
Rauchfuss, who maintains that he has been familiar with the 
sign for over twenty years, regards it as pathognomonic, although 
he admits that in some massive pneumonias he has noticed a slight, 
though rather indefinite dulness on the opposite side of the spine. 
In the several cases, however, in which such an observation was 
made there was no necropsy to prove the absence of fluid. Kos- 
lovsky, who recognizes the diagnostic value of the paravertebral 
triangle, has also seen a slight indefinite dulness on the side oppo- 
site a pneumonia. Rauchfuss observes that the hypothenuse of 
the triangle has sometimes a slight outward convexity. 
Pieraccini, in a case of pneumothorax with a very small amount 
of fluid, noticed a clearer tympanitic note on the healthy side in 
an area analogous to that of the paravertebral triangle of dulness 
in pleural effusions. 
Cecchini noted that, with small effusions, the area of dulness 
varied greatly according to whether the patient lay on the side 
affected, when the triangle almost disappeared, or sat up, when it 
became more marked. With large effusions, the variations with 
changes of position were slight. Plessi studied the auscultatory 
signs in the paravertebral triangle and observed that there is usually 
a marked diminution in the intensity of the respiratory murmur, 
becoming more evident as one approaches the spine. In one case 
he found that the characteristic tubular respiration heard over the 
effusion passed the spine, extending about to the external border of 
the area, so that it was possible to make out the triangle by auscul- 
tation. He also asserts that the coin sound, transmitted character- 
22 Do triangolo de Grocco, seu valor, semeiologico e sua semeiogenesis. Rio. de Jan., 1905,. 
R. Braga. 79 p., 16 pl., 40. 
2i Di un nuovo metodo d' indagine diagnostica; la percussione della colonna vertebral*. 
Policlin., Roma, 1902-3, ix, sez. prat., 1345-1348. 4 
THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
istically through a pleural effusion as a clear, metallic ring, is also 
heard in the same manner throughout the triangular area, as well 
as bronchophony and egophony. Finally, he observed that toward 
the outer part of the triangle, crepitant or fine moist rales were 
often heard, evidence, probably, of compressed lung. 
With regard to the cause of the phenomenon, the studies of 
Baduel and Siciliano are especially important. Endeavoring to 
reproduce, experimentally, the conditions existing during life, they 
filled the abdominal cavity with gelatin in such a manner as to 
support the diaphragm in its normal position. They then injected 
the vessels through the carotid. After this, fluid was introduced 
slowly into the pleural cavity while the subject was in a sitting 
Fig. 1.-Transverse section at the level of the nipples. (From Braune's Atlas 
of Topographical Anatomy.) 
posture. By this procedure a characteristic paravertebral triangle 
was produced. On opening the chest on the opposite side they 
were able to confirm the existence of increased pressure, as the lung 
tended to protrude from the wound as a hernia, while the finger 
could readily detect the displacement of the contents of the medias- 
tinum-aorta, azygos vein, oesophagus, heart. In other cases, 
injecting the pleural cavity with gelatin and filling the gastro- 
intestinal tract with 10 per cent, formalin, they removed the extrem- 
ities and the skin, and, after making numerous incisions to allow the 
entrance of the fluid into the tissues, immersed the trunk in a 10 per 
cent, formalin bath. After a sufficient number of days, transverse 
sections were made which illustrated with great clearness the extent 
to which the pleural accumulation itself extends about and over THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
5 
the bodies of the vertebrte, pushing before it the contents of the 
mediastinum. The accompanying Figs. 1, 2, and 3 illustrate 
clearly the changes in relations following intrapleural injections of 
gelatin. Fig. 1 is taken from Braune's Atlas, while Figs. 2 and 3 
Fig. 2.-Transverse section at the same level as in Fig. 1 in a case of artificially pro- 
duced right pleural effusion, showing the displacement of the mediastinum and the exten- 
sion of the pleural contents over the spine. (From Baduel and Siciliano.) 
Descending aorta. 
(Esophagus. 
Azygos vein. 
Descending aorta. 
Azygos vein. 
(Esophagus. 
Fig. 3.-Section at the same level as in Figs. 1 and 2 in a case of artificially produced 
left-sided effusion. (From Baduel and Siciliano.) 6 
THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
are from the article of Baduel and Siciliano. All sections were 
made at the level of the nipple. 
Comparing the clinical data with the conditions as illustrated by 
these experiments Baduel and Siciliano come to the following conclu- 
sions as to the cause of the sign: Percussion of the vertebral column 
normally gives a clear note because of the contiguity of the pul- 
monary parenchyma. This note becomes flat at the lower limit of 
the lungs. In pleural effusion, however, the fluid not only takes 
the place of one lung, but it extends also anteriorly over the 
body of the vertebra*, thus inhibiting its capacity for sonorous vibra- 
tion-that is, it acts as a mute. This dulness extends naturally 
to a certain extent to the paravertebral region (transverse processes, 
ribs), especially in the lower part of the chest, where the fluid collects 
in greater quantity and exercises its action more markedly. In 
addition to this, Baduel and Siciliano believe that, especially on the 
left, that is the right-sided effusions, the displacement of the con- 
tents of the mediastinum-aorta, oesophagus, azygos vein, and heart- 
plays a certain part, especially in bringing about a compression of 
the lung. 
Ewart has recently added his testimony to that of the other 
clinicians already mentioned, as to the importance of this sign. He 
lays especial stress on the diagnostic value of the variability in the 
size of the paravertebral triangle with change of position, that is, 
its diminution or disappearance when the patient lies on the affected 
side. 
Since his first acquaintance with the descriptions of this sign- 
some two or three years ago-one of us (Thayer) has determined 
its presence in most cases of pleural effusion which have come to 
his notice. As time has gone by he has been more and more im- 
pressed with the constancy of the sign, the ease with which it may 
be demonstrated, and its real diagnostic importance. Accordingly, 
last winter, it occurred to us that it might be of interest to gather 
together a series of cases of pleural effusion which we had examined 
with regard to the presence or absence of the paravertebral area of 
dulness. We fancied, at the outset, that on looking over the his- 
tories of the last two years we should find four or five cases in 
which there were satisfactory records of this phenomenon. Only 
one such case, however, was found. This instance and thirty-one 
others which we have observed during the past year, form the basis 
of the present communication. 
Method of Procedure. Although percussion of the paraver- 
tebral triangle is a simple matter, it requires care and deliberation, 
as do all methods of precision. After percussing out the limits of 
the supposed effusion one should mark out the lower limit of pul- 
monary resonance on the opposite side and then percuss downward 
directly over the spine, marking the point at which dulness (relative) 
begins. It will be found usually that this point corresponds fairly THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
7 
closely with the beginning of relative dulness on the side of the 
effusion; that at all events it is a little higher than the beginning of 
flatness. One should then percuss downward along lines parallel 
to the spine and inward toward the spine along lines parallel to 
the lower limit of pulmonary resonance. In this manner it is usually 
easy to mark out, at the inferior and mesial angle of the healthy 
side of the back, a triangle of dulness. The vertical side of this right- 
angled triangle, represented by the line of the spinous processes, 
reaches to a point somewhat higher than the upper limit of flatness 
on the affected side. The base, represented by the mesial part of the 
line marking the lower limit of the lung on the unaffected side, varies, 
Fig. 4.-Aortic insufficiency; hydrothorax on the right side; paravertebral triangle 
of dulness on the left. 
according to the size of the effusion, from 2 cm. to as much as 
7 cm. in extent. The third side of this dull area is represented by 
a line joining the extremities of these two lines. It has sometimes 
seemed to us, as has been noted by Rauchfuss, that this line showed 
a slight outward convexity. 
Summary of Observations. Of the thirty-two cases with which 
this report is concerned, twenty-four were instances of pleurisy with 
effusion. One of these was carcinomatous, and one was associated 
with a post-pneumonic infarction of the lung. Five were instances 
of hydrothorax in association with cardiac disease. Three were 
empyemas; one, post-pneumonic; one, typhoid; one, an interlobular, 8 
THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
encapsulated empyema following puerperal infection. In all but one 
of these instances fluid was demonstrated by puncture or operation. 
In this case, an instance of infarction following pneumonia, there 
were signs suggestive of pleural effusion with a well-marked para- 
vertebral triangle of dulness which disappeared later with improve- 
ment in the signs. No exploratory puncture was made. In the 
remaining thirty-one cases a distinct paravertebral triangle of dul- 
ness was demonstrated in twenty-nine. 
Sex. Of these 29 cases, 19 were men; 10 were women. 
The age varied from ten to sixty-seven years. 
Side Affected. The effusion was on the right side in fifteen 
cases; on the left in thirteen, and on both sides, alternately, in one. 
The size of the triangle varied with the extent of the fluid, the 
apex, when percussion was carefully carried out, reaching a point 
a little above the limit of flatness on the other side. The base line 
of the triangle ranged all the way from 3 to 7 cm. in length. The 
average size was slightly larger in right-sided than in left-sided 
effusions. In one case (No. 49553) a small, though distinct, 
triangle was made cut in connection with a left-sided effusion, 
which on aspiration yielded only 250 c.c. of sero-fibrinous 
fluid. The upper limits of flatness of the effusion reached, in the 
back, to a point one finger's breadth below the angle of the 
scapula. 
Variation in the Size of the Triangle with Change of Position. 
This important test was made in but four recent cases (Nos. 55951, 
56297, 56479, a case in private practice). In each instance it was 
found that when the patient lay on the affected side the triangle 
nearly or entirely disappeared. In view of the fact that in the one 
case in which a suggestive paracertebral triangle of dulness was 
demonstrated in a pneumonia, change of position had little or no 
effect on the limits of the area of dulness, we are inclined to agree 
with Ewart in regarding this as one of the most important features 
of the sign. 
No definite observations were made with regard to variations 
in the vocal fremitus over the paravertebral triangle. The area is. 
indeed, so small and the subjacent muscle so thick that it is question- 
able whether variations in the fremitus could be easily brought out. 
The character, however, of the voice sounds and respiration in 
Grocco's triangle are interesting. In 8 cases (Nos. 53903, 54097, 
55278, 55218, 54731, 56297, 56762, a case in private practice) it 
was noted that the respiration and voice sounds were diminished 
in intensity over the area of dulness as compared with the adjacent 
parts. In fix e of these cases the respiration was of the same dis- 
tant, tubular quality as that noted over the effusion, and in several 
instances the characteristic nasal character of the voice sounds was 
transmitted across into the area of triangular dulness. In the three 
cases in which it was tried, the coin sound heard over the triangle THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
9 
had the same clear, metallic ring as over the effusion. This metallic 
tinkling quality disappeared instantly when one passed out of the 
triangular area of dulness. In two instances in which a note was 
made as to the character of the respiration in the triangle, no change 
could be made out. In the remaining cases, no satisfactory note 
was made upon the auscultatory signs. 
Cases of Pleural Effusion without the Paravertebral 
Triangle. In two instances of pleural effusion, the paraver- 
tebral triangle was not observed. In the first one of these cases 
an instance of interlobar empyema, its absence, which was easily 
explainable, was of a certain diagnostic help. This case (53985- 
19392) was that of a woman, aged thirty-six years, who was 
admitted on March 3, 1906, complaining of pain in the left back 
which had come on during the puerperium, three weeks before. 
There was irregular fever and a marked leukocytosis. Everything 
pointed to some local suppuration. The local physical signs, dulness 
and suppressed respiration in the left back, were rather indefinite. 
On March 9 it was noted (Thayer) that flatness began in the 
left front at the seventh interspace in the anterior axillary line. 
There was deficient movement of the left chest; dulness throughout 
the back, amounting almost to flatness below the level of the angle 
of the scapula. In the dull area the vocal fremitus was almost, if 
not entirely, absent. On forced breathing there was a distant 
tubular quality. The voice sounds were distant and not nasal, 
except in a small area near the spine, where they sounded as if 
coming through an effusion. The cardiac apex impulse was not felt, 
but the heart sounds were heard best at a point 6.5 cm. to the left of 
the median line in the fifth space. Cardiac dulness (relative) 
extended 4 cm. to the right of the median line. Irregular fever and 
sweating continued. On March 26 a needle was introduced in 
several places in the back without result. On the same day it was 
noted that there was dull tympany at the left apex-a distinct Skodaic 
note; flatness at the eighth rib in the midaxillary line; deficient 
movement of the left back; percussion note, dull and high pitched, 
a little tympanitic as one passed down; not perfectly flat until one 
passed below the angle of the scapula. Vocal fremitus was felt 
through the back. No paravertebral triangle of dulness at the right 
base. The respiration in the upper part of the left chest in front 
was feeble but clear; a few fine rales on cough, increasing in number 
as one passed downward. Posteriorly, the respiration was en- 
feebled, of a somewhat tubular modification. Medium and fine 
moist rales below the spine of the scapular. Below the line of 
flatness respiration was much enfeebled, as were also the voice 
sounds; the same medium moist rales were heard following cough. 
On April 9 it was noted that the left back was nearly flat; the 
dullest area lay between the posterior axillary line and a line be- 
tween the scapular line and the spine. While vocal fremitus was 10 
THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
felt along the spine and just inside of it, it was not so well felt a 
little farther out. The respiration was much enfeebled, distant, 
and tubular. The voice sounds were feeble over the duller area. 
There was no paravertebral triangle of dulness on the right. The 
history and physical signs, in connection with the absence of a 
paravertebral triangle of dulness, and the failure to find fluid on 
puncture, led to the diagnosis of either pulmonary abscess or 
interlobular empyema. On April 16 a needle introduced to a 
depth of 6 cm., just above the level of the angle of the scapula, 
revealed purulent fluid. Operation showed an interlobular empyema. 
The absence of a paravertebral triangle in this case is therefore easily 
explained; the fluid did not reach the spine. 
The second case (No. 53475-19241) was that of a colored woman, 
aged thirty-one years, admitted to the hospital on January 16, 
1906, complaining of abdominal pain and swelling, chills, fever, and 
sweating. The case was one of tuberculous polyorrhomenitis. 
On January 18, 150 c.c. of hemorrhagic, somewhat cloudy fluid 
was removed from the right pleural cavity. On the following day 
flatness began at the fourth interspace in the right front, shifting 
with change of position, over two fingers' breadth. The limits of 
the dulness in the back were not noted. No paravertebral triangle 
of dulness was demonstrable although it was noted that there might 
"be a slight dulness in an area scarcely larger than 3 cm. square." 
Evidence of fluid gradually disappeared, although dulness with 
rather enfeebled respiration persisted at the right base, probably 
dependent upon pleural thickening. Examination in this case 
was made hastily and without great care. Percussion was carried 
out only to the left of the spine-not over the spine. It is probable 
that a more careful note would have revealed a more definite para- 
vertebral triangle in the area referred to. The amount of fluid, 
moreover, was evidently small. No aspiration was, indeed, made 
after this second note, to prove positively the presence of fluid, 
although the movable dulness would appear to settle the question. 
In a third instance the paravertebral triangle, which was demon- 
strated later, was not found before the first tapping. A. T. G. 
(No. 54210-19472), a colored waiter, aged twenty-six years, was 
admitted to the hospital March 21, 1906. There was a well-marked 
tuberculous pneumonia of the left chest, which, on percussion, was 
dull above and flat below. The respiration was tubular throughout, 
but feebler over the lower part of the chest. The vocal fremitus 
was not wholly absent at the base. No paravertebral triangle was to 
be made out. The heart was distinctly drawn toward the right, 
relative dulness extending 5.7 cm. to the right of the median line. 
On the following day, 800 c.c. of clear, straw-colored fluid was 
removed from the left chest by aspiration. 
On April 12 it was noted that there was marked dulness through- 
out the left back, which was almost flat below the angle of the THAYER, FARYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
11 
scapula; in this area the vocal fremitus was suppressed, the respira- 
tory sounds distant, and the voice sounds nasal. There was a 
well-marked paravertebral triangle on the right, the base measuring 
4 cm. 
This is the only instance among our cases examined in which the 
paravertebral triangle of dulness was not demonstrated in the 
presence of a well-marked effusion. Its absence in connection 
with its subsequent appearance, we are unable to explain. Kemig, 
who found the sign constantly in a considerable number of cases, 
had one experience exactly similar to this. 
Two Cases in Which a Paravertebral Triangle of Dulness was 
Detected in the Absence of a Demonstrable Effusion. In a number 
of cases of pneumonia and thickened pleura we have failed to detect 
a paravertebral triangle. Twice, however, the sign was observed in 
cases in which puncture of the chest failed to reveal fluid. 
In the first instance (No. 54731-19642), in which, on entrance, there 
was a well-marked left-sided effusion with an associated paraver- 
tebral triangle of dulness on the opposite side, the base measuring 
6 cm., aspiration of 1600 c.c. was followed on the succeeding day 
by an apparent reaccumulation. Two days later there was flatness 
to the angle of the scapula of the left side with a distinct paraver- 
tebral triangle measuring 9 x 6| cm. Flatness in front began at the 
fifth rib in the recumbent posture, rising one interspace in the 
erect position. The breath sounds were clear in the upper front, 
feeble below; slight pleural rub in the third and fourth interspaces; 
voice sounds distant in the dull area. The left back was tympanitic 
above, flat at the angle of the scapula. The voice sounds were 
distant in the dull area, and the breathing feeble as one passed from 
above downward. There were a few crackles at the line of flatness. 
There was no egophony. Slight vocal fremitus was felt to the left 
base. The needle was introduced in two places, in the eighth 
interspace below the angle of the scapula, and in the ninth space. 
What was believed to be the lung was clearly felt, but no fluid was 
obtained. Two days later the signs were the same. Three days 
after this the patient insisted upon leaving the hospital. In view 
of the absence of fluid on puncture it is difficult to explain the 
persistence of the paravertebral triangle, unless one assumes that 
an existing accumulation was missed in the attempts at puncture- 
that which the sum total of the physical signs, especially the mov- 
able dulness in front, would seem to indicate. It may be that the 
needle was clogged each time with fibrin. 
The second case was one in which the history and physical signs 
suggested pneumonia. The voice sounds in the affected area in the 
left back were, however, somewhat nasal and the respiration rather 
feeble. Percussion of the opposite side revealed a long but not very 
wide paravertebral triangle. The dulness was hardly as definite and 
marked as in our other cases. The apex, moreover, did not reach 12 
THAYER, FABIAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
to the upper limit cf the physical signs. On change of position there 
was little or no change in the paravertebral area of dulness. Explor- 
atory puncture at two different points in the dull area in the left 
back was without result. 
A small strip of dulness on the side opposite a massive pneumonia 
has been described by several observers. It is possible that the 
triangular shape may, in this instance, have been due to an accumu- 
lati >n of fibrin in the pleural sinus. The fact that there was no 
change in the limits of the dulness on change of position is worthy 
of note. 
Notable 'Cases. Several cases seem to us to be deserving of special 
mention. There were three instances of encapsulated pleurisy, in 
Fig. 5.-Paravertebral triangle in a case of encapsulated effusion. (Case 54097.) 
two of which the paravertebral triangle was of real importance from 
a diagnostic standpoint. 
The first one of these cases (No. 54097-19429) was that of a 
man, aged twenty-six years, who was admitted with pericar- 
ditis, with effusion following acute rheumatism. This was followed 
by pleuritic exudates, first on one side and then on the other. On 
February 21 it was noted that there was a well-marked area 
of flatness at the left base, especially in the lower interscapular 
region. Anteriorly to the scapular line, dulness was not marked. 
Over this area the vocal fremitus was diminished, almost absent; 
breath sounds distant, slightly metallic, and tubular; voice sounds 
nasal. The area of flatness as marked out during the visit may 13 
THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
be seen upon the accompanying chart (Fig. 5). On the opposite 
side there was a well-marked paravertebral triangle of dulness, the 
upper limit, 8.5 cm. from the base of the right lung, corresponding 
exactly to the area of flatness on the right; the base, 5 cm. in extent. 
In the triangular area at the base of the right lung the voice sounds 
were nasal and the breathing tubular and feeble, of the same 
character as the sounds over the flat area in the left back. By 
aspiration, 400 c.c. of yellow fluid, with numerous leukocytes, was 
obtained from the flat area on the left. Eleven days later, the 
resonance had cleared up on the left side, the flatness on the right 
side reached the tenth rib, while on the left a triangular area of 
dulness, 6 x 44 cm., was to be made out. In a word, following the 
disappearance of the accumulation on the left side, there appeared 
a right-sided effusion with the development of a paravertebral 
triangle on the opposite side. Thus, in a single case, the paraver- 
tebral triangle of dulness appeared successively on opposite sides of 
the chest. 
The second case (No. 54292) was that of a woman, aged forty- 
three years, admitted with acute lobar pneumonia. Before the 
resolution of the pneumonia, the temperature rose again, and on 
April 9 it was noted that there was dulness throughout the left back; 
the breath sounds were distant and feeble, tubular in the region of the 
left upper lobe and in the interscapular region. The voice sounds 
over the back were distinctly nasal. There was no absolute flatness 
in the left side of the chest. Just below and outside the angle of 
the scapula the voice sounds were almost egophonic. On the right 
side of the chest a paravertebral triangle of dulness, measuring at its 
base about 3 cm., was clearly made out. A needle, introduced in 
the lower part of the back, revealed pus, which was evacuated by 
the surgeon on the same day. Here an unresolved pneumonia com- 
plicated the picture and the presence of a paravertebral triangle of 
dulness of the opposite side was an important element in leading us 
to the diagnosis of effusion. 
The third case (No. 54593) was that of a man, aged twenty- 
three years, admitted on April 22 with a severe typhoid fever. 
On May 10, with the patient lying on his left side, there was flatness 
below the angle of the right scapula with tympany above. The 
flatness ended sharply at the posterior axillary line. Over the 
flat area the vocal fremitus was diminished; respiration distant 
and tubular. There was a somewhat metallic quality to the respira- 
tory murmur and the voice sounds were nasal. On the left there 
was a paravertebral triangle of dulness measuring 8 x 5| cm. A 
needle introduced into the dull area on the right brought cloudy, 
purulent fluid. Operation revealed an encapsulated empyema. 
In this case the demonstration of the paravertebral triangle 
was of material assistance in the diagnosis of an encapsulated 
empyema. 14 
THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
Conclusions. 1. In thirty-two cases of pleural effusion a para- 
vertebral triangle of dulness at the base of the opposite chest 
(Grocco's sign) was clearly demonstrated in thirty. In one of 
the remaining cases, an instance with a small effusion in which 
the examination was rather hastily and imperfectly made, but a 
small, indefinite area of dulness was noted. In the other case 
the absence of the paravertebral triangle was easily explained by 
the position of the exudate-an interlobar empyema. In a third 
instance, in which a triangle was demonstrated later, it was missed 
on the first examination. The sign, therefore, may be regarded as 
practically constant in cases in which there is free fluid in the pleural 
cavity, or in which an encapsulated effusion impinges on the spine. 
2. This triangle is an area of relative dulness, the vertical side of 
which is represented by the line of the apophyses of the vertebrae, 
the apex reaching a point somewhat above the level of flatness of the 
effusion; the base is formed by the lower limit of pulmonary resonance 
on the healthy side for a distance of from 2 to 7 cm. from the spine; 
the hypothenuse, by a line connecting these points. This last line 
shows, sometimes, a slight outward convexity. The dulness is 
more marked as one approaches the spine. 
3. In the triangular area of dulness the respiratory murmur is often 
suppressed and of a quality similar to that heard over the effusion. 
Egophany or a nasal quality of the voice sounds may also be present. 
The coin sound, when the manoeuvre is carried out by placing the 
coin on the front of the chest below the level of the effusion, shows 
the same metallic ring as that which is observed over the affected 
side. These signs may be so marked as to make it possible to 
outline the area of the triangle by auscultation. 
4. When the patient lies on the affected side the triangle of dulness 
diminishes or disappears, and returns again when the erect posture 
is assumed, or when the patient lies on the other side. 
5. The triangle is usually larger on the left side-that is, in the 
case of right-sided effusions-than on the right. 
6. In three cases of encapsulated effusion the presence of a para- 
vertebral triangle of dulness on the opposite side proved of real 
diagnostic assistance. 
7. Our experience justifies the conclusion that the paravertebral 
triangle of dulness is a remarkably constant and characteristic sign 
of fluid in the pleural cavity. It further supports the assertion of 
the discoverer that it may be of particular value in the case of encap- 
sulated effusions. We regard the sign as an important addition to 
our means of diagnosis of effusions in the pleural cavity. 
8. As to its cause, we are inclined to accept the explanation 
offered by Baduel and Siciliano, namely, that the fluid, lying against 
and passing anteriorly over the bodies of the vertebrae, acts as a 
mute in suppressing the sonorous vibrations of the spine. This 
deadening of the resonance is naturally appreciable for a certain THAYER, FABYAN: PARAVERTEBRAL TRIANGLE OF DULNESS 
15 
distance beyond the median line over the area occupied by the trans- 
verse processes and the first part of the ribs. It is more marked 
and extends over a wider area at the base, where the fluid, collecting- 
in the sinus of the pleura, comes into wider contact with the vertebrae 
and pushes farther around toward the opposite side. The displace- 
ment of the contents of the mediastinum-aorta, oesophagus, azygos 
vein, heart-may play a part, especially in effusion on the right side 
of the chest, in producing this dulness as well as in bringing about a 
certain degree of compression of the lung on the opposite side. 
9. Although there may be a small strip of dulness along the spine on 
the side opposite a pneumonia, we have but once detected anything 
approaching a paravertebral triangle. In this instance the dulness 
was not very definite and showed little or no change on change of 
position. CALCIFICATION OF THE BREAST FOLLOWING A 
TYPHOID ABSCESS 
by 
W. S. THAYER, M.D., AND H. H. HAZEN, M.D. 
(From the Rockefeller Institute for Medical Research, New York.) 
From 
THE JOURNAL OF EXPERIMENTAL MEDICINE, 
Vol. IX, No. i, January, 1907. CALCIFICATION OF THE BREAST FOLLOWING A 
TYPHOID ABSCESS.1 
By W. S. THAYER, M.D., 
Professor of Clinical Medicine in Johns Hopkins University, 
AND 
H. H. HAZEN, M.D. 
Plate I. 
The general interest, both pathological and clinical, in the proc- 
esses of calcification in the animal oeconomy, as well as the increas- 
ing frequency of the therapeutical use of various salts of calcium, 
justify a consideration of the following remarkable case. 
D. I., a colored house maid, aged 16, was admitted to the Johns Hopkins 
Hospital on October 2, 1905, on the ninth day of a severe typhoid fever. 
Her family and personal history were unimportant. Eight days before entry 
she began to complain of headache and had a chill. On the succeeding day 
there was abdominal discomfort and occasional " pains in the bones." She felt 
too ill to work and took some medicine which was followed by diarrhoea-from 
two to four fluid movements a day-which continued up to the date of entry. 
There was complete anorexia, and, on several occasions, nausea and vomiting. 
On admission the patient was dull and apathetic. The tongue was heavily 
coated; the pulse, 132; temperature, 101.80. There were a few coarse rales at the 
left base. The abdomen was moderately distended and tympanitic. The 
spleen was not palpable, although the dulness appeared to be increased. Ex- 
amination of the blood showed: Red blood corpuscles, 3,924,000; colorless cor- 
puscles, 6000; haemoglobin, 77 per cent. The urine showed a trace of albumin 
and a positive Diazo reaction. The blood pressure (Riva-Rocci, broad band) 
was 105. Treatment: milk and albumen water, 120 c.c. alternating every two 
hours; tub baths, at 85° F., every three hours if the temperature be above 102.50. 
On the following day the Widal reaction was positive. The patient soon be- 
came very ill. There was considerable tympanities at first which was relieved 
by turpentine stoops. On October 8 the pulse was slightly irregular; blood 
pressure (Riva-Rocci, broad band) between 80 and 90. The temperature of the 
baths was reduced to 750, and strychnine 0.001 (grs. 1/60) was ordered every 
four hours, as well as whiskey 15 c.c. (3ss) p. r. n. The leucocytes varied from 
4000 to 7000 to the cubic millimetre. 
On October 9, the sixteenth day of the disease, there was a semi-fluid stool 
with a trace of blood. 
1 Read before the American Association of Pathologists and Bacteriologists, 
at Baltimore, 19 May, 1906. 
1 2 
Calcification of Breast Following Typhoid Abscess. 
On October 12, the nineteenth day, about 340 c.c. of blood were passed in 
three stools. The temperature fell from 102.70 in the morning to 99-4° at noon. 
The pulse rose to 164, the pressure falling at one time to 81.5. At 11 P. M. an 
infusion of 500 c.c. of 1 per cent, solution of calcium chloride was given under 
the -left breast. The haemoglobin dropped to 50 per cent, in the evening. The 
coagulation time was five minutes. An ice bag was placed upon the abdomen; the 
baths were omitted, and lactate of calcium 2.0 (gr. XXX) every four hours was 
prescribed. 
On the following day, the coagulation time was eleven minutes. Ice sponges 
were begun again. On October 15, the twenty-second day of the disease, 150 c.c. 
of blood appeared again in several stools but without any essential change in 
the condition of the patient. The coagulation time was four minutes on the day 
preceding the haemorrhage, and eight and a half minutes on the day following. 
On October 18, the twenty-fourth day, there was again blood in the stools, for 
the most part in the shape of old clots, amounting to from 200-800 c.c. by meas- 
ure. On the 19th, the red blood corpuscles had fallen to 2,200,000; the colorless 
corpuscles to 3100. From this time on, there was a steady, gradual improvement. 
On October 23, the thirty-fifth day of the disease, the lactate of calcium was 
omitted. On the same day, a large abscess was discovered involving the lower 
half of the left breast, and dissecting around in the interspace just below this 
as far as the mid-axillary line. There was definite fluctuation just beneath the 
skin, and harder masses, 1 to 2 cm. in length, could be felt floating free in the 
pus. The breast was little deformed, the dissection occuring chiefly in the 
areolar tissue. The point of insertion of the needle with which the infusion of 
calcium chloride was made fifteen days previously, was not affected, but the ab- 
scess was just above this spot, and evidently involved a part of the area in 
which the infusion was made. The abscess was on the point of rupture and, 
indeed, did rupture before the operation. Under cocaine, several long incisions 
were made, two over the abscess proper and one in its extension in the mid- 
axillary line. A quantity of thin brown pus containing several large sloughs 
was evacuated. The wound was packed with gauze for drainage. 
On October 31, three days later, the wound was irrigated with boric acid and 
dressed. There was still some sloughing of the actual breast tissues and a 
prolongation of the abscess up, over and under the mammary gland. On the 
whole the wound looked fairly clean; it was packed with iodoform gauze. Cul- 
tures taken at the time of the opening of the abscess showed Staphylococcus 
aureus and Bacillus typhosus. 
On November 8, eight days later, an examination of the wound, which had 
been left open with an iodoform dressing, revealed a cartilaginoid induration 
about the upper part of the opening. There had been an extension around 
toward the back from the lower part of the drainage incision. On the whole, 
the wound was clean and of good color. The patient steadily improved, the 
temperature reaching the normal point on the tenth of November. A light gen- 
eral diet had been allowed for the preceding week. 
On November 16, it was noted that the denuded tissue in the wound was 
slowly changing into a necrotic and almost stony mass. Along the outer side of 
the breast there was a chain of glands, somewhat swollen and extremely hard. 
Neither glands nor wound were painful. The suppuration had not extended 
further toward the back, and the edge of the wound was closing in. Fig. i.-Temperature Chart. 4 
Calcification of Breast Following Typhoid Abscess. 
On November 20, the following note was made (W. S. T.) : "About the 
opening of the wound there is a perfectly distinct rim of stony hardness. The 
stony rim of the crater-like opening extends back on the median side about 2 cm. 
from the edge; on the outer side it is less extensive. The granulations pro- 
truding from the outer part of the wound are rather pale, and in them are to 
be seen whitish streaks and patches that look altogether like the guanin de- 
posits in old ham. These areas feel hard and stony. Passing into the cavity 
of the wound, the under surface of the protruding granulations corresponds ex- 
actly in consistency to that of the outer rim of the crater, the forceps striking 
similar calcareous areas. In the outer part of the breast, above the opening, 
and extending along the second interspace are a number of other hard, nodular 
masses. The largest of these, which is situated a little anteriorly to the mid- 
axilla, in the third interspace, is as large as a good-sized hickory nut. Above 
and to the mesial side of this, the nodules are smaller. A number of smaller, 
indurated areas are to be felt throughout the left breast." 
Bits of the white, gritty deposit were removed from the edges of the wound 
by forceps. These masses were separated easily and with but little bleeding. On 
burning they emitted a brilliant white light. They dissolved in hydrochloric 
acid without effervescence. By quantitative analysis1 it was determined that 
the calcium, estimated as CaO, comprised 20 per cent, of the dry mass. Curettings 
of the tissue were examined for tubercle bacilli without result. A guinea-pig, 
inoculated with scrapings from the edge of the wound, and killed several months 
later, was free from tuberculosis. Bits of tissue from the wall of the abscess 
were sent to Dr. Bloodgood on November 14, the following note being made: 
" The specimens consist of bits of substance that are very firm and seen to be 
composed of fibrous tissue with a number of small areas of calcification. The 
section shows granulation tissue on a pretty fibrous basis. In the granulation 
tissue there are a good many polynuclear leucocytes; lymphoid cells predominate. 
There are some epithelioid cells. No giant cells or tubercles. Areas of calcifi- 
cation are seen." Further examination showed occasional characteristic giant 
cells. 
The tissue was also examined by Dr. Bunting who made the following note: 
" The specimen consists of granulation tissue upon a basis of white fibrous 
tissue. The surface of the granulation tissue shows a fibrin network containing 
clotted blood, and the immediately underlying portion of the tissue is invaded 
by polymorphonuclear leucocytes. The granulation tissue is apparently firm and 
fibrous although, toward the surface, it is extremely cellular, the vessels being 
surrounded by large numbers of mononuclear cells, both large and small and of 
the plasma cell variety. Among these one mitotic figure is found. In the deeper 
layer of the granulation tissue the fibroblasts predominate. In this portion of 
the tissue there are numerous areas which take a diffuse light bluish stain with 
haematoxylin which on high power seem slightly granular. The tissues in these 
areas are somewhat swollen and almost hyaline in appearance. The nuclei are 
pyknotic and the areas are somewhat surrounded and invaded by polymorpho- 
'The mass was dissolved in hydrochloric acid, the subsequent procedure being 
that advised by Neubauer and Vogel for the estimation of calcium in the urine. 
Analyse des Harns, Wiesbaden, 1898, 746. W. S. Thayer and H. H. Hazen. 
5 
nuclear leucocytes. In the deeper layers there are numerous multinuclear for- 
eign body giant cells which do not seem to bear any definite relation to the 
bluish areas described." 
The accompanying photograph (Plate I), taken between No- 
vember 20 and 24, illustrates the condition of the wound. 
The course of the breast abscess was slow. On November 24, the skin on 
both sides had begun to close in but no appreciable change for the better was 
observable in the denuded breast tissue. A mass half the size of an orange 
protruded into the wound, both on the inner and outer sides. The mammary 
gland was still dissected out as previously, the granulation tissue on the sur- 
face being transformed, in islands, into a stony yellow material with pale, slug- 
gish granulations between. The calcereous matter at times became loosened 
and could be picked off in pieces about 2 mm. thick. The hardening of the 
wound was not so marked as a week before. Along the outer margin of the 
gland the indurated areas remained as they were two week previously, rounded 
masses of uniform firmness. In the axilla the glands were somewhat swollen, 
one being, perhaps, as much as 4 cm. in diameter, but they were soft and did 
not feel as if calcified. The patient was much better; up and about the ward. 
On December 5, the iodoform dressing was removed and the wound was 
packed loosely with sterile protective rubber strips. 
On December 8, three days later, the nodules in the breast appeared to have 
diminished somewhat in size, while the calcium deposit in the wound seemed less 
marked. 
Acting on the basis of the experiences of Gerhardt and Schlesinger who found 
that under a carbohydrate free diet, the calcium excretion was increased, the 
patient was put on the fixed carbohydrate free diet which is described later; this 
was continued for two weeks. 
During this period, the healing of the wound progressed rapidly. On De- 
cember 18, a note (W. S. T.) states: "Healing continues. The opening of the 
wound is now not more than 5 cm. in its greatest diameter. The calcified rim 
is smaller. The masses in the upper and outer quadrant of the breast have 
diminished in size and hardness. A few nodules are to be felt in the inner 
part of the breast, but they are very small; it is doubtful whether they have 
increased in number. Two axillary glands are also somewhat enlarged, the 
largest, just under the border of the pectoralis, is firm but does not feel stony." 
Five days later it was again noted (Dr. Thayer) that the calcified rim had 
softened considerably although there was still a good deal of stony material to 
be felt. The nodules in the outer part of the breast had diminished in size 
and firmness. From January 5 to 14, 1906, the patient was again put upon a 
carbohydrate free diet. By January 9 it was observed that the old calcified rim 
about the crater-like opening of the wound had wholly lost its stony hardness, 
having now the consistency of fibrous tissue. One large gland was to be felt in 
the axilla, while in the breast, over the fourth interspace, there was still a 
slight suggestion of a firm nodule. Two sinuses running back from the old in- 
cisions remained; in the anterior of these, gritty substance could be felt with the 
probe. 
On January 15, there was a slight breaking down at a spot in the scar tissue 6 
Calcification of Breast Following Typhoid Abscess. 
below the lower sinus. The wound was packed with iodoform gauze. On 
the following days there was a distinct deposit of calcareous material to be felt 
with the probe in the region where it had been in contact with iodoform gauze. 
On probing the wound the day before, no grating was to be made out. May 
this, possibly, have been a fresh deposition of calcium in new granulation tissue? 
Three days later, seventy-one days after the calcification was first observed, the 
old wound had entirely healed, the hard, sclerotic border having disappeared. The 
indurated masses in the breast were no longer to be felt. The glands in the 
axilla had diminished in size. On removing the dressing of the new opening 
there was a definite induration about the wound, especially in the lower part. 
No deposits of calcium could be seen or distinctly felt. 
On January 21, a small piece of calcium ulcerated through near the lowest 
sinus. From this time on the sinuses continued to heal steadily. On February 
8, but a few small glands were to be felt in the axilla, the largest not so large 
as the end of the little finger and of no especial firmness. There was no indura- 
tion to be felt about the mouths of the openings of the sinuses. The patient 
was discharged, to return to the dispensary for the dressing of the sinuses. On 
one occasion, during the latter part of the patient's stay in the hospital, after 
packing a sinus, in which no calcium could be felt, with bismuth gauze, incrusta- 
tions were found on the following day. It is not impossible, however, that 
this, as well as the appearance of calcium on January 16, was due to the ulcer- 
ating through of deeply seated deposits. 
On May 19, the patient returned in response to a letter in order to be ex- 
hibited before the Society of Pathologists and Bacteriologists during the reading 
of this communication. She was perfectly well. The breast showed a puckered 
scar. There was no induration. The glands in the axilla had almost disap- 
peared. 
The results of the estimations by one of us (H. H. H.) of the 
intake and output of calcium during the several periods above 
referred to, are of considerable interest. At the outset, on Decem- 
ber 3, the patient was put upon a simple diet of eggs and milk, the 
lime content of which could be easily estimated. It was intended 
that this diet should be persisted in for a period of a week or ten 
days but, owing to the strenuous objections of the patient, it was 
kept up only from December 3 to 8. Estimates of the calcium 
ingested in the food and excreted in the urine and feces for three 
days, December 6 to 8 inclusive, showed a retention of 1.346 gms. 
or a daily average retention of 0.448. 
From December 9 to 23, the patient was given the carbohydrate 
free diet which is described later. During twelve days, December 
11 to 23, inclusive, a study of the intake and output of calcium 
revealed an excess of calcium elimination over the intake amount- 
ing to 2.6229, or a daily excess of calcium elimination amounting 
to 0.201. W. S. Thayer and H. H. Hazen. 
7 
From December 24 to January 6 a regular ward diet was allowed. 
Owing to the loss of a specimen the record of the calcium metab- 
olism during this period was unfortunately lost. 
From January 5 to 14, the patient was again upon a carbohydrate 
free diet, and during the eight days between February 7 and 14, 
the excess of calcium elimination over the intake was 1.050 gms., 
or a daily excess of elimination over intake of 0.131. 
From January 27 to February 5, under ordinary ward diet, the 
intake and output of calcium were nearly equal; there was a reten- 
tion of calcium amounting to 0.602 or a daily average calcium 
retention of 0.06 gms. 
During the first period of carbohydrate free diet, crystals of 
calcium oxalate and phosphate were repeatedly found in the urine. 
During the second period, no calcium crystals were to be found. 
Diacetic acid and acetone were demonstrated in the urine on Jan- 
uary 12 and January 13, but there was no especial increase in Ca 
elimination on those days. 
It is undeniable that, while a diminution in the thickness of the 
calcified rim of the wound was noted on the day on which the 
carbohydrate free diet was begun, yet the greater part of the decal- 
cification occurred during the time while the patient was on a carbo- 
hydrate free diet. During the two weeks from December 24 to 
January 6, while the patient was upon a regular diet, but little 
change was to be made out in the extent of the calcium deposits 
in the wound. 
The association of the excess in Ca elimination with the absorp- 
tion of the calcareous deposits in the wound and breast is an inter- 
esting and striking coincidence. While one may not be justified 
in assuming that the eliminated calcium represented that which was 
noted in the breast, it is but natural to suspect that the regime 
under which the excess in calcium elimination occurred had an 
influence upon the absorption of the deposits. The elimination of 
Ca in the urine was, it is true, no greater-indeed not so great-as 
in Gerhardt and Schlesinger's control case. It must, however, be 
remembered, in connection with this case, that we were not dealing 
with a healthy, normal individual, but with one who was conva- 
lescing from a long, wasting disease-a condition in which one 8 
Calcification of Breast Following Typhoid Abscess. 
might not unreasonably expect to find an appreciable Ca retention. 
It may, therefore, be true that the excess of Ca eliminated during 
the periods of carbohydrate free diet, represents a change from the 
ordinary considerably greater than the figures themselves would 
suggest. The fact that during each of the intermediate periods 
there was a Ca retention of a remarkable degree during the first 
period when the diet was, it is true, of very high lime content, is 
striking in this connection. 
It would be interesting to make further observations as to the 
intake and output of Ca during, and in the convalescence from, 
typhoid fever. 
The conditions, general and local, under which the deposition of 
calcium is common are sufficiently familiar. The general condi- 
tions: in individuals in whom some process is going on involving 
the destruction of bone, such as caries, rapidly growing neoplasms 
and senility, the so-called calcium metastases. 
The local conditions: such as caseating areas of tuberculosis in 
lungs, glands, etc., gummata, areas of regressive change in neo- 
plasms, infarcts, atheromatous areas, old thrombi, the retained 
foetus, the incrustation of cartilages and muscles around areas 
of venous stasis and chronic inflammation, the cardiac valves, 
pleural and pericardial exudates, hyaline degeneration in various 
regions, notably in the muscular coats of arteries, in ganglion cells, 
in the periphery of areas of cerebral softening, in disseminated fat 
necrosis, equal all conditions in which the affected areas are ne- 
crotic, degenerated, or of notably diminished vitality. 
Especially interesting are the observations made by Litten who 
showed that a deposition of lime in the cortex of the kidneys fol- 
lowed temporary ligature of a renal artery in rabbits; a well- 
marked calcium deposit may be found after an occlusion of two 
hours' duration. Exactly similar changes have been described by 
various observers as the result of the ingestion of certain poisons, 
such as bichloride of mercury (Salkowski), subnitrate of bismuth 
(Langhans), acetate of lead (Binet), aloin (Gottschalk). Not all 
conditions, however, favoring necrosis, nor all poisons producing 
degenerative changes are followed by the deposition of lime salts. 
Von Kossa has recently made a study of the calcification-pro- W. S. Thayer and H. H. Hazen. 
9 
ducing poisons. Experimenting with a great variety of substances, 
he comes to the conclusion that those poisons which especially 
induce calcification in the rabbit are: 
i. The salts of heavy metals (lead, bismuth, mercury and copper). 
2. Of the metalloids, iodine and, perhaps, arsenic. 
3. Among organic compounds, aloin and iodoform. 
In susceptible animals poisoned by these substances the calcium 
is deposited in the shape of the phosphate; Von Kossa has never 
found a deposit of carbonate. Not all the calcium is, however, 
present in the form of the phosphate; a part is apparently bound 
in some organic compound. 
Inasmuch as the calcium content of the blood and bones of the 
poisoned (aloin) animal remains unchanged, while that of the 
urine is diminished, it is evident that the kidney fails to excrete the 
total amount of the calcium circulating in normal quantity, i. e., 
the deposition is due to a calcium retention. The rabbit is particu- 
larly subject to the action of these poisons, owing probably mainly 
to the fact that its blood has normally an especially high calcium 
content. Von Kossa has, further, demonstrated by the following 
interesting experiments that an increase in the quantity of the 
calcium in the circulation favors its deposition under the influence 
of these poisons. To one animal a certain amount of iodoform was 
administered by the mouth. To another, a smaller amount was 
given and, in addition, chloride of calcium subcutaneously. In the 
latter rabbit alone did calcification occur. The experiment was then 
repeated with three rabbits, one of which received iodoform alone, 
another an injection of chloride of calcium alone, and a third iodo- 
form by the mouth and chloride of calcium subcutaneously. In 
neither of the first two rabbits was there any deposition of calcium. 
In the third there were marked changes. In animals in which the 
calcium content of the blood has been artificially increased it is, 
therefore, possible to bring about calcification with doses of the 
poison essentially smaller than those required under ordinary cir- 
cumstances. 
If one consider the course of events in the case which has just 
been described, a remarkable analogy appears between the condi- 
tions existing here and the experiments of von Kossa. 10 
Calcification of Breast Following Typhoid Abscess. 
I. In a patient suffering from haemorrhage from the bowel in 
typhoid fever there were administered, in the course of eleven days, 
132 grammes of lactate of calcium by mouth and five grammes of 
chloride of calcium subcutaneously. 
2. In the area in which the subcutaneous injection of chloride of 
calcium was given there developed an extensive abscess from which 
Bacillus typhosus and Staphylococcus aureus were obtained. 
3. After opening and draining the abscess was packed with iodo- 
form gauze. 
4. Extensive areas of calcification developed in the granulation 
tissue wherever it was exposed to the action of iodoform as well as 
in other adjacent parts of the breast. 
5. It is possible that a similar deposition of calcium followed the 
dressing of subsequently developed sinuses with subnitrate of 
bismuth.3 
In other words, in an individual in whom the calcium content of 
the organism was probably increased as a result of the administra- 
tion by mouth and hypodermically of lactate and chloride of cal- 
cium, an abscess developed which was dressed with iodoform gauze; 
this was followed by the deposition of calcium in the granulation 
tissue immediately adjacent to a substance (iodoform) which is 
known, experimentally, to favor the deposition of calcium in rab- 
bits. This deposit of calcium disappeared rapidly and completely 
under a carbohydrate free diet. During three weeks of this period 
the average daily excess of calcium elimination over that of calcium 
intake amounted to 0.174 A gr. 
We have been unable to find a similar case in literature. Inter- 
esting and suggestive in this connection are the observations of 
Schujeninow who, with Chiari, demonstrated the deposition of 
calcium in muscle fibres about the borders of laparotomy wounds 
in seventeen out of twenty-four cases. In the earliest case examined, 
calcification was discovered thirteen hours after the incision. This 
reached its height from about the ninth to the twentieth day and 
then disappeared by absorption. It was noted that the calcification 
3 Although the sequence of events here was remarkable, we are rather in- 
clined to regard the appearance of the calcium after the beginning of the 
bismuth dressings as due to the breaking through of deeper lying calcium masses. W. S. Thayer and H. H. Hazen. 
11 
was always near the ligature and occurred in fibres which had un- 
dergone colloid degeneration following the disturbances of circula- 
tion as a result of the ligatures. It would be interesting to know 
whether, in these cases, the wounds were dressed with iodoform. 
In his experiments with rabbits the wounds were closed with iodo- 
form collodion. 
As to the cause of this extensive deposition of calcium our ob- 
servations do not justify a definite conclusion. One can only point 
to the remarkable combination of circumstances-the extensive 
calcification of the granulation tissue and of circumscribed areas 
throughout the breast after an acute abscess developing at the seat 
of an injection of calcium chloride in an individual who had been 
taking, for eleven days, large doses of the lactate of calcium-and 
further to the fact that the calcification did not appear at the outset, 
but only after the wound had been packed with gauze impregnated 
with iodoform, a substance which, experimentally, has been found 
in some animals to favor the deposition of calcium. 
We have endeavored, in several instances, to reproduce this pic- 
ture in rabbits by administering lactate of calcium subcutaneously, 
after which an abscess was to be produced, opened and packed with 
iodoform gauze. 
Five rabbits in all were used. Daily injections of 0.13 per 500 
grammes weight were administered for ten days. In attempting to 
produce an abscess, the following method was evolved. Aleuronat 
meal in from seven to ten times its weight of water to which 3 per 
cent, starch was added, was injected under the skin. Failing to 
produce an abscess in this manner, dead cultures of Bacillus ty- 
phosus were used with fatal results. One abscess occurred spon- 
taneously and one was obtained by the hypodermic injection of 
croton oil in ether. Although both were packed with iodoform 
gauze, in neither case was there a deposit of calcium. No trace of 
calcium was found on necropsy in kidneys or liver. 
Determinations of the intake and outpzit of calcium.-These 
analyses were made by one of us (Dr. Hazen)4 in the clinical 
laboratory of the John Hopkins Hospital under the direction of 
Dr. C. P. Emerson, according to the following method: 
41 desire here to express my indebtedness to Dr. Emerson and Dr. Boggs 
for their assistance in this work. H. H. H. 12 
Calcification of Breast Following Typhoid Abscess. 
At the outset the patient was given a teaspoonful of charcoal by mouth. 
Beginning with the meal following this, a quantity of food exactly similar to 
that given by mouth was set aside for analysis. The first stool after the char- 
coal had appeared in the faeces was saved; the urine was collected as soon as the 
charcoal had appeared. To close the period, charcoal was again administered, 
after which no food was kept. After the appearance of this charcoal in the 
faeces, neither urine nor stools were saved. 
Great care was taken to insure that equal amounts of the same food were 
saved for examination; this was personally watched. The food was accurately 
weighed and dried in a thermostat. The total food for the period was then 
repeatedly run through a sausage grinder, and when thoroughly mixed, samples 
were removed for the determination of the Ca. This was done by burning the 
food until a perfect ash was secured; it was then dissolved in HC1, and the 
same procedure was followed as in the case of the urine. As it was naturally 
impossible to get an exact half-portion of the food in the case of the eggs, 
the following method was adopted. One dozen eggs were analyzed and the 
mean Ca content used as a basis for estimation. It was found necessary to boil 
the eggs hard before burning them. 
All food analyses were made in triplicate, and in no instance was there the 
slightest variation in the Ca determination, good evidence that a uniform mixture 
was secured. 
In the case of the stools the same method was employed as for the food, 
except that they were analyzed in daily quantities. Analyses were made in 
duplicate. 
The urine was saved in twenty-four hour amounts, preserved with chloroform 
and estimated separately. At first the estimation was made according to the 
well-known gravimetric method described in the tenth edition of Neubauer and 
Vogel, p. 746. It was, however, soon found that, in about 15 per cent, of the 
cases, the Ca was not precipitated, necessitating the use of another specimen. 
The following modification was accordingly devised which by careful duplicate, 
comparative tests with the older method, proved entirely reliable, while giving 
invariably a precipitate of oxalate of calcium. 
Two hundred cubic centimetres of the urine were employed. The urine was 
then acidified with HC1 and filtered; NH4OH was added until a precipitate 
formed. This suspension was neutralized with acetic acid instead of HC1. An 
excess of ammonium oxalate and a few c.c. of sodium acetate were then added, 
and the amount put in an evaporating dish. This was covered with a glass 
plate and heated over night on a water bath. It was then filtered through an 
ashless filter paper, until the filtrate was perfectly clear. The precipitate was 
washed with hot water and burned with the paper in a blast flame, in a platinum 
crucible until it lost no more weight. This converted the oxalate into the oxide, 
in which form it was gravimetrically determined. Tests were made in duplicate. 
During an initial period in order to determine what she was 
doing upon a more or less normal mixture the patient was put upon 
a milk and egg diet. The diet consisted of 375 c.c. of milk and two 
eggs every four hours. As the patient objected strenuously to its W. S. Thayer and H. H. Hazen. 
13 
continuance it was abandoned after three days. In the light of 
further work it would seem that this diet was unfortunately chosen, 
as the Ca content of milk is so high -that, in the large quantities 
administered, it was probably partly responsible for the appreciable 
Ca retention which was demonstrated. The results of the estimates 
of the intake and output of calcium during this period are shown 
in the record of Period I in the table. As has been already noted, 
there was a considerable Ca retention. 
Table Showing the Results of Estimates of the Intake and Output of Calcium. 
27/i-5/ii, 
Normal Mixed 
Diet. 
Period IV. 
7/1-X4/1. 
■Carbohydrate 
Free Diet. 
Period III. 
n/xu-23/xii, 
Carbohydrate 
Free Diet. 
Period II. 
and Eggs Diet. 
- 
Period 1. 
6/xii-8/xii, 
Inclusive. Milk 
to 
? 
M 
"to 
3 094 
O' 
Ca in Urine. 
vp 
bo 
4 485 
Ln 
Ch 
H 
5-34° 
Ca in Stools. 
.1 
6.057 
oT 
Ln 
5-955 
Total Ca Excretion. 
Ln 
8 
5 °33 
io£'Z 
Ca in Food. 
o 
S' 
to 
1 
1 
Ca Retention. 
0 
0 
2.622 
1 
Ca Excess 
Elimination. 
to 
Ch 
p 
0.238 
0.205 
Daily Average 
Amount Ca in Urine. 
Ln 
40.4 £ 
jjz£'oi 
Per Cent, of Ca 
Excreted in Urine. 
p 
8 
ooi:S£ 
Ch 
Ch 
8 
11.5:100 
Relation of Ca in 
Urine to that 
in Stools. 
i£Z 0 
0 
Cn 
00 
00 
1.985 
Daily Average 
Excretion of Ca. 
p 
to 
00 
p 
% 
££W 
Daily Average 
Amount of 
Ca in Food. 
0 
& 
•448 
Daily Average 
Retention of Ca. 
p 
p 
to 
0 
Daily Average 
Excretion of 
Ca in Excess. 
00 
00 
Ch 
UX 
0 
89 67^ 
Per Cent, of Ca 
Excreted in Stools. 
From December 11 to 23 the patient was put upon a carbohydrate free diet, 
essentially the test diet advised by v. Noorden in diabetes." An exact half-portion 
of every meal was measured and set aside for analysis. The record of Period 
II on the table shows a reversal of the picture in Period I-a high per cent, of 
Ca elimination in the urine and a distinct excess in elimination of Ca over the 
intake. During this period crystals of oxalate and phosphate of lime were 
repeatedly found in the urine. Acetone and diacetic acid were not demonstrable. 
From December 24 to January 6 inclusive, the patient was on ward diet, but, 
unfortunately, the Ca was not determined, owing to loss of a specimen. 
'Breakfast: 5 grm. (% oz.) tea steeped in 200 c.c. (6% oz.) water; 150 
grm. (5 oz.) ham; one egg. 
Lunch: 200 grm. (6% oz.) cold beef; 60 grm. (2 oz.) fresh cucumber 
(or good quantity of lettuce) with 5 c.c. (teaspoonful) vinegar; 10 c.c. (2 14 
Calcification of Breast Following Typhoid Abscess. 
From January 7 to 14 inclusive, the patient was again upon a carbohydrate 
free regime. During this period no crystals of oxalate of calcium were found 
in the urinary sediment. 
On January 12 and 13, acetone and diacetic acid were found in the urine. 
There was, however, no increase in Ca elimination in the urine on those days. 
The record of Period III in the table shows again an excess in the Ca elimi- 
nated, though not so marked as in the previous period. 
From January 27 to February 5, a study of the calcium intake and output 
was made, while the patient was on ordinary ward diet. Here, again (Table, 
Period IV), a slight Ca retention is demonstrable with a marked diminution in 
the per cent, of Ca eliminated by the urine. 
A study of the table shows that the excess of calcium was ex- 
creted by the urine, the per cent, of calcium excretion in the stools 
falling strikingly during the period while the patient was upon a 
carbohydrate free diet. 
It is unfortunate that the relations between the ammonia and 
calcium output should not have been determined. In the observa- 
tions of Gerhardt and Schlesinger the ammonia output was found 
to run parallel with that of the calcium. 
The patient remained in excellent health throughout the experi- 
ments. She gained materially in weight during the whole period. 
The weight was taken regularly during the experiment, but owing 
to an unfortunate misunderstanding, the entries were not regularly 
made upon her temperature chart. There was a slight loss of not 
more than a pound or two during each of the periods of carbohy- 
drate free diet, with considerable gains during the intermissions. 
Thus, on November 26, the weight was 82% pounds. On Decem- 
ber 3, the day that the milk and egg diet was begun, the weight 
was 86^4 pounds. Two weeks later, December 17, in the middle of 
the first carbohydrate free period, the weight was 84 pounds. A 
month later, on January 14, at the end of the second carbohydrate 
teaspoonfuls) olive oil and salt and pepper to taste; 20 c.c. (4 teaspoonfuls) 
brandy with 400 c.c. (13-14 oz.) Apollinaris water (soda water or ordinary water 
will do) ; 60 c.c. (2 oz.) of coffee without milk or sugar. 
Dinner: 200 c.c. (6% oz.) clear bouillon; 250 grm. (8% oz.) beef (weighed 
raw) basted with 10 grm. (% oz.) butter; 8 grm. (2% oz.) green salad with 
10 c.c. (2 teaspoonfuls) vinegar and 20 c.c. (4 teaspoonfuls) olive oil or 3 table- 
spoonfuls of some good, well cooked vegetable such as spinage; 3 sardines; 
20 c.c. (4 teaspoonfuls) brandy with 400 c.c. (13-14 oz.) Apollinaris water 
(ordinary water or soda water will do). 
Supper: 2 eggs, raw or cooked; 400 c.c. (13-14 oz.) seltzer water (or any 
good water). W. S. Thayer and H. H. Hazen. 
15 
free period, the weight was 103 pounds. On February 8, the day of 
discharge, the weight was 114 pounds. 
I. In a patient with typhoid fever, who had taken, during eleven 
days, 132 grammes of lactate of calcium by the mouth, as well as 
5 grammes of chloride of calcium subcutaneously, there developed, 
eleven days after the subcutaneous infusion, a large abscess of the 
breast from which Bacillus typhosus and Staphylococcus aureus 
were obtained on culture. The abscess was opened and the wound 
packed with iodoform gauze. Eleven days later a deposit of 
calcium appeared in the granulation tissue bordering the wound. 
This rapidly increased until the rim of the opening and the lining 
granulation tissue were converted into a hard, calcareous mass. A 
number of nodules of an apparently similar character appeared in 
other parts of the breast. 
2. A month later the iodoform packing was removed and the 
patient was put on a carbohydrate free diet. This was continued 
for twenty-four of the next thirty-six days. Under this treatment 
the abscess almost entirely healed with complete disappearance of 
the deposit of calcium. 
3. Studies of the intake and output of calcium showed that, dur- 
ing three days under a diet of milk and eggs there was a material 
calcium retention (1.346 grammes) : (&) That during two periods 
amounting to three weeks in all, under a carbohydrate free diet, 
there was an excess of Ca elimination over the intake of 3.672 
grammes, (c) That during ten days following the last carbohy- 
drate free period, under a normal diet, there was a retention of 
calcium amounting to 0.602 gramme. 
4. The disappearance of calcium from the breast was associated 
in time with the carbohydrate free diet and the excessive elimina- 
tion of calcium. 
5. Under the carbohydrate free diet acetone and diacetic acid 
appeared on two occasions in the urine, but were not accompanied 
by any increase in the elimination of calcium. 
6. With regard to the cause of the calcification, we cannot speak 
with certainty. The remarkable association of the deposition of 
SUMMARY. 16 
Calcification of Breast Following Typhoid Abscess. 
calcium at the seat of an injection of calcium chloride in an individ- 
ual who had been receiving large quantities of lactate of calcium by 
the mouth-a deposition occurring in tissues which were in direct 
connection with or in the immediate neighborhood of a dressing con- 
taining iodoform, a poison which in certain animals produces de- 
generative changes in the kidneys and liver which are peculiarly 
prone to calcification, is striking and worthy of note. 
7. In how far the decalcification of the affected area may have 
been due to the carbohydrate free regime with the consequent excess 
in calcium elimination, it is impossible, on the basis of a single case, 
to say. The coincidence in time of the disappearance of calcium 
from the breast with this treatment is, however, remarkable and 
extremely suggestive. 
I. Andrews.-Calcification in Gynecology. Surg., Gynec., and Obst., 1906, ii, 42. 
2. Aschoff.-Verkalkung. In Lubarsch-Ostertag's Ergebn. allg. Path. u. path. 
Anat., 1904, viii, 561. 
3. Binet.-Influence de 1'intoxication mercurielle sur 1'elimination de 1'acide 
phosphorique et du calcium. Rev. med. de la Suisse Rom., 1891, xi, 165. 
4. Boggs.-Ueber Beeinfliissung der Gerrinnungszeits des Blutes in lebenden 
Organismus. Deutsches Arch. f. klin. Med., 1904, Ixxix, 339. 
5. Calvert & Pigg.-Calcification of the pericardium following suppurative peri- 
carditis. Trans, of the Path. Soc. of Lond., 1898, xlix, 31. 
6. Chantemesse & Podwyssotsky.-Les processus generaux. Par., 1906, I, 320. 
7. Dunin.-Chronische Eiterung an den Fingern mit Ablagerung von kohlen- 
sauren Kalk. Mittheilungen aus der Grenzgebciten dcr Med. u. Chir., 1905, 
xiv, 451. 
8. Durck, Hektoen.-Calcification. General Pathologic Histology. Philadel- 
phia, 1904, 90. 
9. Elbe.-Histologische Untersuchungen fiber die Veranderungen bei der Jodo- 
form u. Arsenintoxication des Kaninchens. Rostock, 1899, 32. 
10. George.-Calcification of the vas deferens and seminal vesicles. J. Am. 
Med. Ass., 1906, xlvii, 103. 
11. Gerhardt u. Schlesinger.-Uber die Kalk- und Magnesiaausscheidung beim 
Diabetes mellitus und ihre Beziehung zur Ausscheidung abnormer Sauren 
(Acidose). Arch. f. exper. Path. u. Phar., 1899, xlii, 83. 
12. Goldthwaite, Painter, Osgood.-A study of the metabolism in osteomalacia. 
Am. J. Physiol., 1905, xiv, 389. 
13. Gottschalk.-Uber die Einwirkung des Aloins auf den Koerper, Leipzig, 1882. 
14. Guthrie.-Effect of the intravenous injection of formaldehyde and CaCh on 
the haemolytic power of the serum. Am. J. Physiol., 1904-5, xii, 139. 
15. Haab.-Calcareous degeneration of the cornea. Atlas of External Diseases 
of the Eye. Phila., 1903, 194. 
16. Hammarsten, Mandel.-A Text Book of Physiological Chemistry. New 
York, 1902. 
BIBLIOGRAPHY. THE JOURNAL OF EXPERIMENTAL MEDICINE. VOL. IX. 
PLATE I W. S. Thayer and II. H. Hazen. 
17 
17. Hart.-The acetone bodies: their occurrence and significance in diabetes and 
other conditions. Am. Jour. Med. Sc., 1906, cxxxii, 220. 
18. Kitt.-Lehrbuch der path.-anat. Diagnostik, Stuttgart, 1895, ii, 495. 
19. Klemperer.-Uber die Veranderung der Nieren bei Sublimatvergiftungen. 
Virchow's Arch., 1889, cxviii, 445. 
20. Klotz.-Studies upon calcareous degeneration. Jour. Exper. Med., 1905, 
vii, 633. 
21. Kochel.-Uber die Kalkinkrustation des Lungengewebes. Deutsches Arch, 
f. klin. Med., 1899, Ixiv, 332. 
22. v. Kossa.-Uber die in Organismus Kiinstlicherzeugbaren Verkalkungen. 
Beitr. z. path. Anat. u. Path., 1901, xxix, 163. 
23. Kunkle.-Toxicologie, Jena, 1899-1901, i, 109. 
24. Langhans.-Pathol, anat. Befunde bei mit Bismuth subnitr. vergifteten 
Thieren. Deutsche Zeitschr. fur Chir., 1885, xxii, 575. 
25. Litten.-Untersuchungen fiber den hamorrhagischen Infarktionen. Zeit. f. 
klin. Med., 1879-80, i, 131. 
26. Manwaring.-The action of certain salts on the complement in immune 
serum. J. Infect. Dis., 1904, i, 112. 
27. Neubauer u. Vogel.-Anleitung zur Analyse des Harns. Wiesb., 1898. 
28. Neuberger.-Uber Kalkablagerungen in den Nieren. Arch. f. exper. Path, u 
Phar., 1890, xxvii, 39. 
29. Neumann & Vas.-Uber die Calcium u. Magnesium Ausscheidung unter 
normalen und pathologischen Verhaltnissen. Ungar. Arch. f. Med., 1894, 
ii, 307. 
30. v. Noorden & Belgardt.-Zur Pathologic des Kalkstoffwechsels. Berl. klin. 
Woch., 1894, xxxi, 235. 
31. Obendoerffer.-Die Wirkung der Chinasaure auf den Kalkstoffwechsel des 
Menschen. Berl. klin. Woch., 1904, xli, 1068. 
32. Opie.-Enzymes and anti-enzymes of inflammatory exudates. J. Exp. Med., 
1905, vii, 316. 
33. Rey.-Uber die Ausscheidung und Resorption des Kalkes. Arch. f. exper. 
Path. u. Phar., 1895, xxxv, 295. 
34. Rey.-Weitere klinische Untersuchungen fiber Resorption und Ausscheidung 
des Kalks. Deutsche med. Woch., 1895, xxi, 569. 
35. Richards, McCaffrey & Bisbee.-Calcium Determination. Proc. Am. Acad. 
Arts and Sciences, 1901, xxxvi, 377. 
36. Rudel.-Uber die Resorption u. Ausscheidung von Kalksalzen bei Rhachit- 
ischen Kindern. Arch. f. exper. Path. u. Phar., 1894, xxxiii, 79. 
37. Schetelig.-Uber der Herstammung und Ausscheidung des Kalkes in ges- 
unden und kranken Organismus. Arch. f. path. Anat., 1880, Ixxxii, 437. 
38. Schujeninow.-Zur Frage der Kalkablagerung in der quergestreiften Muskeln. 
Zeit. f. Heilk., 1897, xviii, 79. 
39. Werra.-Uber die Folgen des vorfibergehenden und dauernden Verschlusses 
der Nierenarterie. Arch. f. path. Anat., 1882, Ixxxviii, 197. 
40. Wright and Paramore.-Reduction of blood coagulation time. Lancet, 
1905, ii, 1096. 
41. Zeigler.-Lehrbuch der allgemeinen Pathologic, Jena, 1901. System of Medicine 
Vol. II Part II 
First Proof 
392 
MALARIA 
Prof. W. S. Thayer. 
Synonyms.-Ague; Paludism ; Intermittent Fever; Paludisme (Fr.) 
Wechselfieber (Ger.); Paludismo (It.). 
Definition.-A specific infections disease, due to the invasion of the 
blood by several species of haemosporidia of the genus Plasmodium 
malarias. This disease manifests itself, according to the species of 
infecting parasite, in three types which are distinguished in common 
by the occurrence of periodical, intermittent, or subintrant febrile- 
paroxysms. 
Historical Note.-Easily recognisable descriptions of the malarial 
fevers are to be found in the oldest medical writings, and remarkably 
accurate accounts of many forms of the disease occur in the works of 
Hippocrates, Galen, and Celsus. By the older authors, however, no- 
distinct separation was made of that group of fevers which we now 
know as malarial. 
Three epochs may be recognised in the advance of our knowledge 
concerning malaria. The first of these began with the introduction of 
the use of cinchona in 1640, and the discovery of its specific action in 
a limited class of febrile diseases. With this period are especially 
associated the names of Sydenham, Torti, and Morton. The contribu- 
tions to the literature by these authors and by their worthy successor, 
Lancisi contain much which holds good to-day. The hypothesis of the 
parasitic origin of the disease was, indeed, adhered to by all of these 
authorities, and, in the light of our present knowledge, the accuracy of 
some of the older hypotheses is truly remarkable.1 ' For many'years. 
I have held the opinion that the intermittent fevers are produced by 
parasites which call forth a new paroxysm by the act of their repro- 
duction which occurs at more or less rapid intervals according to the 
species." Alongside of such a remarkably accurate hypothesis it may 
be of interest to quote the curiously chosen words of Dr. Thomas Fuller, 
who, in the preface of his Exanthematologia (4°, London, Charles 
Bivington, 1730), resignedly says: "I believe with all my Heart, that 
Nature doth Geometrize in all her Works, and constantly keepeth exact 
Proportion, Measure, and Number; but withal I am as much assured that 
we have not Capacities to take in a distinct Knowledge of them. . . . 
Can any Man, can all the Men in the World, tho' assisted by Anatomy, 
Chymistry, and the best Glasses, pretend positively and certainly to tell 
us, what particles, how sized, figured, situated, mixed, moved, and how 
many of them are requisite to produce a quartan ague, and how they 
specifically differ from those of a tertian. . . ." 
But despite these clear-headed men, confusion still existed as to the 
proper application of the term malaria until the beginning of the second 
great epoch in 1880, v ith the discovery by Laveran of the specific cause oi tne disease. 
The once prevailing conception of the manner of infection in malaria 
is reflected in the term by which it has come to be known-"maV aria." 
But there were many other hypotheses. Amongst other time-honoured; 
conceptions was that of the transmission of the disease by suctorial 
insects. King (1883), Laveran (1891), and Bignami (189G), suggested 
that the mosquito might be the infecting agent, while Sir P. Manson 
(1894) brought forward arguments in support of the conception that 
this insect might play the part of intermediate host of the malarial 
parasite. But doubt and uncertainty with regard to the manner of 
infection prevailed until the opening of the last epoch in the advance 
of our knowledge-the demonstration of the agency of the mosquito 
in the transmission of malaria (1897-1899) by Major Ronald Ross, and 
the Italian school (Groassi, Bignami, and Bastianelli). 
Etiology.-Manner of Infection.-The infectious agent of malaria- 
Plasmodium malaria-is introduced into the human organism by the 
bite of mosquitoes of the family Culicidae, sub-family Anophelinae, which 
have themselves become infected by biting individuals whose blood 
contained gametes of the malarial parasites. 
It is important at the outset of a consideration of this disease to 
realise that malaria does not appear spontaneously without the existence 
of certain definite conditions; (1) The presence of Anophelinae. (2) The 
existence or recent presence of cases of malaria (relapses or infectio s 
acquired elsewhere) from which the mosquitoes may derive the infection. 
(3) Climatic conditions favouring the activity of the mosquito, suitable 
for its infection and for the further development of the oocysts of the 
parasite. (4) Susceptibility of the mosquito and of the individual 
bitten to infection. In the absence of any one of these factors an out- 
break of malaria is impossible. Thus, there are many regions in which 
Anophelinae are present without the existence of malaria, while again, 
localities which are definitely infected are quite safe at seasons of the 
year in which the climatic conditions are such that mosquitoes do not 
bite, or that the oocysts of the parasite are incapable of development. 
Moreover, it cannot yet be asserted that all Anophelime are capable of 
transferring the disease. While there is, at present, no evidence that 
other Culicidae are capable of acting as hosts of Plasmodium malaria, it is 
known that Culex pipiens plays this part with regard to the closely allied 
parasites of birds. At the present time the following mosquitoes have 
been shewn to be capable of transferring malarial infection. Anopheles 
bifurcatus (Europe); A. maculipennis (Europe and North America); 
A. jesoensis (Japan); A. martini, A. bursati (Cambridge); A. vincenti 
(Tonkin); Myzomyia christophersi, M. culicifacies (India); M. funesta, 
1 Especially striking is the observation of Rasori. 1762-1827. Calandruccio, Agostino 
Bassi di Lodi, it fondatore dMa teoria parasitnria, etc. Catana, 1892, 70. 393 
M. superpicta, Myzorhynchus paludis (West Africa); M. constanii 
Madagascar and Reunion); Eyretophorus cosialis (Africa); Nyssorhynchus 
lutzi (Brazil); N. cubensis (Panama). It is doubtless true that numerous 
other Anopheliuse transfer the disease. The brothers Sergent have 
recently found sporozoites, probably malarial, in the salivary glands of 
A. a.lgeriensis and Myzomyia hispaniola in Algeria. 
Geographical Distribution.-Malarial fevers are wide-spread throughout 
the temperate and tropical regions of the world. The disease is rarely 
seen in cold climates; never above the latitude of 60° N. The severer 
types of infection are endemic in the tropics, the milder forms alone 
prevailing in temperate climates. Malaria is especially common in low 
marshy regions, along the banks and deltas of large rivers and lakes. 
In Europe the disease prevails in the low lands, about the coast of 
Italy, Sicily, Greece, Corsica, and Sardinia, and along many of the 
nvers, such as the Tiber and Po. Malaria is also met with about the 
coast of Spain, Portugal, and France. In the interior of France mild 
forms of intermittent fever are seen in Sologne, Brenne, Bresse, and 
Dombes, although cultivation and drainage are rapidly improving the 
conditions. The same is true of Belgium, the Baltic coast of Prussia, 
Silesia, and the plains of the rivers Rhine, Weser, Elbe, Oder, and 
Vistula. In Austria-Hungary the malady is common in Galicia, along 
the Adriatic coast and the valley of the Danube. Malaria prevails in 
many parts of the Balkan Peninsula and in Southern Russia, especially 
along the Volga, about the borders of the Black and Caspian seas, and 
in the Transcaucasus. 
In Asia malaria is wide-spread. It is common on the coasts of Asia 
Minor, Persia and Arabia, in Turkestan, in Cochin China, Tonkin, 
throughout the south-east coast of China, and in Formosa; in the 
lowlands and along the banks of the great rivers in India, in Ceylon, 
in the Malay Peninsula, throughout the East Indies and in the Philip- 
pines. In Japan the disease is infrequent and mild. 
Australia and most of the islands of Oceania are free from the disease. 
1 In many parts of Africa the malarial fevers are especially prevalent. 
In the North they are observed in Egypt, in those regions which are 
periodically under water, in the lowlands of Abyssinia and Nubia, in 
Algeria, especially on the coast and about the rivers, as well as on the 
coast of Tripoli and in parts of Tunis. About the coast of tropical 
Africa, on the neighbouring islands and along the rivers, the most 
virulent forms of the disease are met frith, especially upon the West 
coast from Senegal to Congo. 
In North America malaria is observed along the eastern coast from 
New England to Florida. North of Maryland, however, the severer 
forms are rare. Mild intermittent fever is also met with in some low- 
regions about the great lakes in the United States and in Canada. The 
disease is common in the valleys of the Mississippi and its tributaries. 
It occurs with great intensity in the lower Mississippi valley, especially 
in the delta and along the coast and the banks of the rivers of Louisiana 
and Texas. Mild forms of malaria prevail in the valleys and along the 
rivers of the Pacific coast. In the lowlands of Mexico .and in Central 
America the severest forms of the disease are seen. The deadly Chagres fever of Panama is a type of sestivo-autumnal malaria. In the Antilles 
malaria occurs more or less extensively. In South America it is frequent 
about the coast, notably in Guiana, but also in the northern part of 
Brazil, in Bolivia, Paraguay, and Uruguay. In the Argentine Republic 
malaria is rare. 
Influence of Climate ami Season.-The climatic conditions under which 
malaria flourishes are those favourable to the development and activity of 
Anophelinfe, i.e. heat and moisture. In temperate climates the disease 
appears only during the warm season of the year;1 while in the tropics, 
although occurring through much longer periods of time, it prevails 
especially in the wet season. In Rome the epidemic occurs in the latter 
six months of the year, the disease being most frequent in August and 
September. In Baltimore our figures agree closely with those of the 
Italian observers, although the largest number of cases appears in 
September ami October. 
Season has also an influence upon the type of malaria. Although 
all forms of the disease are more frequent at the height of the malarial 
season, yet during the months of September and October the majority of 
the cases in Baltimore are infections with Laverania malaria (Plasmodium 
falciparum) (aestivo-autumnal malaria), which, before the month of July, 
are extremely rare, the enormous majority of cases in the spring and 
early summer being due to Plasmodium virax (tertian malaria). 
The following table illustrates the seasonal variations in the prevalence 
of the individual types of malarial fever: 
Jan. 
Feb. 
Mar. 
Apr. 
May. 
Jun. 
July. 
Aug. 
Sept. 
Oct. 
Nov. 
Dec. 
Total. 
Tertian 
12 
12 
28 
51 
76 
68 
131 
161 
153 
168 
54 
17 
931 
Quartan 
3 
1 
0 
1 
0 
0 
3 
0 
2 
1 
4 
2 
17 
Jistivo-autumnal 
5 
1 
2 
5 
2 
3 
37 
99 
191 
203 
63 
22 
633 
0 
1 
1 
0 
0 
1 
3 
3 
4 
11 
6 
2 
32 
20 
15 
31 
57 
78 
72 
174 
263 
350 
383 
127 
43 
1613 
1 What is known of the conditions under which the parasites develop in the stomach- 
wall of the mosquito clearly explains this. The oocysts grow best at temperatures of from 
20°-30° C. They are killed at temperatures steadily under 16° C. The infected mosquito 
may, however. l>e exposed for short periods to temperatures considerably lower than than 
this-as low even, as from 10o-13o C. for an hour-without complete destruction of the 
organisms, provided the subsequent conditions are favourable. If the temperature be under 
16° C. the oocysts are destroyed (Jancs6). Anophelinae may bite at a season considerably 
earlier or later than that which is suitable for completion or the development of the oocyst. 394 
As the preceding table shews, the malarial epidemic in temperate 
climates disappears soon after the onset of cold weather and frosts. 
Most cases of the disease occurring in the first half year are relapses. 
The rare instances of apparently primary malaria observed in the spring 
are in great part, probably, examples of a prolonged period of incubation, 
or cases in which the symptoms of the primary attack were so slight as 
to be overlooked. In Baltimore as in Rome the epidemic of infections 
with Plasmodium vivax (tertian fever) begins in the early summer. The 
epidemic of infections with Plasmodium falciparum (aesti vo-autumnal fever) 
is, properly speaking, an aesti vo-autumnal phenomenon. The few instances 
of infection with Plasmodium malarice (quartan fever) are a manifestation 
of the autumn. 
The valuable observations accumulated by the Italian Society for the 
Study of Malaria have demonstrated that the epidemic of primary attacks 
is almost invariably preceded, for a greater or less period of time, by the 
epidemic of relapses-just as might be expected from that which we 
know of the manner of infection. 
Influence of Moisture.-Moisture plays a very important part in the 
prevalence of malaria. The most malarious regions are low and marshy, 
situated about rivers or lakes. In the tropics the rainy season and the 
period immediately succeeding it are especially dangerous. Moisture is 
necessary for the development of the eggs and larvae of Anophelinae. 
Soil.-The most dangerous localities are those with an impervious 
sub-soil, where pools and collections of standing water are common. 
Swampy districts, where the surface of the ground is covered for a part 
of the time by water, are especially favourable for the development of 
Anophelinae and malaria. For many years it has been known that proper 
drainage and canalisation of such areas are followed by great improve- 
ment in the hygienic conditions with regard to the malarial fevers. 
Lutz has shown that in some wooded and mountainous regions, where 
tht re is no standing water, larvae of Anophelinae may develop in great 
numbers in fluid collected and secreted between the leaves and in the 
folds of certain plants. Epidemics of malaria may break out in such 
localities. 
Altitude.-Malaria is rare at high altitudes. The disease has, how- 
ever, been observed in Italy, and in South America at elevations of nearly 
10,000 feet. Consideration, however, of our knowledge of the habits 
of Anophelinae, would lead to the anticipation that, with suitable teluric 
and climatic conditions, altitude per se would play but a small part. The 
reported existence of malaria in localities which, from general geopraphical 
conditions, might be expected to be free from the disease should always 
be carefully investigated, for relapses may occur in any climate and 
under a great variety of conditions.1 
Drinking Witer.-The popular idea that malarial fever depends often 
upon the character of the drinking water is based largely on errors in 
diagnosis. Investigation usually proves that the condition regarded as 
malarial is in reality enteric fever. There is no evidence that the 
character of the drinking water has any influence whatever upon the 
development of malaria. 
Influence of the Time of Day on the Liability to Infection.-It has long been known that the dangers of malarial infection are greater during the 
evening and at night than by day. Anophelinse are for the most part 
night-biting mosquitoes. 
Influence of Age and Sex.-Children and infants are more susceptible 
to malarial infection than adults. This is, probably, in part, because the 
thin and delicate skin renders them peculiarly subject to mosquito bites. 
•Some years ago I was told of a young woman who always slept with her 
baby sister in order to escape the mosquitoes which usually attacked 
the infant by preference. Koch, who first pointed out the frequency of 
malarial infections in the early years of life among the natives of the 
tropics, regards the prevalence of the disease among the children of a 
given locality as an index of the extent to which malaria exists in that 
region. Apart from this, age and sex have, apparently, no bearing upon 
the prevalence of the disease except in so far as they affect the liability 
of the individual to exposure. 
Race.-In general the dark-skinned races who have, for generations, 
inhabited malarious regions in the tropics appear to possess a relative 
immunity to the disease. This may, however, be in part acquired as a 
result of the frequent infections in youth ; Koch's observations in Africa, 
as well as those of the Italian school, support this interpretation. On 
the other hand, it is undoubtedly true that in the United States the 
negroes who have inhabited the country for many generations, living 
under conditions not essentially different from those of the neighbouring 
whites, are much less liable to malarial infection. Our observations in 
Baltimore shew that the susceptibility of the negro is only about a third 
that of the white. It may be that the thick skin of the African renders 
him somewhat less susceptible to the bites of mosquitoes. 
Occupation.-The influence of occupation on the frequency of malaria 
depends wholly upon whether the individual is obliged to expose himself 
to infection during dangerous seasons of the year and at dangerous times 
of the day. In the rice fields of the southern states of America, the 
disease prevails among those who are obliged to spend their evenings and 
nights on the plantation, while it is rare among members of the same 
family who pass their time, during the dangerous seasons of the year, in 
the sandy " pine lands " often but a few miles distant. Those who live 
in well-screened houses are in little danger, while individuals sleeping in 
huts or unscreened dwellings are especially prone to infection. 
Influence of Population and Settlements on the Prevalence of Malaria.- 
Uninhabited regions, although infested by Anopbelinae are free from 
danger. Infected mosquitoes occur only in the immediate neighbourhood 
of settlements of infected individuals. It has often been observed that 
1 I^have mentioned elsewhere ( )'an instance of a relapse of tertian fever occurring 
during a walking trip in a most healthy region of the Alps, nearly eighteen months after 
the last paroxysm. the members of exploring expeditions have been free from the disease as 
long as they have been entirely removed from native or white settlements. 
Cycles of Severity.-Remarkable and hitherto inexplicable variations in 
the prevalence of malaria in districts in which it is endemic have long 
been recognised. In some regions the disease may, indeed, almost or 
entirely subside to appear again after a period of years. 
Cangenital malaria.- The possibility of the transmission of the parasite 
through the placental circulation has, for years, been a disputed point. 
It was generally accepted by the older observers and such a case at that 
of Duchek, in which a child botn of a malarious mother and dying three 
hours after birth shewed a large pigmented spleen together with pigment 
in the portal vein, is most suggestive. Since the discovery of the parasite 
the presence of organisms in the blood of the new-born child has been 
reported in several instances, notably those of Bein. Bouzian, and Peters, 
but in all of these cases a sufficient length of time had elapsed after birth 
to allow of a fresh infection. On the other hand, in a number of 
recorded cases, the blood of infants born of malarious mothers, as well as 
the placental blood, has been examined by observers who have made a 
special study of this disease (Bignami, Bastianelli, Caccini, Thayer, 
Schaudinn). In none of these was there evidence of infection of the 
child, although parasites were found in the peripheral blood of the parent 
and once in the maternal side of the placenta. Hitte, it is true, asserts 
that he has found malarial parasites in the blood of the umbilical cord 
in two cases; the article, however, seems to me inconclusive. The 
transmission of malaria from parent to offspring is, at all events, a rare 
occurrence. 
Immunity.-There is evidence of the existence of a certain degree 
of immunity, both natural and acquired, against the disease. The 
existence of a natural immunity is suggested ; (1) by the relative 
insusceptibility of some dark races ; (2) by the exemption from disease 
of certain individuals who live in most malarious districts and are 
constantly exposed to infection; (3) by the insusceptibility of occasional 
subjects to experimental inoculation of malarial blood. Generally 
speaking, one attack of malaria does not protect against subsequent 
infections; there is, however, some reason to believe that severe and 
repeated attacks do, in some instances, result in a partial or complete 
immunity of doubtful duration. Cases of this sort have been described 
by Celli, and can be observed in all severely malarious districts, while 
Koch, as has been said, regards the relative immunity of the dark 
skinned races as largely due to the great frequency of infections during 
childhood. The remarkable waves of intensity of malarial epidemics in 
localities in which the disease is endemic, may, as Celli suggests, be due 
to the periodical development and exhaustion of a certain degree of 
immunity among the population. 
Pathological Anatomy.-Death so rarely occurs in the milder forms 
of acute malaria that descriptions of the pathological changes are based 
almost entirely upon appearances observed in cases of pernicious fever 
of the aestivo-autumnal type. The most striking point in the appearance 
of all the organs is the general slaty grey colour, due to the accumulation 
nf nipment nrndiinpd hir rwiaitw T'lno 
395 w p *o - I" *■ wvuv v«s7<w»3» u.xaio £Jl^llldl LHL1UIL IS IHUl U 
extensive in older infections, and may vary considerably in its localisa- 
tion as is true also of the parasitts themselves. This is in part because 
much of the pigment is contained within parasites, the irregular dis- 
tribution of which in the internal organs is one of the most remarkable 
features of malarial infections. While found to a greater or less extent 
in the general circulation, the parasites are nearly always present in 
special abundance in certain organs, notably the spleen and bone-marrow. 
In many pernicious cases, however, individual organs may be the seat 
of a peculiarly intense infection, and this special localisation of the 
infection may and often does result, not only in grave local disturbances 
of function, but also in definite anatomical changes in the affected organ. 
Cases in which individual organs are thus, as it were, picked out often 
present distinctive clinical phenomena, traceable to the disturbances of 
function of the affected part; these special symptoms may dominate 
the clinical picture. 
In mild cases the brain shews few changes. The grey cortex is as 
a rule of a deepened, somewhat chocolate colour which may be striking. 
Areas of punctiform haemorrhage may be found. In severe cases the 
capillaries are crowded with pigment-bearing cells and parasitiferous 
corpuscles, so much so, indeed, as to form a complete injection. The 
endothelium of the capillaries is swollen and phagocytic, containing 
parasites, pigment, and often degenerated and infected red corpuscles. 
Thrombosis with these elements-the so-called " pigment thromboses "- 
with resultant haemorrhage may occur. These haemorrhages, usually of 
focal distribution, may be sufficiently extensive not only to cause acute 
manifestations, but to result in secondary sclerotic changes (Spiller). 
Monti and Ewing have described degenerative changes in cortical 
ganglion-cells, changes due doubtless in part, to circulatory disturbances 
although, according to the latter observer, " the comparative uniformity 
of the lesions noted indicates that a general toxaemia is, even in cerebral 
cases, the more important." 
The thoracic organs shew, as a rule, little that is characteristic beyond 
the occurrence of pigment-bearing phagocytes in the capillaries. In a 
case in which cardiac failure was a striking feature, Ewing found large 
numbers of young parasites and pigmented cells completely filling 
distended capillaries throughout the heart-wall. Similar observations 
have been made by Benvenuti. 
The spleen is enlarged, and in acute cases, as in one studied by Barker, 
soft and almost diffluent. It is usually of a dark cyanotic colour due 
to pigment, and, in old cases, may be almost black. The enlargement 
may be so great as to result in rupture, either spontaneous or after slight 
injuries; thus I know of an instance of rupture foilowing aspiration for 
diagnosis. The pulp is crowded with red blood-corpuscles containing 
parasites which are usually in the later stages of development-bodies' System of Medicine 
Vol. II Part II 
First Proof 
396 
with central pigment clumps or blocks and segmenting bodies. Younger 
forms are relatively uncommon. There are great numbers of phagocytes, 
usually mononuclear elements, some of which are about the size of the 
mononuclear leucocyte of the blood, some macrophages laden with 
pigment, parasites, infected or degenerated red blood-corpuscles, and, 
sometimes, entire smaller phagocytes. Focal necroses of the pulp are 
not uncommon. Chronic or frequently repeated infections result in more 
or less characteristic changes in the spleen, which may become greatly 
enlarged. On section, the surface is of a somewhat slaty colour; the 
trabeculae are very prominent; the reticulum, vascular sheaths, and 
septa are thickened, while single or multiple lymphatic cysts may arise. 
The gradual development of these changes has been minutely described 
by Bignami. Amyloid change has been observed after long and chronic 
infections. 
The liver is usually enlarged and of a dark brown, or, if the infection 
be severe, of a slaty, grey colour. There is always marked cloudy swel- 
ling. The capillaries are dilated, and contain numerous pigment-bearing 
phagocytes, large macrophages being commonly present. The endothelium 
of the capillaries is often phagocytic. The number of parasites and 
phagocytes in the liver varies greatly in different cases and in different 
parts of one organ, although, as a rule, the vessels contain few intra- 
corpuscular parasites. Pigment-bearing cells are often found in the peri- 
vascular tissue of the portal spaces, while the liver-cells themselves may 
contain pigment and altered red blood-corpuscles. Disseminated areas of 
focal necrosis, associated with capillary thromboses, may occur (Guarnieri, 
Barker) ; the necroses may be so large as to be recognisable by the naked 
eye. With frequently repeated infections the liver may undergo changes 
resulting in enlargement with the development of more or less well- 
marked perilobular fibrosis, which has, however, little tendency to con- 
tract ; there is considerable irregularity in the size of the lobules, and 
more or less capillary dilatation. As in the case of the spleen, these pro- 
gressive changes have been ably described by Bignami. Amyloid change 
may occur after long continued and repeated infections. There is no 
satisfactory anatomical evidence that malaria alone is a cause of portal 
cirrhosis of the liver. 
Kidneys.-The renal changes in malaria are usually slight as compared 
with those in the liver and spleen. The kidneys may be slightly en- 
larged, the cortex rather pale, the markings a little indistinct. There is 
usually little or no evidence of pigmentation. Microscopically, infected 
red corpuscles and pigment-bearing leucocytes are often found in moderate 
numbers in the glomeruli and intertubular vessels. In some instances 
more severe changes may be found-degeneration and exfoliation of the 
capsular epithelium with albuminous exudates into glomeruli and focal 
necroses in the cortex, especially in the area of the convoluted tubules. 
These changes, as may be readily seen, cannot be correlated with the 
insignificant number of parasites which are present, and are probably 
dependent upon circulating toxic substances. Ewing has described a 
remarkable case of fatal acute haemorrhagic nephritis in aestivo-autumnal 
malaria. In this instance the cortex was remarkably light in colour, 
while the medulla and papillae were extreme!v dark and slightly rusty. The cortical markings were completely obscured, and there was wide- 
spread degeneration of the epithelium. The glomeruli contained a 
moderate number of pigmented cells and a few parasites, while the capsules 
were distended by a granular coagulum. Most of the cortical capillaries 
were quite obstructed by the pressure of the distended tubules. The 
capillaries in the medulla and papillae were crammed with infected cells 
and parasites, while the discharging tubules were filled with casts, some- 
times entangling infected red blood-corpuscles and pigmented leucocytes. 
There was a large superficial infarction from occlusion of vessels by 
thrombi of infected red b'ood-corpuscles, and numerous miliary haemor- 
rhages from rupture of capillaries crowded with infected globules. In 
this instance the lesions produced by the special localisation of the para- 
sites in the kidney dominated the clinical picture, and brought about the 
death of the patient. The grave changes occurring in haemoglobin uric 
fever are discussed elsewhere (ride, p. ). Amyloid change has been 
described in very chronic infections. 
The changes in the gastro-intestinal tract are usually insignificant, con- 
sisting of a slight degree of melanosis. In other cases, however, the main 
localisation of the infection appears to be in the intestine. Here there is 
great injection of the mucosa with haemorrhages and superficial necrosis 
and ulceration. The vessels are loaded with infected corpuscles and 
pigment-bearing cells, with resultant thrombosis, necrosis, and haemor- 
rhage. Such cases may present symptoms like cholera. Amyloid change 
has been observed after chronic infections. Pensuti has reported a 
remarkable case of chronic malaria with amyloid change in association 
with wide-spread atrophy of the intestinal mucosa. Inasmuch, however, 
as the case is unique, its dependence upon malaria cannot be definitely 
asserted. 
The bone-marrow is often extensively pigmented. The small vessels 
contain great numbers of parasitiferous corpuscles and numerous macro- 
phages. After frequently repeated infections there are usually signs of 
active hyperplasia, the marrow of the long bones becoming red in con- 
siderable areas. The degenerations which sometimes occur during acute 
infections may, however, result in considerable injury to the blood- 
forming function. A megaloblastic type of marrow, associated with 
changes in the blood characteristic of pernicious anaemia, has been 
described by Bignami and Ewing. There may be a complete lack of 
hyperplasia, resulting in fatal aplastic anaemia. 
Supra-renals.-Barker has described pronounced changes in the supra- 
renals, i.e. irregular areas of vascular dilatation with numerous parasites 
in the distended vessels. Macrophages may be present in varying 
numbers, while the endothelium of the capillaries, as well as the true 
adrenal cells, are phagocytic. The other organs shew little that is 
characteristic. 397 
Clinical Description.-The malarial fevers fall into three main types, 
according to the species of parasite causing the infection:- 
(1) Tertian fever {Plasmodium vivax). 
(2) Quartan fever {Plasmodium malaria). 
(3) ^stivo-autumnal fever {Laverania malaria, Plasmodium falciparum). 
The first two varieties, tertian and quartan, are sometimes classed as 
the regularly intermittent fevers, in contradistinction to cesHco-autumnal fever, 
the manifestations of which are considerably more variable. 
Our knowledge of the period of incubation in malaria is based upon 
the results of experimental inoculations by the bites of infected mosquitoes 
(Grassi, Bastianelli, Bignami, P. T. Manson, Jancsd), and on the observa- 
tion of cases developing under close medical supervision, where the time 
of inoculation could be determined with comparative accuracy (Mariotti- 
Bianchi, Jackson). The interval between the time of invasion and the 
first febrile symptoms varies somewhat according to the type of infection. 
In quartan fever the period of incubation is about 3 weeks; in tertian 
fever it averages about 14 days; in a?stivo-autumnal fever, from 10-12 
days. But the period of incubation may be much prolonged. Experi- 
mental inoculations have shewn that it varies inversely as the number of 
parasites introduced, while the physical condition, race, natural or 
acquired resistance, and general surroundings of the patient, as well as 
the virulence of the parasite itself, must obviously play a part in deter- 
mining the rapidity of the development of the symptoms. Celli has 
demonstrated experimentally an incubation-period of 47 days in quartan 
fever, while in another instance, in which the patient was treated before 
inoculation with phenocoll, the interval between infection and the onset 
of symptoms was 66 days. A possible explanation of the apparently 
prolonged periods of incubation in some cases is that, after spontaneous 
recovery from an infection the symptoms of which have been so mild as 
to have passed unrecognised, a relapse has simulated a primary attack. 
Symptoms-1. Tertian Fever.-Infection with the tertian para- 
site is the commonest form of malaria in temperate climates. The 
symptoms vary according to the presence of one or more groups of 
organisms. 
{a) Single Tertian Infections {Tertian Fever).-Infections with a single 
group of tertian parasites are characterised by intermittent febrile 
paroxysms, occurring at intervals approximately forty-eight hours apart, 
each paroxysm following closely upon the segmentation of the infecting 
group of organisms. Prodroma are slight. Two or perhaps four days 
before the initial attack the patient may complain of slight indefinite 
symptoms-headache, backache, anorexia, pains in the limbs, symptoms 
such as are common in any acute infection, though, often, the first seizure 
may come, as it were, entirely unheralded. The paroxysm is divided into 
three characteristic stages-the cold stage, the hot stage, and the defer- 
vescence or sweating stage. 
The cold stage is immediately preceded by indefinite feelings of malaise, 
headache, and general lassitude, often by vertigo, and sometimes by 
nausea and vomiting. By this time a slight rise in the body temperature 
has already set in. Chilly sensations, at first interrupted by slight flushes 
of heat, soon follow, increasing until the patient falls into a general rigor. The chill may be very severe. The sufferer shakes from head to loot, 
and begs for coverings and hot applications; the teeth chatter; the 
movements are so violent that the bed may shake: the face is drawn and 
pinched; the extremities cold and shrunken ; the skin is cool and often 
rather cyanotic; sometimes pale and moist. The pupils are usually 
dilated ; the pulse small, rapid, and of rather high tension, sometimes 
irregular. Nausea and vomiting are common during the paroxysm, and 
there may be diarrhoea. The urine is increased in quantity. There is 
severe headache, and aching pains in the back and legs ; sometimes 
vertigo and tinnitus aurium. The duration of the chill varies from ten 
minutes to an hour. Not infrequently no actual shaking may occur, the 
patient complaining only of chilliness. Occasionally sensations of cold 
may be entirely absent. Out of 332 cases of tertian fever occurring at 
the Johns Hopkins Hospital, chills or chilly sensations were present in 
97'5 per cent. During the chill the temperature rapidly rises, reaching 
its maximum, as a rule, within two hours after the onset of the paroxysm. 
With the subsidence of the chill, intermittent flushes of heat usher in 
the so called hot stage, of the paroxysm. There is a subjective sensation 
of intense heat; the skin is flushed, hot, and dry; the conjunctivae 
injected. The pulse remains rapid, but is softer and not infrequently 
dicrotic. The patient complains bitterly of headache, vertigo, pains in 
the back and extremities, and often of tinnitus aurium ; he is very restless, 
and frequently delirious, tossing about and throwing aside the bed clothes. 
In one of our cases a patient with tertian fever sprang out of the window 
in his delirium. But the patient may be dull and apathetic, complaining 
of severe headache and backache, and presenting an appearance not unlike 
that in typhoid fever. Somnolence, and even coma, though very rare in 
this type of malaria, may occur. There is intense thirst. There may 
be a slight cough, while nausea, vomiting, and diarrhoea are common. 
Abdominal pain, sometimes referred to the region of the spleen, is not 
unusual. There may be bleeding from the nose. In children, convulsions 
of varying severity not infrequently take the place of the malarial 
paroxysm. The patient's appearance is characteristic; he is usually 
flushed, the conjunctivae suffused and injected, the tongue dry and coated. 
The sallow, earthy hue of the skin, associated with a slight yellowish tint, 
is remarkably characteristic of the disease. If many paroxysms have 
occurred there is usually a slight anaemia. Herpes about the lips and 
nose is common. There is often slight bronchitis. The spleen is enlarged 
and usually palpable; soft in early cases; harder in those of long dura- 
tion, and after repeated attacks it may attain a considerable size, extend- 
ing to or even below the umbilicus. Splenic enlargement is especially 
notable in children. Erythema or urticaria, sometimes of a remarkable 
morbilliform character, not infrequently accompanies the paroxysm. A 
purpuric rash is sometimes observed. Erythema nodosum has been 398 
described (Moncorro, Riva-Rocci). During the hot stage the temperature 
reaches its maximum, which is often above 105° F. The duration of this 
stage is usually four or five hours, though it may be considerably longer. 
The onset of the sweating stage brings relief from the sensation of heat. 
The sweating soon becomes profuse, and sometimes drenching. The 
temperature falls rapidly, the pulse beconiing slow and regular, while the 
patient sinks often into a refreshing sleep. Within a few hours, rarely more 
than four, the temperature falls below normal, usually remaining sub- 
normal during the greater part of the intermission. The length of the 
entire febrile paroxysm in cases of single tertian malaria averaged, in our 
cases, about eleven hours. These paroxysms are more frequent during 
the day than at night, the onset occurring generally in the late morning 
hours. 
During the greater part of the intermission, which lasts, as a rule, 
fully thirty-seven hours, the temperature is subnormal. The patient feels 
remarkably well-often, indeed, the effects of the paroxysm have entirely 
Chart 1.-Tertian Fever. 
disappeared-and gets up and goes about his business, believing that he 
is cured. But almost exactly forty-eight hours from the onset of the first 
paroxysm a second similar attack occurs, and, if treatment be neglected, 
febrile periods and intermissions alternate with great regularity. 
Although, as is well known, the cycle of existence of the tertian parasite 
is about forty-eight h'>urs, yet the periods of sporulation often occur at 
intervals slightly shorter or longer than this time. In such instances the 
resultant paroxysms appear at intervals somewhat less or somewhat more 
than forty-eight hours-so-called "anticipating" or " retarding " attacks. 
Retardation is sometimes observed in connexion with spontaneous recovery 
or after taking quinine. 
Examination of the blood reveals the presence of one generation of 
tertian parasites. The first intracellular forms of the schizont become 
evident during the paroxysm. These are extremely delicate, pale, 
hyaline discs about r5-3/x in diameter. They are actively amceboid. 
Soon after the beginning of development fine, brownish, pigment-granules 
appear, and increase in number with the growth of the parasite. On the 
day of intermission the young schizont has at rest a diameter of more 
than half that of the normal red blood-corpuscle. But the organism is 
rarely at rest; its amoeboid activity throws it generally into irregular 
and bizarre shapes. The index of refraction of the oarasite differs so 
slightly from that of the containing corpuscle that the outline of the 
body is often barely distinguishable, while the pigment-^' mules, collecting, 
as they do, at the bulbous extremities of several pseudopodia, give the 
impression at first glance of three or four separate parasites, instead of a 
single irregularly-shaped organism. The surrounding corpuscle at this 
stage is already materially larger than its neighbours, and is, moreover, 
less decolourised. In some cases the decolourised corpuscle shews a number 
of glistening granules which, in specimens stained by Romanowsky's 
method, take a deep red colour-the so-called Schiiffner's granules. On 
the day of the paroxysm, five or six hours before its onset, the parasites are nearly as large as the normal red corpuscle, and wholly immobile; 
the pigment is coarser, darker, and less active, and the surrounding 
corpuscle wholly decolourised and scarcely discernible. Shortly after 
this, beginning several hours before the paroxysm, early segmenting 
forms are seen. The pigment collects at one point in the organism, 
which assumes a somewhat granular appearance ; glistening dots repre- 
sen ing the chromatin of the individual segments begin to appear, and 
finally the outlines of the 12-24 separate merozoites become distinct. 
Segmenting bodies may be seen throughout much of the paroxysm. 
Large vacuolating and fragmenting bodies are also common at this 
period. After several paroxysms the large, non-motile, spherical, 
pigmented gametes may be seen in varying numbers, and if the specimen 
be studied for over ten minutes, flagellation of microgametocytes may be 
observed with the liberation of microgametes. 
The parasites are less abundant in the peripheral circulation during 
the period immediately preceding, and at the time of the paroxysm, than 
they are during the periods of intermission, because the mature bodies 
tend to accumulate in the internal organs, especially in the spleen. The 
onset of a paroxysm may be predicted with certainty from the discovery 
of segmenting bodies in the circulation. During the paroxysms, and to 
a certain extent at other periods of the infection, evidences of phago- 
cytosis can be found in the presence of pigmented white elements, 
sometimes polymorphonuclear, often mononuclear in character, containing 
granules or blocks of pigment similar to those seen in segmenting forms. 
On a slide of fresh blood active phagocytosis may be observed at any 
stage of development of the parasite, whenever an organism breaks out 
of a red cell. The elements taking part in the phagocytosis observed in 
the fresh specimen are polymorphonuclear leucocytes; those containing 
the pigment blocks are usually mononuclear elements. 
Further examination of the blood reveals a slight anaemia, if there 
have been several paroxysms. The leucocytes are reduced in number, 
the percentage of polymorphonuclear neutrophils decreased, that of the 
large mononuclear elements augmented. The urine in tertian fever 
shews no especially characteristic changes. A slight trace of albumin is 
often present, having been found in 38'3 per cent of 344 cases. 
(J) Double Tertian Infections {Quotidian Fever).-Infections with two 
groups of tertian parasites are commoner than single tertian infections. 
In these instances segmentation of a generation of parasites occurs daily, 
resulting in quotidian intermittent fever. Though the time of segmenta- 
tion of the groups of parasites reaching maturity on successive days are 
often nearly the same, yet an analysis of the temperature chart usually 
shews a definite relation between the hours of onset and the character of 
the paroxysms occurring every other day. The symptoms differ in no 
essential from those in single tertian infections. The paroxysms are, however, somewhat shorter, lasting on an average between ten and 
eleven hours. The dependence of the symptoms upon two groups of 
parasites may sometimes be demonstrated by the administration of a 
small dose of quinine at about the time of a paroxysm. The drug, 
exercising its most active influence upon the extra-cellular organisms, 
segmenting bodies, and free merozoites, may, if administered at this time, 
by destroying the segmenting group of parasites, change the type of 
fever from quotidian to tertian. Examination of the blood shews two 
groups of tertian organisms at different stages of development corre- 
sponding to the time of onset of the paroxysms. Thus at the time of a 
paroxysm, while one group is represented by full-grown parasites, 
segmenting forms, and fresh hyaline bodies, the second generation is 
present in the shape of half-grown, pigmented, amoeboid, intra-cellular 
elements. 
(c) Multiple Tertian Infections {Irregular Remittent Fever).-Occasionally 
infections with multiple groups of tertian parasites may occur. In such 
cases the paroxysms, becoming subintrant, result in apparently irregular 
remittent fever. The diagnosis may be made by examination of the 
blood. Occasionally in severe multiple infections but few parasites are 
to be found in the peripheral circulation, the greater part of the develop- 
ment going on in the internal organs. Such cases, however, are unusual 
and exceptional. 
2. Quartan Fever.-Infections with the quartan parasite are 
almost everywhere rarer than tertian malaria. In some localities they 
are not observed. In Italy there are certain regions where quartan fever 
is especially frequent. In Baltimore, out of 1613 cases of malaria, there 
were but 17 instances of quartan infection. 
{a) Single Quartan Infections (Quartan Fever).-In infections with a 
single group of quartan parasites the paroxysms, corresponding with the 
segmentation of parasites, occur with great regularity at intervals of 
approximately seventy-two hours. The paroxysms ditter in no way from 
those of tertian fever, the periods of intermission-associated likewise 
with subnormal temperature-are, however, twenty-four hours longer. 
399 
Chart 2.-Quartan Fever. 
Slight anticipation or retardation may occur as in tertian fever. The 
diagnosis is readiiy made by the examination of the blood, which shews 
a single group of quartan parasites. Fresh young schizonts begin to 
appear in the red blood-corpuscles, as in tertian fever, during the 
paroxysm. A few hours later pigment granules appear at the periphery 
of the parasite, the amoeboid movements of which are much less active 
than in the tertian organisms. On the second day the schizont is some- 
what larger, very slightly amoeboid, the pigment lying at the periphery. 
The organism is at this stage easily distinguishable from the Plasmodium 
vivax by its relative lack of amoeboid activity, its greater refractiveness, 
and the slight motility and peripheral arrangement of the pigment- 
granules. The surrounding red corpuscle is often rather smaller than 
its neighbours; it may already be of a somewhat deeper colour. On the 
third day the parasite is a little larger, and often of a somewhat ovid shape; it is quite motionless. The pigment is coarse and peripherally 
arranged. The infected corpuscle is represented by a small rim of 
rather greenish or brassy-coloured refractive protoplasm. The whole 
body is smaller than the normal red blood-corpuscle. On the day of the 
paroxysm, sometimes as much as eight to ten hours before its onset, 
evidences of segmentation are observable. The small rim of surrounding 
corpuscle is barely visible, while the pigment begins to collect towards 
the centre of the parasite, flowing in in radiating lines. This is rapidly 
followed by the development of the characteristic regular segmenting 
bodies with six to twelve merozoites. Large vacuolating and fragmenting 
forms, as well as evidence of phagocytosis, are especially common at this 
period, as in tertian fever. Large pigmented, sexually-mature forms 
(gametes) and flagellation may be observed at any time in older 
infections. Gametes are, however, less frequent in quartan than in 
tertian fever. Segmenting bodies begin to appear eight or ten hours 
before the onset of the paroxysm. The quartan parasites, occurring with 
much greater relative frequency in the peripheral circulation than either 
of the other species of malarial organism, are to be found in the fresh 
specimen of blood in even very mild infections. The discovery of 
segmenting organisms in the peripheral circulation in tertian fever is an 
almost certain warning of a paroxysm. In quartan fever, however, all 
stages of the organism may be studied in the blood in infections so mild 
as to be wholly free from fever. 
(b) Double Quartan Infections.-In infections with two groups of the 
quartan parasite, paroxysms occur on two successive days, followed by a 
day of intermission. The paroxysms are in every way similar to those 
observed in single quartan infection. The diagnosis is easily made by 
examination of the blood. 
(c) Triple Quartan Infections (Quotidian Fever').-Triple quartan infec- 
tions result in quotidian intermittent paroxysms, which may resemble in 
every way double tertian fever. A careful study of the chart will 
generally, however, reveal a similarity between the hours of onset and 
character of the paroxysms, occurring seventy-two hours apart, sufficient 
to indicate the nature of the infection. Examination of the blood reveals the 
presence of three groups of quartan parasites. Since, as mentioned above, 
quartan organisms are so common in the peripheral circulation, it is often 
the case that single or double quartan fever may occur in a patient whose 
blood shews three distinct groups of parasites, only one or two of which 
have reached a degree of development sufficient to cause a definite febrile 
reaction. The urine in quartan fever shews no characteristic changes. 
A trace of albumin is often present. 
3. 2Estivo-Autumnal Infections (AEstivo-Autumnal Fever).-The 
restive-autumnal fevers prevail in the tropics, occurring in temperate 
climates only at the height of the malarial season. Infections with System of Medicine 
Vol. II Part II 
First Proof 
400 
Laverania malaria {Plasmodium falciparum) are especially notable for 
their tendency toward irregularity, and toward the development of 
remittent or subcontinuous fever, as well as for the frequency with 
which " pernicious " symptoms appear. The continued and remittent 
character of the fever in many cases depends probably on the arrangement 
of the parasites in groups, the segmentation of which extends over long 
periods of time, resulting in paroxysms of greater duration, which, 
through their special tendency to anticipation and retardation, often 
become subintrant. Again, infections with multiple groups of parasites, 
are frequent. In most cases definite paroxysms may be easily traced 
Chart 3.-Remittent Fever: zEstivo-Autumnal Infection. 
upon the carefully kept clinical chart, and on analysis the febrile curve is 
more or less regular. Inasmuch as the cycle of development of the 
common variety of sesti vo-autumn al parasite lasts about forty-eight hours, 
the intermittent fever of aestivo-autumnal malaria is of the tertian type 
-a fever which has fairly definite characteristics {malignant tertian fever). 
The striking feature of sestivo-autumnal fever is the great length of the 
paroxysms, which are often of over twenty-four hours duration, differing 
materially from those of the regularly intermittent fevers. The onset 
may be abrupt, but is frequently gradual and insidious. The chill was 
absent in nearly one-third of our cases, and, when present, was often 
abortive or delayed, coming on only after the paroxysm was well under 
way. The general symptoms are usually severe, the gravity of these 
so-called "dumb chills" being well recognised by the inhabitants of 
malarious districts. There is severe headache, intense aching pains in 
the back and extremities, often vertigo and tinnitus aurium ; nausea, 
vomiting, and diarrhoea, especially in children, are frequent. Delirium, 
mild and muttering, or in some pernicious cases violent and maniacal, 
is common. In other instances the dull, drowsy, apathetic condition 
suggests enteric fever. The same cutaneous manifestations may be 
observed here, as in the regular intermittents. During the fastigium of 
the paroxysm there may be considerable oscillations and variations in 
the temperature curve. Marchiafava and Bignami have described as 
characteristic a pseudo-critical fall in temperature, followed by a pre- 
critical rise ; this we have often seen. The defervescence is more gradual, 
and the sweating stage less distinctive and characteristic than in tertian 
and quartan fever. Paroxysms may occur at intervals considerably 
greater or less than forty-eight hours. Thus I have observed an instance 
of sestivo-autumnal fever, with paroxysms recurring with considerable 
regularity, at intervals of as much as fifty-six hours, as well as cases in 
which the paroxysms repeated themselves every thirty-eight hours. The 
pseudo-critical depression may be so marked as to give rise to a complete 
intermission, resulting in a complicated clinical picture. Infections with 
two groups of parasites, causing quotidian or continued fever, are very 
common. 
Although, like many others who have worked at malaria, I have been 
unable to distinguish any definite morphological differences among the 
sestivo-autumnal parasites just'/"'n" a division into distinct varieties or species, it must be acknowledged that the observations of Bignami and 
Bastianelli,|Mannaberg, Craig, Caccini, and others, appears to show occa- 
sionally cases of sestivo-autumnal fever occur with quotidian paroxysms, 
due to infection with a single group of parasites whose cycle of existence 
is limited to approximately twenty-four hours. The paroxysms differ 
from those already described only in being, as a rule, rather shorter than 
those due to parasites with a longer cycle of development. Cases of 
irregularity, due to prolongation, anticipation, or retardation of the 
paroxysms, with resultant subcontinuous or remittent fevers are common. 
The average length of the aestivo-autumnal paroxysm in our cases was 
between twenty and twenty-one hours. 
Irregular Fevers.-Anticipation or retardation of the paroxysms, 
excessive oscillations in the temperature curve during the febrile period, 
as well as highly developed pseudo crises, often result in a very irregular 
temperature curve. Tne irregularity may be so great that careful study 
of the chart fails to reveal the fundamental type of the infection. 
Remittent or Subcontinuous Fevers.- As a result of prolongation, antici- 
pation, or infection with multiple groups of parasites, the paroxysms not 
infrequently become subintrant, with consequent, remittent, or continued 
fever. The absence of the chill, the dull, drowsy, typhoid condition, the 
muttering delirium, the enlarged spleen, the coated tongue, the not infre- 
quent intestinal symptoms may closely simulate typhoid fever. This 
type of fever has indeed been called Subcontiuua typhoid,ea (Baccelli). 
Examination of the blood, in sestivo autumnal fever, reveals infection with 
Laverania malarice (Plasmodium falciparum'). As has been mentioned else- 
where, these parasites differ from those of tertian and quartan fever in 
that a greater part of their cycle of existence is passed in the vessels of 
the internal organs, the younger forms alone being observed in the peri- 
pheral circulation. Towards the middle and latter part of the paroxysm 
and immediately afterwards, small, refractive, ring-shaped and amoeboid 
bodies are to be found which gradually develop a very few, extremely 
fine, peripherally arranged pigment-granules. The ring-shaped bodies 
are often contained in shrunken or cremated, brassy-coloured corpuscles. 
Sometimes in these brassy-coloured elements the haemoglobin retracts 
from the periphery of the corpuscle, forming a layer above the parasite. 
Gradually the number of pigment-granules increases, though, as a rule, 
only two or three fine bits of pigment are to be found in each parasite. 
In infections in which the organisms are arranged in well-defined groups 
it may be extremely difficult to demonstrate any parasite in the peri- 
pheral circulation during the period immediately preceding the paroxysm. 
Not infrequently in severe infections a few mature bodies, half the size 
of the red corpuscle, with a single central pigment block or clump, may be 
found at this period. Segmenting bodies are rare in the peripheral circu- 
lation. Aspiration of the spleen, however, may shew a great abundance of the mature forms with central pigment clumps or blocks, as well as 
segmenting bodies. This infrequency of the parasites just before and at 
the end of the paroxysm is a very important and characteristic point. 
Later, and on the following day, small hyaline or early pigmented forms 
may be numerous. In the case of parasites with cycles of development 
of forty-eight hours or longer, the bodies are somewhat larger, and the 
pigment slightly more abundant than in infections with organisms having 
a shorter cycle, in which segmentation has been described, while the 
parasite is still free from pigment (Marchiafava). After the process has 
existed from five days to two weeks, gametes, large ovoid and crescentic 
forms, with collections of coarse, centrally arranged pigment-granules, are 
usually present. A highly important diagnostic point in the aestivo- 
autumnal fevers is that, although at and just before the onset of the 
paroxysm, the parasites may be present in the peripheral circulation in 
very small numbers, yet phagocytes containing blocks of pigment are 
usually fairly abundant. The diagnostic importance of these elements 
should not be overlooked. In suspected cases in which organisms are 
not found in the fresh blood, examination should always be made of 
dried specimens stained by one of the modifications of Romanowsky's 
method. The blue rings with deeply staining chromatin dots are much 
more quickly recognised than the delicate hyaline bodies in the fresh 
blood. 
Pernicious Fevers.-Tertian and quartan fevers, when untreated, 
usually pursue a favourable course, terminating in spontaneous recovery, 
and, although frequent relapses may bring about grave cachexia, acute 
symptoms of a dangerous character are of the utmost rarity. The same 
cannot be said of aestivo-autumnal fever, which, if untreated, gives rise in 
many instances to the gravest manifestations. The rapidity of the multi- 
plication of the parasites, their especial malignancy (from the standpoint 
of their supposed toxic influence), and the tendency toward the invovel- 
ment of certain vital organs, bring about the malignant manifestations 
commonly termed " pernicious." These symptoms lately or never appear 
with the initial paroxysms; they are the result of neglect of treatment. 
Pernicious fever occurs in various types. 
The Comatose Type.-After several paroxysms, which may or may not 
have shewn a tendency to increase in severity, a fresh attack occurs, 
beginning often with a period of excitement, perhaps delirium, nausea, 
and vomiting, and followed rapidly by drowsiness, somnolence, or 
genuine coma. There may be restlessness and jactation ; the respiration 
may be quiet, loud, and stertorous, or of the Cheyne-Stokes character. 
The pulse, at first full and slow, becomes towards the end rapid, feeble, 
and irregular. The skin is often hot and dry ; the pupils ddated, con- 
tracted, or irregular. The conjunctivae are usually injected, the tongue 
dry and coated. Slight jaundice of the skin and conjunctivae is an 
important sign. There is usually moderate anaemia. The deep reflexes 
may be present or absent. Local spasms may point to a special localisa- 
tion in the central nervous system of changes due to the focal accumula- 
tion of parasites. The spleen is usually palpable. During the attack 
the temperature is usually high, sometimes above 106° F.; as it falls the 
401 patient gradually regains consciousness. Defervescence may be asso- 
ciated with active delirium, lasting perhaps (Marchiafava and Bignami) 
for several days and ending fatally. Again, an improvement may last 
but a few hours, being rapidly followed by a fatal recurrence. Coma 
may last a few hours or for as long as four days ; in favourable cases 
it slowly passes off with defervescence and the sweating stage, although 
for some time after the attack the patient is usually dull, stupid, and 
apathetic. Should a succeeding paroxysm occur, it is generally fatal. 
Marchiafava and Bignami have observed cases in which the coma lasted 
from four to five days, death occurring at a time when the parasites had 
almost completely disappeared from the circulation, both peripheral and 
central. In these cases definite organic changes (punctiform haemorrhages) 
are usually present in the central nervous system. 
Other Cerebral and Spinal Manifestations.-The pernicious paroxysm 
may be associated with active, maniacal delirium, and in some instances 
tetanic convulsions have been observed. In children and young people 
the manifestations may simulate meningitis. Well-marked bulbar 
symptoms are not uncommon, and in a case of this kind Marchia ava 
demonstrated special involvement of the medulla at the autopsy. Dis- 
turbances of speech are not unusual. Transient hemiplegia, aphasia, or 
amaurosis may occur. Marked vertigo with symptoms, especially of 
cerebellar type, are not infrequent; while in a number of instances a 
group of symptoms imitating disseminated sclerosis has been described 
(Torti and Angelini). Bestianelli and Bignami have reported a case 
with symptoms closely resembling those of so-called electric chorea. An 
interesting example of tetany occurring with the paroxysm was observed 
by Al best. 
Choleriform Pernicious Fever.-The special localisation of grave aestivo- 
autumnal infections in the intestinal tract may result in symptoms 
simulating Asiatic cholera-sudden, profuse, watery diarrhoea with 
collapse, the patient sinking before death into an algid condition 
(Marchiafava). In other cases, without intestinal manifestations, the 
paroxysm may be ushered in by a train of symptoms not unlike those of 
the algid stage of cholera-algid pernicious fever. The patient falls rapidly 
into a profound collapse. The eyes are sunken ; the features drawn; the 
skin cold, blue, and often bathed in a profuse sweat; the tongue dry, 
tremulous, and protruded with difficulty; the patient is so weak that he 
cannot raise his hand ; the voice is feeble and husky; the pulse is im- 
palpable at the wrist, and the temperature often little, if at all, elevated 
-in one of our cases it was subnormal during the last two days of life. 
The mind is, how'ever, usually clear almost to the end. As a result of 
the slight fever and the quiet, listless condition of the patient, the early 
symptoms of an algid paroxysm may be entirely unnoticed. In one of 
our cases a patient wrho had walked to the out-patient department died 
within two hours after admission. The paroxysm may be associated 402 
with violent, sanguineous vomiting and severe epigastric pains-airdialgic 
pernicious fever. Souli6 and Gillot have recorded a case simulating per- 
forated peritonitis. A patient was admitted to the hospital in collapse, 
with a history of melaena on the preceding night. He was very ill, and 
unable to give a satisfactory account of himself. There was vomiting; 
the facies was peritoneal; the abdomen distended and exceedingly 
tender. Everything pointed to peritonitis, following a typhoid perfora- 
tion. Examination of the blood, however, shewed numerous sestivo- 
autumnal parasites. The patient recovered promptly on vigorous treat- 
ment with quinine. Vomiting, polycholia, and jaundice may be prominent 
features, and make up the so-called bilious paroxysm. Cases in which 
the access is accompanied by great dyspnoea, thoracic pain, cough, blood- 
stained sputa, and evidences of acute bronchitis, have been classed by 
Baccelli as pneimonic pernicious fever. Pernicious symptoms-prostration 
and collapse-may develop in association with a great accentuation of 
the sweating stage of the paroxysm-sudoriferous or diaphoretic paroxysm. 
Of peculiar malignancy are cases with manifestations of purpura 
hsemorrhagica-the hcemorrhagic paroxsym. 
Examination of the blood in pernicious fevers reveals, in the great 
majority of cases, very large numbers of aestivo-autumnal parasites. The 
mere accumulation of plasmodia may be so great as to justify a fatal 
prognosis. Thus, a patient, admitted under my care shortly after a 
malarial paroxysm, was perfectly conscious, and looked weak and 
exhausted, but not especially ill ; the temperature was normal, the pulse 
under 100 ; there was a slight anaemia and distinct jaundice. The 
blood shewed a massive aestivo-autumnal infection-thirty to sixty 
parasites in a single field of the oil-immersion lens. In spite of vigorous 
treatment death followed in fourteen hours. Occasionally, especially in 
cases with celebral manifestations, the number of parasites in the 
peripheral circulation may not be very large, and, as has been mentioned, 
death may occur after days of treatment, at a time when the organisms 
have wholly disappeared from the blood of the ear or finger. The presence, 
common in pernicious fever, of larger forms of the parasite with central 
pigment-blocks, is specially important, and, according to Bastianelli and 
Bignami, is absolutely diagnostic of a great accumulation of plasmodia in 
the internal organs. The presence in the peripheral circulation of 
macrophages containing larger and smaller clumps of pigment, and often 
fragments of red corpuscles, which, in my experience, is the rule in 
pernicious fever, may be a sign of great importance. I have found these 
bodies in considerable numbers in cases of pernicious fever in which the 
parasites were not especially numerous. 
Combined Infections.-Infections with more than one species of the 
malarial organism at the same time are not uncommon. The usual 
combination is of tertian and sestivo-autumnal parasites. One species of 
organism generally prevails, and is responsible for the manifestations. In 
such infections alternating relapses have been described, due first to one 
and then to the other species of parasite, the course of events suggesting 
that the prevalence of one parasite has some inhibitory influence on the 
growth of the other. With the decadence of one species, however, the other begins to ueveiop, producing symptoms in its turn, occasionally, 
however, active groups of parasites of different species may exist 
simultaneously in the blood, and give rise to a complicated clinical 
picture. Marc has reported an interesting case of combined tertian and 
quartan infection. Wood of Wilmington, North Carolina, has shewn me 
preparations of the blood of a similar case. 
Relapses: Fevers with long intervals.-Untreated malarial fever 
unless it become pernicious, commonly undergoes spontaneous improve- 
ment, and in some instances, especially in tertian infections, the recovery 
may be permanent. Usually, however, even after fairly vigorous 
treatment during the original attack, there are relapses which may follow 
in more or less regular cycles. These may be divided into relapses 
occurring after short intervals and those following at longer periods 
(Caccini). 
Relapses at short intervals are apt to recur after periods approximating 
in time the duration of the ordinary incubation ; they are observed in 
tertian fever at intervals of from five to eighteen days, and in a'stivo- 
autumnal fever at periods from five to nine days. In quartan fever, in 
which relapses are especially common, there seems to be no particular 
rule as to the*time of outbreak, wh:ch is generally traceable to some 
definite exciting cause. Caccini has never observed spontaneous recovery 
in quartan malaria. These relapses appear to be due to the fact that, 
as a result of treatment or through natural powers of resistance of the 
human organism, so great a part of the infecting group of parasites is 
destroyed that a period, which approximates closely to that of the 
ordinary incubation, must be passed through before it reaches again a 
size sufficient to produce distinct paroxysms. In some instances the 
relapse consists of a single attack, after which a period of time practically 
or exactly equal to the previous intermission may elapse before a second 
recurrence. This sequence of events may continue for some time, 
giving rise to so-called fevers with long intervals. Carducci finds that in 
sestivo-autumnal fever the usual period of intermission is about seven 
days. In such cases the persistence through long periods of time of a 
low grade of infection may produce grave cachexia. Relapses of this 
sort are commonest in children, especially in those under five years of 
age ; this may be due to the lessened resistance of the infantile organism 
or to the greater difficulty of carrying out sufficient treatment. Relapses 
at short intervals, though frequent in all forms of fever, are commonest 
in tertian infections, probably because, on account of the mildness of the 
manifestations, proper treatment is often neglected. 
Relapses after long intervals.-Another variety of relapse occurs after 
periods of from several months to over a year. These outbreaks appear 
to depend upon various exciting causes, such as insufficient food, articles 
of diet which produce disturbances from special individual idiosyncrasy, 
gastro-intestinal disturbances, hard physical labour, mental strain, 403 
exposure to cold or wet, change in temperature or climate, trauma, 
surgical operations, pregnancy and parturition, infections, such as 
pneumonia and enteric fever and drugs (tuberculin, iodide of potassium). 
Relapses after long periods of time are especially common in tertian 
fever, less so in sestivo-autumnal infections. Relapses of tertian fever 
usher in the malarial season in temperate climates. In the intermissions 
between such relapses the patient appears perfectly well. No parasites 
are found in the circulation, and there is no anaemia. Treatment by 
quinine during the intermission has no effect whatever in preventing the 
relapse. 
The form in which the parasites persist throughout these long 
periods, and the part of the body in which they are hidden, are entirely 
unknown. It is not impossible that these late relapses may be due to 
parthenogenetic segmentation of macrogametes, such as has been described 
by Schaudinn. We have seen pictures exactly similar to his. Italian 
observers point out that in the malarial epidemic relapses are always 
more frequent than primary attacks. 
While recrudescences are especially frequent in quartan fever, the 
remarkable tenacity of which has been known for generations, relapses 
at long intervals are not common. The infection, though mild in its 
manifestations, persists for considerable periods of time, breaking out at 
intervals under any provocation, such as those above mentioned. 
The Urine in Malaria.-There are no constant variations in the 
amount of urine in malaria. The greatest quantities are passed during 
the early parts of the paroxysm. A post-malarial polyuria is common, 
beginning a few days after the disappearance of fever, and lasting some- 
times as long as thirty days; this is more marked after tertian and 
quartan than after sestivo-autumnal fever. The colour of the urine is 
usually high, depending on the increased amount of urobilin. There is 
no characteristic change in the acidity. The specific gravity varies 
inversely with the amount; it is often relatively high in post-malarial 
polyuria. The total nitrogen excretion is increased both during the 
acute stages of the illness and in the post-malarial polyuria, but the uric 
acid is not increased. The chlorides are present in normal proportion, 
being increased during the paroxysms, thus contrasting with the condition 
in fevers associated with local inflammatory processes, and are markedly 
increased in post - malarial polyuria. The elimination of sulphates 
corresponds closely to the variations in the excretion of nitrogen. The 
phosphates are often increased in quantity, but, uniike the other solid 
constituents, they are diminished during the febrile paroxysm; they are 
much increased in post-malarial polyuria. In the regularly intermittent 
fevers, tertian and quartan, a trace of albumin was present in 38'6 per 
cent of 352 cases in the wards of the Johns Hopkins Hospital. In 
aestivo-autumnal fever it was more frequent, occurring in 58'3 per cent 
of 165 cases. In the great majority of instances there was only a slight 
trace. In many of the cases in which albumin is found occasional 
hyaline casts may be detected in the sediment. In pernicious fever 
traces of bile may be found. 
Cause of the Malarial Paroxysm.-There has been much specula- tion as to the cause of the remarkable periodical paroxysms of malaria. 
Not only the character of the manifestations themselves, but the 
degenerative changes found in many organs-brain, nerves, liver, 
kidneys suggest that the access is associated with the presence of some 
circulating toxic substance or substances. The definite coincidence of 
the paroxysm with the fission of a generation of parasites has led most 
observers to assume that the poison, whatever it may be, is set free by 
the parasites at their time of segmentation. All attempts to isolate a 
specific toxic substance have so far been without result. 
Sequels. -Results of frequently relapsing or repeated Infections. Cachexia. 
Masked or Larvate Malarial Infections.-Frequent relapses or often repeated 
malarial infections may give rise to a great number of clinical manifesta- 
tions. In prolonged cases the patient may be reduced to a state of 
grave cachexia, the characteristic features of which are anaemia, great 
enlargement of the spleen; and a liability to anasarca and dropsy. In 
an advanced case the condition of the patient is truly pitiful. The 
emaciation, the dead, sallow, anaemic, earthy grey complexion, the 
sunken eyes, the listless, feeble air, the large spleen, and the oedema 
make a most characteristic and easily recognisable picture. In children 
the growth is often retarded, and well-marked infantilism may result 
(Cardarelli). Ancemia is among the commonest and most important 
sequels. Changes in the blood arise not only from the destruction of 
corpuscles in the individual malarial attack, but also as a result of 
changes in the blood-forming organs, as well as in other vital parts. The 
moderate anaemia which follows the first acute attacks is generally 
compensated by active regeneration. In long continued or recurrent 
infections, however, pronounced anaemia may develop. This is usually 
of the type of an ordinary secondary anaemia, the colour-index of the 
red corpuscles being reduced, and the leucocytes diminished in number, 
with a rather high percentage of mononuclear elements, especially of the 
large mononuclear variety. Nucleated red blood-corpuscles (normoblasts) 
are present. Bignami and Dionisi and Ewing have described cases pursuing 
an unfavourable course, in which the blood presented the characteristics 
of the megaloblastic type of pernicious anaemia, as well as rapidly fatal 
anaemias with a diminution in the number of leucocytes, an excessive 
percentage of small mononuclear elements, and an absence of nucleated 
red corpuscles-aplastic anaemia. Malarial hemoglobinuria is described in 
a special article (vide p. ). 
Among the cutaneous manifestations in chronic cases, especially 
when cachectic, is purpura, which may appear as a severe or even fatal 
purpura haemorrhagica (Ascoli). The peculiar earthy colour of the skin is 
so characteristic as to be often recognisable by the skilled observer. A 
remarkable phenomenon, occurring especially in chronic cases, is anasarca, 
which may, as Ascoli has pointed out, simulate sometimes the oedema 
of nephritis, sometimes that of cardiac failure, although the urine may be System of Medicine 
Vol. II Part II 
First Proof 
404 
quite free from albumin. Common in cachectic subjects, such oedema 
may appear in individuals in relatively good condition. An instance of 
this sort came under my observation some years ago. A man of about 
fifty entered the hospital in fairly good condition with well-marked 
oedema of the legs, and slight ascites, without apparent cause. There 
was no reason to suspect any defect in the heart, liver, or kidneys. 
Some days after admission the patient had a relapse of tertian malaria, a 
clear history of which had not been previously obtained. With rest and 
tonic treatment the oedema generally clears up. Multiple cutaneous 
gangrene is sometimes met with. A remarkable case of this nature has 
been reported by Prof. Osler. E. J. Wood of Wilmington, North 
Carolina, tells me that he has, in the last few years, seen several similar 
cases, in all of which the coincidence or immediately preceding existence 
of malaria has been proved by examination of the blood. 
Nephritis.-Acute nephritis is not an uncommon sequel, occurring in 
1'7 per cent of 1832 cases analysed at the Johns Hopkins Hospital. 
Rare in tertian and quartan infections, it is by no means infrequent in 
aestivo-autumnal fever. There is nothing remarkable in the character of 
the disease which pursues the course of an ordinary acute toxic nephritis. 
Of 26 cases of malarial nephritis 14 recovered; 4 died; in 9 the result 
was doubtful; in 2 chronic nephritis supervened. We have since seen 
several additional cases of chronic nephritis of undoubted malarial 
origin. 
Gastro-intestinal Tract. -Diarrhoea and dyspepsia are common in 
cachectic patients, but there are no especially characteristic gastro-intestinal 
manifestations. 
Liver.-As has been described in the section upon pathological 
anatomy, distinct changes in the liver associated with enlargement and 
chronic perilobular hepatitis often follow repeated malarial infections. 
These changes, however, give rise to no characteristic clinical manifesta- 
tions. While there is little anatomical evidence that malaria induces 
hepatic changes capable of producing the clinical manifestations of portal 
cirrhosis, some authors insist on the occasional clinical sequence of atrophic 
cirrhosis of the liver upon ma aria (Kelsch and Kiener, Lodigiani, 
Phillips). 
Nervous System.-The grave nervous phenomena accompanying per- 
nicious paroxysms are usually associated with fever. Sometimes, how- 
ever, the paroxysm may be represented by the nervous manifestations 
alone, fever being almost or entirely absent. After pernicious paroxysms 
the nervous phenomena clear up, as a rule, rather slowly; sometimes, 
indeed, they may persist for considerable periods of time. In chronic or 
frequently repeated attacks, especially of aestivo-autumnal malaria, the 
patient may present nervous phenomena of great variety and persistency. 
The commoner of these manifestations-vertigo, motor instability, tremor, 
ataxia of the cerebellar type, dysarthria, increasing as they do in per- 
nicious paroxysms to hallucinatory delirium, coma, and even convulsions 
-are, as Ascoli has well pointed out, in many ways analogous to those 
observed in alcoholism. The dulness, the uncertainty of memory, the 
listlessness, the apathetic condition, the tremor, the slow, uncertain speech 
of the cachectic patient, are very similar to the manifestations of chronic alcoholism. The psychical phenomena, aiso, are usually oi a coniusional 
type with a tendency toward hallucinatory delirium. Slow, hesitating 
speech, marked muscular weakness, or sometimes increased muscular 
excitability with exaggerated reflexes, are common. In a number of 
instances a clinical picture simulating that of insular sclerosis has been 
described (Torti and Angelini, Panichi, Bignami and Bastianelli, Spiller). 
Most of the hemiplegias occurring in connexion with malaria, as in one of 
our cases, are probably in individuals with pre-existing vascular changes, 
in whom the paroxysm has acted as the exciting cause for the rupture of 
thrombosis. 
Neuralgias, especially of the fifth nerve, may occur in chronic malaria, 
although intermittent facial neuralgia is much too often ascribed to 
paludism. Neuritides of the type of ordinary toxic multiple neuritis have 
been described by a number of observers (Eicbhorst, Saquep6e and Dopter, 
Schupfer, Fajardo and Couto, Luzzatto). Necropsies in the cases of 
Fajardo and Couto and Luzzatto shewed widespread and extensive paren- 
chymatous neuritis. In the latter case degenerative changes in anterior 
horn cells were also found. Cachectic subjects seem to be especially liable 
to neuritis from other recognised toxic causes. Deafness from neuritis of 
the auditory nerve has been described, although some of these instances 
are probably due to the administration of quinine. Optic neuritis, 
followed by atrophy, retinal haemorrhages, and retino-choroiditis, have been 
observed. Bindi reports an instance of angioneurotic oedema in a cachectic 
patient. In the reported cases of epilepsy of supposed malarial origin, it 
is quite possible that malaria acted only secondarily, as the exciting cause 
in a predisposed individual. Neurasthenia and hysterical conditions may 
follow malaria as in the case of any severe infection. Post-malarial 
psychoses are rare. Marchiafava and Bignami describe a case of acute 
maniacal delirium with a fatal result following a pernicious attack, while 
conditions of slight mental confusion with hallucinations may last for a 
week or two after malignant paroxysms. In one of our cases the patient 
remained in a depressed, confused condition with hallucinations for several 
months after an attack of tertian fever. 
Masked Malarial Infections.-Before the discovery of the parasite a 
great number of conditions having no relation to the disease were 
described as masked or larvate malaria. With our present knowledge 
such confusion should not exist. It has, however, long been known that 
parasites may be present in the circulation for considerable periods of 
time without causing symptoms which are definitely recognised as due to 
paludism. Latent infections are especially common among the natives of 
the tropics (Koch, Stephens and Christophers, Craig). Some of these 
cases occur in individuals who take irregular and improper treatment. 
In others, apparently because of the resistance of the organism, or from 
other causes, the infection never develops sufficiently to cause frank, 405 
characteristic paroxysms.1 Moreover, as has been already mentioned, 
grave, even pernicious manifestations of a nervous character may occur 
with normal or but slightly elevated temperature In 395 out of 1267 
cases of malaria studied by Craig in the army hospital at San Francisco, 
the symptoms were such that malaria was not recognised before the 
demonstration of the parasite in the blood. These facts emphasise the 
importance of regular examinations of the blood, especially in malarious 
regions or where there is the possibility that the patients may have been 
subjected to infection. 
Complications.-Pneumonia is so frequently a complication or sequel 
of malaria, and is so common in cachectic patients that, previously to the 
discovery of the parasite, it was often regarded as of malarial origin. 
The diminished resistance in cachexia favours, no doubt, the incidence of 
pneumonia as it does of any severe secondary infection ; moreover, pneu- 
monia may occur as a complication of a severe malarial attack, just as it 
may in enteric fever. The malarial infection may produce active 
symptoms during the course of the pneumonia, though it commonly 
remains latent during the attack, breaking out with convalescence. We 
have observed combined infections of pneumonia and malaria in several 
cases in the wards of the Johns Hopkins Hospital. The so-called pneumonic 
pernicious paroxysm has no connexion with true pneumonia. 
Enteric Fever.-Much has been written about the co-existence of 
malaria with enteric fever. In the great majority of instances the 
malarial outbreak occurs during convalescence from the enteric fever, 
though occasionally the two infections may exist simultaneously in an 
active stage, as in a case reported by Craig. The once prevalent belief 
that a special form of fever existed, resulting from a combination of the 
typhoid and malarial poisons, to which the name typho-malaria might 
properly be given, is without foundation. 
Dysentery and malaria may co-exist, and cachectic patients are un- 
questionably disposed to intestinal disorders. The combination of 
malarial infection with dysentery of the amoebic type is not uncommon. 
There is no such thing, however, as a specific malarial dysentery. 
Instances of combined infections of malaria with cholera, smallpox, and a 
number of other acute diseases have been de.-cribed. They present, howr- 
ever, no characteristics worthy of special mention. Tuberculosis and 
malaria were formerly thought to be antagonistic. The discoveries of 
recent years, however, have proved not only that acute tuberculosis does 
not exclude malaria, but that the existence of paludism in a tuberculous 
patient has a distinctly deleterious influence upon the course of the case, 
favouring the increased activity of the latter disease. Post-partum and 
post-operative relapses of malarial fever are not uncommon. Inasmuch as 
such relapses are not confined to malarial districts and may assume a per- 
nicious character, careful examination of the blood should always be made 
in the presence of anomalous symptoms after operation or in the puer- 
perium. It should, however, be remembered that the terms post-partum 
and post operative malaria have been greatly abused. It is probably fair 
to say that a large proportion of the cases reported in literature represent 
septic infections. 
Diagnosis.-Since the discovery of the parasite the diagnosis of malaria has become a relatively simple matter. 
Tertian and Quartan Infections.-In single tertian or quartan fever the 
characteristic intermittent paroxysms with the regular stages of chill, 
fever, and sweating justify of themselves a probable diagnosis. Herpes, 
ansemia, the earthy, greyish, slightly jaundiced colour of the skin, and 
the palpable spleen also help in the diagnosis. 
The intermittent febrile paroxysms of pulmonary tuberculosis, so fre- 
quently confounded with malaria, are rarely as regular, and are usually 
of much greater duration. They occur generally in the afternoon, while 
the malarial paroxysm begins more commonly in the morning hours. 
The chills, fever, and anaemia associated with infective endocarditis, 
septicaemia, and pyaemia may simulate malaria ; the paroxysms are, how- 
ever, irregular and shorter, two or three occurring sometimes in twenty- 
four hours. In two instances of influenza I have seen remarkably regular 
tertian ami quotidian paroxysms closely resembling those of paludism, but 
the thoracic symptoms were characteristic, and influenza bacilli were 
demonstrated in the sputa. The essential procedure in d agnosis is the 
eramimition of the blood,2 which reveals the characteristic parasites. 
Another very important point is the uniform absence of leucocytosis in 
tertian and quartan malaria, and its presence in most of the conditions 
which may give rise to a mistake in diagnosis. The presence of an 
appreciable leucocytosis is strong evidence against the existence of uncom- 
plicated malarial fever. When but few parasites are to be found, pigment- 
bearing leucocytes may be an important aid in diagnosis especially at the 
time of the paroxysms. The skilled observer can usually distinguish 
malarial pigment from extraneous particles. The differential diagnosis 
between tertian and quartan infections is best made by examination of 
the fresh, unstained specimen of blood. The tertian organisms are 
larger, paler, more actively amoeboid. The pigment, especially in the 
younger forms, is in smaller particles and more actively motile. The 
merozoites in the segmenting organisms are more numerous (15-30)£and 
not so regularly arranged. The surrounding corpuscle becomes 
decolorised and expanded with the growth of the parasite. The quartan 
organism is smaller, more sharply outlined, less amoeboid, slower in its 
movements; its pigment is coarser and less motile, and often more peri- 
pherally placed. The merozoites are less numerous (6-12) and more 
regularly arranged ; the surrounding corpuscle is apt to retract about the 
parasite, and becomes of a deeper colour. The same characteristics may 
be made out, though with somewhat less distinctness, in the stained 
1 Craig asserts that the evidences of intracorpuscular conjugation of the parasites, a pro- 
cess which he, in common with Ewing, regards as essential for the maintenance of an acute 
infection, are absent in latent malaria. 
2 Tn this connexion I venture to quote an observation made elsewhere : It is impossible 
to make reliable examinations of the blood for malarial parasites without first being familiar 
with the ordinary appearances of normal blood and the commoner pathological changes. 406 
specimen. In quartan fever the organisms are found with great frequency 
at all stages of development. In tertian fever they are somewhat less 
frequent in the blood at the period immediately preceding and during 
sporulation than during their earlier stages. 
Response to the therapeutic test-the immediate disappearance of the 
fever under treatment with quinine, is a strong, though not positive 
evidence of its malarial origin. The persistence of intermittent fever after 
vigorous treatment with quinine excludes malaria. Multiple and com- 
bined infections may be readily recognised by examination of the blood. 
The simplest, and in many instances, the most satisfactory method of 
studying the parasite is in specimens of the fresh blood which, with the 
portable microscopes now available, can be readily examined at the bed- 
side. If this be impossible the preparation of dried specimens stained by 
one of the different forms of the Romanowsky stain, especially that of 
Leishman and its various modifications (Wright, Hastings, Goldhorn) is 
an easy method of diagnosis. 
^stivo-autumnal Malaria.-In this form the diagnosis is not so simple. 
Where the paroxysms are distinctly intermittent, paludism may be at 
once suggested by the raised temperature, the characteristic change in the 
complexion, the jaundice, the frequently complicating herpes and the 
palpable spleen. The symptoms, however, may be obscure, and the 
disease is most commonly confounded with enteric fever. The intermittent 
or regularly remittent character of the fever may become evident only 
after long observation of carefully kept charts, while the absence of chills, 
the pains in the head, loins, and extremities, the general apathetic con- 
dition of the patient, the coated tongue and the enlarged spleen all 
simulate enteric fever. The examination of the blood usually settles the 
question. The leucocytes are normal or reduced in number in both 
infections, but in malaria sestivo-autumnal organisms as well as pigment- 
bearing phagocytes can nearly always be found. A special diagnostic 
difficulty met with in aestivo-autumnal fever is the small size of the para- 
sites ami the absence of pigment which, to the unskilled observer, renders 
them difficult to recognise in fresh blood. Again, artefacts and de- 
generative changes in the blood - corpuscles are often confusing.1 At 
maturity the aestivo-autumnal parasites are very scanty in the peripheral 
circulation, collecting usually in the internal organs, so that at a period 
immediately preceding and during the early part of the paroxysm, if a 
single group be present, but few organisms may be found. It is very 
important, therefore, in any doubtful case, to prepare stained specimens 
of blood. The characteristic ring - body, with its striking chromatin- 
granule, is much more readily distinguished in the stained specimen than 
in the fresh blood. If, in a suspected case, no parasites are found in an 
examination made early in the paroxysm, the procedure should always be 
repeated some hours later, when the result will probably be positive. 
Like Marchiafava and Bignami I have never found it necessary to puncture 
the spleen for diagnostic purposes. The procedure is moreover by no 
means free from danger in unskilled hands. In cases which have lasted 
over five days the frequent presence of the sexually mature forms, the 
large ovoid and crescentic bodies, is of great diagnostic help. It is, how- 
ever, in the pernicious fevers that confusion is most likely to arise. The comatose paroxysm may be mistaken for sunstroke, uraemia, or cerebral 
haemorrhage. The differential diagnosis from sunstroke may be extremely 
difficult, especially in cases in which the latter occurs in an individual 
already suffering from mild or chronic malaria. Jaundice, anaemia, and 
enlarged spleen would suggest malaria, while hyperpyrexia would be 
rather in favour of sunstroke. Although in some cases with cerebral 
manifestations there may be no great excess of parasites in the peripheral 
circulation, they are almost always present in sufficient numbers to allow 
of a speedy diagnosis. The frequency of pigment-bearing macrophages is 
a point of great importance in the diagnosis of pernicious fever; thus in 
a case of comatose paroxysm, in which the number of parasites was 
relatively small, I found numerous pigmented macrophages. As pointed 
out by Marchiafava and Biguami, these persist in the circulation for some 
♦lays after the parasite has disappeared as a result of treatment. The 
tetanic, meningeal, eclamptic, and hemiplegic types of malaria can also be 
recognised by the condition of the blood. In some instances, especially 
in an algid paroxysm or in afebrile atta< ks with grave nervous phenomena, 
the disease may be wholly unsuspected in the absence of systematic 
examination of the blood. The haemorrhagic paroxysm may suggest 
yellow fever, which indeed it may complicate. The disproportionately 
slow pulse in yellow fever is an important diagnostic point, while the 
quantity of albumin in the urine is usually much greater than in malaria. 
Examination of the blood is sufficient to determine the presence of the 
latter disease, although, as demonstrated in the recent epidemic in New 
Orleans, this may exclude co-existing yellow fever.1 
Chronic Malarial Cachexia.-The diagnosis of chronic malarial cachexia 
is rarely difficult if the history of the patient and the conditions under 
which he has lived are taken into account. It must be distinguished 
from secondary or primary anaemia, leukaemia, and the various types of 
splenomegaly-the so-called primary splenomegaly-splenic anaemia, or 
Banti's disease, and especially from kala azar. The enlarged spleen, the 
grave anaemia, the liability to haemorrhages and dropsical effusions, common 
to these various conditions, may render the diagnosis rather difficult. 
Leukaemia, of course, can readily be excluded by examination of the 
blood. The same, however, cannot be said of primary splenomegaly or 
Banti's disease, in which the type of anaemia is closely similar to that 
usually observed in malarial cachexia, while hepatic enlargement is 
common in both maladies. In such cases one must depend largely upon 
the history of the case. A febrile recurrence, with the presence of 
1 Nearly every year articles appear in reputable journals describing as a "new variety of 
malarial parasite " the peculiar navicular bodies with rotatory motion about a central axis so 
commonly observed in red blood-corpuscles. Incidentally the same structures have been 
described as parasites of measles and of yellow fever. 
2 Lanaux of New Orleans has shewn me several interesting charts of combined infections 
with malaria and yellow fever ; his communication upon this subject will appear shortly. parasites in the circulation, or the discovery of gametes of the sestivo- 
autumnal organism, settles the diagnosis. Kala azar (vide p. ) may 
be suspected in a patient coming from a district such as Assam, where it 
is known to exist, who has an enlarged spleen and spleen fever, unrelieved 
by quinine, and no malarial parasites in his blood. Splenic puncture 
should enable the Leishman-Donovan body to be recognised. On the 
other hand, kala azar may be complicated by malaria, and the most 
decisive test-splenic puncture-is not without danger. There is nothing 
characteristic in the nephritis of malarial origin. 
Masked Malarial Infections.-In regions in which malaria is common, 
or among patients who come from malarious localities, examination of 
the blood in all doubtful or unusual manifestations should never be 
neglected, as this may lead to the discovery and relief of a considerable 
number of unsuspected cases of malaria. 
Prognosis.-The prognosis of tertian and quartan infections is almost 
always good; I only know of two recorded instances of pernicious fever 
occurring in tertian malaria (French, Ewing). Spontaneous recovery is 
not infrequent in tertian fever. Frequent relapses are, however, the 
rule, and unless thorough and persistent treatment be carried out, grave 
cachexia may develop. Quartan fever, though benign in its manifesta- 
tions, is peculiarly tenacious, relapses often occurring, under slight 
provocation, through long periods of time.1 Under treatment with quinine 
recovery is universal. 
In cestivo-autumnal fever the prognosis depends upon the gravity, of 
the infection and the duration of the case. If untreated, spontaneous 
recovery may occur, but the development of grave cachexia is common, 
and pernicious manifestations are by no means unusual. If the diagnosis 
be made early, and thorough treatment with quinine be initiated, the 
progno is is perfectly good. If, however, pernicious symptoms have 
developed, the prognosis is always extremely grave. An absolutely 
favourable prognosis cannot be given until at least forty-eight hours 
after the beginning of treatment. Not infrequently the subsidence of 
one paroxysm may be rapidly followed by a second, which, despite all 
treatment, may prove fatal. If, however, this paroxysm be recovered 
from, a favourable prognosis may be given in most instances. The 
presence of an excessive number of parasites in the peripheral circulation 
in the interval following a pernicious paroxysm is of grave import. 
The converse, however, does not justify a corresponding good prognosis, 
inasmuch as there may be a relative infrequency of parasites in the peri- 
pheral circulation in cases of grave cerebral manifestations (yide p. ). 
Nor does the disappearance of the parasites from the blood under treat- 
ment of itself justify a favourable prognosis, for, despite this, the 
pernicious paroxysm may continue to a fatal termination. The prognosis 
in chronic malarial cachexia is usually good as far as life is concerned, if 
the condition have not lasted too long, and if the patient be in a position 
to take proper therapeutic and prophylactic measures. Removal to a 
healthy non-malarious district or, even at home, proper treatment will 
usually be followed by recovery. Without such measures, however, 
though rarely dying from the malarial cachexia alone, the patient falls a 
407 prey sooner or later to some secondary infection-chronic nephritis or, 
perhaps, amyloid disease. The prognosis in malarial nephritis is as a rule 
good, although chronic progressive changes may occur. The same is true 
of the remarkable nervous phenomena which may follow malaria. While 
proper treatment is followed, in the great majority of instances, by perfect 
recovery, yet such cases as that of Spiller suggest that permanent changes 
may remain. 
Treatment.-The treatment of malaria may be divided into (1) general 
management, (2) medicinal measures. 
Genera! Management.-Wherever possible, the patient should be con- 
fined in bed until all febrile manifestations have subsided and the 
parasites have disappeared from the peripheral circulation. But, 
unfortunately, it is not always easy to enforce this in mild cases. In 
some tertian infections rest in bed, with proper diet and care, are alone 
sufficient to effect a temporary or even a permanent cure, and there is a 
decided difference between the course of tertian and quartan infections in 
individuals who keep about their business and in those who submit for 
a period of a week or several days to thorough treatment. Rest in bed 
should be insisted upon in all cases of aestivo-autumnal fever. 
During the short cold stage of the paroxysm the patient should be 
made as comfortable as possible. V arm coverings are allowable, even if 
the fever have already begun. Hyperpyrexia, especially in aestivo- 
autumnal fever, where the paroxysms are of longer duration, should be 
met by cold sponges or tub baths. 
In teitian and quartan fever there is, as a rule, no occasion for 
modifying the diet. In the more severe aestivo-autumnal fevers the lack 
of appetite and general prostration of the patient may render a liquid or 
soft diet, consisting of broths, soups, milk, raw or soft boiled eggs, and 
the like, more convenient. If there be no gastro-intestinal symptoms, 
solid food may be given if the patient so desire. Abundance of water 
should be allowed. 
Medicinal Treatment.-We are fortunate in possessing a drug which 
exercises a true specific action on malaria. All malarial infections yield 
to quinine, provided treatment be instituted in time. The effect of the 
drug depends upon its poisonous action upon the parasites. As early as 
1867 Binz correctly concluded that the efficacy of quinine in paludism 
depended upon its action as a protoplasmic poison upon some lower 
organism, an hypothesis based upon his experience concerning the 
influence of quinine upon the infusoria. Various observers (Golgi, 
Mannaberg, Romanowsky, Marchiafava, Bignami, Baccelli, Lo Monaco, 
and Panichi), who have studied the changes occurring in parasites after 
1 Thus Galen (Glaucon, ix, ; Kuhn, xi. 25) says: "Among the intermittents the 
shortest and most tractable is the tertian ; the longest, but that which is per se 
free from danger, is the quartan." - iirl ptv ovv rots 8ia\ei7rovati> 6^u-rarjs re a pa 
Kal iirieiKtraros o TpiraUs tart • paKpiraros 8e Kal &kIv8vvos oaov tip eavrou 6 
rerapraios. System of Medicine 
Vol. II. Part II 
First Proof 
408 
the administration of quinine, confirm Laveran's observation that the 
organisms rapidly disappear after the drug has been taken. This is 
true of all forms of the malarial parasite excepting the gametes, especially 
those of the sestivo-autumnal organism (crescentic and ovoid' forms),, 
which may persist for weeks or, rarely, for months during treatment. 
These bodies, however, are, in ordinary circumstances at least, incapable 
of giving rise to the asexual cycle of the parasite, and are, therefore,, 
harmless while in the human body. Quinine exercises its action rapidly 
on the merozoites daring their extra-corpuscular and earlier intra- 
corpuscular stages. The mature schizonts are more resistant. If quinine 
be introduced into the circulation at about the time that the parasites 
have reached maturity, it will not prevent the segmentation of the 
ripening group, but it will destroy the young merozoites. If it be 
introduced into the circulation in sufficient quantities during or soon 
after the paroxysm, it wdl go far toward destroying the group of 
parasites which have caused the fresh infection. In order, then, to 
prevent the further development of a group of malarial organisms, 
quinine should be administered so as to be present in solution in the 
blood at the time of segmentation or during the earlier part of the 
intra - corpuscular life of the parasites, that is, during the several hours 
before and during the paroxysm, and during the twenty-four hours 
immediately following it. 
Effects of-Quinine upon the Human Being (Cinchonism).-In most indi- 
viduals ordinary therapeutic doses of quinine are without seriously 
unpleasant consequences, producing, at the most, slight tinnitus aurium 
and deafness. Larger doses produce more pronounced deafness, vertigo, 
and headache, which may be severe. This is followed in graver cases by 
great muscular weakness, tremor, staggering gait, dilatation of the 
pupils, amblyopia, amounting sometimes to total blindness, and, if 
the dose be large enough, finally convulsions and death. A number 
of cutaneous disturbances have been observed after quinine. Urticaria 
and scarlatiniform erythemas are common; the latter may be followed 
By desquamation. There are great varia'ions in the susceptibility of 
different individuals to the toxic effects of quinine. Most patients are 
able to take doses up to grs. v. (0'325 gramme) without discomfort. 
Many, however, suffer from tinnitus aurium and headache with doses as 
large as from grs. x.-xv. (0'65-1 gramme); these symptoms are, however, 
transient and free from serious consequences. Occasionally patients are 
met with who, through individual idiosyncrasy, shew such a marked 
susceptibility to the action of quinine that its use is really impossible. 
In such cases gastro-intestinal symptoms of great severity, vomiting and 
purging, with marked urticarial or scarlatiniform eruptions follow even 
the smallest doses. This susceptibility usually extends to the other 
cinchona derivatives. These cases are, fortunately, very unusual. I 
have met with but two. As is mentioned elsewhere (p. ), quinine 
may, in rare instances, be followed by hsemoglobinuric fever. In the 
vast majority of cases in which patients assert that they "cannot take 
quinine," it will be found that the reason for the prejudice is that larger 
doses than necessary have been administered. 
Absorption and Elimination of Quinine.-Quinine is rapidly absorbed ; it is eliminated almost exclusively by means oi the kidneys, uie nrst 
traces appearing in the urine from 15-17 minutes after ingestion, and 
the greater part of elimination being accomplished within the first 
twenty-four hours. Mariani, however, has shewn that elimination 
continues for at least six days, one-half to two-thirds of the molecule of 
the alkaloid being demolished during its long sojourn in the tissues, so 
as to render its intermediate or final products unrecognisable. By 
intravenous administration a large quantity of quinine may be rapidly 
introduced into the circulation. I have seen cinchonism follow within 
a few minutes of the intravenous introduction of grs. xv. (1 gramme) of 
the acid hydrochlorate. The intra-muscular injection of quinine has the 
advantage of more prolonged action, but this is less intense because of 
the notable quantity of the drug, which is precipitated at the seat of 
injection. On this precipitation depends the paradox that to pro- 
duce the same effect the dose of quinine must be larger when given by 
hypodermic injection than when given by the mouth. The absorption 
of quinine by the gastro-intestinal mucosa, although varying considerably 
in its rapidity, is usually complete. Fever does not interfere with its 
absorption except in the presence of special gastro-intestinal disturbances. 
The administration of quinine at the time of a meal seems to promote its 
absorption into the general circulation ; if taken with food it appeal s to 
remain in the circulation in a somewhat higher proportion during the 
second and third days after the administration. The absorption of 
the less soluble preparations of quinine is at least as complete as that 
of the more soluble salts. Quinine is cumulative in its action. On daily 
repetition of a given amount, the fresh dos*', entering the circulation, is 
added to the active residue of the former doses, so that the amount of 
quinine in the vessels arrives, within the first week, at its maximum 
limit, an amount such as is found in the first twenty-four hours only 
after the ingestion of a single dose equal to double that which is 
administered daily. 
Preparations and Manner of Administration.-Of the various salts of 
quinine, the sulphate, the bisulphate, and the dihydrochlorate are most 
commonly used. The sulphate which is the cheapest salt is that in 
general use, and is thoroughly satisfactory for administration by the 
mouth. For hypodermic,1 intravenous, or rectal administration, the more 
soluble forms, especially the dihydrochlorate, which is soluble in less than 
its own quantity of water, are more suitable. Quinine is best absorbed 
when administered in solution. The ordinary sulphate of quinine is 
easily rendered soluble by adding to the aqueous mixture one drop of 
dilute hydrochloric or sulphuric acid for each grain (0-065 gramme) of the 
1 In the hypodermic administration of quinine it is extremely important to introduce 
the needle deeply ; intra-muscular injections are, indeed, safer. Superficial injections are 
often followed by painful and disfiguring necroses of the skin. 409 
salt. The taste is, however, very bitter and unpleasant. It can be some- 
what masked by preparations of ginger or chocolate. Quinine may also 
be given in the form of capsules, tablets, or pills. The insolubility and 
common adulteration of quinine pills renders their use unsafe. The 
administration of quinine tablets, such as those at present prepared by 
the Italian government, has proved very satisfactory. A preparation 
known as euquinine, the ethyl ether of quinine-carbonic acid, was placed 
upon the market a few years ago, recommended because of its tasteless- 
ness ; it has a slightly bitter taste, but much less so than quinine. The 
dose is about a half again that of the sulphate. The Italian government 
has used with great success in children a confection consisting of a 
mixture of chocolate and tannate of quinine. The tannate is so slowly 
absorbed that about one-fifth of the dose escapes with the faeces. The 
dose should be somewhat more than twice that of the sulphate. 
For hypodermic use the acid hydrochloride is the most satisfactory 
salt, although the bisulphate, which is soluble in nine or ten parts of 
water, will answer in an emergency. For intravenous administration we 
have used the following solution advised by Baccelli:- 
Acid hydrochloride of quinine . . grs. xv. (1 gramme) 
Chloride of sodium . . . gr. Q (0-075 gramme) 
Distilled water .... Siiss. (10) 
The solution should be perfectly clear, and may be injected luke-warm. 
The rectal administration of quinine is rarely necessary, and is rather 
unsatisfactory. Readily soluble salts should be used. 
There has been much discussion as to the time at which quinine 
should be given. The answer depends upon the nature of the case, and 
upon what one desires to accomplish. Single large doses of quinine by 
the mouth have the best effect if given three to four hours before the 
onset of the paroxysm. This does not prevent the impending paroxysm 
but, by destroying a large part of the group of organisms resulting from 
the segmentation of the mature generation, prevents its recurrence. It 
is at about the time of the paroxysm, immediately preceding, during, 
and following it, that the most vigorous treatment should be given in 
cases where such methods are necessary. 
Treatment of Tertian and Quartan Fever.-The patient should be put 
to bed if possible. He should be assured that the results of treatment 
will be much more rapid and complete if he be willing to give up 
business for a few days. As a rule, it is quite sufficient to administer at 
regular intervals from grs. ii.-v. (0'12 to 0-325 gm.) of the sulphate of 
quinine three times a day, when possible after meals. Most tertian 
infections yield readily to doses as small as grs. ii. (0'12 gm.) three times 
a day. If the paroxysms have been severe it may be well to give a large 
dose of quinine, grs. x.-xv. (0-65-1 gm.), three to five hours before the 
next attack is expected. If the patient be seen during a paroxysm, a 
single dose of grs. v. (0'32 gm.), given immediately after defervescence, 
especially if followed by regular treatment, is usually sufficient to prevent 
further symptoms on the part of the segmenting group of parasites. 
After three or four days' treatment it is usually well to reduce the dose 
to grs. ii. (0'12 gm.) three times a dav. This treatment should then be continued for at least three weeks. If the patient insist on remaining up 
and about, it may be necessary to continue larger doses, grs. v. (0'3 gm.) 
three times a day for as much as ten days, although, in most instances, 
grs. ii. (012 gm.) every four hours will be quite sufficient. Considerably 
larger doses are necessary when the patient is up and about than when 
he is in bed. The parasites disappear, usually, from the blood in from 
twenty-four to sevent}-two hours after the beginning of treatment. 
Treatment of ^stivo-Autumnal Fever.-The patient should be confined 
to bed until the fever has gone, and all traces of the asexual cycle of the 
parasites have disappeared from the circulation. In ordinary cases gr. v. 
(0'32 gm.) of the sulphate of quinine every four hours is a sufficient 
dose. This should be continued usually for about a week, the dose being 
gradually reduced until at the end of about ten days the patient is taking 
gr. ii. (0'12 gm.) quinine three to four times a day. This treatment, as 
in tertian and quartan fever, should then be continued for at least three 
weeks. If relapses occur the dose should be incre sed again. If the 
paroxysms are severe from gr. xv.-xx. (1-1'3 gm.) may be given at the 
outset and a few hours bef re the time of onset of the next expected 
recurrence. 
Many observers recommend the intermittent administration of 
quinine, large doses of the drug, grs. ii.-x.-xxx. (0'65 girif), being 
administered during the period of apyrexia from three to five hours 
before the expected paroxysms, for three or four days, gr. xv. (1 gm.), 
being repeated every six or seven days for a month or more afterward. 
Koch, in order to avoid relapses, advises the administration of gr. xv. 
(1 gm.) of quinine about e\ery seven days for two days in succession, 
this treatment being continued for two months. Without the benefit 
of comparative statistics of our own, we have always been under the 
impression that the results of continuous treatment were more satis- 
factory than those of intermittent. The demonstration of the cumula- 
tive action of the drug by Mariani supports this method of treatment 
theoretically, while practically the prophylactic results of continued 
administration of the drug are more satisfactory (Celli). In pernicious 
paroxysms, most vigorous treatment is demanded from the onset. The 
acid hydrochloride of quinine should be given intravenously in doses of 
grs. xv. (1 gm.). This dose may be repeated if necessary, several times 
at intervals of four hours. The treatment will usually prevent any 
further dangerous manifestations from the segmenting generation of 
parasites, although it may be that a severe and even fatal paroxysm may 
occur within forty-eight hours due to another group of organisms. If the 
parasites remain present in large numbers, from grs. v.-x. (0'35-0'65 gm.), 
or the sulphate or acid hydrochloride should be administered by the 
mouth when possible, every four hours during the first twenty-four hours 
following the paroxysm. If the patient remain unconscious, gr. kv. {1 gm.) should be given intravenously every six to eight hours, until the 
parasites begin to disappear from the blood when the dose may be 
reduced to grs. v. (0'32 gm.) every four hours. In cases in which the 
patient asserts that he cannot take quinine, its administration ip smaller 
quantity or hypodermically will usually accomplish the desired result 
without serious discomfort. Many patients who are unpleasantly 
cinchonised by doses of gr. x (0 65 gm.), or even gr. v. (0'325 gm.) of 
the sulphate may be successfully treated if put to bed and given small 
amounts, gr. i.-iii. (0'065-0'2 gm.), at regular intervals. Quinine is 
contra-indicated oidy in those rare cases in which through special idiosyn- 
crasy, violent symptoms follow even the smallest doses. In these 
instances which are happily rare, the patient should be removed to the 
most healthy region possible; absolute rest in bed should be insisted 
upon, and treatment with methylene blue employed. 
Various other drugs have been used in the treatment of malaria. 
Few, however, deserve serious mention. Other cinchona derivatives such 
as cinchonin, cinchonidin, quinidia, and quinoidia have been recommended. 
Their efficacy is, however, far less that of quinine, and the occasions for 
their use are limited. 
Methylene blue was shewn by Gutmann and Ehrlich to have a certain 
anti-malarial action. My own experience confirms that of most observers 
that its efficacy is far below that of quinine, and uncertain. I have seen 
a relapse occur in bed, under continued treatment. I have, however, 
used it with success in tertian infection in an individual who with an 
idiosyncrasy against quinine, the patient having been previously removed 
to a healthy mountainous region and confined to bed. It may be given 
in capsules in doses of from grs. ii.-iii. (0'13-0'2 gm.) every four hours. 
The strangury, which so commonly follows its ingestion, may be relieved 
by the administration of small quantities of powdered nutmeg. Phenocoll, 
about which much has been written by Italian authors, is of little value. 
The same holds good for the various arsenical preparations such as the 
arrhenal of Gautier.1 
Symptomatic Treatment.-Various manifestations require symptomatic 
treatment. Vomiting, purging, excitement or delirium during the 
paroxysm may be controlled by hypodermic administration of morphine. 
In collapse during pernicious paroxysms, active stimulation must be 
resorted to. Alcohol, strychnine, or digitalin may be freely administered. 
During an algid paroxysm heat should be applied externally, while 
subcutaneous infusion of saline solution may be of value. Hyperpyrexia 
should be treated by cold sponging or baths. Anaemia following malaria 
should be treated by rest, diet, iron, and arsenic. 
Chronic Malarial Cachexia.-The patient should, if possible, be re- 
moved to a healthy locality or at least placed at home in conditions such 
as to remove him from sources of further infection. An attempt should 
then be made to eliminate an existing infection and prevent relapses by 
the administration of small doses of quinine grs. ii.-iiss (0'12-0'18 gm.) 
three times a day. If there be grave anaemia he should be kept 
absolutely at rest, and as far as possible, out of doors. Exercise should 
be forbidden ; the diet should be nourishing and simple; massage and 
hydrotherapy are often of considerable benefit. The anaemia should be 
410 treated by iron and arsenic. No preparations of iron are as good in 
the treatment of anaemia as the Tinct. Ferri Perchloridi (Tinct. Ferri 
Chloridi U.S.P.), and Pilula Ferri (Pil. Ferri Carbonatis U.S.P.). 
There is nothing specific in the treatment of post-malarial nephritis, 
or of the various complications of the disease. 
Personal Prophylaxia.-As the important question of public prohpy- 
laxia is considered by Major Ross, it is necessary to add a few words 
only, with regard to those personal measures which should be adopted by 
individuals who are obliged to live in a malarious locality. These 
measures are mechanical and medicinal. The former consist in pre- 
cautions to avoid the bites of infected mosquitoes. In dangerous regions 
mosquito netting should always be carried, and used in such a way that 
mosquitoes cannot enter-, for an improperly used net is as bad as none at all. 
If one be obliged to expose himself among infected mosquitoes it is well 
to wear a hat provided with a net such as that devised for the railroad 
employees in Italy, and to protect the ankles with garters, and the hands 
with gloves. 
The medicinal measures consist in the use of quinine. There is no 
doubt of the great value of quinine as a prophylactic, but there is 
considerable difference of opinion as to the best method of administration. 
Good results have been reported from the use of daily doses of from 
grs. iss.-iiiss. (0'1-0'25 gm.), while others prefer giving larger doses with 
several days' intermission, grs. viiss.-xv. (0'5-1 gm.) every four to eight 
days. Experiments on a large scale carried out by the Italian society 
for the study of malaria shew that a daily portion of about grs. vi. 
(0'4 gm.) of quinine is better borne and gives more satisfactory results 
than larger intermittent doses-an observation which is also in accord 
with the conclusions of Mariani as to the cumulative action of the drug. 
Arsenic is of no value as a prophylactic. 
W. Osler. 
W. S. Thayer. 
1 There are few more discouraging illustrations of the weakness and fallibility of human 
judgment than those revealed by a review of the literature appearing every year concerning 
new remedies for malaria. He who attempts to study the therapeutical effects of a drug on 
malarial fever should read and take to heart the classical experience of Chomel quoted by 
Laveran from Trousseau and Pidoux. Chomel, wishing to test the properties of a powder 
of holly, chose twenty-two patients suffering from intermittent fever, but before giving the 
powder in question he put them under simple expectant treatment. Nineteen recovered 
spontaneously. Of the remaining three, one had a quartan fever and two quotidian. The 
powdered holly was administered to these patients without effect ; all recovered quickly 
under quinine. If at the outset Chomel had given the powder of holly to his twenty-two 
patients it might have been concluded that it had cured the fever in nineteen out of 
twenty-two instances. 411 
REFERENCES 
The literature on malaria is so extensive that a complete list of all the books and 
communications consul.ed in the preparation of this article would be unnecessarily 
long and confusing. Elaborate tables of references may be found in the treatises of 
Marchiafava and Bignami in the Twentieth Century Practice of Medicine, and that of 
Mannaberg in the English translation of Nothnagel's Encyclopaedia of Practical 
Medicine. These two works are the mo t exhaustive in literature. It will be 
unnecessary to give special references to this valuable work of Daniels, Stephens, 
Christophers, and others appearing in the reports of the Malaria Committee of the 
Royal Society of London. 
A mass of information of great value to the student of malaria is stored in the six 
volumes of the Atti della Societd per gli studi della malaria, -8vo, Roma, vol. i. 1899 ; 
vols. ii.-vi. 1901-5. The annual summaries of the work done under the auspices 
of this society by Professor Celli, communications of great importance, appear in 
various other publications, notably in the Centralbl. fur Bakteriologie. 
In the following list appear a few of the more important contributions consulted in 
the preparation of this art.cle :- 
I.-Text-Books and Monographs 
1. Baccelli. Studien uber Malaria. Berlin, 1895.-2. Blake, Sir Henry A. 
Ancient Theories of Causation of Fever by Mosquitoes. Colombo, 1905.-3. Blanchard. 
Les Moustiques. Paris, 1905.-4. Bouzian, A. 0. Recherch.es sur I'hematozoaire du 
paludisme. Montpellier, 1892, No. 10.-5. Celli. La Malaria, etc., 3rd ed. Roma- 
Milano, 1903.-6. Celsus. De Medicina, libri viii.-7. Christophers, S. R. Second 
Report of the Anti-Malarial Operations at Mian Mir, 1901-3. Calcutta, 1904. 
-8. Craig. The AEstivo-Autumnal (Remittent) Malarial Fevers. New York, 1901. 
-9. Daniels. Studies in Laboratory Work (in Tropical Medicine). London, 1903. 
-10. Fajardo. O impaludismo. Rio de Janeiro, 1904.-11. Galen. Caludii Galeni 
Opera Omnia, ed. Kuhn. Leipzig, 1821-33, 20 vols. ; also (Euvres anatomiques, physio- 
logiques, et medicales de Galien, trad, par Ch. Daremberg. Paris, 1854.-12. Grassi, 
Battista. Die Malaria: Studien eines Zoologen, 2nd ed. Jena, 1901.-13. Idem. 
Ibid. Nachtrag zur zweiten vermehrten Auflage. Jena, 1903 (G. Fischer).-14. Hippo- 
crates. The Genuine Works, etc., transl. by Francis Adams. New York, 2 vols. 
-15. Hitte, Leon. Sur le paludisme congenital. Montpellier, Imp. Serre et 
Roumegous, 1902, No. 73.-16. Kelsch and KiLner. TraitE des maladies des pays 
chauds. Paris (Bailliere), 1889.-17. Lancisi. De noxiis paludum efluviis, lib. ii. 
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genesi," Policlin. Roma, 1902, ix.-m. 193-216.-189. Sergent, E. and E. " Cam- 
pagne antipaludique en Algerie (1903," Atti d. Soc. per gli studi d. malaria. Roma, 
1904, v. 301.-190. Idem. " Essai de campagne antipaludique salon la methode de Koch (Lac de Grand-Lieu) (1903)." Atti d. Soc. per git studi d. malaria. Koma, 1904, 
v. 335.-191. Idem. " Anopheles algeriensis et ■ yzomyia hispaniola convoient la 
paludisme," Compt. rend. Soc. de biol. Paris. 1905, lix. 499.-192. Idem. Etudes 
epidemiol igiques et prophylactiques du paludisme en Algerie en 1904," Atti d. Soc. 
per gli stud. d. malaria. Roma, .1905, vi. 105.-193. Sewell, h. P. "Anti-Malarial 
Operations at Main Mir," Jour. Hoy. Army Med. Corps. London, 1905, v. 132-134.- 
194. Signorelli, Angelo. Tabe e malaria. Contribute allo studio delle associazioni 
morbose in genere. Roma, 1904, i. ; Artero. -195. Smith, T. " The Sources 
favouring Conditions and Prophylaxis of Malaria in Temperate Climates, with 
special reference to Massachusetts," Boston Med. and Surg. Jour. 1903, cxlix. 57, 87, 
115, 139.-196. Spiller. "A Case of Malaria presenting the Symptoms of Dis- 
seminated Sclerosis, with Necropsy," Am. Jour. Med. Sc. Phila. 1900, cxx. 629.- 
197. Stephens, J. W. W. "Native Malaria and Malarial Prophylaxis," Climate. 
London, 1902-3, iv. 273-283.-198. Idem. "The Prophylaxis of Malaria," Jour. Trop. 
Med. London, 1904, vii. 253.-199. Stephens and Christophers. "Summary of 
Researches on Native Malaria and Malarial Prophylaxis ; on Blackwater Fever : Its 
Nature and Prophylaxis," Thompson- Yates and Johnston Lab. Reps. n. s. vol. v. 1903, 
221.-200. Steuber. " Malariaimmunitat und Kindersterblichkeit bei den Einge- 
borenen in Deutsch-Ostafrika," Deutsche med. Wchnschr. Leipzig u. Berlin, 1903, xxix. 
72.-201. Terburjh. "Le paludisme aux Indes Neerlandaises," Att. d. Soc. per gli 
stud. d. malaria. Roma, 1904, v. 259.-202. Thayer, W. S. "On Nephritis of 
Malarial Origin," Am. Jour. Med. Sc. Phila. 1898, n.s. cxvi. 560, 646.-203. Idem. 
"Recent Investigations concerning tho Hoomatozua of Malaria,"Med. Reg. Richmond, 
1S99, iii. 243.-204. Idem. "On Recent Advances in our Knowledge concerning the 
iEtiology-of Malarial Fever," Tr. Cong. Am. Phys, and Surg. N. Haven, 1900, v. 50. 
-205. Todd. "Malignant Malaria with Urticarialand Petechial Eruptions," Jour. 
Trop. Med. Lond. 1900, iii. 30.-206. Torti and Angelini. "Infezione malaria 
cronica coi sintomi della sclerose a placche," Riforma med. Napoli, 1891, vii. pt. ii. 
817-825.-207. Vaccari, A. "Le manifestazioni cutanee da malaria," Gazz. d. osp. 
Milano, 1903, xxiv. 141.-208. Vagedes. " Die Malaria unserer Kolonien im Lichte 
der Kochschen Forschung," Festschr. z. 60 Geburtst. von^Robert Koch. Jena, 1903, 
177-202.-209. Wendland. "Ueber Chininprophylaxe in Neuguinea," Arch. f. 
Schiffs-u. Tropen- Hyg. Leipzig, 1904, viii. 431-454.-210. Williamson. "'Statistics 
of Blood Examinations in Cases of Malaria in Cyprus during a Period of Twelve 
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Method for the Differential Staining of idood Films and Malarial Parasites," Jour, 
med. Research, 1902, vii. 138.-212. Zeri, A. " Afasia da malaria ; contribute alia 
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"Ueber malaria und Moskitos," XIII. Cong, internal, de mid. Sect, de Bacterial. et 
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prophylaxe in Kamerun," Arch. f. Schiffs- u. Tropen- Hyg. Leipzig, 1904, viii. 329-373. 
W. O. '. 
W. S. T; Experimental Studies of Cardiac 
Murmurs. 
BY 
W. S. THAYER, M.D., 
PROFESSOR OF CLINICAL MEDICINE IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE, 
MARYLAND, 
AND 
w. g. MacCallum, m.d., 
ASSOCIATE PROFESSOR OF PATHOLOGY IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE, 
MARYLAND. 
FROM THE 
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 
February, 1907. Extracted from the American Journal of the Medical Sciences, February, 1907 
EXPERIMENTAL STUDIES OF CARDIAC MURMURS. 
By W. S. Thayer, M.D., 
PROFESSOR OF CLINICAL MEDICINE IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE, 
MARYLAND, 
AND 
W. G. MacCallum, M.D., 
ASSOCIATE PROFESSOR OF PATHOLOGY IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE, 
MARYLAND. 
In connection with experiments on the production of valvular 
lesions which have been carried on by one of us1 during the past 
year, we have made a series of observations on the cardiac sounds 
with especial reference to transmission of murmurs in the dog's heart. 
Having studied the character of the heart sounds of the normal dog 
we have produced, as far as possible, the lesions commonly observed 
in man, each in several cases. In other experiments we have made 
a few observations concerning the development of functional basic 
murmurs. In the present communication it is our desire to refer 
to some of the more interesting points which have been brought out 
by that work which we have already done. 
Methods. After etherization, the anterior part of the chest is 
removed, artificial respiration established, the pericardium opened, 
and the heart thoroughly exposed. 
A special stethoscope (Fig. 1) has been devised, the bell of which 
is of small diameter (1 cm.), so that the sounds heard over a small 
organ may be better localized, and long (6.8 cm.), so that it may 
be placed readily upon the rather deep lying structures. 
Position of the Heart. The arrangement of the chambers of 
the dog's heart when exposed in situ is somewhat different from 
that of the human heart. A much larger part of the anterior 
surface of the organ is occupied by the left ventricle, while the right 
auricle occupies a smaller area in the upper right-hand corner, and 
the tip of the appendage of the left auricle is usually visible below and 
adjacent to the pulmonary artery, just as it is not,2 as a rule, visible 
in the human heart despite the orthodox illustrations. 
1 MacCallum, Johns Hopkins Hosp. Bull., 1906, xvii, 260. 
2 It should be noted, however, that in some dogs an auricle which was evident intra 
vitam, disappears postmortem. Similar conditions may exist in man. 2 
THAYER, MACCALLUM: CARDIAC MURMURS 
Normal Heart Sounds. The heart sounds of the dog are closely 
analogous to those of the human being. The first sound over the 
left ventricle is duller and more muscular; over the right ventricle 
somewhat more flapping and valvular. With the heart exposed, 
it is possible to put the stethoscope directly over the aortic and 
pulmonic rings. The difference in the character of the second 
sounds, which is so often to be detected in the human being, is here 
very striking. The second sound at the aortic orifice is of very 
much greater intensity than that at the pulmonic ring, of a more 
ringing and musical cjuality, while the second sound over the pul- 
Fig. 1.-Stethoscope with a long bell of small diameter for auscultation of the dog's heart. 
monic valves has a deader, more wooden character. This difference 
is marked and characteristic, so much so as to confirm me (Thayer) 
in the conviction which I have often expressed, that it is sometimes 
possible, in the human being, to determine the origin of the second 
sound to which one is listening, by its character alone-a point 
which may be of importance in cases in which the second aortic 
sound is heard best to the left of the sternum. 
Aortic and Pulmonic Stenosis. In our first experiment we pro- 
duced aortic and pulmonic stenosis. This is a perfectly simple 
procedure, carried out by the passage of a cord about the vessel 
just above the valves. This may be tightened to produce any degree THAYER, MACCALLUM: CARDIAC MURMURS 
3 
of stenosis desired. The production of a stenosis causes the charac- 
teristic thrill and rough murmur transmitted upward in the course 
of the current, just as is observed in man. The experiment differs 
in no essential point from that which may be performed with a 
lubber tube attached to a faucet. 
A striking and particularly interesting point is the ease with which 
murmurs may be produced in the pulmonary artery. Very slight 
pressure over the conus arteriosus or over the artery results in the 
development of a systolic thrill and murmur immediately beyond 
the point of pressure. The ease with which these murmurs are 
produced by pressure suggests immediately that a similar process 
may account for some of the frequent basic pulmonary murmurs 
which are heard in man. If systolic murmurs can be produced 
in man by a degree of pressure over the conus arteriosus as slight, 
relatively, as that necessary to bring about the same phenomenon 
in the dog, it is but natural to assume that the resistance offered 
by the chest wall alone may, in many instances, result in systolic 
murmurs in the pulmonary area.3 
Aortic Insufficiency. In eight instances (experiments I, II, IV, 
V, VI, VII, X, XII) an aortic insufficiency was produced. In all 
cases a loud diastolic murmur developed at the aortic ring; this 
murmur sometimes replaced the second sound; sometimes the two 
sounds were heard in association. 
Always loudest at the aortic ring, it was transmitted a short dis- 
tance upward along the aorta, but best downward toward the ventricle. 
Over the ventricle the murmur was always much feebler, and in 
some instances it was inaudible at the apex. In some cases it was 
heard loudest on the anterior surface of the ventricle at about the 
middle of the line separating the right and left ventricles; in other 
instances, it was more distinct around toward the left, just below 
the pulmonic valves. Sometimes it was feebly audible through 
the right ventricle. The character of the murmur was exactly the 
same as that of the souffle of aortic insufficiency in the human being. 
Especially characteristic was the softness of the sound over the 
ventricle. The first sound over the left ventricle became dull and 
humming, just as in aortic insufficiency in man. 
In several cases in which, after the production of extensive lesions, 
the ventricle became dilated and feeble, the murmur diminished 
greatly in intensity, sometimes disappearing wholly over the ven- 
tricle, although still faintly audible at the aortic ring. 
In three of these eight cases a soft systolic murmur appeared 
also at the aortic valves. Marked pulsation of the peripheral vessels 
3 In the discussion upon this communication, Dr. Janeway referred to the frequency of 
pulmonic systolic murmurs during forced expiration. May it not be that this phenomenon 
is due in part, at least, to the fact that, by the retraction of the lung, that which normallj' 
acts as a cushion between conus and chest wall is removed? 4 
THAYER, MACCALLUM: CARDIAC MURMURS 
occurred just as in man, resulting, in some cases, in an exquisite 
hammer pulse, with a pistol-shot tone in the femorals. 
In one case in which we were studying the basic murmurs in the 
heart of an animal which had been' bled repeatedly and afterward 
infused with salt solution, there developed an exquisite aortic insuffi- 
ciency with a double (systolic and diastolic) murmur at the ring and 
over the left ventricle which was visibly dilated. Later a typical 
murmur of mitral insufficiency, associated with pulsation of the 
left auricle was to be made out. A sharp second sound was also 
audible at the aortic ring. The accompanying tracing (Fig. 2) 
show's, in an interesting w7ay, the difference between the character of 
the femoral pulse curve before and after the development of aortic 
insufficiency. Unfortunately, the cannula in the left auricle had 
become clogged so that the pulsation of the blood in this cavity with 
the onset of mitral insufficiency wras not recorded. The necropsy, 
in this case, showed that the valves were intact, although subendo- 
cardial hemorrhages in both ventricles wTere probably evidences 
of the distention to which the wTalls had been subjected by the arti- 
ficial plethora. 
The most interesting points brought out by these cases of aortic 
insufficiency would seem to be the intensity of the diastolic murmur 
at the ring and its feebleness over the aorta above and over the right 
and left ventricles below7, a condition in every way analogous to 
that observed in the human heart, and wholly in accordance with 
the well-known fact that the murmurs of aortic insufficiency are 
often very difficult to hear. Especially interesting wTas the pro- 
duction of a functional aortic insufficiency from dilatation, an observa- 
tion supporting entirely the conception of those observers who have 
insisted upon the important part which the muscle of the left ventricle 
plays in the closure of the aortic ring. 
Mitral Stenosis. In tw7o cases (experiments VII and IX) attempts 
wrere made to produce a mitral stenosis. It is needless to say that 
it w'as impossible to bring about changes in the valve analogous to 
those in a valvular stenosis in the human being. The nearest 
approach that was made to this was to apply a clamp at about 
the position of the mitral ring. The tightening of such a clamp 
resulted in great distention of the left auricle, rise in pulmonic 
pressure, and an immediate increase in the intensity of the second 
pulmonic sound, with a corresponding enfeeblement of the second 
aortic sound. In one case it was possible, at a certain point of rather 
moderate tightening of the clamp, to detect a slight presystolic 
murmur, heard best midway between the clamp and the apex, 
over the left ventricle. This murmur disappeared with further 
tightening or with relaxation of the clamp. In the other case no 
murmur could be produced. The first sound instead of becoming 
snapping and valvular, as in the characteristic valvular stenosis, 
became duller and more humming. Infusion stopped. 
Well-marked diastolic murmur at aortic ring and over left 
ventricle. Systolic murmur (feeble) at aortic ring. 
Infusion continued. 
Femoral artery. 
Pulmonary artery. 
Fig. 2-(a) Tracing illustrating the development of aortic insufficiency from dilatation of the left ventricle after bleung and interarterial infusion with large quantities of salt solution. 
Exquisite to-and-fro systolic and diastolic murmur at aortic ring. 
Infusion. To-and-'O murmur at aortic ring with loud second sound. 
Loud systolic murmur at mitral and in left auricle. 
I'ig. 2-(6) Same tracing later -cannula in pulmonary artery clogged. 
Fig. 2-(c) Same tracing later-mitral insufficiency has developed. THAYER, MACCALLUM: CARDIAC MURMURS 
5 
Mitras risufficiency. In six cases mitral insufficiency was pro- 
duced by tearing the valves or chordae tendinese with the knife-hook 
described elsewhere,4 which was passed through the auricle or 
through the carotid (experiments II, IV, VI, X, XI, XII). The 
production of a mitral insufficiency resulted in the development of a 
blowing, rather soft, systolic murmur heard with moderate intensity 
over the left ventricle. This murmur replaced the first sound 
wholly or in part; its general character was closely similar to the 
analogous murmur in man. 
In the dog's heart, however, it is possible to place the stetho- 
scope over the left auricle just beyond the valves at the point at 
which, theoretically, the murmur should be most intense. This is, 
indeed, the case, the murmur in most instances being Aery loud 
and associated with a thrill of great intensity. The murmur was, 
in some instances, transmitted to the pulmonary veins of both sides; 
in one case it was audible over the back of the animal. In one 
case, with distention of the ventricle, a characteristic murmur of 
mitral insufficiency developed as a result of dilatation of the ring. 
It would greatly simplify the teaching of auscultation of the heart 
if it were possible to make demonstrations such as the foregoing 
before the student. For years one of us5 has been in the habit 
of employing a very simple mechanism, taught him nearly twenty 
years ago by a valued teacher6-a rubber tube attached to a faucet 
of running water. By producing any degree of pressure upon the 
tube at a given spot, and by increasing or diminishing the rapidity 
of the flow of the fluid, many points of importance with regard to 
the origin and transmission of cardiac murmurs may be illustrated. 
Indeed, a student who is really familiar with the anatomy of the heart 
and surrounding organs, and with the character and theories with 
regard to the origin of the heart sounds, can, after such a demon- 
stration, work out the diagnosis of the simpler valvular lesions with 
little assistance. The very simplicity of the demonstration some- 
times leads the student to doubt its complete applicability to condi- 
tions existing in the living animal. For years I7 have been in the 
habit of teaching students that the murmur of mitral insufficiency 
is doubtless loudest at the mitral ring and just beyond this point in 
the left auricle-that its intensity at this point is probably great- 
that there is probably also a well-marked thrill over the left auricle 
-that the deep position, however, of the left auricle and the mitral 
ring render these conditions undemonstrable-that the murmur is 
audible at the apex alone because this is the only point at which it 
is possible to approach the left ventricle-that the murmur of mitral 
insufficiency is not, as a rule, very intense because, as in the experi- 
ment with the rubber tube, the murmur and thrill diminish rapidly 
as one passes above the point of constriction. But obvious as such 
4 MacCallum, loc. cit. 
6 Dr. W. W. Gannett, of Boston. 
6 Thayer. 
7 Thayer. 6 
THAYER, MACCALLUM: CARDIAC MURMURS 
an explanation may seem, it is often difficult to impress the student. 
What a luminous demonstration it would be if one could supplement 
the experience with running water with experimentally produced 
lesions as above described-if it were possible for the student to put 
his finger and his stethoscope on the left auricle as well as on the apex 
of the heart. 
There is no reason why such demonstrations could not be made 
to small sections of students. We are daily inculcating in our 
students a wholesome skepticism with regard to all things that are 
insusceptible of proof; and wherever palpable confirmation of our 
theoretical explanations of morbid phenomena can be offered, we 
should not fail to produce it. 
In one case of dilated heart a characteristic murmur of mitral 
insufficiency developed as the result of a dilatation of the ring. 
Protodiastolic Gallop Rhythm, and Murmur. In one instance 
(experiment IX) an interesting phenomenon was observed. This 
experiment was started with the idea of observing whether, with 
aortic insufficiency, the pressure in the left auricle was increased 
without coincident mitral insufficiency. Cannulae were inserted 
into the left femoral artery, into the appendage of the left auricle, 
and into the peripheral end of a pulmonary artery. By so doing 
the heart was rotated over toward the right, while the left auricle 
was held rather tensely in position by the cannula in the auricular 
appendage. This appeared to have the effect of placing the heart 
in a position in which it was, in a way, suspended by the left 
auricle. There then became audible over the left auricle and just 
below the valves a first, a second, and then, after a momentary 
pause, a third sound-a diastolic rumble in every way similar to 
the early diastolic murmur heard in some cases of mitral stenosis. 
When the heart became more rapid this rumble extended into 
presystole, simulating, closely, a mitral stenotic murmur. There 
was no mitral regurgitation. Gradually the murmur disappeared 
and one heard only a thud, which became clearer with the decreasing 
rate of the heart's action. One was able to observe the systole of 
the ventricle immediately followed by the second sound, which 
occurred while the ventricle was still in a state of contraction. Then 
followed the sudden dilatation of the ventricle which occurred abruptly 
with a distinct shock, having altogether the appearance of an active 
muscular process. Synchronously with this shock occurred the 
third sound. This thud was clearly analogous in time (a) to the 
so-called opening-snap heard in mitral stenosis and ascribed to the 
sudden tension of the thickened mitral valves with the beginning 
of diastole. Its character, however, was precisely that of (6) the 
sound in protodiastolic gallop rhythm heard under so many 
circumstances, especially in nephritis, dilated heart, adherent peri- 
cardium, etc., and ascribed variously to the impact of the auricular THAYER, MACCALLUM: CARDIAC MURMURS 
7 
blood upon a ventricle which has lost its elasticity (Potain),8 or to 
an active muscular dilatation of the ventricle (Brauer).9 
The case is interesting because we were able to see, so to speak, 
the association of this sound with a definite moment in the heart's 
cycle-that is, the shock of what appeared to be an active diastole, 
and the association of a murmur with conditions which seemed to 
suggest the suction of blood into the ventricle. 
It may be well here to mention the fact that the presence of a 
third sound at just this period of the heart's cycle is not infrequent 
in the apparently normal heart, especially in children. The sound 
is sometimes a dull thud, sometimes merely a hum, and occurs 
shortly after the second sound, that is, at the beginning of ventricular 
diastole. Sometimes it is followed by the faintest suggestion of an 
echo, so that I10 have long been in the habit of maintaining that 
the entrance of blood from the auricle into the ventricle through 
a normal orifice is associated in some instances with a slightly 
audible sound. 
Basic Systolic Murmurs. In four cases (experiments III, VIII, 
IX, XI) we have studied the effect of changes in the heart's action 
on the sounds at the arterial orifices. The question here is too 
complicated to justify elaborate discussion on the basis of our few 
experiments, but a brief summary of what we have observed may 
be of interest. 
A. Aortic Murmurs. 
1. Systolic murmurs at the aortic ring were never found in 
the normal heart. 
2. Variations in arterial pressure produced by nitroglycerin or 
adrenalin did not result in their appearance. 
3. These murmurs appeared in conditions of rather low pressure. 
4. In two instances (III and XI) they followed bleeding alone. 
In such cases the administration of adrenalin with a rise in pressure 
caused the disappearance of the murmur. 
5. Systolic aortic murmurs were especially frequent after infusion 
of salt solution following bleeding. 
6. In general, aortic systolic murmurs were especially frequent 
after bleeding followed by infusion, in association with what appeared 
to be rather abrupt action of the ventricle and rather large excur- 
sions of the pulse. They sometimes followed hemorrhage alone. 
They never appeared as the result of modifications in pressure 
following the administration of nitroglycerin or adrenalin. 
B. Pulmonic Murmurs. 
1. As has been already noted, pulmonary systolic murmurs 
may be produced with great ease by slight pressure on the conus 
arteriosus or the pulmonary artery. 
8 Clinique medicale de la Charite, 8°, Paris, 1894, 27. 
9 Verhandl. d. XXI Cong. f. inn. Med., Wiesbaden, 1904, 187. 
10 Thayer. 8 
THAYER, MACCALLUM: CARDIAC MURMURS 
2. In two instances a pulmonary systolic murmur developed after 
considerable hemorrhage. 
3. In one instance with a low general pressure following nitro- 
glycerin, a pulmonary systolic murmur developed. The adminis- 
tration of adrenalin and nitroglycerin had, however, but little 
effect in modifying the pressure in the pulmonary artery. 
4. The administration of adrenalin resulted in an increase 
in systolic pulmonary murmurs when present, during the first 
strong beats which followed, but during the period of very high 
pressure occurring in the general circulation, the pulmonary mur- 
murs as well as murmurs at the aortic area, tended to diminish, 
returning, however, again, if present before, with a fall of pressure 
at a period when aortic murmurs still remained absent. 
5. Infusion of salt solution resulted commonly in the develop- 
ment of systolic pulmonary murmurs. 
6. In a general way, conditions which resulted in especially 
abrupt action of the right ventricle with a large excursion of the 
pulse wave in the pulmonary artery seemed to favor the develop- 
ment of systolic murmurs at the pulmonary orifice, especially if 
there had been a preceding hemorrhage followed by infusion of 
salt solution. 
Murmurs were produced more readily in the pulmonary artery 
than in the aorta, notwithstanding the very slight variations in pres- 
sure which occur in the lesser circulation. This was probably 
due, at least in part, to the fact that with a more or less indistensible 
ring, the pulmonary artery beyond is much less resistant than the 
aorta, and capable of greater dilatation with ventricular contractions 
of moderate force, thus producing, just beyond the pulmonary ring, 
those conditions favorable to the development of fluid veins, and 
consequently a thrill and murmur. 
In general, our observations seem to show that a change in the 
character of the circulating blood, such as that which results in 
the replacing of a considerable quantity of blood by salt solution 
(diminished viscosity ?)is extremely favorable to the development 
of systolic murmurs at the base. 
In conclusion, it may not be amiss to repeat that we have been 
strongly impressed, during these studies, with the feeling that where 
auscultation is taught in small sections, several exercises in the 
study of experimental cardiac murmurs in the dog would do more 
toward making clear in the mind of the student the essential facts, 
without which rational diagnosis of cardiac lesions is impossible, 
than any other method of instruction with which we are familiar. = 1907 = 
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PHILADELPHIA: I FlC*A NEW YORK: 
706-8-10 Sansom Street. L4VQ DI ULI1L1 O W m Fifth Avenue ON THE IMPORTANCE OF SIMPLE PHYSICAL AND 
PSYCHICAL METHODS OF TREATMENT.1 
By William Sydney Thayer, M. D., 
Professor of Clinical Medicine, Johns Hopkins University, 
Baltimore. [Erom The Johns Hopkins Hospital Bulletin, Vol. XVIII, No. 200, 
November, 1907.] 
ON THE IMPORTANCE OF SIMPLE PHYSICAL AND 
PSYCHICAL METHODS OF TREATMENT.1 
By William Sydney Thayer, M. D., 
Professor of Clinical Medicine, Johns Hopkins University, 
Baltimore. 
[425] 
In accepting the kind invitation of your president to speak 
before you this evening, it has occurred to me that it may not 
be out of place to express a few thoughts with regard to the 
importance of certain simpler physical and psychical methods 
of treatment of disease. That which I am about to say may 
seem trite to many in this audience, and yet, although the 
conditions to which I shall refer are tacitly recognized 
by many, nevertheless, as a profession, we have been rather 
slow to meet them as we should. We must all agree that the 
end of the efforts and studies of the physician should be to 
prevent or heal or ameliorate disease-to further and perfect 
the art of medicine. And while recognizing our inefficiency 
and helplessness in many respects, we must realize what 
enormous advances have been made in recent years. If one 
look back, however, at the history of medicine during the 
last century he cannot fail to be impressed with the fact that 
the first nine decades of the nineteenth century, associated as 
they were, with progress in the medical sciences, such as has 
rarely been recorded in a like period of time, were yet not to 
a like degree fruitful in advance in the art of practice. 
Based on the anatomical foundations laid by Morgagni and 
Bichat and extended by such men as Muller, Schultze, and 
1 Delivered before the Louisiana State Medical Society at New 
Orleans, May 14, 1907, and appearing in the N. O. Med. & Surg. 
Journal. 
(1) 1425] 
Virchow, a brilliant line of students, Auenbrugger, Laennec, 
Corvisart, Skoda, and others introduced accurate methods of 
detecting changes in organs and tissues intra vitam. At the 
same time their associates and followers, Bright, Addison, 
Bouillaud, Schbnlein, Louis, and Trousseau, not to speak of 
their numerous living students and successors, by careful and 
acute clinical studies, laboriously correlated with the anatomi- 
cal appearances at autopsy, developed a degree of diagnostic 
exactitude which transformed medicine. And this period of 
anatomical study was associated with and followed by the 
great awakening in physiology and experimental medicine 
started by Magendie and continued by Claude Bernard, and 
later by the brilliant bacteriological and parasitological studies 
initiated by Pasteur and Koch, and by that progress in phys- 
iological chemistry which is throwing day by day more light 
upon the functions of the human body in health and disease. 
But throughout the greater part of the last century the 
minds of the bulk of active scientific investigators were oc- 
cupied with the anatomical, physiological, and bacteriological 
study of disease, and the clinical application of their methods 
and results to diagnosis. At the same time a realization 
of the folly of the old, blind expectations as to the specific 
action of many drugs and the possibility of influencing re- 
gressive structural changes by medicine, brought about, it 
must be acknowledged, a certain therapeutic pessimism. The 
medical world became more and more interested de sedibus et 
\causis morborum in which discoveries were daily made, than 
in attempts to detect new methods of treatment. Some of 
our medical clinics became, as has been said, great diagnostic 
institutes. 
While among the wiser members of the profession this 
interest in pathological anatomy and bacteriology and chem- 
istry, in the scientific study of disease, and the realization 
of the folly and vanity of random experiment on the human 
being with new drugs with the expectation of finding new 
medicines with specific action against disease, brought about 
only a judicious conservatism in practice, yet, in other less 
balanced minds, an overpowering interest in one side of the 
question led to a lack of that attention to the details of the 
[426: 
(2) art of healing which, after all, is the final duty of the physician I 
to his patient. 
But it cannot be said that the condition of the patient 
suffered. In those very clinics which were most criticised and 
most vehemently accused of therapeutic nihilism the treatment 
of the patient was steadily improving. The delivery from 
poly-pharmacy, the employment of the simpler physical means 
of treatment, instead of constant, aimless experiment with 
drugs, with the action of which we were wholly unfamiliar, 
and which more often than not were harmful rather than 
beneficial-these were great blessings. But the tree of medi- 
cal science had not yet begun to bear its first fruit of real 
improvements in the art of healing. In the last twenty years, 
however, great changes have come to pass. The introduction 
of scientific methods of study into certain branches of medi- 
cine have inevitably brought about habits of more exact think- 
ing in other branches. Let us consider for a moment some 
of the changes which have been taking place in the practice 
of medicine as a result of the development of more scientific 
methods. 
(1) As I have already said, men trained in exact methods 
of thought and action could not fail to realize the folly and 
danger of an indiscriminate use of drugs. Several years ago, 
while reading, on a railway train, a book lent me by a dis- 
tinguished teacher and master, whose name many of you may 
guess, I found on a slip of paper between the leaves, the sketch 
of a thought upon this very question which expressed well 
that which we should feel. What surprising and unlooked-for 
reactions might occur if we were to drop chemicals at random 
into a glass found standing in a laboratory and containing 
a fluid of unknown constitution! We might well hesitate to 
risk the experiment. And yet, as physicians, we have been in 
the habit of introducing thoughtlessly into the complex chemi- 
cal fluids of the body, an infinite variety of substances with the 
nature of which we are too often unfamiliar, without the least 
conception of what far-reaching evil effects our act might 
have. This may seem an exaggerated statement. But let me 
take one example. Nearly twenty years ago, a new antipyretic, 
highly recommended-as they always are-was placed in the 
[426] 
(3) [426] 
hands of the profession. This was given to a number of 
patients in the wards of a large hospital. Ill effects were soon 
noticed. Experiments were made upon animals and the 
drug was found to be one of the most powerful destroyers of 
the blood with which we are familiar. Only a few months 
ago it was chosen by one of my colleagues as the best type of 
poison to administer to animals for the purpose of produc- 
ing experimental anaemia, in order to study the regenerative 
changes in the bone marrow. Its constitution was not unlike 
that of other antipyretics which are relatively harmless in their 
effect, and to its thoughtless use in different parts of the world 
we cannot doubt that human lives were sacrificed. The 
harm which may be done by the pointless and careless use of 
drugs often outweighs any possible advantages. We are com- 
ing to realize that as far as possible we should use only drugs, 
the physiological action of which we understand, and which 
can be easily controlled. We must, as physicians, know what 
we are doing and consider carefully before entering on medi- 
cal experiments. And experimental physiology and pharma- 
cology are reproducing and solving for us many a problem 
which, in the human being, would be difficult or impossible to 
approach. 
(2) One of the first and most brilliant advances in therapy 
dependent upon careful physiological study and observation 
was the introduction by George Murray of thyroid feeding 
in the treatment of myxcedema and cretinism. It is true that 
no similar animal extract has as yet proved of like efficacy, 
but the discovery has opened a hopeful field for future study 
and the recent observations of MacCallum concerning the use 
of the extract of parathyroid glands in tetany, may prove of 
almost equal importance. 
(3) Consider again the immense progress associated with 
the development of the use of the antitoxine of diphtheria, 
and to a lesser extent, that of tetanus; with the hopeful action 
of preventive vaccines against typhoid fever, cholera, dysen- 
tery, and plague, and the studies upon opsonic immunity-the 
opening of the whole field of specific serum prophylaxis and 
therapy. 
One must, with regret, pass with a mere word of reference 
(4) the wonderful results of preventive medicine in yellow fever, 
malaria, plague, and cholera, which have been achieved 
through systematic scientific study of the nature of these 
diseases, their mode of transmission, and the conditions under 
which they prevail. 
(4) The fascinating investigations of Ehrlich and his stu- 
dents as to the manner of action of various chemical sub- 
stances in different infections give us ground for hope that 
ere long principles and laws may be discovered, the therapeutic 
value of which we cannot to-day estimate. Everywhere there 
are signs of re-awakening of therapeutic enthusiasm-an en- 
thusiasm based on the fact that the seeds which science has so 
patiently and sedulously sown are germinating and bringing 
forth a new therapeutic art, born of research and experiment, 
accurate thinking and reason-widely different from the blind 
empiricism of the past. 
(5) Almost equally important, though not perhaps as bril- 
liant as these more specific measures, is the awakening which 
is gradually coming over the profession with regard to the 
enormous therapeutic reservoir which we have in the rational 
and carefully planned application of the more simple physical 
and mental methods of treatment. Few of us often consider 
the part that the pure physical and psychical methods of treat- 
ment play in the care of the great majority of maladies which 
come under our observation. It is no exaggeration to say 
that these methods are the most important that we have. The 
difference between modern therapy, or, we must probably say, 
the therapy of the near future, and that of the past, is going 
to be, it seems to me, largely the difference between using these 
methods blindly and without a realization of what we are 
doing on the one hand, and on the other, of applying them 
intelligently and with a full conception of the opportunities 
which lie before us. As it is, we are only beginning. We 
often forget and neglect. 
Let us take a few examples and consider that which we do 
and that which we might accomplish. 
If one of us be tired and worn out from loss of sleep, what 
do we do? Is our first act to take a tonic? No. It is, if we 
can, to rest and sleep. 
[426] 
[427] 
(5) [427] 
If, from overwork and strain, we find ourselves nervous and 
perhaps sleepless, what do we seek to do ? To take a hypnotic ? 
No. If possible, we take a vacation. And we know that if we 
can get away from the hurry and cares of daily duties we 
shall recover immediately. The tonic and the hypnotic are 
makeshifts-and sometimes dangerous makeshifts. 
If there come to us a woman who, in the same way, from 
constant strain and care, added, it may be, to an inherent 
instability of body or mind, has become worn out, introspec- 
tive, and neurotic, do we not to-day realize that in the ma- 
jority of cases that which will best start her on the 
right path is to separate her from her surroundings, to 
put her to bed, to give her a trained nurse who shall have 
had experience in caring for individuals in like nervous or 
mental conditions; to carefully re-educate, as the popular 
term now is, the digestive functions, by beginning with the 
simplest and most limited nourishment, gradually progressing 
until the patient, without realizing the fact, is taking a full 
diet; by the induction of medical obedience; by constant 
and carefully planned mental encouragement and stimula- 
tion, and later, by exciting the patient's interest in some 
bodily or mental occupation, to take her mind from herself, 
while at the same time, by the use of massage, baths, packs, 
and perhaps electrical treatment, the skin is kept in good 
condition and the muscles in such a degree of nutrition that, 
when she again seeks to use them, she may find herself recon- 
stituted in body as well as in mind? This is what the Weir 
Mitchell rest cure, lately so ably set forth by Dubois, means. 
When, after two or three months, the patients, as they often 
do, return better and stronger than they have been for years, 
wre hardly realize that the treatment which they have received 
has been purely physical and psychical, that those medicines 
which have been employed, if indeed, any have been employed, 
have played a wholly secondary part. 
Again, let us consider the conditions in typhoid fever. We 
have for some time realized well enough that it is useless 
to attempt to treat locally and by internal medication that 
which long before the time it is recognized, has been a gen- 
eral septicaemia. To expect to cure typhoid fever by disinfect- 
(6) ing the intestinal tract, even if it could be done, would be 
just as absurd as expecting to cure a case of secondary syphilis 
by local treatment of the cutaneous manifestations. What 
do we do? The first thing on which we insist in the treat- 
ment of a case of typhoid fever is physical rest, that the heart 
and muscles which are already weakened by the circulating 
toxic substances may not be overstrained. We regulate the 
diet so that the patient may be supported as far as may be, 
that the loss of body nitrogen may be kept at the lowest pos- 
sible point, while yet avoiding such nourishment as may in any 
way interfere with the somewhat impaired digestive processes. 
We use cold water in the form of baths or spongings or packs 
for its remarkably stimulating effect on the general mental 
and nervous condition of the patient, and for the apparent 
benefit which results from the coincident lowering of the tem- 
perature. But what we often forget is that such baths and 
spongings should always be associated with careful massage. It 
is one of the commonest defects in our treatment of typhoid 
fever, and other prolonged maladies, febrile and afebrile, that 
we forget to look out for the condition of the muscles. We 
should never think of putting a neurasthenic upon a prolonged 
rest cure without insisting upon massage and hydro-therapy in 
its various forms in order to prevent the atrophy which follows 
long disuse; but in these other conditions in which, as in 
typhoid fever, there is greater muscular degeneration as a 
result of the toxaemia, we too often entirely forget the great 
importance of massage, and abandon it, if it have been given, 
with the falling temperature and the discontinuance of the 
baths. Every typhoid fever patient, after his temperature has 
fallen, should still have at least one alcohol sponging associated 
with thorough general massage daily. It is surprising to see 
the difference in the strength of a patient with pneumonia, 
for instance, who is given general massage as soon as 
his temperature falls to normal, and that of the man who 
passes his convalescence entirely at rest. The one finds his 
legs strong and ready to bear him; the other, with a heart 
weakened by disease, finds his muscles far less able than 
they were before to support him; extra effort is required, 
more strain is put upon the heart, and the process of learn- 
[427] 
(7) [427] 
ing to walk again is a far more serious matter. There is, 
it seems to me, really greater need for proper attention to the 
muscles in typhoid fever and in convalescence from pneumonia 
than in the treatment of a neurasthenic. 
The same applies to the treatment of patients with all 
manner of surgical injuries. The difference between the con- 
dition of him whose muscles have been carefully attended' to 
and that of his fellow who arises with a general atrophy of 
disuse is enormous and can be appreciated only by one who 
has seen the two conditions. 
Consider for a moment the treatment of diseases of the 
heart, muscular or valvular. Eest and regulation of the 
manner of life of the patient are here the essential features- 
medicines should be the last resort. There are conditions of 
lack of compensation in which rest alone is of course insuffi- 
cient, where the brilliant effects of digitalis, diuretics, and 
purgatives are happily familiar. But excepting at such a 
period, the problem in the great bulk of conditions associated 
with weakened heart, is another. It is a question of bring- 
ing the heart back into training. The task before the patient 
with a dilated heart differs from that which is to be met by 
the young man who is training for a race only in degree. On 
the one hand, it is a question of taking steps to prepare normal 
muscles and a normal heart to withstand extraordinary effort. 
On the other, 'tis to prepare a weakened heart to bear burdens 
which, for a healthy man, would be normal. The brilliant 
results so often obtained at Nauheim and elsewhere by the 
application of those measures elaborated by Schott and others, 
which consist simply in lessening the burdens of the heart 
through the baths and by graduallly training it to increased 
effort by means of carefully graduated and progressively 
increased resistance movements, show how much can be accom- 
plished by the simplest physical measures when carried out in 
an exact and painstaking manner, according to a carefully 
laid and scientifically controlled plan of action. Only with 
loss of compensation-that loss of compensation which may 
be so long delayed by purely physical methods of treatment- 
do we fall back upon digitalis to save the day. And at the 
[428] 
(8) very end, when digitalis has failed, it is the lancet which gives 
the patient a new lease of life. 
Let us consider again the treatment of a colitis, say an 
amoebic dysentery. The first necessity is absolute physical 
rest; next, regulation of the diet, and lastly, the question of 
medicine. And medicine by the mouth, as we so well know, 
is of little value here. In the end it comes to the use of 
irrigation of the colon with water judiciously medicated. 
Similar considerations apply to the treatment of pulmonary 
tuberculosis. In no disease have so many drugs been 
employed; in no disease have so many fantastic methods of 
treatment been advised; in no disease are the essentials so well 
met by the careful carrying out of simple physical and psychi- 
cal methods. Absolute rest, especially if there be fever. Free- 
dom from care and responsibility. Careful attention to the 
diet. Life in the open. Above all, the placing of the patient 
in a position in which, from a mental standpoint, he may 
be encouraged and stimulated. In no disease is attention to 
the environment of the patient-the importance of which has 
been so ably emphasized by James-more necessary than in 
pulmonary tuberculosis. Year after year hosts of poor con- 
sumptives go forth in search of that far-off climate which, 
alone and unaided, is to bring them back to health. As well 
might they seek the fountain of youth! Allured by the 
enchantment of distance, they abandon the comforts of home, 
the restraining influence of wise advisers, the encouragement 
of companionship and example, for a cheap boarding-house or 
the solitude of the plains, and strangers in a strange land, 
homesick and doubting, writing thousands of miles for the 
advice which should be near at hand, they die in the midst 
of that paradise of which they had dreamed for the want of 
the hundred little physical attentions and mental stimuli 
which are the most important elements in the care of the 
tuberculous patient. The psychical stimulation associated 
with treatment in sanitaria is not the smallest element in its 
success. 
One might go on through the whole list of human ills, not 
excluding those for which we happily possess drugs with spe- 
cific effect. Indeed it may be worth while to refer briefly 
[428] 
(9) 1428] 
1 to the necessity of attention to the simple physical and mental 
side of the treatment of disease such as syphilis and malaria, 
types of the latter maladies. I think of a specific instance- 
a colleague who consulted me some years ago, with grave 
involvement of the central nervous system following accidental 
luetic infection in the practice of his profession. Despite 
vigorous treatment he had grown progressively worse. The 
outlook seemed almost hopeless. But it was noted that he 
had attempted to combine the treatment with attention to his 
daily duties. It was insisted that he leave home, take to his 
bed and put himself under the absolute control of a wise phy- 
sician and nurse. Six months later a robust, healthy looking 
man entered my consulting room-I had not known him. 
The medication had not varied essentially from that which he 
had given himself, but the physical rest, the freedom from 
care and responsibility, the attention to his general bodily 
condition, and the mental encouragement and stimulation had 
turned the scale. 'Tis a common picture. 
In like manner we are all familiar enough with the ease 
with which the milder forms of malaria may be treated, if the 
patient be willing to spend a few days away from work and 
at rest; how much less quinine will accomplish a good result, 
while the necessity of rest in the treatment of the severer 
forms of the disease needs no mention. 
It is undoubtedly true that wiser physicians always have 
recognized and taken advantage of these facts. True success 
in practice is usually dependent upon the attention of the 
physician to the little physical and psychical details of his 
work. But the world at large takes a very different view of the 
practice of physic and it is ever amazing to see how deep-rooted 
is its faith in medical magic. Nevertheless, the public is slowly 
and half unconsciously beginning to appreciate these things. 
One of the most interesting evidences of this is in the rise and 
development of the trained nurse. What does the patient 
mean when he says, as he so often does, that, after all, a good 
nurse is more important than a physician? He means that 
the measures carried out by the trained nurse, the care she 
has taken of his skin, his muscles, the judicious preparation 
and administration of his diet, the little attentions which pro- 
(10) mote his general physical comfort, the confidence inspired by 
her cheerful and tactful behavior, have had more to do with 
his recovery than any other prescription that the doctor has 
given him-and he is right. 
And what does our increasing dependence on the trained 
nurse mean? It means simply that we know that physical 
and psychical details of treatment are the most powerful 
measures which we can apply in our efforts to bring our 
patient back to health-that we have in the nurse an indi- 
vidual highly trained in the application of these measures. 
What, indeed, is the secret of the success of that gentry who 
use their hands so much better than they use their heads, the 
so-called Osteopaths? Is it not in great part that, by prac- 
tice and experience, many have become fairly skilled masseurs 
whose treatment is of real value to the admiring patients 
whose "dislocated " vertebrse they so marvelously manipulate ? 
But why have I dwelt so long upon these rather simple 
points? Because it seems to me true that although many of 
us may realize where our power lies, we have been delivering 
over the application of these important methods of treatment 
to the trained nurse and to the surgeon, while standing aloof, 
in some instances with a traditional and pharisaical pride in 
the thought that we are not as the osteopath-we use our heads 
only-not our hands-an attitude which is a fatal stumbling- 
block to progress in the art of medicine. 
Must we not, on reflection, be painfully conscious that not 
one of us has ever been properly instructed in massage, and 
that few of us are familiar with the many ways in which hot 
and cold water may be used to advantage? And if, indeed, 
one of us have worked in a part of the world where methods 
of physical therapy are properly taught, where is he to find 
the establishment in which his prescriptions can be suitably 
carried out? 
The tired business man consults us in the summer. He 
cannot take a vacation; he has no horse. The country club 
where he might take the several afternoons a week of golf 
which would do him so much good, is too far away. A few 
hours a week of suitable hydro-therapy and massage and 
Swedish movements would give him an excellent substitute 
[428] 
1429] 
(11) [429] 
for the life and exercise in the open which is the medicine that 
he needs. But what have we, as a rule, at hand? Only the 
Turkish bath, which is often far too exhausting for a man 
in his condition, and the charlatan who poisons his mind 
and plunders his pocket. 
In one city an interesting beginning has been made. A 
few years ago several members of the medical profession, 
recognizing the need of an institution for hydro-therapy, 
massage and other methods of physical treatment, succeeded 
in raising a moderate sum of money, as a result of which suit- 
able rooms were obtained and fitted out with a satisfactory 
system of baths. A male and a female attendant were ap- 
pointed, each trained in massage and Swedish move- 
ments. The establishment was put in charge of a young 
physician who was well qualified by study and experience. 
The institution is open in the morning for women, in 
the afternoon for men. The physician under whose gen- 
eral charge the establishment is placed-who, by the way, is 
an active man in all respects-a teacher and an investigator- 
has published a small pamphlet with a description of the 
various methods of hydro-therapy and the conditions under 
which they may be best applied. A patient may be sent 
with definite prescriptions for whatever treatment may be 
desired and this is faithfully carried out by the attendants. 
A moderate fixed fee is charged for each treatment. After 
two years the establishment became self-supporting and now 
it is making a good income, which might well, some day, be 
applied toward the establishment of a department for thorough 
instruction in methods of physical therapy in a neighboring 
university. I wish that I might say that this institution were 
in Baltimore. 
In general, however, we are sadly behind our colleagues on 
the continent. In connection now with many of the better 
hospitals, there are properly organized institutes for physical 
therapy-institutes to which a patient may be sent for mas- 
sage, for the various forms of hydro-therapy or for fitting 
exercises. I know of but one hospital in this country which has 
a thoroughly developed department of this sort. At the Mass- 
achusetts General Hospital, through the generosity of a 
(12) lady in Boston, there is a complete set of Zander apparatus 
which has been of the very greatest assistance, while of late 
a system of baths has been added. 
That upon which I would particularly insist is that we are 
neglecting a very important feature of medical education. 
We should give more time in our schools and hospitals to 
instruction in the care of the patient in its more literal sense. 
Courses should be given to the students in the essentials of 
nursing. The student, as well as the nurse, should be trained 
in massage, in Swedish movements, in hydro-therapy, in elec- 
tro-therapy. Few physicians in active practice may have time 
to give massage personally. But many a young man could 
accomplish much were he able to give proper massage and to 
direct specifically suitable measures for the physical develop- 
ment of the tired, nervous patient, who now receives, if he be 
lucky, a little advice which he cannot carry out and a pre- 
scription for tincture of nux vomica, or, all too frequently, 
alas, a depleting diet and an elaborate course of medicinal 
treatment directed at his poor stomach, which, tired with the 
rest of his frame, has happened to attract his special atten- 
tion and has be«n made the scapegoat. 
If this be true with regard to the simpler physical methods 
of treatment, how true is it also in connection with the psy- 
chical influence which the physician should exert on his 
patient. As has been said above, true success in practice has 
always depended on the attention of the physician to the 
little physical and psychical details of his work. The encour- 
agement, the stimulation, the mental lift which the good 
physician gives to his patient are the most important elements 
in his practice. This you may say is nothing new. No, 
indeed, it is probably as old as man, and as has been said, 
many thoughtful, conscientious physicians fully understand 
it. They realize that the good which they accomplish depends 
not so much upon the contents of their prescriptions, as on 
the time which they give to their patients, on the honesty 
and simplicity with which they explain to them the nature of 
their condition, and the earnestness with which they give of 
their own store of common sense and reason and optimism to 
the doubting and anxious invalid. 
[429] 
(13) [429] 
I But do we always reflect that this power of suggestion, this 
mental control which the physician should exert over the 
patient is not universally comprehended ? And is it not true 
that before our students we rarely insist upon such matters 
as clearly as we ought? We are rather accustomed to expect 
them to absorb these conceptions by intuition-and the results 
are sometimes odd. I think of an amusing example which 
may serve as an excellent illustration. A young woman left 
a medical school at the end of her third year and became a 
Christian Scientist. When asked the cause of her action she 
is said to have replied that she had discovered that her profes- 
sor of medicine-a most successful practitioner-was after all, 
nothing more than a faith healer, and that she therefore felt 
it useless to go further. 
Another instance of the lack of appreciation and realization 
of the most important powers which the physician can exert 
is the manner in which some of our colleagues tend to look 
upon the modern revival of interest in the analysis of the 
mental phenomena of disease and the more studied application 
of psychical methods of treatment. They seem to regard the 
rather ponderous and impressive term " psycho-therapy " as 
the symbol of some wholly new and mystical method of 
influencing their patients. 
But the awakening of interest in the study and application 
of psychical methods of treatment is important and hopeful- 
and not its least importance lies, perhaps, in the fact that we 
are reminded that many have forgotten to teach their students 
-some have failed to realize themselves-that by the mental 
control which we gain over our patients we can often accom- 
plish more than by any other means. 
The so-called " Christian Scientist " has discovered this, 
finds for himself a satisfactory explanation in his circum- 
scribed religion, and with a simple ignorance of the elements 
of the natural sciences, constructs a grotesque system, which, 
while helping some, leads many astray. 
Many of our Homoeopathic brothers must realize well that 
'tis rather their confident assertions than their dilutions that 
tide their patients over the passing malady. 
The quack, having made peace with his conscience, knows 
[430] 
(14) that, by his fantastic advertisements and ludicrous promises 
he will always gain the confidence of and actually help a 
sufficient number to keep his pocket padded-the main end of 
his existence. 
The maker and advertiser of proprietary medicines knows 
that the false statements printed on his bottles inspire a con- 
fidence that is of benefit to some; that the statements are 
false, that they cruelly deceive many, he may, perhaps, fail to 
consider. 
But the physician does not always realize that that which 
superstition and ignorance and ill faith may accomplish, he 
too can do equally well by properly directed effort, honestly 
and intelligently, and if you will, scientifically. 
Just as it is true that the general practitioner is called 
upon, as a rule, to apply only the simpler forms of physical 
therapy, so it is with regard to methods of psychical treat- 
ment. In all those conditions in the treatment of which the 
mental influence of the physician on the patient is especially 
called into play, the individual is a most important factor, and 
it will probably always be the case, that in the graver nervous 
and mental maladies, the best results will be obtained by men 
especially gifted and specially trained. But many a patient 
might be saved from a long nervous breakdown or from the 
hands of the quack and the charlatan, if we were to remember, 
ourselves, and to teach our students to give more time and 
thought to the care of the mental attitude of the sick. An 
hour's patient attention and explanation and encouragement 
will often do more for the sufferer than months of routine 
treatment. 
These, gentlemen, are the conceptions which I have wished 
to bring before you. They are neither new nor original, but 
they have, nevertheless, a bearing of some importance on the 
practice of medicine. 
It is, of course, needless to add that, if I have insisted upon 
the value of more studied attention to physical and psychical 
methods of treatment, it is not that I would in any way 
detract from the value of drugs or deny the necessity of a 
thorough knowledge of their physiological action. Drugs are 
of course indispensable in the practice of medicine. To say 
[430] 
(15) [430] 
that there are few specifics, and to warn against the indis- 
criminate use of substances of uncertain constitution, is far 
from denying the value of medicines. It is only by knowing 
how to take advantage of every current, to catch every pass- 
ing breath of air, that the skilful yachtsman wins the race. 
The administration of a drug, intelligently, at the right 
moment and in the right manner, may tide the patient over 
the crisis which had otherwise been fatal. But it is none the 
less true that had it not been for other vitally important 
physical and mental measures this opportunity might never 
have been offered. 
16 Observations on tbe 
Ueacbing of Clinical flbebicine 
b« 
William Spbnep Ubaper, flb. 2). 
REPRINTED FROM THE 
PROCEEDINGS OF THE SEVENTEENTH ANNUAL MEETING 
OF THE 
Association of American Medical Colleges 
HELD AT WASHINGTON, D. C., MAY 6. 1907. OBSERVATIONS ON THE TEACHING OF 
CLINICAL MEDICINE. 
By William Sydney Thayer, M. D., Professor of Clinical 
Medicine, Johns Hopkins University, Baltimore. 
In the few words which, through the kindness of 
your President. I have the privilege of saying to-day 
I shall endeavor to bring out some of the things which 
we have been trying to do in the medical clinic of the 
Johns Hopkins University while dwelling, at the same 
time, upon some improvements which we feel might 
be made. 
The idea which has inspired the development of our 
system, that which has been so often emphasized by 
Dr. Osler, is that the one satisfactory way of teaching 
medicine is by the direct observation and study of di- 
sease in the Out-patient department and at the bedside 
-that in comparison to clinical medicine, all other 
methods are makeshifts. 
In brief, the system which we have worked is as fol- 
lows : The school has a four years' graded course. 
Instruction in chemistry, organic and inorganic, as 
well as in the elements of botany and biology, are re- 
quired for admission to the school. The first two 
years are devoted entirely to laboratory work in anat- 
omy, physiology, physiological chemistry, pathological 
anatomy and pharmacology 
Second Year Class. 
Instruction in clinical methods is not begun until 
the middle of March of the second year. 
Preliminary Course in Auscultation and Percussion 
-At this period in the curriculum the second-year 
students are given from ten to twelve exercises of two 
hours each, twice a week, on the theory and practice 
of physical exploration of the normal subject. This 
course, which is given by Dr. T. R. Brown, is one in 
which I have been especially interested and which I 
conducted for some years. It is based on the concep- 
1 tiort that it is necessary, before beginning the study of 
diagnosis, to be familiar with the physical basis of the 
methods of examination which one must employ, and 
with the practical application of these methods in ex- 
ploring the position and function of normal organs. 
The students are first introduced to the inspection of 
toe normal body. They are trained, for instance, in 
the observation of the normal chest, the expansion 
of the lungs, the pulsation of the heart and vessels of 
the neck. They are then led to the study of palpitation 
of the chest and abdomen. Theories concerning the 
cause of vocal fremitus are considered, and the 
student is led to suggest the physical changes which 
might modify these normal signs. From this they 
are induced to consider what physical alterations might 
be brought about by the more common pathological 
changes with which they have become familiar in the 
laboratory. 
They are then taught methods of percussion; the 
variations in the note in collapsed and inflated lungs, 
are demonstrated by experiments on pigs' lungs and 
bladders. The physical theories with regard to these 
percussion sounds are then discussed, and again the 
students are led to a consideration of what modifica- 
tions of the percussion sound they might expect in the 
ordinary pathological conditions. 
At the same time, in sections, the class is trained in 
topographical percussion of the lungs and abdominal 
organs. These exercises are accompanied by demon- 
strations of topographical anatomy on the cadaver and 
on models. I always endeavored to give to the class 
one or two demonstrations of the percussion of the 
heart on a fresh cadaver. The heart was first out- 
lined by percussion; a number of hat pins were then 
introduced so as to mark out the boundaries. The 
beads of the pins were then cut off by a forceps, the 
chest opened and the relations of the pins to the out- 
lines of the heart compared. In a similar manner are 
taught the theory and practice of auscultation of the 
normal heart and lungs. 
The whole class has from ten to twelve exercises, 
the first hour of which consists in an informal talk 
and demonstration, and the second in practical work in 
sections. 
2 Third Year Class. 
Physical Diagnosis-The main work of the third 
year is in physical diagnosis. The instruction is given 
in the out-patient department under the charge of Dr. 
Futcher, Dr. McCrae and eleven associates. Each stu- 
dent has four hours a week of practical work. This is 
arranged as follows: The class which, this year, con- 
sists of 66 members, is divided into four groups. 
In the first half year each group has every week: 
(1) A two hours' exercise in systematic instruction 
in physical diagnosis in small sections. For this pur- 
pose each group is subdivided into four sections so 
that each instructor has under him from four to five 
students. From October to February, these sections 
are taken systematically through the physical diagnosis 
of the common pulmonary and cardiac changes. 
(2) The whole group, undivided, spends two hours 
a week in the Medical Out-Patient Department. Their 
work during this part of the year is elementary, con- 
sisting of history and record taking and, indeed, the 
ordinary duties of under assistants. 
In the second half year each group has: 
(1) A two hours' exercise in the physical diagnosis 
of diseases of the abdomen. 
(2) Two hours of dispensary practice. The student 
is now supposed to have acquired a sufficient knowl- 
edge of physical diagnosis to examine cases inde- 
pendently. A schedule is arranged by which each 
student is assigned to a special instructor for each 
exercise throughout the second half year. The whole 
out-patient staff is called into service in order that 
every student may have individual instruction. In no 
instance does an instructor have more than two men 
on a given day. Each student is given a case. Of 
this case he is expected to take the history and make 
a thorough physical examination and diagnosis, report- 
ing at the end of an hour to his instructor, who goes 
over the case with him. In a book is kept a complete 
record of the cases which each student has seen to- 
gether with an estimate of the value of his work by 
the instructors into whose hands he has come. These 
records are of considerable value in determining the 
standing of the student at the end of the year. 
In May, Drs. Futcher and McCrae give a practical 
3 examination to each student, as well as a two hours'' 
written examination at the end of the year. The stand- 
ing of the student depends upon the record which he 
has made: (1) in his practical work during the sec- 
ond half year; (2) in his practical examination; (3) in 
his written examination. The personal familiarity 
which the instructor acquires with the student in such 
work has been found to be of great value, and has en- 
abled us in a good many instances to reach much more 
definite conclusions as to the character and ability of 
the men than a single examination would justify. 
Recitation-Once a week the whole class meets Dr. 
Futcher for a recitation in which the entire subject of 
physical dagnosis is taken up in systematic review. 
Diagnostic Clinics-At twelve o'clock on Mondays, 
Wednesdays and Thursdays, Dr. Barker, Dr. Futcher 
and I have a clinical exercise in which several patients 
are brought in from either dispensary or wards for 
examination before the class. The object of this class, 
which was established by Dr. Osler, and was one of 
the most valuable parts of his instruction, is to teach 
general methods of diagnosis. The exercise has al- 
ways been an informal one. If an interesting question 
arises, a student is requested to look up the matter and 
to report at some future meeting with a five-minute 
paper. Each student is also expected to follow, as far 
as he can, the subsequent history of the case which he 
has shown and to report on it at a later day. At the 
end of each month a student is appointed to read a 
round-up of the cases which have been seen. 
Medical Clinic-On Saturdavs, from twelve to one, 
Dr. Barker gives a more formal medical clinic in which 
the fourth-year class especially takes part, but to which 
the third-year men are also invited. 
Microscopical and Chemical Diagnosis-During two 
afternoons in the week Dr. Boggs conducts a class in 
microscopical and chemical diagnosis. To these exer- 
cises two hours and a half are assigned. The students 
are here instructed in the methods of examining 
blood, sputa, gastric contents, urine, faeces, etc. This 
is much more than a mere demonstrative course. The 
students are given thorough training and are required 
by repeated tests to prove their ability to count blood 
accurately, to make satisfactory examinations of urine 
sputa, etc. At the end of the year the class is obliged 
4 to pass a practical examination. Each student has a 
locker of his own with a microscope and reagents, and 
often does a good deal of work outside of hours. 
Medical Anatomy-A course in medical anatomy is 
given by Dr. Cohoe once weekly from the first of 
April to the first of June. This consists of demonstra- 
tions of practical points on the cadaver. 
Fourth-Year Class. 
Ward Service-The work of the fourth year con- 
sists mainly of practical service as assistants in the 
wards. The class is divided into three groups, 
each group spending two months and a half in 
the medical, surgical and gynaecological-obstetrical 
services, respectively. The schedule is so arranged 
that the student is able during the period of 
medical service to devote the greater part of his 
mornings to the wards. He acts as an under as- 
sistant, or, to use the term employed in the English 
hospitals, from which the idea of this service has been 
taken, as a "clinical clerk." Each student has a certain 
number of patients assigned to him. Under the di- 
rection of the ward physician he takes the history of 
the new case, keeps the notes and is responsible for 
examinations of the blood, sputa and excreta. He has 
access to the wards from eight in the morning until 
six at night. During the physician's visit in the morn- 
ing the student is expected to give a thorough history 
of his cases, to keep account of the course of events, 
and to defend his diagnoses. Regular ward visits are 
made from nine to eleven on Mondays and Wednes- 
days. and from half past eight to ten on Fridays, by 
Dr. Barker and myself. These visits are attended by 
this section of students as are also the visits of Dr. 
Emerson, the resident physician, and Dr. Morris, the 
first assistant, on alternate days. The class is divided 
into two sections so that on any given morning one- 
half is with Dr. Barker and one-half with me, while 
the visits to the wards are arranged in rotation so that 
the student's time is equally divided between the two 
instructors. 
Clinical Lecture-From twelve to one on Saturdays 
a clinical lecture is given by Dr. Barker in the amphi- 
theatre. At this exercise selected cases are shown and 
5 discussed. Members of the fourth-year class are ex- 
pected to read the history of cases shown and to report 
on the progress of those which have been discussed 
at the previous exercises. 
Recitations-Once a week Dr. Emerson holds a reci- 
tation for the entire fourth-year class, endeavoring to 
carry them systematically over the subject of medicine. 
These recitations will be held next year in the third 
instead of the fourth year. 
Clinical and Pathological Conference-From five 
to six o'clock, once a week, a clinical and pathological 
exercise is given by Dr. MacCallum and myself for a 
consideration of the fatal cases of the week. Owing 
to the closely crowded schedule, and to the fact that 
necropsies often have to be performed on short notice, 
it is frequently impossible for students or physicians 
to be present at the necropsies on cases which have 
been seen in the wards. The exercise is designed to 
fill this gap. At these meetings, to which the third 
and fourth year clases are invited, the history of each 
case is carefully summarized and read, and the diag- 
nosis, which has been written down before the necropsy, 
is discussed. Dr. MacCallum then demonstrates the 
specimens, after which there is a discussion of the im- 
portant points which have been brought out. 
Therapeutics-Practical therapeutics are discussed 
during the morning visits. In addition to this Dr. 
McCrae gives a special course which extends through 
the third and fourth years. This consists of two exer- 
cises a week of an hour's duration each in the amphi- 
theatre and wards. 
Electives-There have been given in the last year 
two elective courses in medicine, one upon the Medical 
Physiology of the Diseases of the Circulatory System 
bv Dr. Ilirscbfelder, and the other on Special Methods 
of Investigation of the Infectious Diseases by Dr. Cole. 
It has become possible to give these courses through 
the organization of three new laboratories: (1) A 
laboratory for research in matters pertaining to phy- 
siological chemistry; (2) a laboratory for biological 
research, and (3) a laboratory for physiological re- 
search, presided over respectively by Drs. Voegtlin, 
Cole and Hirschfelder. Through the establishment 
of these laboratories it has become possible to give 
6 elective courses or opportunities for special researcn 
work. 
Examinations-At the end of the fourth year there 
are given (1) a practical examination in the wards of 
the hospital, each student being assigned a case for 
examination; (2) a two hours' written examination. 
In determining the final standing of the men much 
consideration is given to the character of the work 
which they have done during their term of service as 
clinical clerks in the wards. 
In the main this system has seemed to us satisfac- 
tory. It has differed from that which exists in most 
other institutions in this country only in the replace- 
ment of didactic lectures by practical ward work and 
recitations. This method, we are convinced, is wise. 
In Dr. Barker's weekly clinic, and in the long morning 
visits, it is perfectly possible for the professors of medi- 
cine to treat at length any subject which they feel 
should be set forth didactically, while the great advan- 
tages of direct personal observation of the patient are, 
it seems to me, hardly to be denied. The objection may 
be raised that too much is expected of the student- 
that he will not of himself read systematically. This 
objection is thought to be met by the regular pro- 
gressive series of recitations which take the student 
over the whole subject of me'dicine just as would a 
course of didactic lectures. In the schedule for next 
year these recitations will be changed to the third year. 
There is another objection which might be raised-• 
namely, the great demands of such a system upon the 
time of the instructor. That the demands upon the 
time of the instructor are considerable cannot be de- 
nied. Dr. Futcher, for instance, gives from six to 
eight hours a week to pure instruction, apart from his 
routine dispensary work. Dr. Barker and I give, 
throughout the year, seven and a half hours a week to 
actual instruction. Many of the junior instructors in 
the dispensary also give an equal amount of time. But 
the answer to this is, it seems to me, that medicine can- 
not be taught without time and labour, and that the 
time has come when the medical school should demand 
of its professor of medicine a limitation of his practice 
outside of the hospital, while affording him the financial 
assistance sufficient to enable him to devote the greater 
part of his time to hospital practice and teaching. 
7 There is also a third objection which is very com- 
monly raised to a system such as ours, an objection 
based upon the fear of hospital trustees that the pres- 
ence of students in the wards may in some way inter- 
fere with the proper treatment of patients. This ob- 
jection depends upon a complete misconception of the 
true conditions. And it is rather remarkable to one 
who has had experience with the system of clinical 
clerks, and has observed its operation in England, to 
see the persistency, in a country as progressive as ours, 
of so unfounded a prejudice. As a result of seventeen 
years' experience in the wards of the Johns Hopkins 
Hospital I can say without hesitation that no one im- 
provement, nay more, not all the improvements which 
have developed in our system since the opening of the 
hospital, have resulted in such real benefit to the pa- 
tients as the introduction of students into the wards. 
Fourth-year students, in their capacity of clinical 
clerks, form simply an additional force of trained as- 
sistants. A few months' experience with the help 
which such a body of men gives to the physician in the 
care of his patients makes one indeed wonder how he 
could have conscientiously undertaken his work in the 
days when he had to depend upon a limited number 
of internes for all the emergencies which arise in a 
general hospital. On the other side, the advantage to 
the student is obviously great. 
In conclusion, I should like to emphasize one point 
which, it seems to me, is much to be desired in the 
development of the teaching of clinical medicine. This 
goes back to the very beginning of the teaching of 
physical diagnosis. The student is ordinarily taught 
general and topographical anatomy and the physiology 
of the thoracic and abdominal organs in his first and 
second years. And it is not until the end of his second 
or third year's study that he is introduced to methods 
of exploring the condition and functions of these or- 
gans and determining the presence or absence of patho- 
logical changes. It has long seemed to me that the 
study of topographical percussion and of the characters 
of the normal respiratory sounds in the human being 
should form a part of or an accompaniment to the 
course in anatomy and physiology rather than that of 
clinical medicine. And I hope to see the day when it will 
6e possible for clinicians to work hand in hand with 
8 anatomists and physiologists in such a manner that the 
student may be taught to control that which he is learn- 
ing on the cadaver with regard to the position and size 
of internal organs by the simpler methods of physical 
exploration on the normal subject-to control that 
which he is taught by the physiologists with regard to 
the heart sounds and the respiration by intelligent 
auscultation of these sounds, not only in quadrupeds, 
but on human beings. To bring this about requires 
only a little more time and a little co-operation between 
the anatomist the physiologist and the clinician. But 
no one step could be of greater importance in leading 
the student to approach physical diagnosis by the 
proper path. 
Finally, there is another subject on which I wish par- 
ticularly to touch. It is a matter which relates to the 
teaching of medicine from a broader standpoint. The 
last twenty years have seen great improvements in our 
methods of teaching and a gratifying elevation in the 
requirements for the qualifications to practice. The 
introduction of a four-year graded course was a con- 
siderable step in advance. Yet we must not forget that 
it is far from an ideal system. The four years' train- 
ing is everywhere a crowded course. If, for instance, 
we look over the schedules of our own third and fourth 
year work we must realize that it is impossible for a 
student to accomplish thoroughly all that is there laid 
out. But with the gathering together of large bodies 
of men in classes-the system of ranking-the prizes, 
both material and in the shape of hospital interneships, 
which go to the men who stand highest, many students 
are always goaded to seek for general rank, working 
in a way which is bad for their health as well as for 
their best medical development. Again, if a student, 
for instance, find some special interest-let us say 
in anatomy-and, as sometimes happens, finds himself 
drawn into a piece of original work of real importance, 
he can pursue this only by neglecting another equally 
important branch or by dropping from his class and 
repeating a whole year's work. 
Now it is obvious that any prescribed system such 
as the ordinary four-year medical course cannot suit 
all men. It must be and is planned to be the course 
which shall best adapt itself to the average student. 
There are many men in every class, and by no means 
9 always the poorest men, who would, if left to them- 
selves, accomplish their work more thoroughly by ar- 
ranging their time differently and by spending perhaps 
three or six or nine months more than the time al- 
lotted in a prescribed schedule. Under the present 
system they are crowded through prematurely and 
obliged to work in a manner which injures their health 
and impairs their efficiency as physicians. A prescribed 
course with a class system encourages cramming for 
examinations, no matter how we may endeavor to 
avoid it. 
All this is, of course, to a lesser extent true of boys" 
schools, and we all, I think, realize that, with satisfac- 
tory private instruction, the pupil can do more and 
better work in a shorter period of time than he can in 
classes which are of necessity so arranged as to suit 
the intellect and capabilities of the average boy. But 
where we have schools and academies and small col- 
leges for boys, we have universities for men-universi- 
ties which offer one the opportunity to follow whatever 
line of study he will under those conditions which are 
best suited to his temperament, his habits, his capabili- 
ties, his tastes. Now medicine is a subject to be ap- 
proached by men, not by boys, and it should, in my 
opinion, be taught by university methods. The man 
who undertakes the study of medicine should have 
reached a period of development at which he is capable 
of deciding how and under what conditions he can do 
his best and most efficient work, and such a man ought 
to have freedom in the selection of his courses and of 
the time which he chooses to give to them. lie ought 
not to be bound down to schedules prescribed for a 
large class; he should be able to present himself for 
his final examinations when he is ready. Such an op- 
portunity should be offered at at least two or three 
stated periods in the year. This is what is accom- 
plished by the semestral or trimestral system in foreign 
universities, and it seems to me that we ought to en- 
deavor to follow their wise system. Let the require- 
ments be high ; let there be a minimal time limit of four 
years at least; let the student be given advice as to the 
manner in which his course should be arranged and 
planned; let those courses then be given on a semestral 
or trimestral basis, and let the student be free to spend 
as much time or as little (within the prescribed limits) 
10 in his work as he will, and present himself for his ex- 
aminations at the end of any semester or trimester ac- 
cording to his own best judgment. This system would, 
it is believed, develop a higher order of work and a 
better product. 
Again, under such a system, it is but a step to the 
introduction of extra-mural teaching, and the time 
ought not to be far away when any good man who 
controls clinical opportunities or a laboratory, may find 
an opportunity to offer the advantages of his clinic or 
his material to the students of his community, as well 
as to show his own capabilities as a teacher. The Uni- 
versity of Chicago is already in advance of our other 
schools in these respects. Teaching is on a trimestral 
basis; the class system is practically abolished; exami- 
nations are held four times a year. A man is there 
able to enter on the study of medicine with the same 
deliberation with which any one of us to-day would 
take up the study of some new scientific problem. 
Such a system as this cannot be set up in a day, but 
it is the end toward which we ought, it seems to me, to 
look. I trust that it may not be too far off. 
DISCUSSION. 
Dr. B. D. Myers, of Bloomington, Indiana.-Mr. President: 
I would like to refer to one or two things in connection with 
Professor Thayer's paper. I understand from his paper, that 
in the first two years absolutely no clinical work is given on 
a sick patient. Of course, physical diagnosis can be taught on 
the student himself as well as on the patient. 
Another point: Do you substitute your quiz work for lec- 
ture work in clinical medicine? 
Dr. David Streett, of Baltimore.-I would like to ask Dr. 
Thayer whether we understand that they cover the whole 
course by recitation at the Johns Hopkins. I will say that in 
the college with which I am connected we have the didactic 
and recitation clinic system, and we cover surgery in the sec- 
ond vear. and also medicine, by necitation. We aim to cover the 
whole work of the second year, but never feel we can do that 
without didactic lectures. I fail to understand how we can 
conduct a course in medicine and surgery without giving stu- 
dents clear, definite lines, so that they will know something, 
ex cathedra, on the subject taught them. If we take the text- 
books we use, on each subject we will find the student wades 
through a lot of matter consisting of facts taught at that 
time, but it occurs to me it is not possible for him to digest 
all things and come to any general conclusion. For that 
reason, it seems to me, the student ought to have in his work 
a short lecture course, so that he may have a platform on 
which to stand. This matter of teaching clinical medicine 
11 opens up a big field for Johns Hopkins, but it is a new thing 
to me. 
Dr. Thayer (closing the discussion).-I think the two ques- 
tions that have been asked cover practically the same ground. 
In the third year the work is mainly devoted to systematic 
instruction in physical diagnosis, and general diagnosis clinics. 
In the fourth year the work is carried on at the bedside of 
the patient. Students in the fourth year are taken from one 
end to the other of Osler's practice of medicine recitations. 
Medicine is thus covered as it would be by a series of didactic 
lectures except that the students are obliged to read more than 
one might in such a course of lectures. At the same time, 
students are required to devote eleven and a half hours a week 
to ward visits at the bedside of patients. It is not at all in- 
frequent for a professor to stop in his rounds and give a lec- 
ture of one hour on some special point. This is practically 
didactic teaching at the bedside. Eleven and a half hours a 
week are spent at the bedside of patients, and one recitation 
a week takes the student through the book on medicine. 
Dr. Taylor.-Does the student read up before he is quizzed, 
or is he quizzed first and then reads afterwards? 
Dr. Thayer.-A regular lesson, a certain number of pages, 
are given out for each recitation, so that the book is covered 
in the year. 
12 A HITHERTO UNDESCRIBED DISEASE CHAR- 
ACTERIZED ANATOMICALLY BY DEPOSITS OF 
FAT AND FATTY ACIDS IN THE INTESTINAL 
AND MESENTERIC LYMPHATIC TISSUES. 
By G. H. Whipple, M. D., 
Instructor in Pathology, Johns Hopkins University. [From The Johns Hopkins Hospital Bulletin, Vol. XVIII, No. 198, 
September, 1907.] 
A HITHERTO UNDESCRIBED DISEASE CHAR- 
ACTERIZED ANATOMICALLY BY DEPOSITS OF 
FAT AND FATTY ACIDS IN THE INTESTINAL 
AND MESENTERIC LYMPHATIC TISSUES. 
By G. H. Whipple, M. D., 
Instructor in Pathology, Johns Hopkins University. 
The following case was characterized clinically by a grad- 
ual loss of weight and strength, stools consisting chiefly of 
neutral fat and fatty acids, indefinite abdominal signs, and a 
peculiar multiple arthritis. The diagnosis lay between neo- 
plasm and tuberculosis of the mesenteric structures. Patho- 
logically the lesions of interest were found in the intestines 
and the lymphatic tissue draining this region. The intes- 
tinal mucosa showed enlarged villi due to deposits of large 
masses of neutral fats and fatty acids in the lymph spaces 
and an infiltration of the interglandular tissue by large mono- 
nuclear and polynuclear giant cells. The submucosa in 
many places shows similar deposit in the enlarged lymph 
spaces and invasion by large mononuclear cells. The mesen- 
teric glands in gross showed the most striking changes, but 
under the microscope the picture closely resembled that seen 
in the intestine. The glands showed the same deposits in even 
greater amounts, and a chronic inflammatory reaction with 
replacement of much of the gland tissue by fibrous scar 
tissue, masses of large mononuclear cells or polynuclear 
giant cells of the foreign-body type. The lymphatic tissue 
of the bronchial glands, bonemarrow, and lungs showed no 
abnormalities of importance. The other organs are described 
below, but no changes were found which seemed related to the 
intestinal lesions. 
[382] 
1 [382] 
Clinical History. 
(58,803), X, physician, aet. 36, single, was admitted to the Johns 
Hopkins Hospital on April 12, 1907, complaining of " loss of 
weight and strength; rheumatism; bronchitis; shortness of 
breath; dilated (sic) abdomen; tumor of abdomen." 
Family history.-Unimportant. No history of tuberculosis in 
any branch of family. 
Previous history.-Up to five years before the entry the patient 
had been a remarkably healthy man. Measles and whooping- 
cough as a child. Chills and fever at 10. Slight attack of 
pleurisy at 14-in bed only a day or so. In 1899, mild attack 
of influenza. 
Has had some trouble with his nose for which a small portion 
of each inferior turbinate bone has been removed without benefit. 
Tonsils were excised when he was a child. 
As long as he can remember he has had a slight hacking cough 
and a desire to " clear his throat." For four and a half years 
the patient has, he says, had a " bronchitis " with chronic cough, 
which has always been worse in cold and damp weather. 
The patient has been working as a medical missionary in the 
East, mainly in Constantinople, whither he went in 1899. In his 
work he has frequently been thrown with tuberculous patients. 
The present illness began insidiously, five and a half years ago, 
immediately on his arrival in Turkey. The first symptoms were 
attacks of arthritis coming on in various joints. They were 
transient, the first lasting but six or eight hours. These recurred 
again and again three or four times a week in damp weather, 
once a week perhaps, in dry weather, lasting from six to twenty- 
four hours; rarely severe enough to keep him from work. Nearly 
every joint has been affected. Sometimes the joints were hot, 
swollen, and tender; at other times, only painful. Again the 
pain might seem to be in the muscles; or with pains in the joints 
there were also pains along the course of both sciatic nerves. 
The attacks were never associated with fever and on but one 
occasion were they of sufficient severity to confine him to bed and 
for but two days. These attacks were associated with a gradual 
loss of weight and strength. In the course of a year he developed 
a cough which has continued ever since, varying, however, greatly 
in severity according to weather and climate-better in dry sea- 
sons and climates, worse in damp. This was associated with an 
expectoration of moderate quantity, of a yellowish color, tenacious 
and raised with difficulty-more abundant in the morning. 
Although gradually losing weight and strength he kept at work, 
with occasional vacations, until September, 1906, when he came 
back to America, spending a month in the Adirondacks, where he 
gained five or six pounds. Thence he proceeded to Atlanta where, 
(2) in the course of five or six weeks, his cough became much worse, 
the expectoration increased, and a slight evening fever developed, 
the temperature rising to about 100°. There were occasional 
" night sweats " and notable loss of strength and weight. Physi- 
cal examination showed nothing definite. 
Examination of the sputa for tubercle bacilli was negative. 
In December, 1906, the patient, fearing tuberculosis, went to 
New Mexico, where his bronchitis improved. The loss of weight, 
however, continued, and a diarrhoea set in which has persisted 
ever since, the stools, from three to four a day on an average, of 
fluid or semi-solid character. Examination by the patient him- 
self, revealed a deficiency in bile and an excess of fat. 
Shortly after reaching New Mexico, three and a half months 
ago, the patient observed a swelling of the abdomen, which gradu- 
ally increased until the circumference amounted to thirty-three 
inches, since when it has remained stationary. Soon after this a 
mass became palpable below and to the right of the umbilicus, 
while there was a still larger indefinite area of dulness and 
resistance in the same region. There has been some tenderness 
on pressure in this region. 
About four weeks ago both ankles, especially the left, became 
hot, swollen, red, and tender and attempts to walk were painful. 
This condition, although somewhat improved, still persists. 
For the last four or five weeks he has noticed dyspnoea on exer- 
tion. The appetite has always been good. No history of jaundice. 
[382] 
[383] 
Blood Examinations. 
April 14. Fresh blood-red cells are pale and irregular in size, 
there being many microcytes. No nucleated red blood cells. No 
myelocytes. No marked poikilocytosis. 
R. B. C„ 4,468,000; W. B. C., 8180; haemoglobin, 52%. 
Differential count: 
Polymorphonuclears 410-80.4% 
Small mononuclear lymphocytes 16- 3.1% 
Large mononuclear lymphocytes 32- 6.2% 
Eosinophiles 47- 9.2% 
Large mononuclear cells 2- 0.4% 
Mastzellen 3- 0.6% 
510 
April 21. R. B. C., 4,464,000; W. B. C., 8420; Haemoglobin, 54%. 
April 29. R. B. C., 3,932,000; W. B. C., 6780; Haemoglobin, 53%. 
April 30. Coagulation time, 5 minutes 30 seconds. 
(3) [383] 
May 1. Differential count: 
Polymorphonuclears 491-89.3% 
Small mononuclear lymphocytes 19- 3.5% 
Large mononuclear lymphocytes 19- 3.5% 
Eosinophiles 17- 3.1% 
Mastzellen 1- 0.2% 
547 
April 14. Stool is almost white or creamy and has a smooth 
silky appearance. Under the microscope one sees enormous num- 
bers of fatty acid crystals. They appear as small needle-like 
crystals arranged in tufts or rosettes which do not stain with 
Soudan III. This stain shows an abundance of neutral fat in 
fine globules. Vegetable cells are present and a few pieces of 
striped muscle. No parasites nor eggs are seen after long search. 
Several examinations for tubercle bacilli negative. 
April 24. Stool is clay-colored. Microscopically it resembles 
the ones previously examined with perhaps some increase in neu- 
tral fat. 
April 28. Stool darker colored. No bile was demonstrable. 
Fatty acids and neutral fat present in large amounts. 
Dr. Boggs. April 20. Stool almost completely composed of 
split fats and soaps in crystalline form indicating interference 
with fat absorption. Neutral fat small in amount. Some undi- 
gested starch present. Reaction of stool is acid. 
Dr. Voegtlin. April 30. 
Examination of Stools. 
Neutral fat, 10 gms. 
Fatty acids, 6 gms. 
Organic salts, etc., 4 gms. 
Dried stool, 20 gms. 
Diet.-While in the medical ward the patient was on a full 
diet with four raw eggs daily and eight ounces of milk every two 
hours. In spite of this forced feeding the patient lost weight 
every week, weighing 145 pounds two weeks before his death. 
Normal weight, 175 pounds. 
April 12. Clear, yellow color. Specific gravity, 1029; acid re- 
action; no sugar; no albumin; red finely-granular sediment; no 
casts; many uric acid crystals; diazo negative. Later examina- 
tions showed the same general picture. 
April 29. Calcium oxalate crystals were present. No bile. 
Urine obtained shortly before death showed the presence of a 
considerable amount of acetone but no diacetic acid. 
Urine Examinations. 
(4) May 3. .001 gr. of tuberculin was given. No reaction followed. 
No sputum was obtained except a small amount of clear mucus 
showing no tubercle bacilli. 
[383] 
Clinical Notes. 
Dr. Thayer. April 15, 1907. The patient was thin, and though 
sunburned was evidently pale. There remained still a good deal 
of tonsillar tissue with well-marked crypts. 
The thorax was unsymmetrical, the cartilages of the fifth and 
sixth ribs of the left side being evidently prominent. The move- 
ments of the right upper front were rather freer than those of 
the left side, and on percussion there was a slight dulness with 
a trace of tympany in this area. On quiet respiration the inspi- 
ration was here a little wavy but no adventitious sounds were 
heard. Elsewhere, the respiration was clear. 
Heart.-Sounds best audible in the fourth space, inside of the 
mammillary line, about 7.7 cm. from mid-sternal line, at which 
point dulness begins. Sounds, clear throughout; second pul- 
monic a little louder than second aortic. 
The abdomen was rather full. Just to the left of the median 
line in the epigastrium there was a slight prominence which sug- 
gested a small properitoneal hernia. The abdomen was more 
resistant on the right than on the left, and especially in the right 
lower quadrant where the fulness seemed more marked; there 
was a " rather elastic resistance," especially below and to the 
right of the navel. Tympany on percussion; somewhat duller 
in the middle of the abdomen and in the left flank. No movable 
dulness. 
The liver was not palpable, extending by percussion to a 
point a little above the costal margin in the mammillary line, 
and in the median line to a point midway between the umbilicus 
(5) [883] 
and xyphoid cartilage. The splenic dulness reached the costal 
margin but the border could not be distinctly felt. 
A few small glands were palpable in the axillae and the epi- 
trochlears were both palpable. 
The left ankle was swollen, the skin tense and shiny. On the 
outer side of the foot and on the dorsum there was a diffuse 
discoloration suggesting old cutaneous haemorrhage. A greenish- 
yellow coloration extended from the toes to above the malleoli, 
while at points there were deeper bluish areas gradually fading 
into the yellow-green. The ankle was quite hot. On the legs 
and thighs were a few faded, brown purpuric spots no larger 
than a pin-head. 
In the middle of the left leg, just to the left of the tibial crest, 
there was a discolored, greenish, slightly indurated spot having 
the appearance of a fading patch of erythema nodosum. On the 
right leg and calf were several similar areas. 
Dr. Baetjer. April 17. Radiograph of ankles does not show 
any bone changes. There is, however, a slight thickening of the 
periarticular tissues around joints. This does not seem to be 
tuberculous. No exostosis nor erosion of any bones. 
Dr. Barker. April 19. There is a little general pigmentation. 
Glands in right posterior portion of neck are palpable. Chest 
shows expansion a trifle better on the right side. There are pig- 
mented moles on chest. Vocal fremitus is normal. Percussion 
clear. A slight fraction heard in left lower back and a few fine 
crackles in right supraspinous region. Heart sounds clear. 
Abdomen full, slightly more marked on right side. Slight tender- 
ness to right of navel. Dulness in right flank; none in left. 
Slight swelling of left, but more of right ankle. 
Dr. Thayer. April 20. Abdomen is a little generally distended 
and everywhere tympanitic. Less tenderness to-day than last 
time. There is a muscular resistance to deep palpation in the 
right upper quadrant just above and to right of umbilicus. No 
definite mass is felt. 
Dr. Baer. April 18. Both ankles are markedly swollen and 
pit on pressure. There is a slight amount of local temperature, 
no decided pain on pressure over bones. Dorsal flexion is some- 
what limited. Abdomen is much distended with a decided 
movable mass just below umbilicus. 
Dr. Thayer. April 25. Left ankle is not so swollen and looks 
better. Abdomen is not so swollen-a doughy resistance. Just 
below navel is felt a nodule the size of a walnut. Palpation here 
causes a little pain in left side of abdomen. Some suggestion of 
a lesion at left apex but nothing definite. On deep inspiration in 
left lower axilla in sixth and seventh interspaces there is an 
exceedingly soft friction rub-definite in forced inspiration and 
[384] 
(6) expiration. This is present also over left lower back, rather 
more audible than in front. An occasional fine crackle at ex- 
treme base of right lung. 
Dr. Thayer. April 29. Auscultation of left apex shows a wavy- 
interrupted inspiration but no adventitious sounds. Percussion 
note a little higher pitched than on right. In the left lower 
axilla and back a soft friction is audible, reaching to within 
three finger's breadths of angle of scapula. Over a small area 
below angle of scapula in right lower back a very rough scratchy 
friction is heard. Percussion note at both bases is impaired. 
Heart, no enlargement; sounds clear; pulmonic second sound is 
accentuated. Abdomen is very full with limitation of respira- 
tory movements, walls not so resistant as before. A rather in- 
definite tumor felt to right of umbilicus, it is slightly tender. 
At times to right and above navel a tumor is felt, very movable 
and rather sausage-shaped. 
May 5. Patient transferred to surgical wards for exploration. 
Operation May 6. No fluid in abdominal cavity. Mesenteric 
glands very much enlarged and hard. Abdomen was closed. 
Diagnosis, tuberculosis of mesenteric glands. Patient did well 
for 48 hours after the operation. He perspired quite freely at 
times and was troubled with joint pains but slept a good deal. 
He was on a liquid diet and had frequent enemata, which were 
not very effectual. Dyspnoea was noticed two hours before death 
and respirations then numbered 40 per minute; pulse 120. 
Dr. Cole. May 8, 1907. The patient was seen by me at 9.30 
p. m., at which time he was perfectly conscious, propped up in 
bed and suffering from extreme polypnoea. The distress seemed to 
be both with inspiration and expiration. There was only moderate 
cyanosis, though the skin was cold and clammy. There was no 
striking odor to the breath. A few rales were heard over both 
lower lobes, but no areas of consolidation were made out and 
the condition in the lungs did not seem to be sufficient to account 
for the extreme grade of dyspnoea. Pulse was rapid, but regular, 
and of fair quality. He did not seem to be in immediate danger. 
An attempt was made to have him void as a condition of acidosis 
was at once suspected and it seemed advisable to obtain some 
urine for examination. He was unable to void and preparations 
were being made to catheterize him when he suddenly died. 
[384] 
Clinical Discussion.-Dr. W. S. Thayer. 
The clinical pictures of this case were in many ways 
remarkable. The cough, the fever, the progressive emacia- 
tion, the abdominal swelling and tenderness, the remarkable 
character of the stools, indicative of defective fat absorp- 
(7) [384] 
tion, were decidedly suggestive of a pulmonary and mesenteric 
tuberculosis. 
On the other hand, the physical signs did not justify a 
diagnosis of pulmonary tuberculosis and the sputa were 
negative. The signs at the left apex were interpreted clin- 
ically as evidence of an old retraction and not of an active 
process. Again the blood picture was distinctly not that 
of a tuberculosis. The anaemia was more marked than com- 
mon and the eosinophilia present on entry was peculiar. In 
addition to this were the condition of the ankles with the 
remarkable history, together with the purpuric manifesta- 
tions and the areas suggestive of erythema nodosum- 
symptoms which raised the question as to whether the case 
might belong to that ill-defined group which has been roughly 
brought together through the common manifestations of 
erythema multiforme exudativum and arthritis. 
Further examination of the stools confirmed the existence 
of permanent interference with fat absorption without 
deficiency in fat splitting or azotorrhoea, while the absence 
of reaction to .001 tuberculin was strong evidence against 
the presence of an active tuberculous process. 
These observations, together with the result of the explora- 
tory laparotomy led to a final diagnosis of sarcoma or Hodg- 
kins' disease of the mesenteric glands. 
It is a matter of great regret to me that I was unable to see 
the patient after the operation. The remarkable manner of 
death was as Dr. Cole observed, suggestive of an acid intoxi- 
cation. 
As one looks back upon the history of this case in connec- 
tion with the remarkable observations at autopsy, it is diffi- 
cult to resist the conclusion that we are here dealing with a 
definite and hitherto unrecognized clinical picture with which 
we shall meet again. 
Autopsy Protocol. 
Dr. X. Aet. 36 years. Ward C, 2. Autopsy No. 2883. 
Died 10.40 p. m. May 8, 1907. Autopsy 2 p. m. May 9, 1907. 
Dr. Whipple. 
Anatomical Diagnosis.-Neutral fat and fatty acid deposits 
(8) in intestinal mucosa, mesenteric and retroperitoneal glands 
and thoracic duct; chronic lymphadenitis; anaemia; emacia- 
tion ; organizing peritonitis, pleuritis, pericarditis, and 
aortic endocarditis; cardiac dilatation and hypertrophy with 
fatty degeneration; chronic passive congestion of viscera; 
splenic tumor; hyperplasia of bonemarrow; cloudy swelling 
of viscera; laparotomy wound; bronchopneumonia and 
oedema of lungs; caseous apical scar and tuberculous bron- 
chial lymphadenitis. 
Body is that of a well-developed, large-framed, white male, 180 
cm. in length. Rigor mortis well marked. The skin of the face 
and hands shows a deep brownish pigmentation (sunburn). The 
skin over the trunk and limbs shows no excess of pigment. Over 
the dorsum and lateral aspect of the left ankle and instep are 
several diffuse purple spots and the joints show a boggy swelling. 
The abdomen is slightly distended, shows a recent surgical in- 
cision about 10 cm. in length closed by silver sutures just to the 
right of the umbilicus. The abdomen on incision shows a slight 
excess of slightly turbid yellow fluid. The intestinal coils are 
moderately distended with fluid and gas. The loops of ileum 
and the caecum are adherent by rather elastic, but easily torn 
adhesions to the under surface of the scar described above. The 
peritoneal lining everywhere has lost its gloss and is covered by 
grains and shreds of moist thready tissue. This exudate is quite 
well marked in the pelvis where the threads are quite con- 
spicuous and cannot be separated from the intestinal coat without 
considerable force. The same milky adhesions are present over 
the spleen and liver. The appendix is clear. 
Thorax shows both pleural cavities to be invaded by this same 
type of inflammation. The cavities contain a little excess of 
fluid and the serous surfaces are frosted over by these rather 
elastic moss-like gray adhesions which are most conspicuous over 
the diaphragmatic surfaces and the posterior portion of the lower 
lobes. The fat in the region of the mediastinum shows numer- 
ous ecchymoses. The pericardial cavity is everywhere obliter- 
ated by elastic gelatinous-looking adhesions, in which new-formed 
blood-vessels can be seen with great distinctness. No fresh fibrin 
is found anywhere. The two layers can be separated with some 
difficulty, showing ecchymoses here and there. 
Heart, together with the pericardium, weighs 680 gms. It is 
dilated and hypertrophied. The right auricle shows some dila- 
tation with firm pale gray clots. The tip of the auricle is clear. 
The tricuspid valve measures 15 cm. in circumference. The 
valve leaflets are delicate. The pulmonary valve is normal. The 
intima of the right heart is thin and smooth, through which one 
[384] 
[385] 
(9) 1385] 
sees well-marked mottling of the muscle columns with yellow 
flecks. The left auricle is moderately dilated, its intima smooth. 
The mitral valve measures 12 cm. in circumference, and is deli- 
cate. The aortic ring measures 8 cm. in circumference. Two of 
the cusps are normal. The third cusp situated posteriorly and 
just above the anterior curtain of the mitral valve shows a small 
sessile vegetation 6 mm. in long diameter, situated on the line of 
closure close to the Corpus Arantii. It is of an opaque yellow 
color on its upper portions, but its base shows invasions by deli- 
cate capillaries growing up from the base of the valve. The 
intima of the left heart is smooth and the muscle shows through 
it, of a brownish color, mottled with yellowish flecks. The 
coronary vessels show a few patches of sclerosis. The heart 
muscle is pale and flabby and of a mottled yellowish-brown color 
on tangential section. The wall of the left ventricle averages 
13 to 15 mm. in thickness. 
Lungs.-The left lung is voluminous. The vessels and bronchi 
at the hilum are clear. The pleural surface shows the adhesions 
described above, some of which are invaded by delicate capil- 
laries. On section the lung tissue is everywhere very moist and 
exudes a frothy serous material. It is of a yellowish-red tint in 
the upper lobe, becoming deeper red in the lower lobe. Here and 
there one sees a few slightly raised purplish areas of irregular 
size and extent, which are rather dryer than the surrounding 
tissue and just palpable. At the bifurcation of the main bronchus 
one finds a calcified lymph-gland, measuring 2 cm. in long diame- 
ter. In the apex of the upper lobe is found a small calcified 
nodule 3 to 4 mm. in diameter, above which the pleura shows 
fibrous tags. Further examination of this scarred apical portion 
shows two or three other small foci of cheesy material, none of 
them exceeding 5 mm. in diameter. The right lung shows a 
condition in general resembling the left. There are numerous 
subserous haemorrhages over the lower lobe. Cut section re- 
sembles the other lung. It is very moist. The right lung is even 
more voluminous than the left. 
Spleen weighs 375 gms., measures 18 by 9 by 4 cm. It is ad- 
herent by old adhesions to the diaphragm. Its capsule shows 
numerous irregular milky areas of thickening. On section the 
Malpighian bodies appear very conspicuously as large indefinite 
milky dots, 1 to 1% mm. in diameter. The spleen pulp is of a 
brick-red color, and scrapes off with ease on the knife. The 
trabeculae are easily seen. The organ is flabby and flattens out 
on the table. 
Stomach is greatly distended with sour-smelling clotted ma- 
terial. Its mucosa shows considerable postmortem digestion and 
occasional ecchymoses. The duodenum shows a velvety mucosa, 
stained with bile. The bile papilla is normal. The bile and pan- 
(10) ereatic ducts open side by side, they are delicate and normal 
everywhere. 
Pancreas is rather large and pale. Consistency is about nor- 
mal. Cut section shows a pale watery-gray parenchyma, on 
which one sees distinctly minute opacities of pin-point size. The 
stroma does not seem to be increased in amount, but is quite loose 
and cedematous. 
Liver weighs 2570 gms., measures 29 by 24 by 9 cm. Its upper 
surface is covered over by moss-like elastic adhesions, some of 
which show invasion with blood-vessels. The lower surface shows 
a similar, but less extensive peritonitis. Cut section is every- 
where quite uniform and pale. The lobulation is distinct, the 
lobules being rather swollen, with a pale-red center and a more 
opaque-gray periphery. Here and there are seen a few minute 
areas of yellowish opacity, one of which looks like a small 
tubercle. Consistency is about normal. 
Kidneys weigh 420 gms. The left kidney measures 13 by 6 by 
314 cm. The capsule comes off easily, leaving a pale smooth 
surface, showing occasional retention cysts. Cut section shows 
a pale-gray cortex, averaging 6 to 7 mm. in thickness. The 
striations are perfectly regular. The majority of the glomeruli 
appear as minute red dots. The tubular portion of the cortex is 
swollen and gray. The pyramids are normal. The pelvis is 
normal. The right kidney resembles the left. 
Adrenals are of normal size. On section show an opa:que-yel- 
low cortex, 1 mm. in diameter, and a thin brown medulla. 
Thyroid appears normal; the neck organs could not be removed. 
Aorta shows a few small patches of yellowish thickening. It 
retains its elasticity well. 
Bladder shows a pale smooth mucosa. 
Rectum normal. 
Prostate, seminal vesicles, and testicles normal. 
Marrow of femur is of a mottled yellowish-pink color and 
rather firm. 
Intestine.-The jejunum is dilated, shows a pink or red vel- 
vety swollen mucosa, which is flecked over thickly with little 
pin-point yellowish grains, which seem to be intimately con- 
nected with the mucosa, even in some cases beneath it. No 
ulcerations are seen. The lower portion of the jejunum shows a 
rather paler mucosa of the same description, and everywhere 
thickly dotted over with these little yellowish-white grains. The 
Peyer's patches in the ileum are not conspicuous. The large 
intestine shows a pale smooth mucosa. 
Mesenteric glands present a most remarkable appearance. 
They are greatly enlarged, some of them measuring 3 to 4 cm. in 
long diameter. They are rather elastic to the touch. There are 
many small glands close to the mesenteric attachment, about % 
[385] 
(11) [386] 
cm. in diameter. On section the smaller glands are found to be 
of an opaque pale-yellowish color, with almost complete disap- 
pearance of the gland tissue. There is an indefinite translucent 
reticulum, through which one sees minute grains of opaque yel- 
low color. These are thickly sown throughout all the glands, and 
in some instances seem to be located in cyst-like pockets, from 
which these little grains can be scraped out on the edge of the 
knife. Some of the larger glands present considerable injection 
and show some small haemorrhages into this translucent stroma, 
which everywhere is dotted over with these little grains of yel- 
lowish color. The glands on section bulge beyond the capsules. 
A similar condition is seen in the glands at the root of the 
mesentery in the neighborhood of the pancreas. Some of the 
glands here measure 2 cm. in long diameter. Some of them are 
quite opaque and yellow. They seem to be full of little cystic 
areas, some of which contain a viscid fluid, others little yellow 
grains. The retroperitoneal lymph-glands about the coeliac axis 
show exactly the same picture. 
Thoracic duct is dissected out. Smears made from its content 
and stained show no bacteria but many mononuclear leucocytes 
and large mastzellen. The fluid from the thoracic duct shows 
numerous small highly refractile droplets and small rosettes of 
pale greenish acicular crystals often attached to the side of a 
fat droplet. 
Scrapings from the cut section of the mesenteric glands under 
the microscope show typical tufts and balls of delicate spindle- 
shaped crystals. These crystals dissolve with a slight amount of 
heat and are reformed on cooling. They come down in little 
star-like masses of-needle crystals, which are much smaller than 
the original crystals. The crystals dissolve easily in alcohol and 
ether, and are evidently fatty acid. Similar crystals are found 
in the scrapings from the intestinal mucosa. Fresh cut section 
of the glands shows a neutral reaction to litmus. No bacteria are 
made out in smears. One of the small mesenteric lymph-glands 
is inoculated subcutaneously into a rabbit; animal died in seven 
weeks; negative for tuberculosis. 
Tissues hardened in Zenkers fluid, formalin, or alcohol. The 
routine stain was haematoxylin and eosin. 
Heart.-The pericardial cavity is almost entirely replaced by a 
loose cedematous granulation tissue of connective tissue and 
wandering cells in which blood-vessels are quite conspicuous. 
There are numerous chinks in this granulation tissue which are 
lined by cubical epithelium derived evidently from that of the 
pericardial cavity. In some small areas there is an exudate of 
polymorphonuclear leucocytes, red blood-cells, and fibrin. The 
Microscopical Preparations. 
(12) [386] 
heart muscle-cells are of about normal size but show a moderate 
grade of fragmentation. The aortic valve shows a dense hyaline 
mass of old fibrin which is being invaded by fibroblasts, wander- 
ing cells, and blood-vessels. 
Lungs.-The pleura is thickened and infiltrated with many 
wandering cells and new-formed blood-vessels. There are nu- 
merous adhesions consisting of scar tissue or organizing granu- 
lation tissue. Beneath the pleura many of the alveoli show an 
exudate of red blood-cells and heart-failure cells mixed in with a 
fine pink granular coagulum. Other alveoli show a hyaline-like 
exudate of fibrin which is being invaded by wandering cells, 
fibroblasts, and capillaries. In such areas the alveolar walls are 
greatly thickened, consisting mainly of a thick mass of young 
fibroblasts and blood-vessels. The alveolar epithelium here is 
cubical and beneath it are many phagocytes full of coarsely 
granular yellow pigment. In all sections of lung tissue the 
alveoli show some coagulated serous material and numerous 
heart-failure cells. In some areas the alveoli show a fresh exu- 
date of fibrin, red blood-cells, and leucocytes. The bronchi in 
some instances show a similar exudate and the epithelium is well 
preserved. The capillaries are congested and the larger blood- 
vessels are normal. The lymphatic tissue of the lung is normal 
in amount and character. Coal pigment is present in moderate 
amount. 
Spleen.-The capsule is thickened and shows signs of a chronic 
inflammatory process. The trabeculae are thickened but widely 
separated from each other by an increase in spleen pulp. The 
blood-vessels show some thickening of their walls and in some 
instances a hyaline degeneration of the subintimal tissue. The 
Malpighian bodies are enlarged, but as a rule show no abnormali- 
ties. Some of them show an increase of stroma with disappear- 
ance of lymphoid-cells in the immediate neighborhood of the 
central arteriole and others show many polymorphonuclear leuco- 
cytes in their peripheral zone. The venules of the spleen pulp 
are full of blood and their walls are somewhat thickened, show- 
ing evidences of some chronic passive congestion. The pulp- 
cells are increased in number, between which are seen numerous 
cells of polyblastic type (Maximow), red blood-cells, and leuco- 
cytes. The stroma of the pulp is definitely thickened and easily 
made out. Numerous accumulations of coarsely granular yellow 
pigment are found in the pulp, often some of the smaller grains 
being included in large phagocytes. 
Marrow of femur.-There is considerable increase in the cel- 
lular elements, but the fat-cells are quite in evidence making up 
more than half of any section and appear quite normal. The 
giant cells and myelocytes occur in normal proportion. The 
eosinophile cells are not increased in number. Red blood-cells 
(13) [386] 
are not conspicuous, but the nucleated reds are quite numerous 
and definitely increased in number. They occur in clumps of 
3 to 20, which are scattered thickly throughout the sections. 
The same yellow pigment as described in the spleen is present 
in all parts of the cellular marrow and is often included in large 
phagocytes. The lymphatic tissue of the spleen and marrow 
shows none of the remarkable changes found in that of the 
mesentery and intestine, but the changes here are dependent on a 
secondary ansemia. 
Blood-clots. Sections show no change of importance. 
Liver.-The capsule is thickened and shows many adhesions 
made up of scar tissue and blood-vessels. The stroma at the mar- 
gins of the lobules is increased in amount and invaded by many 
polymorphonuclear leucocytes which are present as well in the 
capillaries of the lobules. This change is most marked just 
beneath the capsule and seems to have a direct relation to the 
extensive perihepatitis. The capillaries in the central portion of 
the lobules are dilated with a corresponding atrophy of the liver 
cells which here contain fine yellow pigment. The liver 
cells at the margin of lobules are swollen and granular, some of 
them showing small fat vacuoles. The bile-ducts are perfectly 
normal. 
Adrenals.-Its cortical cells are regularly arranged and of the 
usual appearance. Many of them show fat vacuoles. The me- 
dulla is inconspicuous. The perirenal fat is quite normal in 
appearance. 
Kidneys.-The cortex shows a regular architecture, but there is 
a slight diffuse increase in connective tissue between the tubules. 
The glomeruli are of normal size, but many show some thicken- 
ing of their capsules. The convoluted tubules show a swollen 
pink-staining granular epithelium which shows the " brush 
border " quite well and whose nuclei stain sharply. Their lumina 
are slightly dilated and contain foamy or granular-looking dSbris 
but no casts and no exudate of cells. The pyramids show normal 
tubules which contain no casts, but the interstitial stroma is 
quite oedematous. Blood-vessels are normal and the capillaries 
contain little blood. 
Pancreas.-Sections from various parts of the organ show no 
changes of importance. The islands of Langerhans are rather 
large, sharply outlined by a thin capsule, and made up of normal- 
looking cells, a few of which show mitotic figures. The acini 
in many places show postmortem changes, but elsewhere are 
normal, as are the pancreatic ducts. The interlobular stroma 
is loose, its meshes being separated by a pink granular coagulum 
in which can be made out a few mononuclear wandering cells. 
The fat-cells in this stroma are normal. The interacinar stroma 
is very delicate. 
[387] 
(14) Skin and subcutaneous tissue from abdomen is quite normal. 
The fat-cells are sharply contoured. 
Thyroid.-Its acini are regularly arranged and contain normal 
colloid. The interacinar stroma is loose and oedematous, showing 
as well some pale-staining colloid material. 
Jejunum and ileum.-Sections made from various levels in the 
small intestine all show the same general picture. 
Frozen sections stained lightly with osmic acid and Soudan III, 
show deposits of fat in the villi and submucosa. Fatty acid 
crystals are not stained and show up very clearly as rosettes of 
needles which are intimately associated with the neutral fat 
(compare Fig. 1) and make a beautiful contrast. Tissue hard- 
ened in formalin and stained by the Marchi method (1) shows 
the presence of large masses which reduce the osmic acid and 
are called fat droplets for the sake of brevity. The fat in the 
tissue at the mesenteric attachment stains as usual, appearing 
as large oval or circular, sharply and evenly contoured masses of 
a uniform jet black. Large black masses are seen in the inter- 
glandular tissue of the mucosa and in the submucosa (Fig. 2). 
These are not evenly contoured, but show nodular or even ser- 
rated margins and all manner of shapes. They do not stain 
uniformly and one may see the center or any portion of a large 
mass which has a feathery or fern-like appearance, due evidently, 
to the presence of the crystals of fatty acid. In some instances 
the outlines of typical rosettes are preserved in the Marchi prepa- 
rations of the intestine, but this finding is common in the gland 
tissue. The crystals reduce the osmic acid, but they are not as 
black and opaque as the fat droplets. The majority of the black 
masses fill the spaces in which they lie but some only partly do 
so, the rest of the space being filled with a fine reticulum of 
coagulum suggesting lymph. Some of these spaces in the villi 
contain a fine spider-web-like reticulum of coagulated material in 
which may be embedded a few mononuclear cells or a small 
droplet of fat (Fig. 8). A lining endothelium can often be made 
out in such cases, suggesting that these are dilated lymph radicles 
perhaps occluded by a fat embolus located proximally. One may 
see droplets of varying size, many of which do not exceed twice 
the diameter of a lymphocyte, and they may be so closely packed 
that it seems sure that there is a deposit of this fatty substance 
outside of the lymphatics as well as in their lumina. The epithe- 
lial cells lining the crypts of Lieberkuhn show no fat droplets, 
but there are many goblet cells with accumulations of mucus. 
They are quite normal in appearance. The interglandular stroma 
shows but few very fine grains of fat such as one finds in its 
venules in the circulating white corpuscles. A few of the large 
mononuclear cells of the plasma-cell type show these fine black 
grains, but the peculiar cells which are distinctly abnormal in 
[387] 
(15) [387] 
this location do not show any fat grains, or at the most only a 
few. These cells have a vesicular nucleus and a pink-staining, 
frothy-looking protoplasm. With ordinary stains the cells seem 
to be packed with fine fat vacuoles of nearly uniform size, but 
these do not stain with osmic acid. The polynuclear giant cells 
are not numerous and show only occasional fat grains. The soli- 
tary follicles show no large accumulations of fat, but they are 
invaded by numbers of the large mononuclear cells. Some of 
the plasma cells here show a few grains of fat. The muscularis 
mucosae is quite thickly sprinkled with fine black grains, which 
seem to be both intra- and extra-cellular. The capillaries and 
venules in this neighborhood often show some fatty grains in 
the endothelial cells. 
Sections stained with haematoxylin and eosin show the very 
conspicuous vacuoles (Fig. 3), many of which contain a finely 
granular, pink-staining reticulum. Some of these vacuoles are 
lined by endothelial cells, giant polynuclear cells, numbers of the 
large mononuclear " foamy " cells, or a combination of any or 
all of them (Fig. 3). Other vacuoles are surrounded by a thin 
capsule of quite dense fibrous tissue in which are embedded many 
or few of the wandering cells. The interglandular tissue is made 
up of numbers of lymphocytes, plasma cells, and eosinophiles 
in about the normal number, plus the unusual mononuclear cells 
(Fig. 4). There seem to be two kinds of large mononuclear cells 
or very different types of the same cell. One resembles exactly 
the "polyblast" of Maximow (2) and is not very numerous here. 
Its protoplasm stains a deep pink and is finely granular, while 
its nucleus is vesicular, but shows well-marked strands and 
grains of chromatin. The majority of the giant cells appear to 
be formed by a fusion of such cells and show the same type of 
nucleus and protoplasm. The second type of cell has a pale 
vesicular nucleus, which is poor in chromatin, 5 to 7 p in 
diameter and often eccentrically situated. Its protoplasm is 
abundant and has a foamy appearance, due to the presence of 
closely-placed vacuoles or granules which are often quite uniform 
in size, but may vary from 5 p down to the size of an eosino- 
phile granule. Some of the granules seem refractile and suggest 
mastzellen, but stains for these cells (1) show the same " foamy " 
protoplasm with non-staining vacuoles. Mastzellen are present 
in considerable numbers. 
The " foamy " cells average 20 to 30 p in diameter but show 
evidence of active motility and are of every conceivable form. 
Mitoses are seen in these cells very rarely. They are occasion- 
ally phagocytic to red blood-cells, old blood pigment or nuclear 
fragments. A few cells are seen which may be transition forms 
between them and the common polyblast, showing a vesicular 
(16) nucleus and finely granular pink protoplasm, in which are a few 
of the vacuoles described in the " foamy " cells. 
Maximow (2) describes cells (" eiterphagocyten ") which in 
some points resemble these " foamy " cells, but his cells contain 
granules which stain by various methods. Such cells he con- 
siders to be derived from the mononuclear lymphocytes of the 
blood, as is true of the polyblasts. The " foamy " cells form giant 
cells either by fusion or nuclear division, the protoplasm retain- 
ing its peculiar appearance (Fig. 4). Some nuclei show signs 
of degeneration, but this is unusual, and the activity of the cells 
speaks against their being types of degenerating polyblasts. 
They are most numerous in the tips of the villi and about the 
fat deposits where they often make up the entire field, with 
almost complete absence of the lymphocytes and plasma cells. 
As a result of all this invasion of foreign cells and fat deposits 
the villi are greatly increased (more than double) in length and 
diameter. Their capillaries are dilated, and the connective tissue 
is increased in amount. There is evidence of an occasional old 
or recent extravasation of red blood-cells into the villi, where 
one may see a few phagocytes packed with yellow granular pig- 
ment. Well-preserved red blood-cells may be seen free in the 
tissue round the bases of the crypts. A few polymorphonuclear 
leucocytes are seen in these areas. The solitary follicles are but 
slightly enlarged and the prevailing cell is the lymphocyte. Some 
are invaded by numbers of the " foamy " mononuclear cells but 
no very striking changes are seen. 
The muscularis mucosae shows hypertrophy. The submucosa in 
some places is almost normal, but as a rule is much thickened, 
its vessels dilated and thickened, and the stroma filled with 
wandering cells. The predominant mononuclear cell is the poly- 
blast and they often contain fine grains of fat (Marchi). Many 
of the " foamy " mononuclears are present, usually in the loose 
stroma just below the muscularis mucosae and in the neighbor- 
hood of fat deposits. The fat droplets in some places are so 
closely placed as to suggest subcutaneous fat, but close inspection 
shows that they are of irregular size and shape. Their margins 
are often outlined by giant and mononuclear cells (Fig. 3) and 
they are separated from each other only by a delicate granulation 
tissue of fibroblasts, capillaries, and wandering cells. Again, the 
tissue will be dense and fibrous, containing only a few fat drop- 
lets and wandering cells. Numbers of extravasated red blood- 
cells are seen in the submucosa, often in large clumps, but usually 
diffusely scattered. Yellow granular blood pigment is frequently 
seen included in phagocytes and is most abundant in those areas 
where the fat deposits are most numerous. Large eosinophile 
mononuclears are quite numerous in all parts of the submucosa. 
Careful search with oil immersion lens in sections stained by 
[387] 
[388] 
(17) [388] 
various methods failed to reveal any bacteria or parasites which 
could have any relation to the lesion. The muscle coats and the 
ganglia of the plexuses are normal. The ganglion cells show 
some fine fat grains in their protoplasm. The serous coat shows 
an organizing granulation tissue of wandering cells, capillaries, 
etc., of the usual type. 
Unstained frozen sections show refractile fat globules and 
great numbers of long acicular fatty acid crystals arranged in 
sheaves and rosettes. Stained lightly with osmic acid such sec- 
tions give a picture represented in Fig. 1, which shows well the 
large and small droplets thickly sown through the gland tissue 
and a rosette of crystals. Marchi preparations show even more 
extensive fatty deposits (Fig. 5) than were seen in the intestine. 
The gland deposits are larger, even more irregular and closely 
packed, but in general closely resemble those described above. 
In places the fat is deposited in threads which are twisted, 
beaded, and packed together, resembling a reconstruction of the 
glomerular capillaries. Such deposits are often seen in a fol- 
licle and no endothelial cells can be made out in relation to them. 
Giant cells are numerous and closely applied to the margins of 
these fat deposits, often in little lacunae as though they were in- 
gesting and eroding its substance. These cells may show a fine 
granular protoplasm and a few fat droplets; other giant cells 
in the stroma may show clumps of small fat droplets in their 
protoplasm which may have the " foamy " appearance. Some 
of the giant and mononuclear cells with the foamy protoplasm 
show minute comma-sliaped black deposits which often outline 
one segment of a vacuole in the protoplasm, others are rod- 
shaped, again beaded like small filaments of chromatin, but 
always in the protoplasm. Often they are associated with defi- 
nite grains of jet black fat deposits in the protoplasm and for 
this reason are thought to be some form of fat. The wandering 
mononuclear cells show varying amounts of fat deposits, some 
only a few minute grains, others large clumps of large and small 
droplets, and some are so crowded with fat droplets that the 
protoplasm and nucleus may be almost obscured. Cells with 
the foamy protoplasm seem less actively phagocytic toward the 
fat, and great numbers of them are entirely free from it. Just 
beneath the thickened capsules of some of the larger glands is 
seen a fine cloud of minute fat droplets (Fig. 5) which are very 
thickly packed all through the rather (edematous stroma. Some 
of these grains are intra-cellular, but many are surely extra- 
cellular. In such areas the large foamy mononuclears may be 
very numerous and yet show almost no phagocytosis of fat. It 
is possible that this material has recently reached the cortex of 
Glands. 
(18) the gland from the afferent lymphatics. Some of the larger 
lymphatics at the hila of glands (efferent) are filled with a fine 
granular coagulum of albuminous material in which may be seen 
scattered small fat granules. The fat cells of the mesenteric 
tissues adjacent to the gland capsule are sharply contoured by 
thin cell membranes and look entirely normal except for some 
infiltration of the intercellular tissue by small round cells, chiefly 
lymphocytes and plasma cells. Sections of various glands stained 
with haematoxylin and eosin show how extensive is the change in 
the larger glands. The tissue is honey-combed with the fat vacu- 
oles and much of the cellular structure is replaced by dense 
fibrous tissue which is poor in cells (Fig. 6). It takes a deep 
blue stain with Mallory's connective-tissue stain. The capsule 
and trabeculae are thickened and the blood-vessels dilated and 
increased in number. 
Some of the small glands which are slightly involved show 
almost normal lymphatic follicles and cords, but the peripheral 
lymphatic sinus may be greatly dilated by an exudate of red blood- 
cells, mononuclear wandering cells, a few polymorphonuclear 
leucocytes and lymphocytes, mixed with a finely granular pink 
coagulum. There are small irregular fat deposits which usually 
first appear in the medulla of the gland between the intact lymph- 
cords. They are outlined roughly by collections of giant and 
mononuclear cells, but endothelial cells are rarely made out. The 
adjacent tissue is at once invaded by numbers of large mononu- 
clear cells, eosinophiles, young fibroblasts, and capillaries forming 
a loose cellular granular tissue about the deposits. It is quite 
possible that this cellular reaction may preceed the fat deposits. 
This granulation tissue gradually becomes dense and fibrous 
causing the great distortion of the gland architecture seen in 
several of the photographs (Figs. 6 and 7). Free red blood-cells 
are present in great numbers in both large and small glands, but 
the ecchymoses are more striking in the older glands. Phago- 
cytosis of red cells by polyblasts is present, but not conspicuous, 
and is relatively infrequent when we consider the number of 
both types of cells. Changed blood-pigment included in phago- 
cytes or chinks of the stroma is hard to find except in the larger 
glands. In some of the small glands the eosinophile cells are 
very definitely increased in number, mononuclears predominating, 
and suggest the presence of some parasite. 
A small gland which was preserved in 15 per cent formalin and 
stained by the Levaditi method, showed some very peculiar struc- 
tures. Studied with 1/12 objective these sections show great 
numbers of a rod-shaped organism (?) which, with this stain, is 
about the diameter of the spirochcete of syphilis but not of spiral 
shape and rarely exceeding 2 y in length. The majority of these 
structures closely resemble in form the tubercle bacillus. They 
L388] 
(19) [388; 
'] are very sharply contoured and appear as jet black rods, some- 
times bent but more often straight or only slightly curved. Some 
show a slight swelling of one end and others a beaded appear- 
ance. They are most numerous in the vacuoles, which are not 
completely filled with fat and contain a filmy granular reticulum 
(Fig. 9). The structures are most numerous at the edge of the 
vacuoles, where the " foamy " cells are in evidence, and are con- 
tained in great numbers in these cells. When a cell contains very 
many of these structures they seem to clump together and lose 
their sharp outline as though damaged by the process of inges- 
tion. These structures are present at the edge of the fat droplets 
in less numbers and become less numerous in the adjacent tissue. 
Careful search made in corresponding sections stained by various 
aniline dyes reveals no corresponding structures. If we compare 
them with the various spirochates which take this stain we, 
perhaps, may imagine that we are dealing with some organism 
which resists the common stains but reduces the silver salts, 
effecting considerable increase in its size. Whether this is the 
active agent in this peculiar pathological complex cannot be de- 
termined from the study of this single case, but its distribution 
in the glands is very suggestive. No tissue from the intestines 
nor viscera was available for the Levaditi stain and all the smears 
from the thoracic duct and glands were used before the study of 
the glands by the silver method revealed these peculiar bodies. 
The vacuoles do not all contain fat deposits, some of them 
(Fig. 8) showing only a delicate tracery of granular pink coagu- 
lum. In such spaces there may be a few degenerated cells or 
] small fat droplets or the coagulum may show an exact mould of 
a rosette of fat crystals which have been dissolved. Some of 
the smaller glands have a very oedematous stroma, and all the 
cellular elements are widely separated. Here the large mononu- 
clear cells show many degeneration forms in which the proto- 
plasm is full of very large irregular vacuoles and the nucleus 
very faint or even non-staining. In all sections many areas are 
found where there are large accumulations of the large foamy or 
granular mononuclears and here the degeneration forms are 
often conspicuous. Mastzellen are present in all sections, but 
not numerous. One large giant cell with pink granular proto- 
plasm is seen in mitosis, the chromatin threads being very 
coarse and arranged as though the division was to result in three 
or four cells. 
Briefly the microscopical findings in the intestinal and 
mesenteric lesions may be summarized as follows: The villi 
of the small intestine are enlarged, the submucosa thickened, 
and the mesenteric glands enormously enlarged by deposits 
[389] 
(20) of osmic acid reducing bodies (neutral fats and fatty acids). 
Such deposits are most numerous in the glands, but alike in 
all these situations. They are of all sizes from minute grains 
intra- or extra-cellular in location, up to huge irregular drop- 
lets and there is the greatest variety of forms (Fig. 2 and 5). 
Many of the larger masses show rosettes of fatty acid crystals 
(Fig. 1) and they may occupy spaces which are lined by 
endothelium suggesting dilated lymph channels (Figs. 6 and 
7). The majority of the larger deposits are outlined by 
polynuclear giant cells or large mononuclear cells of poly- 
blastic type which in some instances seem to be eroding 
the fatty material and are closely applied to its edge. 
(Fig. 8). The epithelium of the mucosa is normal as far 
as the microscope shows. The interglandular stroma contains 
about the usual number of lymphocytes, plasma cells, and 
eosinophiles, but there is an infiltration with great numbers 
of polyblasts-large mononuclear, ameboid cells with pink 
granular protoplasm. A second type of cell which is very 
conspicuous has an abundant foamy protoplasm, a pale vesi- 
cular nucleus and is actively ameboid; this may be a type of 
polyblast. Ecchymoses are numerous wherever we find the 
fatty deposits. The submucosa shows invasion with great 
numbers of these polyblastic cells especially about the fat 
deposits which in some places are abundant (Fig. 2) ; in 
others absent. There may be a very definite eosinophilia in 
such areas. The glands show the most extensive changes, 
especially the larger ones (Fig. 6-7). In some the lymphatic 
nodules and cords are quite intact, the process seeming to 
begin in the sinuses of the glands with invasion of the char- 
acteristic cells and small irregular fat deposits. The next 
stage is an invasion by fibroblasts and capillaries with more 
or less extravasation of blood, increase in size and number 
of the fat deposits and distortion of the gland architecture 
(Fig. 8). The large mononuclear cells increase rapidly in 
numbers and giant cells become conspicuous. The final stage 
shows a very large gland packed with fat deposits of all sizes 
and shapes, whose stroma is made up of dense fibrous tissue 
full of ecchymoses and great numbers of giant and mononu- 
[389] 
(21) [389] 
clear cells (Fig. 6-7). Gland tissue treated by the Levaditi 
method shows great numbers of a peculiar rod-shaped organ- 
ism (?) which does not stain by the aniline dyes and is most 
numerous in the vacuoles and in the neighborhood of the 
peculiar " foamy " cells which often include these structures 
(Fig. 9). Whether this is the etiological factor in this dis- 
ease can not be determined from this case. 
Bacteriology. 
A bacillus belonging to the colon group was isolated from the 
mesenteric glands. Cultures from the parenchymatous organs 
showed a white coccus of low virulence. 
A small gland was planted subcutaneously in a large gray 
rabbit. The animal died of pneumonia seven weeks after the 
inoculation. Autopsy showed a small subcutaneous abscess full 
of soft yellow pus. The glands draining this area were only 
slightly enlarged. Microscopical sections show an abscess wall 
of granulation tissue containing many large mononuclear pha- 
gocytes closely resembling those described in the human tissue. 
The central part shows necrosis. Gland-tissue from the axillae 
shows merely a moderate grade of chronic inflammation and 
there is no evidence of tuberculosis. 
Chemistry. 
The microscopical picture was so suggestive of an ab- 
normal fat or a mixture of fats, fatty acids, and perhaps 
some toxic substance which resisted absorption by the sur- 
rounding granulation tissue that a chemical study of the 
glandular tissue was attempted. The small amount of avail- 
able material did not permit of extended chemical investiga- 
tion, but the following facts are clearly brought out. 1. 
The ratio of fat to fatty acid. 2. The saponification value. 
3. Several negative qualitative tests. 
Liver, spleen, kidney, and small intestine.-About 10 to 15 gms. 
of each organ were ground up in about 50 cc. of 95 per cent 
alcohol and allowed to stand in bottles for several days. The 
tissues were extracted and tested for fatty acid which was found 
to be present in traces in the first three tissues, and to a greater 
degree in the intestine. Neutral fat was present in all, apparently 
in normal amount. 
Mesenteric glands.-About 3 gms. of material (a single large 
(22) gland) preserved in 95 per cent alcohol was extracted in the 
Soxhlet apparatus for six hours, the alcoholic and ether extracts 
united and evaporated to an oily residue. Glycerine was tested 
for and shown to be absent. The oily residue was made alkaline 
and the fat removed by repeated extractions with ether. The 
alkaline solution showed a typical soapy appearance. This was 
shown to contain a soap by the following reactions: 1. One 
portion acidified with hydrochloric acid gave a precipitate which 
was soluble in alcohol. 2. A second portion treated with calcium 
chloride gave a typical precipitate of calcium soap which was 
insoluble in alcohol. The solution was made acid and the fatty 
acid removed with ether. The ether was evaporated and the 
residue weighed. The neutral fat extracted by this method 
weighed 0.75 gms. and the fatty acid 0.07 gms., giving a ratio of 
10 to 1. 
A second determination was made by another method. Four 
medium-sized glands weighing about 4 gms. were cut open 
and preserved for three weeks in about 50 cc. of 80 per cent 
alcohol. This alcohol was filtered off and evaporated over the 
water bath to a dark brown oily residue-1st fraction. The glands 
were then ground up thoroughly with sand and absolute alcohol 
and the alcohol filtered off. The residue of tissue macerated with 
the sand was extracted in the Soxhlet apparatus for 24 hours 
with ether and the ether and alcohol extracts combined. This 
was evaporated on the water bath to a white waxy material-2d 
fraction. The glands were further extracted in the Soxhlet for 
a second 24 hours, but this ether extract on evaporation gave 
only a trace of fatty material-3d fraction. 
Material from the 1st fraction (0.1116 gms.) was dissolved in 
neutral 80 per cent alcohol and titrated against a known solution 
of alcoholic potash (7.8873 gms. per liter). It required 1.05 cc. 
of the alcoholic potash solution to neutralize the free acid. Then 
8 cc. of the alcoholic potash were added and the solution heated 
over a water bath with return condenser for one hour to saponify 
the neutral fat. At the end of this time the solution was a deep 
cherry red showing an excess of alkali was still present. It was 
found that 2.58 cc. of the alcoholic potash had been used up by 
the fatty acids which were set free in the saponification. This 
gives an approximate ratio of 5 to 2 for the fats and fatty acids 
in the 1st fraction. Material taken from the 2d fraction (0.198 
gms.) was treated in an identical manner. This solution re- 
quired but 0.35 cc. of alcoholic potash to neutralize the free 
fatty acid, but 3.69 cc. were used up during the saponification. 
This fraction showed a much higher percentage of neutral fat, 
the ratio to fatty acid being roughly 10 to 1. The saponification 
number of this material from the 2d fraction as determined by 
[389] 
[390] 
(23) [390] 
Dr. Loevenhart was 144.4. When the weights of the 1st and 2d 
fractions were combined the ratio of fats to fatty acids was 
found to be about 85 to 15 per cent-1.552 gms. fat and 0.234 gms. 
fatty acid extracted from all the tissue.' Tests for bile pigments 
were negative. Tests for phosphorous were made as follows and 
shown to be negative. Material from the 1st and 2d fractions 
boiled 5 to 10 minutes with potash, then acidified with nitric 
acid and an equal amount of ammonium molybdate added. On 
boiling this solution no yellow precipitate was obtained, but the 
addition of one drop of an acid sodium phosphate solution gave 
the yellow precipitate in abundance. This test excludes the 
presence of lecithin in any appreciable amount. The 1st fraction 
showed many crystals of various types. Some of these were 
needles of fatty acid and others chlorides or phosphates. No 
crystals of cholesterine were seen. The 3d fraction showed a 
few tufts of beautiful slender acicular fatty acid crystals. 
It is unfortunate that the tissue was not sufficiently fresh 
to test for enzyme action (lipase), but the following facts 
are suggestive. Fatty acids (0.23 gms.) were present in these 
abnormal mesenteric glands and presumably the majority of 
them were derived from high melting point fats because the 
well-formed crystals were present in large numbers even with 
a room temperature of 32 C. Neutral fats were present 
(1.55 gms.) and showed a low saponification number (144.4) 
which indicates either some abnormality of the fat or the 
presence of some non-saponifiable substance mixed with it. 
Lecithin and cholesterine were suspected but shown to be 
absent. In the determination of the saponification number 
no allowance was made for the included fatty acid (10 per 
cent) which would tend to raise rather than lower the num- 
ber, making the contrast with normal fats somewhat less 
striking but would in all probability leave it abnormally 
low. The saponification numbers of the common fats are 
tripalmitin = 208.8, tristerin = 189.1, triolein = 190.4, 
horse fat = 199.4, hog fat = 195.6. 
Discussion 
Many features of this case were of great interest but it 
seems that in the light of our present knowledge a lengthy 
discussion would be of little value. The finding of acetone 
in the urine shortly before death and the extreme air hunger 
(24) at this time suggested some acidosis which may have been 
dependent on the disturbance in fat metabolism. However 
the acetone could be accounted for by the starvation of the 
tissues following the obstruction of the mesenteric lymphatics 
and we know that in spite of heavy feeding the patient was 
steadily losing weight. The large amount of unsplit fat in 
the stools (one-half by weight) may be explained by the in- 
complete action of the lipolytic ferment owing to lack of 
absorption of its split products. Again there may have been 
some lack of lipase in the pancreatic secretion, but the normal 
appearance of the gland is opposed to this view. The de- 
posits of neutral fat and fatty acids in the tissues may indi- 
cate some disturbance in the synthesis of fat which Loeven- 
hart (3) and others (4, 5) have shown to be effected by 
lipase. Several facts indicate that this fat is in itself in some 
way abnormal or that it holds in suspension some abnormal 
or toxic substance. 1. The saponification number is very 
low. 2. The fat causes a tissue reaction resembling the re- 
action due to an inert foreign-body. 3. The peculiar wander- 
ing and phagocytic mononuclear cells. 4. The presence of 
many minute ecchymoses and changed blood pigment sug- 
gests some toxin capable of effecting the solution of the 
capillary walls. The pathological changes are limited to 
the apparatus which has to do with the absorption of fats 
while the lymphatic tissue of the marrow, spleen, bronchial 
glands, etc., is relatively normal except for the changes con- 
secutive upon a rapidly advancing secondary anaemia, resem- 
bling that seen in cancer cachexia. All this suggests very 
strongly that here we are dealing with some obscure disease 
of fat metabolism. 
The disease is of some duration as evidenced by the extreme 
changes in some of the larger glands which show dense scar 
tissue and cellular reaction which must be of months' stand- 
ing. From a comparison with the intestinal lesions it would 
seem probable that the earliest changes took place in the glands 
rather than in the mucosa where the dense scar tissue is 
much less in evidence although in general the picture is the 
same. Examination of the contents of the thoracic duct 
[390] 
(25) L390J 
excludes the possibility of any occlusion of its radicles 
between the glands and receptaculum. The presence of fatty 
acid crystals in its contents must be explained by the escape 
of such material from the glands and the same explanation 
holds for the mastzellen. The presence of many eosinophile 
cells in the smaller glands probably accounts for the same 
type of cell found clinically in the blood, but no clear explana- 
tion has been found for this reaction. 
The presence of peculiar structures in the Levaditi sec- 
tions which do not stain by the aniline dyes, suggests a pos- 
sible relation to the group of spirochaetes. It is not claimed 
that this is the etiological factor in this disease but its dis- 
tribution in the glands is very suggestive. It is always found 
in the peculiar vacuoles and cellular granulation tissue which 
are the striking features of the microscopical picture in the 
glands and intestine. 
There seems no sufficient reason to correlate the intestinal, 
arthritic, and serous lesions but it is possible that the organ- 
izing inflammatory reaction affecting the pleura, peritoneum, 
and aortic valve may be closely related to the peculiar 
arthritis and purpura which we were unable to examine at 
autopsy. 
In searching for a name to designate this condition great 
difficulties were encountered. It would seem that no suitable 
name can be applied to it until the etiological factor is deter- 
mined. The term Intestinal Lipodystrophy is suggested as 
this seems to offer less objections and to have more points in 
its favor than any one word or combination of words which 
have been considered. 
In conclusion I wish to express by most sincere thanks to 
Dr. Thayer for his careful clinical analysis of the case which 
was under his care in the private wards, to Dr. Loevenhart 
for valuable assistance in the chemical study of the tissues, 
to Dr. Voegtlin for analyses of the stools and urine, to Dr. 
Ford and Mr. Harrison for the bacteriological examinations, 
to Dr. Welch and Dr. MacCallum for their interest and val- 
uable suggestions, to Mr. Brodel and Mr. Ridges for assist- 
ance in preparing the illustrations. 
391] 
(26) References. 
[391] 
1. Mallory and Wright: Pathological Technique, 1904. 
2. Maximow, A.: Zieglers Beitrage, Bd. 38, s. 301, 1905. 
3. Loevenhart: Jr. Biolog. Chern., Vol. II, No. 5, p. 427, 
1907. 
4. Taylor: Univ. Cal. Pub. Path., I, p. 33, 1904. 
5. Pottevin: Compt. rend de l'Acad. d. sci., CXXXVI, p. 
1152, 1903. THE JOHNS HOPKINS HOSPITAL BULLETIN, SEPTEMBER, 1907 
PLATE XXXIII 
Fig. 1.-Frozen section 0 fa^Sren^er^c gland stained 
lightly with osmic acid. RoSeg. 5 acid crystals and de- 
posits of fat among lymphoc? 
Fig. 2.-Marchi preparation. Cross section of one of the cir- 
cular valves of the jejunum. Large central deposit of fat in 
the submucosa and on either side deposits in the mucosa. Soli- 
tary follicle (u). 
Fig. 3.-Fat vacuoles (a) in mucosa and submucosa. Giant 
cell (b). Large mononuclear "foamy" cells (c). THE JOHNS HOPKINS HOSPITAL BULLETIN, SEPTEMBER, 1907. 
PLATE XXXIV. 
Fig. 4.-Interglandular tissue oflOnScu^Ucosa: fat vacuole (a); giant cell 
(&), and "foamy" cells (c). ls Mucosae just appears at the base. 
Fig. 5.-Marchi preparation. Cortex of large mesenteric gland. Large fat 
■droplets (a); fine thickly placed fat droplets (&), and thick gland capsule 
free from fat (c). 
Fig. 6.-Large gland full of dense scar tissue (&); fat vacuoles 
lined with endothelium or giant cells. Normal lymphatic 
cells (ci). THE JOHNS HOPKINS HOSPITAL BULLETIN, SEPTEMBER, 1907. 
PLATE XXXV. 
Fig. 7.-Large gland dep Packed fat vacuoles (a); 
"foamy" cells at edge of and in stroma (&); giant 
cell (c). 
Fig. 8.-Small gland with more recent changes; red blood cells scattered 
through the tissues. Vacuole (a) contains a filmy granular coagulum. Rim 
of ''foamy " poly- and mononuclear cells (&) at edge of fat deposit. 
Fig. 9.-Section of gland stained by Levaditi method. Vacuole (ci) con- 
taining rod-shaped organism (?). Studies on Arteriosclerosis, with Special 
Reference to the Radial Artery. 
BY 
W. S. THAYER, M.D., 
PROFESSOR OF CLINICAL MEDICINE, JOHNS HOPKINS UNIVERSITY, 
AND 
MARSHAL FABYAN, M.D., 
ASSISTANT IN PATHOLOGY, JOHNS HOPKINS UNIVERSITY, BALTIMORE, MARYLAND. 
AMERICAN JOURNAL OF THE MEDICAL SCIENCES 
From the 
December, 1907. Extracted from the American Journal of the Medical Sciences, December, 1907 
STUDIES ON ARTERIOSCLEROSIS, WITH SPECIAL REFERENCE 
TO THE RADIAL ARTERY. 
By W. S. Thayer, M.D., 
PROFESSOR OF CLINICAL MEDICINE, JOHNS HOPKINS UNIVERSITY, 
AND 
Marshal Fabyan, M.D., 
ASSISTANT IN PATHOLOGY, JOHNS HOPKINS UNIVERSITY, BALTIMORE, MARYLAND. 
Among the first things which we record in the every-day examina- 
ton of a patient is the palpability and consistency of the radial 
artery. While there has been much discussion as to what inferences 
one is justified in drawing with regard to the condition of the 
general arterial tree or of special central vessels, from the condition 
of the radial, we have, as a rule, little conception as to just what 
we are feeling in the radial artery itself. 
In order to gain information upon this point one of us (Fabyan) 
over a year ago, undertook the study of the radial arteries from a series 
of consecutive cases which had been previously observed, clinically, 
in the wards of the hospital. At the same time, for the sake of 
comparison, there were removed from each case, bits of the aorta 
just above the valves and from a point just above the origin of the 
mesenteric artery, as well as a piece of the mesenteric vessel just 
below its point of origin. 
The first question which we asked ourselves was: What is the 
character of the normal radial artery and what are the common changes 
with which one meets? 
The material consisted of 61 cases, the ages of the patients varying 
from fifty-six days (in a seven months' child) to eighty-three years. 
We were immediately impressed with the fact that the radial artery 
varies greatly in its general characters at different ages. 
At birth the artery is delicate, translucent, extremely thin, and 
collapsing. The surface on opening is perfectly smooth. The 
intima consists of a single endothelial layer, lying directly on the 
surface of a deeply undulating elastica interna. The media, which 
consists of transversely arranged, smooth muscle fibres with rather 
large vesicular nuclei, has a depth of about seven to eight layers of 
cells. Connective tissue, if present in the intima and media, is ex- 
tremely scanty, none being revealed by the Mallory or van Gieson 2 
THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
stains. There is, however, a relatively large amount of elastic 
tissue which appears on cross section as very thin, parallel, slightly 
Fig. 1.-Radial artery of a seven months' child (Case 58) who died fifty-six days after 
birth of bronchopneumonia (hematoxylin and eosin). This artery was not palpable 
clinically. 
Fig. 2.-Radial artery of a seven months' child (Case 58) who died fifty-six days after 
birth of bronchopneumonia (Weigert's elastic tissue stain). 
wavy lines. The elastica externa is neither as coarse nor as deeply 
undulating as the interna (Figs. 1, 2, and 3). THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
3 
The adventitia, considerably thicker than the media, consists 
of compact connective-tissue fibres with relatively large nuclei. 
The elastic fibres are fairly numerous, running in various directions. 
The picture alters progressively with the age and growth of the 
individual. The changes are especially striking in the intima which, 
sometimes as early as the middle of the first decade (Figs. 4 and 5), 
becomes distinctly thickened. This thickening consists in the 
appearance, uniformly, or at local points in the intima, of a fresh 
Fig. 3.-Radial artery of a child, aged two and half years (Case 15), who died of 
general spastic paralysis and bronchopneumonia. This artery was not palpable clini- 
cally. 
Fig. 4.-Radial artery of a child five years old (Case 61) who died of bronchopneu- 
monia following measles (hematoxylin and eosin). This specimen shows a beginning 
elastic muscular thickening of the intima with the separation of a second layer of elastica 
from the surface of the intima. This artery was not palpable clinically. 
strip of elastica which appears to be lifted up or split off from the 
surface of the interna. In specimens stained by Weigert's method 
the elastica interna takes a clear, grey-blue color. With growth 
and development the inner surface of the interna becomes irregular 
and roughened in outline and of a deep black hue. Gradually, the 
irregular, rough, deeply staining inner layer is at points lifted from 
the surface of the interna, forming a separate, more or less parallel 4 
THAYER, FABYAN! STUDIES ON ARTERIOSCLEROSIS 
strand (Fig. 6). This strand on cross section appears beaded, and in 
longitudinal sections much smoother, justifying, in our opinion, the 
Fig. 5.-Radial artery of a child five years old (Case 61) who died of bronchopneu- 
monia following measles (Weigert's elastic tissue stain). The specimen shows the early 
separation of an inner layer of elastica from the surfaces of the interna. This inner layer 
has at points a somewhat beaded appearance. 
Fig. 6-Radial artery of a child five years old (Case 61) who died of bronchopneu- 
monia following measles (Weigert's elastic tissue stain). The specimen shows the same 
changes noted in Fig. 5 under a higher power. 
conclusions of Hallenberger,1 that it represents a collection of longi- 
tudinal fibres. In some specimens, connective-tissue cells may be 
1 Ueber die Sklerose der Arteria radialis, Marburg, 1906, 8. This valuable communication 
did not appear until some time after the beginning of our studies, and was unknown to us 
until our work was nearly done. It is satisfactory to find that our observations are in 
most particulars confirmatory of Hallenberger's results. THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
5 
seen apparently making their way through the interstices of the 
fenestrated membrane, giving rise to the picture on which Hallen- 
berger bases his hypothesis that ingrowth of connective tissue 
causes the separation of these inner layers of longitudinal elastic 
fibres. At the same time between these two layers, and some- 
times between the inner layer and the endothelium there appear 
a few connective-tissue cells and smooth muscle fibres which have 
in the main a longitudinal course. 
The media also increases in thickness with the growth of the indi- 
vidual. The elastica in this coat is very scanty in amount, merely 
an occasional thin wavy fibre. Just external to the elastica interna 
there may be a delicate layer of connective-tissue fibres. 
In the second decade the artery gradually assumes the character 
of the adult vessel; the walls become thicker but the vessel still lies 
Fig. 7.-Radial artery of a girl, aged fourteen years (Case 35), who died of pneumonia 
and pericarditis (hematoxylin and eosin). The specimen shows early elastic muscular 
thickening of the intima. This artery was just palpable clinically, but was not regarded 
as thickened. 
collapsed like a ribbon on its muscular bed. The surface shows on 
section a number of delicate, transverse striations, as well as two 
longitudinal lines which correspond to the points at which the artery 
folds when in a state of collapse. The cause of the transverse stria- 
tions is uncertain. Their appearance at the same time with the de- 
velopment of longitudinal elastic and muscular fibres in the intima, 
and the fact that they disappear when the artery is stretched, have 
suggested to us that they may be due to the contraction of these fibres. 
The intima has increased materially in thickness. A second strip 
of elastica is usually present. More, longitudinally arranged, smooth 6 
THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
muscle cells have appeared as well as a small number of connective- 
tissue cells. 
The media is also thicker (Fig. 7), the elastic tissue being rela- 
tively less marked and not as uniformly dispersed as in the first 
decade. Delicate fibrils running in various planes seem to arise 
from the interna and externa. No connective tissue is demonstrable 
excepting a fine layer just external to the interna. 
Fig. 8.-Radial artery of a healthy man, aged thirty-two years (Case 38), who died of 
a traumatic cerebral hemorrhage (hematoxylin and eosin). Elastic muscular thickening 
of the intima with a local sclerotic patch showing a fine elastic network. This artery 
was palpable clinically, but was not regarded as a thickened vessel. 
In one case in this decade, a boy with chronic nephritis, there 
were local areas in which the intima was slightly more thickened 
(observable only by the microscope). In these areas, beside the 
second strand of elastica, there was a meshwork of finer elastic 
fibrils with an appreciable increase in connective tissue. Outside 
these points the elastica interna seemed less wavy and appeared 
rather stretched. 
In the third and fourth decades there is no great change in the 
constitution of the vessel. The gross appearance of the artery when THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
7 
laid open is the same excepting that in a few cases an occasional 
longitudinal line of irregular length is to be noted. The signifi- 
cance of these is not entirely clear, but their association, as a rule, 
with the presence of microscopic areas of connective-tissue thick- 
ening of the intima which contain numerous fine elastic fibres has 
suggested to us that they may be due to irregularities in the contrac- 
tion of the vessel associated with these changes. 
The intima and media tend to become somewhat thicker. The in- 
tima always shows a second strand of elastica and in several instances 
as many as two or even three additional strands. In addition to 
these, sometimes in irregular patches, sometimes more or less uni- 
formly, the larger strands are replaced by a meshwork of fine fibrils 
with a marked increase in connective tissue (Fig. 8). These areas of 
connective-tissue thickening are especially noticeable in the vessels 
of a laborer, aged twenty-two years (No. 37), who had been a very 
heavy worker; of a laborer, aged twenty-five years (No. 60), with 
Fig. 9.-Radial artery of a day laborer, aged twenty-two years (Case 37), accustomed 
to heavy physical exercise, who died of pneumonia. Longitudinal section (hematoxylin 
and eosin). In the depths of the sclerotic intima is an area of calcification. 
chronic nephritis; of a man, aged thirty-one years (No. 48), with 
aortic insufficiency; of a sailor, aged thirty-five years (No. 33), with 
mitral and aortic insufficiency and dilated heart. In one of these 
cases, that of the man, aged twenty-two years, there was a spot of 
calcification in the deeper part of a marked connective-tissue 
thickening of the intima (Fig. 9). 
The media becomes gradually somewhat thicker, and connective 
tissue begins to be demonstrable by van Gieson's stain. The con- 
nective tissue is always more marked just outside the elastica interna 
at points of local thickening of the interna. 
In several instances the media was, on measurement, considerably 
thicker than the average. Of these cases, 4 in number, 1 was a 
day laborer, aged twenty-two years (No. 37), who had been a very 
heavy worker. This patient also showed a very thick intima with 
a marked, fine, elastic meshwork and considerable connective tissue 
(Fig. 10). 8 
THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
The second was a laborer, aged twenty-five years (No. 60), an 
exceedingly heavy drinker and a heavy worker with chronic neph- 
ritis. In this case there was also a considerable thickening of the 
intima with the separation in some places of two strips of elastica 
and areas of greater connective-tissue thickening. 
One was a man, aged twenty-seven years (No. 42), an exceedingly 
heavy drinker with an hypertrophied heart. Here the intima, 
though not very thick, showed the separation of one strip of elastica 
with small areas of irregular thickening with fine elastic meshwork. 
Fig. 10.-Radial artery of a day laborer, aged twenty-two years (Case 37), accustomed 
to heavy physical exercise, who died of pneumonia (hematoxylin and eosin). The speci- 
men shows a local intimal thickening with increase of connective tissue and a fine net- 
work of elastic fibres. Marked thickening of the media. This artery was palpable clini- 
caly, but was not considered an unduly thickened vessel. 
The fourth case was a man, aged thirty-one years (No. 48), with 
aortic insufficiency; this man had been also a very heavy worker. 
The intima showed areas of local connective-tissue thickening with 
a fine, irregular, elastic meshwork. It may be noted that 3 of these 
4 cases were also among those selected as examples of especial 
thickening of the intima. 
In the fifth decade a decided change occurs. The lumen of the 
vessel as viewed in gross, remains open and irregularities in the 
wall may be felt on palpation. In cases which are especially THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
9 
thickened the transverse striations have disappeared and longi- 
tudinal lines of varying length are to be noted. In no case are 
there raised plaques. Plaques are, however, represented by slight 
cuppings about 3 to 4 mm. in length and about 2 mm. in breadth. 
Their surface is perfectly smooth; they are usually rather less 
circumscribed than those observed, for instance, in the coronary 
artery and of grayer color. Not infrequently these areas show 
calcification. 
The intima has become diffusely thickened and begins to contain 
considerable connective tissue (Figs. 11 to 14). In a number of 
Fig. 11.-Radial artery of a day laborer, aged forty-one years (Case 54), who died of 
aortic insufficiency and pericarditis (hematoxylin and eosin). Diffuse sclerosis of the 
intima. This artery was regarded clinically as a thickened vessel. 
cases further strands of elastica appear to have separated off from 
the interna, sometimes as many as three. The areas with connective- 
tissue thickening and a diffuse fine meshwork of elastic fibres are 
more numerous. In some of these areas the elastica interna can 
no longer be distinguished as a separate layer (Fig. 12). 
In 6 out of 19 cases in this decade there were areas of calcification 
in the deep layers of the intima. The tissue about these areas is 
homogeneous, nearly free from nuclei and takes usually a rather 
deep, eosin stain. The elastica interna, externally to the calcified 
spots, is usually stretched and may appear to be broken; it may, 
apparently, have entirely disappeared. 10 
THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
In 1 case, a man, aged forty years, there was evident bone for- 
mation extending from the intima through the destroyed elastica 
into the media. 
The media in this decade reaches its maximum average thickness, 
but the increase from the last decade is, relatively, considerably 
Fig. 12.-Radial artery of a day laborer, aged forty-one years (Case 54), who died of 
aortic insufficiency and acute pericarditis (Weigert's elastic tissue stain). Diffuse sclerosis 
of the intima. The elastica interna has disappeared. Meshwork of fine elastic fibres 
throughout the intima. 
Fig. 13.-Radial artery of a day laborer, aged forty-two years (Case 44), who died of 
chronic nephritis (Weigert's elastic tissue stain). At points there are multiple strands 
of elastica. At other points there is a fine elastic network. In places the interna seems 
thinned and stretched. This artery was regarded clinically as a thickened vessel. 
less than that of the intima. Opposite the thicker plaques in the 
intima the media is often considerably thinned, the nuclei elongated, 
narrowed, and diminished in number; there is a good deal of 
connective tissue. In 3 of those cases in which calcification was 
noted in the intima there was also a medial calcification, most THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
11 
marked in the inner part of the coat, close to the elastica interna, 
opposite the points of intimal calcification. In 1 instance it was 
very extensive, involving nearly the whole width of the coat in 
places, producing a picture similar to that described by Moncke- 
berg.2 One can sometimes trace the deposition of lime salts 
directly into muscle cells from which the nuclei have disappeared, 
while in the periphery of these areas there may be evident hyper- 
trophy of the individual muscle fibers. The tissue about the calci- 
fied areas has sometimes a homogeneous appearance staining with 
eosin, while the nuclei have disappeared. 
The elastic tissue in the media is scanty-merely a few thin, 
straight fibres parallel, in cross sections, to the lumen. In this 
decade there were 6 cases in which the media was especially thick- 
ened. Of these, 3 were instances of chronic nephritis, 1 of aortic 
insufficiency, and 2 occurred in individuals who had been extremely 
heavy workers and alcoholics. 
Fig. 14.-Radial artery of a day laborer, aged forty-two years (Case 44), who died of 
chronic nephritis (Weigert's elastic tissue stain.) Longitudinal section shows multiple 
strands of elastica in the intima. 
After the fifth decade there is a progressive increase in the thick- 
ness of the intima. From one to three, more or less regular elastic 
strips may be split off from the interna, but with advancing years 
these are less marked and a diffuse connective-tissue thickening 
of the intima with fine, irregular, elastic fibres becomes the common 
type (Figs. 15 and 16). Calcification in the deep layers of the 
intima (Fig. 17) becomes commoner with age, 4 out of 5 cases in 
the eighth and ninth decade showing this change. 
The media after the fifth decade becomes, on the whole, rather 
thinner; there is a marked increase in the connective tissue and 
the tendency to calcification is greater. Opposite points of especial 
2 Ueber die reine Mediaverkalkung der Extremitatenarterien und ihr Verhalten zur Arterio- 
sklerose; Arch. f. pathol. Anat. u. Physiol, u. f. klin. Med., 1903, Band clxxi, 141. 12 
THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
Fig. 15.-Radial artery of a tailor, aged sixty-four years (Case 49), with chronic neph- 
ritis and hypertrophied heart, who died of an oesophageal carcinoma (hematoxylin and 
eosin). Diffuse sclerosis of the intima. Clinically this artery was palpable and regarded 
as a thickened vessel. 
Fig. 16.-Radial artery of a tailor, aged sixty-four years (Case 49), with chronic nephritis 
and hypertrophied heart, who died of oesophageal carcinoma. Longitudinal section (hema- 
toxylin and eosin). Diffuse sclerosis of the intima. THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
13 
intimal thickening the media may be much thinned and evidently 
stretched, while the muscle fibres have in great part disappeared, 
having given way to connective tissue. The elastica interna in 
such cases is either much stretched or absent (Fig. 18). In some 
instances, as shown in the photograph of the artery of a man, aged 
eighty-three years, the whole vessel may be changed into an irregu- 
lar, nodular tube (Fig. 19). 
It thus becomes clear as pointed out by Jores3 from a general 
standpoint, and by Aschoff,4 and Hallenberger,5 with regard to the 
radial especially, that an elastic muscular thickening of the intima 
appears in the radial artery at a relatively early age, that is, within 
the first decade. With growth and the associated increase in 
pressure the artery strengthens itself-in the intima by the sepa- 
ration of one or more fresh strands of elastica from the inner 
surface of the fenestrated memberane, and the appearance about 
Fig. 17.-Radial artery of a carpenter aged sixty-six years (Case 50), with carcinoma of 
the stomach, who died of acute peritonitis; high power (hematoxylin and eosin). Calcified 
area in a sclerotic intima. This artery was clinically a thickened, beaded vessel. 
these of a few connective-tissue cells and longitudinal muscle 
fibres; in the media and adventitia by a gradual hypertrophy and 
hyperplasia. After full growth has been reached, at the end of 
3 Wesen und Entwickelung der Arteriosklerose, Wiesbaden, 1903, 8. 
4 Sitzungsberichte der Gesell. zur Befbrderung der gesammten Naturwissenschaften zu 
Marburg, 1905, Nr. 8, 117. 
6 Op. cit. 14 
THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
the second decade, there is little change in the thickness of the 
adventitia. The intima, however, tends to become slightly thicker 
from the development of more elastic tissue and smooth muscle 
Fig. 18. Radial artery of a blacksmith, aged seventy years (Case 52), a syphilitic, with 
chronic fibrous myocarditis, chronic mitral and tricuspid endocarditis and hypertrophy and 
dilatation of the heart, who died of pneumonia (hematoxylin and eosin). Extensive sclerotic 
plaque of intima with calcification. Widespread sclerosis of media which opposite the plaque 
is much thinned and stretched. Clinically this was a thickened vessel. 
Fig. 19.-Radial artery of a farmer, aged eighty-three years (Case 1), with chronic nephritis 
and hypertrophied heart, who died of bronchopneumonia (hematoxylin and eosin). Exten- 
sive calcification of the intima and media. Clinically this vessel was hard and nodular. 
fibres, while the depth of the muscular media shows a slight increase. 
Gradually, however, during the third and fourth decades, especially 
in individuals subjected to heavy physical strain, there appear 
areas in the intima in which there is a distinct, connective-tissue THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
15 
thickening; the regular elastic strands which are separated from the 
interna are replaced by numerous, finer, more irregular fibrils, while 
on the outer side of the elastica, a delicate layer of connective tissue 
also appears. Opposite these areas the elastica interna is less 
deeply undulating and seems somewhat stretched, while connective 
tissue begins to appear between the muscle fibres of the media. 
In other words, the strain has begun to tell upon the vessel wall, 
and the yielding tube fortifies itself by the connective-tissue thicken- 
ing of the intima and to a lesser extent of the media. As Aschoff 
has well expressed it, the artery of the child and that of the 
young adult with its increased amount of elastic tissue has a low, 
elastic resistance but a high limit of elasticity. Gradually, with 
the wear and tear of age or as the result of unusual and excessive 
strain, the elastic resistance becomes unequal to the burden imposed 
upon it and the limit of elasticity tends to be passed. The giving 
vessel then strengthens itself with a substance which has a much 
higher elastic resistance, but a lower limit of elasticity, namely, 
connective tissue. 
But these changes are not marked until the fifth decade when the 
arte y begins to assume an essentially different appearance. The 
vessel wall, unable to stand the strain, tends to stretch, and an 
additional support is offered by the development of firm, connective 
tissue in the intima, together with an increase in that upon the medial 
side of the interna and, in lesser degree, throughout the media. 
The vessel is here usually felt as a firm tube. 
Finally, in these sclerotic vessels, degenerative changes set in, 
which are somewhat different from those seen in the larger arteries, 
consisting as they do, of local areas of coagulation necrosis with 
calcification, especially marked in the deep layers of the connective 
tissue thickenings of the intima and in the muscle fibres of the media, 
particularly opposite these points. These changes may, as has 
been pointed out by Monckeberg, go on to actual bone formation. 
Although, in one instance, there was an apparent atheromatous 
softening in the sclerotic intima of a man, aged seventy years, in 
not one of our cases did we see the superficial proliferation so common 
with fatty changes in the aorta. 
When these facts are onsidered it becomes evident that it may 
often be difficult to draw a sharp line between the normal and the 
pathological radial artery. That which is normal at 50, would 
be pathological at 30 years. A connective-tissue thickening of the 
intima is not to be regarded as pathological in old age. 
Regressive changes, necrosis, calcification, and atheroma( which, 
as Jores has pointed out, occur especially, if not only, in a sclerotic 
intima, must be regarded as pathological. 
It is a striking fact that in not one of our cases did we see calci- 
fication of the media unaccompanied by similar changes in the 
intima. 16 
THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
Is the normal radial artery ever palpable? To this question there 
can, of course, be but one answer. In the great majority of these 
cases, after the age of twenty years, the radial artery was palpable. 
Recognizing the fact, however, that if one rolls the artery carefully 
against the bone the normal vessel is often palpable, we divided our 
cases, clinically, into those which were not palpable or palpable and 
not regarded as thickened, and in which the vessel appeared to 
be distinctly thickened. When we compared our clinical notes 
with our pathological observations the result was extremely inter- 
esting. In the first and second decades none of the arteries were 
considered as thickened; in the third and fourth decades 77 per 
cent, were regarded as essentially normal, but in the fifth decade, at 
exactly that period when the connective-tissue thickening of the 
intima becomes especially marked, it appears that 63 per cent, of 
the arteries were regarded, clinically, as thickened vessels. 
The arteries which were regarded clinically as thickened showed, 
in the majority of cases, anatomical thickening of the intima. 
The beaded, goose-necked artery corresponded in practically 
every case to calcification of the intima or of intima and media. 
It was our impression that the great frequency of the palpability 
of the arteries might be due in part to the fact that the majority of 
our patients were colored. But an analysis of our tables seems 
to show that, while the frequency of palpable arteries is indis- 
putably somewhat greater among the colored, the difference is by 
no means as marked as we had fancied that it would be. The 
observations of one of us (Thayer) show clearly that the percentage 
of palpability of the radials in this group of hospital patients 
was much higher than that in healthy individuals in higher walks 
of life. 
A study of the individua cases shows that, as a rule, the thickened 
vessel becomes evident to the palpating hand. There are, of course, 
striking individual exceptions, especially in very fat people. The 
palpability of the vessel depends apparently on the general thick- 
ening of the coats, especially, however, upon the changes in the 
intima which are progressive throughout life. In cases of aortic 
insufficiency and in chronic nephritis in which measurements show 
a considerable thickening of the media as well, this doubtless 
plays a part in the palpability of the vessel, but according to 
our measurements and tables the part is subordinate. It is a 
striking fact, moreover, that the thickening of the intima and the 
media go usually hand in hand. An analysis of our tables shows 
that in those cases in which heart hypertrophy was found, the 
media and intima were almost uniformly thicker than the average, 
and selecting from these cases those in which aortic insufficiency or 
chronic nephritis was present, the thickening of both coats appeared, 
on the whole, yet, more marked, but it was rather striking that the 
change was more noticeable on the whole in the intima than in the THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
17 
media. The same observations are true of those cases in which 
especially high pressure was noted intra vitam. 
Comparison of the changes in the radial with those in the mesenteric 
artery and aorta. 
The structure of the mesenteric artery is in some ways different 
from that of the radial. 
In gross, the appearances are much the same but on a larger scale. 
The same transverse striations are visible in the opened vessel of 
the young adult, and the irregular, longitudinal lines are present in 
the more thickened artery. The elastica interna is a much thicker 
band. The media contains much more elastic tissue which is 
arranged as a well-marked meshwork. In areas throughout the 
muscular coat there are conspicuous aggregations of these fibres. 
The adventitia is very much thicker and contains more elastic 
tissue than that in the radial artery; this tends to have a longitudinal 
course (Figs. 19 and 20). 
The changes in the intima and media are in the main identi- 
cal with those in the radial. The same elastic, muscular intima 
develops early in life and the same connective-tissue thickening 
in the later decades. Here, also, the change from elastic muscular 
to connective-tissue thickening begins to be specially noticeable in 
the fifth decade. 
Two points, however, are striking in the mesenteric arteries which 
have been examined, namely: (1) Calcification is apparently 
much less frequent than in the radials. (2) In several cases plaques 
were seen with fatty softening of the deeper layers of the intima 
and superficial proliferation-a picture which we have never seen 
in the radial. 
In the aorta, as pointed out by Jores, the elastic-muscular intima 
thickens progressively with age. This is beautifully borne out by 
Fabyan's measurements. Indeed, our tables, showing the thickness 
of the intima of the radial and the mesenteric arteries and the aorta, 
side by side, show a striking, progressive increase in the depth of 
the intima from birth to old age in all vessels, with the onset of 
connective-tissue sclerosis especially notable in the fifth decade. 
The disposition of the elastica in the aortic intima is much less 
regular than in the other vessels. The regressive changes, com- 
moner in the thicker intimas, are particularly prone to be in the form 
of necrosis with fatty change and softening (atheroma) associated 
with active proliferation of the intima on the surface of the plaque. 
In the aorta and mesenteric artery likewise over-strain and high 
pressure appear to result in changes analogous and more or less 
parallel to those in the radials. There are exceptions in individual 
cases which are sometimes striking. But, on the whole, when one 
finds an undue thickening of the intima in the radial, analogous 
changes are usually found in the mesenteric artery and aorta. 18 
THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
Fig. 20.-Mesenteric artery of a child, aged five years (Case 61), who died of bronchopneu- 
monia following measles (Weigert's elastic tissue stain). The specimen shows the different 
arrangement of the elastic tissue from that seen in the radial artery. A second strand of elastic 
tissue has been separated from the surface of the interna. 
Fig. 21.-Radial artery of a child, aged five years (Case 61), who died of bronchopneu- 
monia following measles (Weigert's elastic tissue stain). Shows the same conditions as Fig. 
20, but under a higher power. THAYER, FABYAN: STUDIES ON ARTERIOSCLEROSIS 
19 
What inferences, then, are we justified in drawing from the presence 
of a thickened radial artery? 
In old age a thickened radial artery represents conditions which 
are normal and to be expected, not only in peripheral, but in central 
vessels. 
An unduly thickened radial at an earlier age may mean one of 
two things: 
1. The vessel has been subjected to unusual and exceptional strain, 
or 
2. It is a vessel which, from inherent weakness or other individual 
circumstances, has been unable to cope with conditions which might 
ordinarily be regarded as normal. 
m In either case the result has been the same; the artery has been 
obliged to fortify itself by progressive thickening of its walls, especially 
by a connective-tissue sclerosis of the intima and media. 
As a rule, although there are striking individual exceptions, when 
the thickening of a radial artery is unduly marked, similar 
changes occur in the intima of the mesenteric artery and aorta. 
The early sclerosis of the intima, associated as it commonly is 
with like alterations in the muscular coat, constitutes a predispo- 
sition to those regressive changes (calcification, atheroma) which 
may be dangerous in other parts of the body. The distribution 
of such changes is irregular and too often not to be determined 
intra vitam, but the unduly palpable radial artery indicates a 
strong possibility of their existence in some part of the body at 
least, and may thus reasonably be regarded as a signal of danger. REMARKS 
MADE AT A MEETING HELD IN COMMEMORATION 
OF 
MAJOR JAMES CARROLL, M. D„ U.S.A. 
BY 
WILLIAM SYDNEY THAYER, M. D. REMARKS MADE AT A MEETING HELD IN COMMEMORATION 
OF MAJOR JAMES CARROLL, M. D., U.S.A.1 
'Tis sad indeed that, after so brief a period, we should meet again in 
this room to pay tribute to the memory of another of that little group of 
men who will always be remembered as the conquerors of a great 
pestilence. 
That Lazear and "Reed and Carroll, so young, so vigorous, so strong, 
should, one after another, be taken away in the midst of their careers, 
seems a strange and cruel stroke of fate. One is almost overwhelmed by 
the pity of it all-by the thought that after years of hard work-the 
deserved recognition by the government but just acquired-with the pros- 
pect of happy and honoured days with his growing family and his chosen 
work, Carroll, too, should have had to go. 
And yet, out of our very tears, the same feelings rise that have come to 
us all during the past few years, as we have thought of Lazear and Reed. 
How often do we measure the happiness and success of a man's life by 
the accident of his death ! * How often do we allow the sudden or tragical 
end of a noble and useful and happy career to overshadow in our minds 
all the radiance of that which has gone before! 
Despite the tragedy of their untimely end these men have led happy 
and successful lives. 
We go through life, members of the human ant-hill, buoyed up by 
our better and happier thoughts and aspirations and ambitions; each has 
in him the feeling that there is in this world something that he can do or 
say or write or inspire that is new or great or exalting. In our strug- 
gles-in our dreams, we seem almost to reach it. We cannot-we will 
1 Excerpt from the Bulletin of the Johns Hopkins Hospital, 1908, XIX, 7. 
2Maeterlinck: La sagesse et la destinee, Paris (Charpentier), 12 mo., 
1899, 122. not-we must not realize that the end can come before this something 
is accomplished. And so, reaching out, straining, too often, alas, grop- 
ing for the elusive opportunity, we go our way, one after another, mil- 
lions on millions. And the unexpressed thoughts and ambitions and 
aspirations die with us-futile except in so far as they have guided us to 
better lives. How few, how very few of us leave behind much more than 
the affectionate admiration and love of our immediate friends! 
But these three men have left a lasting monument. They have accom- 
plished-a small part, perhaps, of what their generous hearts may have 
hoped, but that which has proved a great and blessed gift to mankind. 
They will never be forgotten, and their example will stimulate hosts of 
men to more earnest effort. 
Who shall say that these have not been enviable lives? 
And what a fine example Carroll has left us 1 Born in the old country 
-our old country, England-a poor boy, he brought to us those qualities 
which we love to call English-honesty, simplicity, fearlessness, steadfast- 
ness of purpose. Working his own way, beginning his medical studies 
at an age when too many begin to abandon theirs, he helped to accom- 
plish this great work. 
A patient student, an earnest worker, an honest man; it fell to him 
and his fellows to make one of the great discoveries of the age. And now, 
alas, as if jealous fate had decreed that this work were enough for one 
life-time, he has joined his two colleagues in bidding farewell to the joys 
and the sorrows, the ambitions and the disappointments, the hopes and 
the fears of this world. 
But when we think of what these, our friends, have done, in the midst 
of our sorrow' there rises a sense of exultation and pride-for who of us 
would not change his lot for theirs! On the Early Diastolic Heart Sound 
(the So-Called Third Heart Sound) 
BY 
william Sidney thayer, m.d. 
BALTIMORE, MD. 
Medical House Pupil, Massachusetts General Hospital, i88q; Professor of 
Clinical Medicine, Johns Hopkins University 
Reprinted from the Boston Medical and Surgical Journal 
Vol. clviii, No. 19, pp, 713-726, May 7, 1908 
BOSTON 
D. C. HEATH & COMPANY 
120 Boylston Street 
1908 ON THE EARLY DIASTOLIC HEART SOUND 
(THE SO-CALLED THIRD HEART SOUND). 
BY WILLIAM SYDNEY THAYER, M.D., BALTIMORE, MD., 
Medical House Pupil, Massachusetts General Hospital, 1889; Pro- 
fessor of Clinical Medicine, Johns Hopkins University. 
If one place the hand in the region of the 
cardiac apex of a young individual with a chest 
wall not too thick, the systolic impulse of the 
heart is easily palpable. A slight shock may 
also be felt at the time of closure of the aortic 
valves. On auscultation one hears the two 
heart sounds; the first, more prolonged and low 
pitched but with a clearly defined ending; the 
second, short, definite, high pitched, clean cut. 
In the long pause between the close of the aortic 
valves and the beginning of the next systole, there 
is often silence. This, however, is not always 
the case. As I have already pointed out in 
another communication,1 a third sound is not 
infrequently audible, especially in young people 
with thin chest walls. The sound is softer and 
of lower pitch than the second sound; sometimes 
it is a dull, distant thud; sometimes merely a 
hum; it occurs shortly after the second sound, 
that is, at the beginning of the long pause. It is, 
however, always appreciable at a time later than 
that occupied by a true reduplication of the 
second sound, and it is audible only or with 
greatest intensity at or near the apex. In some 
1 cases it may be heard over the lower part of the 
right ventricle. At times, the sound is followed 
by the faintest suggestion of an echo resembling 
a slight, early mitral diastolic murmur. This 
resemblance has, in some cases, been sufficiently 
striking to suggest that the phenomenon might 
be due to a similar mechanical cause; so much 
so, indeed, that I have long been in the habit of 
maintaining that the entrance of blood from 
auricle into ventricle is associated in some in- 
stances with a slightly audible sound. This 
early diastolic sound may be associated with a 
shock which is just perceptible to the palpating 
hand. The condition is rendered more readily 
appreciable, and may be brought out in cases in 
which it is not otherwise audible by a simple 
manoeuvre. If the patient turn well upon the 
left side in such a position that the chest over- 
hangs the edge of the bed, the apex impulse of 
the heart which is thrown more directly against 
the chest wall, becomes more forcible and may be 
more easily studied by the hand and the stetho- 
scope. On palpation of a heart in this position 
it is not very uncommon to feel, first, the systolic 
impulse, then a slight suggestion of the shock 
accompanying the closure of the aortic valves 
and second sound, and then, with the relaxation 
of the ventricle, a third impulse following rather 
closely after the second sound. In some eases 
in which an impulse is palpable auscultation 
reveals no actual well-defined sound. One is, 
however, sensible of a slight shock to the tympanic 
2 membrane analogous to that which is felt with 
the palpating hand. The sound and shock may 
be more appreciable at the end of expiration. 
This sound is certainly not an abnormal phe- 
nomenon. It has been familiar to me for over 
twenty years, and I have frequently mentioned 
it to my students. It has always been a matter 
of interest to me that an event so definite, one 
which must be familiar to many clinicians and 
physiologists, has not been more generally recog- 
nized. 
Barie,2 indeed, in 1893, says: 11 If one auscult 
a large number of healthy individuals, one per- 
ceives that the long pause is not absolutely free 
from sound but that there may be heard a slight 
rudimentary sound, barely perceptible, which if 
exaggerated will give rise to gallop rhythm." 
Within the last year the sound has been noted 
by several observers. Hirschfelder, in an article 
on " Some Variations in the Form of the Venous 
Pulse,"3 describes two cases in which a wave was 
observed in the jugular pulse immediately after 
the fall following the so-called v wave -i.e., the 
fall following the opening of the auriculo-ventri- 
cular valves - between this and the a wave of 
auricular contraction. In one of these cases, 
" ... the heart sounds were loud and clear, but 
at the end of expiration a very faint third sound, 
coinciding with the time noted in protodiastolic 
gallop rhythm, was audible in the tricuspid area, 
at the time when the venous pulse was taken. 
This sound was not loud enough to be definite, 
3 and none of the tracings which I have made at 
other times upon cases with gallop rhythm have 
shown this peculiar variation; so that as yet no 
definite conclusions as to the relations of this 
unusual wave of the venous pulse to either the 
closure of the tricuspid valve or the gallop rhythm 
are warrantable." Hirschfelder, however, calls 
attention to the probable correspondence of this 
wave with the shoulder of the cardioplethysmo- 
gram and the time at which the mitral and 
tricuspid valves are, according to Henderson, 
closed by the floating together of the cusps. 
Recently, an interesting note has appeared by 
Einthoven,4 " On a third heart sound." While 
studying the heart sounds by means of his string 
galvanometer, Einthoven met wdth a case in 
which vibrations were recorded occurring at a 
period in diastole similar to that in which our 
sound is audible. These vibrations began on an 
average 0.13 (.11-.15) second after the begin- 
ning of the second sound, and 0.32 second before 
the beginning of the following first sound, that 
is, somewhat before the end of the first third 
of diastole with a pulse rate of 73. 
A. J. Gibson,5 of Oxford, has also observed and 
well described a similar sound. Gibson's article 
is interesting, not only because of his excellent 
description of this sound, but because, although 
approaching the subject from a somew7hat differ- 
ent standpoint, his conclusions as to the probable 
cause of the phenomenon are similar to ours 
which wyere reached quite independently from 
4 him and before the publication of his article; they 
are also similar to the explanation hinted at by 
Hirschfelder. Gibson met with the sound in the 
course of some studies upon a wave of the jugular 
pulse similar to that described by Hirschfelder. 
At approximately the same time at which this 
wave appears, he detected in two cases, " . . . 
a third sound between the second sound and the 
succeeding first sound. It was heard only at the 
apex in one, while in the other case it was heard at 
the apex and over the jugular pulsation in the 
neck. The sound is by no means easy to hear; 
extraneous sounds must be eliminated as far as 
possible and special attention paid to the interval 
in which the sound is expected. Nor is it possible 
to hear the sound at every systole; from my own 
observation it is best heard in the short interval 
between expiration and inspiration. The quality 
of the sound is low pitched and clear with no 
suspicion of harshness or anything suggesting a 
murmur. Except for the pitch it recalls in type 
the second sound as heard in fat persons. It is 
slightly increased in intensity and raised in pitch 
by pressure on the abdomen." 
Our interest in this subject was accentuated 
in November last in the course of some studies 
which we were making upon the dog's heart. At 
this time it was accordingly determined to note 
all cases in which an early diastolic sound and 
shock were observed in apparently normal hearts. 
The results of some of these observations which 
form the basis of this communication were pre- 
5 sented before the JLsculapian Club in Boston in 
December, 1907,* but are now published for the 
first time. 
During four months, in the course of ordinary- 
ward visits and in my consulting room, I have 
met with 24 cases in which an early diastolic 
sound was heard in an otherwise apparently 
normal heart. 
The condition of the patients at the time of 
examination was as follows: 
Incipient tuberculosis (afebrile), 
Convalescents, on the eve of discharge from 
hospital: 
1 
From slight arthritis, 3' 
„ appendicitis (operation), 1 
„ typhoid fever, 2 
„ catarrhal jaundice, 1 
,, obscure hsematuria, 1 
8 
These patients were, to all intents, 
healthy individuals. 
Healthy individuals, - A physician (Hirsch- 
felder's case), 
A healthy hospital employee in whom the 
third sound had been discovered while 
convalescent, some weeks before, from 
influenza, 
A laboratory assistant in whom the sound 
was discovered after the man had been 
used as an example of a normal individual 
in the preparation of the tracings shown 
in Fig. 2, 
A healthy boy of fourteen brought to my con- 
sulting room by an over-anxious parent, 
4 
6 Cyclic albuminuria, with normal heart and 
blood pressure, 2 
Exophthalmic goitre, a mild incipient case 
with an apparently normal heart and pulse 
rate, 1 
Chronic tonsillitis, 1 
Neurasthenia, 1 
Overwork and debility, 1 
Chronic appendicitis, 1 
Cholelithiasis, in a period of rest, 1 
Rather delicate girl with suspected tuberculosis, 1 
Nervous, but otherwise healthy boy of fifteen, * 1 
Chronic adenitis (Hodgkin's disease?), 1 
24 
The ages of these patients were as follows: 
First decade, 1 
Second „ 11 
Third „ 8 
Fourth ,, 2 
Fifth ,, 2 
The youngest individual was five years of age; 
the oldest, forty-four. 
The pulse, of normal rate in all cases, tended 
rather to be slow than rapid; the rate ranged 
between 50 and 88 to the minute. 
The blood pressure was within normal limits in 
all cases, tending to be rather low than high. 
The averages for each decade were as follows: 
Maximum. Minimum. 
First decade, 100-115 (1 case) 
Second decade, 106.6 '(9 cases) 78.8 (7 cases) 
7 (In the seven cases in which the 
minimal pressure was taken the 
maximal pressure, averaged 110.) 
Third decade, 114 (8 cases), 77.5 (6 cases) 
(In the six cases in which the 
minimal pressure was taken the 
average maximal pressure was 
119.6.) 
Fourth decade, 135 (1 case) 95 (1 case) 
Fifth decade, 120 (1 case) 78 (1 case) 
In some of these cases the sound was heard 
only when the patient was lying on his back or 
on his left side, disappearing in the erect posture. 
In some it was heard in all postures. In most it 
was increased in intensity in the left lateral 
decubitus. In all cases the sound was loudest 
at the point of maximal impulse in the region 
of the apex; in several it was heard to a lesser 
extent over the right ventricle. In none was it 
audible at the base. 
In several cases it was associated with a dis- 
tinctly palpable shock limited to the point of 
maximal impulse. This shock was actually 
visible in a few of these instances. While ex- 
amining one case in which the third sound was 
especially clear (the case from which the tracing 
in Fig. 4 was taken), the stethoscope was handed 
to a second-year student who had never examined 
a heart, and was quite unaware of the existing 
conditions. The student heard the sound and 
described it accurately. 
The early diastolic sound in the dog.- But it is 
8 not only in the human heart that a sound may 
be heard at this period. I have three times ob- 
served similar sounds in the normal dog's heart. 
To the first case reference has already been made, 
- a dog studied with Dr. MacCallum two years 
ago. In this instance cannulse had been inserted 
in the left femoral artery, the appendage of the 
left auricle and into the peripheral part of a sev- 
ered branch of the pulmonary artery. By so do- 
ing the heart was slightly rotated over toward the 
right, while the left auricle was held rather tensely 
in position by the cannula in the auricular append- 
age. There then became audible in the left auri- 
cle and just below the valves a first, second, and 
then, after a momentary pause, a third sound, a 
diastolic rumble in every way similar to the early 
diastolic murmur heard in some cases of mitral 
stenosis. Gradually the murmur disappeared, 
and one heard only a thud which became clearer 
with the decreasing rate of heart's action. One 
was able to observe systole of the ventricle, im- 
mediately followed by the second sound which 
occurred while the ventricle was still in a state 
of contraction. Then followed the sudden dilata- 
tion of the ventricle which occurred abruptly 
with a distinct shock, having altogether the 
appearance of an active muscular process. Syn- 
chronously with this shock occurred the third 
sound, the character of which was precisely that 
of the sound in protodiastolic gallop rhythm 
heard under so many circumstances. We were 
able in this case practically to see the association 
9 of this sound with a definite moment in the 
heart's cycle, that is, the shock of what seemed 
almost like an active diastole. 
Since this time Dr. Stewart and I have had 
two similar experiences. In the first case, at 
the outset of some observations upon the heart 
of a small fox terrier, the sounds were found to 
be perfectly clear. During the process of opening 
the chest there was an unusual amount of haemor- 
rhage. When the heart was exposed, with a pulse 
rate of about 100, a distinct third sound was 
audible over the left ventricle; it was not heard 
over the right chamber. This was exactly like 
the early diastolic sound in the human being, a 
slight dull thud following the second sound after 
a period somewhat less than that which separates 
the first from the second sound. In this instance 
the dilatation of the ventricle with diastole 
appeared to be rather rapid but by no means as 
strikingly so as in the previous case. An attempt 
was made to study the effects of vagus stimula- 
tion. The response was curiously slow and 
unusual. Stimulation at first produced no result, 
but, after removing the electrode from the nerve, 
the heart stopped. With resumption, the first 
fifteen or twenty beats were very slow, and during 
these beats, the third sound was more distinct. 
On large doses of strychnine the heart was seen 
to draw itself together visibly. The diastolic 
relaxation was much diminished; the rate rose to 
about 120; the sound wholly disappeared. Ne- 
cropsy showed no abnormalities. 
10 In another dog in which this sound was present, 
a slight interruption in the dilatation of the 
ventricles could be seen if one fixed the atten- 
tion on a bit of epicardial fat on the surface of 
the right ventricle as it moved under the un- 
opened pericardium. The sound appeared and 
disappeared at various times during the observa- 
tion, and the auscultatory changes could always 
be controlled by the appearance or disappearance 
of this slight irregularity in diastole. It was 
evident that the first part of the filling of the 
ventricle, that before the interruption, was by 
far the most rapid, and the third sound occurred 
clearly in association -with this rapid filling. 
How may we account for this early diastolic 
sound and shock heard and felt so often in human 
beings and observed in these three instances in 
dogs? Although during the last twenty years 
I have often heard the sound in apparently 
healthy individuals, the explanation of the phe- 
nomenon has never seemed clear. Two years ago 
both Dr. MacCallum and I were struck by its 
association with what appeared to be a very 
sudden diastole, so sudden that it seemed to us 
as if it might almost be an active muscular proc- 
ess, and we asked ourselves whether it might 
not be a muscular sound due either to active 
diastole or to the tension of a distended ventricle 
associated with the sudden entrance of blood 
from the auricle. The conception of an active 
11 muscular diastole we may probably dismiss. 
There is no direct evidence to support the 
idea. 
In considering the cause of this sound and 
shock in early diastole it may, however, be inter- 
esting to inquire into: 
(1.) The exact time relations of the sounds. 
(2.) The relation of the third sound and shock 
to the events observed on the cardiogram. 
(3.) Their relations to the jugular pulse. 
(4.) Their relations to the volume curve of 
the distending ventricle. 
(5.) Their relations to sounds and shocks heard 
and felt at this period under various pathological 
conditions. 
(1.) The time relations of the sound. -As to 
the first of these points it will be impossible to 
speak until we shall have obtained a registration 
of the heart sounds such as is possible only with 
an instrument analogous to Einthoven's string 
galvanometer. Einthoven in his case, in which 
the pulse varied from 73 to 81 to the minute, 
found that the average time between the begin- 
ning of the first and that of the second sound was 
0.33 second. The relation of the length of 
systole to the length of the whole cardiac cycle 
was as 0.33 : 0.80 or about as 41 : 100. The 
beginning of the third sound which, it should be 
remembered, was in this case inaudible, occurred 
0.13 second (0.11-0.15) after the beginning of 
the second sound, and 0.32 before the beginning 
of the following first sound. The length of the 
12 Fig. 1. Normal cardiogram showing protodiastolic and presystolic elevations. 
13 first sound was 0.08; of the second, 0.05; of the 
third, 0.02-0.03 second. 
(2.) The relation of the third sound and shock 
to the events observed on the cardiogram. - An 
approximate estimation of the position of the 
third sound in diastole may be obtained when 
we take into consideration the events observed 
upon the cardiogram. If one consider, now, the 
normal cardiogram, an excellent example of 
which is shown in Fig. 1, which is reproduced 
from a tracing taken by my assistant, Dr. Stewart, 
from a patient with exposed heart from the clinic 
of Prof. F. Muller, in Munich, it will be seen that 
there are two slight elevations during diastole, 
one closely following the katacrotic limb of the 
systolic elevation, the other preceding the onset 
of systole. These waves were pictured and 
described by Marey,8 who ascribed the early 
diastolic wave to the influx of blood from the 
auricle, the presystolic elevation to the increased 
rapidity of its flow as a result of auricular systole. 
It is with the early diastolic elevation that we 
are especially interested. Now in our cases in 
which an early diastolic sound was heard in appar- 
ently normal hearts, this elevation was invariably 
prominent, so much so that in some cases it 
could be observed by the hand, the ear and the 
eye; it was well recorded on the cardiogram in 
all of 12 cases in which tracings were taken. 
As to the relation between the sound and the 
shock there can be little doubt. They are equally 
appreciable by the ear and are clearly synchro- 
14 nous. The comparison of that which one feels, 
hears and sees with what is registered on the 
cardiogram can leave no doubt in one's mind 
that the third sound is closely connected with 
this early diastolic elevation, and it is difficult to 
avoid the assumption that the two phenomena 
are associated with the same causal elements. 
At what time in diastole does this elevation 
occur? In eight tracings from seven cases, the 
approximate duration of systole estimated by 
measuring the distance from the onset of the sys- 
tolic elevation to the shoulder of the cardiogram, 
was 0.32 second (0.28-0.345). The beginning of 
the protodiastolic elevation occurred 0.1 + (0.085- 
0.14) second and the summit 0.18+ second 
(0.155-0.215) from the shoulder of the cardio- 
gram. The length of diastole, estimated by meas- 
uring the period between the shoulder of one sys- 
tolic elevation and the onset of that succeeding, 
was, on an average, .594. The average rate in 
these cases was a little over sixty-five per minute. 
The sound, then, must occur somewhere within 
the period occupied by this protodiastolic eleva- 
tion, between 0.1 and 0.18 second after the end of 
systole. This is very closely analogous to the 
time at which Einthoven detected the vibrations 
in his case, namely, 0.11-0.15 second after the 
onset of the second sound. 
(3.) The relations of the protodiastolic sound 
and shock to the jugular pulse. - Assuming, as 
we are clearly justified in assuming, that the early 
diastolic sound is synchronous with the proto- 
15 diastolic elevation on the cardiogram, we have 
sought to determine the time of its occurrence 
on the curve of the jugular pulse. As a result 
of the study of seven simultaneous cardiographic 
and venous tracings taken from six individuals, 
with apparently normal hearts, in whom an early 
diastolic sound was audible, it has been possible 
to determine, within fairly definite limits, the 
events in the venous pulse which correspond to 
the protodiastolic elevation. 
The normal jugular pulse (Figs. 2, 3, 4) shows 
three marked elevations. The a wave which cor- 
responds to the auricular systole, is closely fol- 
lowed by the c wave which marks the onset of 
ventricular systole. The c wave is succeeded, 
during systole, by a deep depression associated 
with the emptying of the heart and the pulling 
down of the auriculo-ventricular valves by the 
papillary muscles. This depression is followed 
by an abrupt rise, the so-called v wave, near the 
base of the ascending limb of which occurs the 
closure to the aortic valves. The summit of 
the v wave at which point occurs the opening of 
the auriculo-ventricular valves, is followed usually 
by a sharp fall and then a plateau or a slight 
gradual rise up to the time of the next a wave. 
Other waves may occur during this period. One 
which has been pointed out especially by Hirsch- 
felder, and subsequently by Gibson, may occur 
immediately after the depression following the v 
elevation. This has been called by Hirschfelder 
the h wave. 
16 In these six cases the onset of the protodiastolic 
elevation on the cardiogram, during which the 
third sound occurs, is found when allowance is 
made for transmission time, to correspond invari- 
ably to a point somewhere on the katacrotic 
limb of the v wave. Sometimes this is near the 
summit; usually nearer the base; sometimes 
Fig. 2. Cardiogram and jugular curve from a healthy man of 
nineteen who showed a slight early diastolic sound. 
a, a wave, c, c wave, h, h wave. I, beginning of systole. 
2, approximate end of systole. 3, beginning of protodiastolic 
wave of cardiogram. 4, summit of protodiastolic wave of cardio- 
gram. 
Transmission time may be estimated by measuring the period be- 
tween 1 and thebeginning of the c wave on the jugular curve. Time 
marked in J seconds. 
almost at the base. The summit of the proto- 
diastolic elevation corresponds, after allowing 
for transmission, to the base of the v wave or to 
a point on the plateau or elevation following 
this. It is interesting that in five of these six 
cases an h wave was present.* Four times it was 
* On looking over our tracings a few days before sending our manu- 
script to the printer, it was found that there was no record of a 
17 a well-marked elevation; once it was but slight 
and inconstant. In the sixth case in which the 
third sound was but slight, there were, at one or 
two points, slight suggestions of an h wave. In 
three of the tracings the summit of the proto- 
diastolic elevation, with allowance for trans- 
mission, reached, with some beats, a point on 
the anacrotic limb of the h wave. 
(4.) The time relations of the sound and shock 
and protodiastolic elevation on the cardiogram to 
the cardio-plethysmogram. -The important ob- 
servations of Yandel Henderson7 have demon- 
strated that diastole is, in most instances,' a 
considerably more rapid process than has gen- 
erally been assumed. His observations, which 
have been confirmed in many points by Stewart,8 
in his studies of aortic insufficiency in the dog, 
show that a large part of the filling of the ven- 
tricle may, in some cases, occur in the first mo- 
ments of diastole in a very short period of time, 
the plethysmogram showing an abruptly ascend- 
ing limb indicating a rapid dilatation of the 
ventricle, followed by a fairly 'definite shoulder 
after which the filling is more or less gradual up 
to the time of auricular systole when there is 
again a slight rise in the volume curve. Occa- 
jugular pulse showing the a, c and v elevations alone, which was 
suitable for publication. Dr. Eyster and Dr. Stewart accordingly 
kindly consented to take the tracing which is shown in Fig. 2, from 
a healthy laboratory assistant of nineteen. On examination of the 
tracings, a well-marked proto-diastolic elevation was found on the 
cardiogram, and an h wave in the venous pulse. As Dr. Stewart 
informed me that he had not made a careful examination of the man's 
heart, I asked him to come to my consulting room at the end of his 
day's work. He was found to have a most characteristic third 
sound. 
18 Fig. 3. Cardiogram and jugular tracing from a healthy physician of thirty-five who 
showed an early diastolic sound (Hirschfelder's original case). 
a, a wave, c, c wave, v, v wave. h, h wave. 1, beginning of systole. 2, approxi- 
mate end of systole. 3, beginning early diastolic wave. 4, summit of early diastolic wave. 
Transmission time may be estimated by measuring the period between 1 and the be- 
ginning of the c wave on the jugular pulse. 
Time marked in 1-50 seconds. Fig. 4. Cardiogram and jugular tracing from a healthy individual of eighteen with an early diastolic sound of 
great distinctness. 
a, a wave, c, c wave, v, v wave, h, h wave. 1, beginning of systole. 2, approximate end of systole. 3, be- 
ginning of protodiastolic wave of cardiogram.' 4, summit of protodiastolic wave of cardiogram. 
Transmission time may be estimated by measuring the period between 1 and the beginning of the c wTave on 
the jugular tracing. 
Time marked in 1-50 seconds. sionally, the filling is so complete in the early 
part of diastole as almost to justify Henderson's 
somewhat schematic division of the long pause 
into diastole and diastasis. In such plethysmo- 
grams the ascending limb of the volume curve 
rises almost vertically to a point nearly as high 
as that maintained at the end of diastole, and 
terminates in a sharp shoulder, the summit 
remaining nearly flat until the slight rise asso- 
ciated with auricular contraction. 
The evidence offered by the plethysmogram 
of a sudden change in the rapidity of dilatation 
of the ventricle occurring in the early part of 
diastole, appeared to me interesting in connection 
with the time of occurrence of the early diastolic 
sound and shock with which we have been 
concerned. And, indeed, on studying various 
plethysmograms made by Dr. Stewart from the 
hearts in dogs with and without aortic insuffi- 
ciency, and plotting on these, the time at which 
the various events of the heart's cycle should 
fall, it was found that an abrupt shoulder, when 
present, coincided closely with the period at 
which the protodiastolic elevation is observed 
on the cardiogram. The period of time elapsing 
between the foot of the ascending limb of the 
plethysmogram, at which time aortic closure 
should occur, and the shoulder amounted, in 
one instance, to a period as short as 0.15 in a 
pulse of 85. This may be compared with our 
Case VII, in which, in a little girl five years of 
age, with a pulse of 87, the summit of the proto- 
21 diastolic elevation fell 0.15 second after the 
shoulder of the cardiogram. 
In an attempt to throw further light on this 
question the plethysmogram of a normal dog's 
heart was taken by Henderson's method, while 
synchronous records were made of the carotid 
pressure and of the pressure in the right auricle 
by means of a Fredericq sound introduced through 
the jugular vein. Unfortunately, the heart's 
action was very rapid and diastole so shortened 
that it was impossible to study the relations 
properly. With vagus stimulation, however, 
some observations were made which, while they 
must perhaps be accepted with reserve, are yet 
not devoid of interest. In such curves, where 
the early part of diastole is rapid and the shoulder 
on the cardiogram is well defined, the c wave in 
the venous pulse corresponds exactly with the 
beginning of the systolic fall. The dicrotic 
notch on the carotid tracing occurs, with allow- 
ance for transmission time, just at the foot of 
the ascending limb of the plethysmogram. The 
v wave of the venous pulse begins just before the 
end of systole, while its summit falls at a point a 
little way up the ascending limb. The shoulder 
of the volume curve falls on the katacrotic limb 
of the v wave near the beginning of or on a 
shoulder analogous, apparently, to the d wave 
of Bard. In other words, the relations of the 
cardio-plethysmogram to the jugular pulse tend 
also to show that the shoulder of the volume 
curve corresponds closely, as to its time of occur- 
22 Fig. 5. Cardioplethysmogram, right auricular pressure and carotid pressure of a dog. 
It will be seen that the shoulder of the plethysmogram (6) falls at a point on the kata- 
crotic limb of the v wave (6) approximately in the same position as in a human being. 
The shoulder on the katacrotic limb of the v wave is not dissimilar to the d wave of Bard. _ 
The second shoulder immediately following 6 corresponds exactly with the base of this 
wave. rence, with the summit of the protodiastolic 
elevation of the cardiogram. 
(5.) The relations of the normal protodiastolic 
sound and shock to similar events observed at this 
period in various pathological conditions. - When 
one considers the time at which this additional 
sound and shock occur, as well as the character 
of the sound, one is immediately struck by the 
analogy which exists with sounds heard during 
the long pause of the cardiac cycle in a variety 
of pathological conditions. 
(a) The so-called opening snap of mitral stenosis. 
In mitral stenosis the diastolic murmur begins 
often shortly after the closure of the aortic valves, 
with a short, sharp sound associated with a shock 
closely analogous to that occasionally observed 
in normal hearts. Although as a rule the sound 
is sharper than the normal third sound, there are 
instances in which its character is very similar. 
Sometimes this " opening snap," as it is called, 
is distinct in the absence of a murmur. This 
sound was first noted by Sansom, who says:9 
" It is a sound of tension due to the first inrush 
of blood into the ventricle, such inrush being 
more sudden and forcible than under normal 
conditions, from the increased blood pressure in 
the left auricle, due to the constriction of the 
mitral orifice." The sound is well described by 
Potain: 10 " After the second sound of the heart 
the diastolic silence begins; during this silence 
the mitral valve opens; the blood passes from 
the auricle into the ventricle. Normally there 
24 is nothing to indicate the succession of these 
phenomena. In mitral stenosis, and especially 
if the stenosis be of moderate degree, the mitral 
valve, through the adhesion of the leaflets at 
their extremities, is arrested in the act of open- 
ing, and at this moment is thrown into a sud- 
den tension by the action of the blood rushing 
through the auriculo-ventricular orifice. This 
sudden tension determines then the sound, dis- 
tinct, short, snapping, which follows the second 
sound of the heart and is of maximum intensity 
at the apex. These characteristics distinguish 
it from reduplications of the second sound, the 
maximum intensity of which is at the base. It is 
through failure to make this distinction that 
certain authors have been led to assert that this 
reduplication is sometimes heard best at the 
apex. It is evident that in the cases observed 
by them there was a normal second sound fol- 
lowed by an opening snap. These same char- 
acteristics distinguish it also from gallop rhythm. 
The sound is clear; that of gallop rhythm, dull. 
. . . From the standpoint of diagnosis the open- 
ing snap is a part of the other signs of mitral 
stenosis, preceding always a more or less marked 
diastolic rumble." 
Although Potain's hypothesis might well ex- 
plain the origin of the sound in rather highly 
developed constrictions with great thickening 
of the valves, it is difficult to see how it could 
well apply to those cases in which there is but 
moderate stenosis. The valve here could hardly 
25 be " arrested in the act of opening." In many 
cases the actual narrowing of the valve is not 
very great although the shortening of the chordae 
tendineae may be considerable. In the course 
of diastole in the normal heart it is probable that 
with the first rush of blood into the ventricle 
and the rapid dilatation of its walls, the valves, 
borne up on the entering blood, are brought 
rather suddenly into a position at least approach- 
ing apposition. If then, as is true in most cases 
of mitral stenosis, there is a greater or less short- 
ening of the chordse tendineae, it would seem 
easily conceivable that with the initial rush of 
blood from an engorged auricle, the valves might 
be arrested in their upward course and thrown 
into a tension sufficient to produce this sound. 
And this moment would be just that at which 
the mitral diastolic murmur should begin, asso- 
ciated with the further passage of blood through 
the then narro'wed orifice. 
It has seemed to me that in some cases of 
mitral stenosis the opening snap followed the 
second sound at a period somewhat earlier than 
that at which one ordinarily hears the early 
diastolic sound. 
The cardiogram of mitral stenosis with open- 
ing snap shows a well marked exaggeration of 
the protodiastolic elevation. We have not a 
sufficient number of satisfactory tracings to 
justify the expression of an opinion as to whether 
this elevation follows the second sound more 
closely than in a normal cardiogram. This was 
26 Fig. 6. Cardiogram from a case of mitral stenosis showing a well-marked protodiastolic elevation. 
1, beginning of systole. 2, approximate end of systole. 3, beginning of protodiastolic elevation. 4, summit 
of protodiastolic elevation. 
The venous tracing is of no value. 
Time marked in 1-10 seconds. not the case in the patient from whom the cardio- 
gram in Fig. 6 was taken. It would be well 
worth while to study the relation in time of the 
protodiastolic elevation to the shoulder of the 
cardiogram in a series of cases of mitral stenosis. 
(6) Protodiastolic gallop rhythm. - Potain,11 fif- 
teen or twenty years ago, pointed out clearly 
that there were two distinct, principally different, 
forms of gallop rhythm, the one presystolic in 
time, the other protodiastolic; the one associated 
on the cardiogram, with a wave which imme- 
diately precedes the systolic elevation, the other 
associated with a wave which follows closely 
upon the base of the katacrotic limb. H. Chau- 
veau 12 and F. Muller13 have called attention to the 
fact that " these two points in the diastolic part 
of the cardiogram in which higher waves are seen 
in gallop rhythm, are also usually marked on the 
apex curve of the normal heart by evident but 
smaller elevations; and one must assume that the 
larger waves which distinguish the cardiogram 
of gallop rhythm represent a pathological exag- 
geration of movements which are also appreciable 
in the normal heart."14 Protodiastolic gallop 
rhythm is observed in some dilated hearts, 
especially in aortic insufficiency, as well as in 
certain cases in which there is reason to believe 
that there are myocardial changes, notably in 
the course of or just after acute infections, as in 
typhoid fever, f The third sound occurs shortly 
t Further studies as to the relations between presystolic and 
protodiastolic gallop rhythm, and especially concerning the clini- 
cal conditions under which each form occurs, are highly to be desired. 
28 Fig. 7. Cardiogram and jugular tracing from a man about twenty-five, with acute 
polyarthritis showing a protodiastolic gallop rhythm and shock. 
a, a wave, c, c wave, v, v wave. 1, beginning of systole. 2, approximate end of 
systole. 3, beginning of early diastolic wave. 4, summit of early diastolic wave. 
Transmission time may be estimated by measuring the period between it and the begin- 
ning of the c wave of a jugular pulse. The v wave of this tracing has a peculiar bifid 
summit. There is no distinct h wave. after the second at the same period in which the 
early diastolic sound is sometimes observed in 
normal hearts. (Fig. 7.) 
In aortic insufficiency the sound is often asso- 
ciated with a well-marked shock at the apex, a 
shock which may frequently be accurately timed 
by placing one hand at the apex of the heart and 
another over the pulmonic valves. It then 
becomes possible to make out the 1, 2, 3 rhythm 
which is audible at the apex: (1) the long, slow, 
systolic impulse, the so-called choc en dome, asso- 
ciated with the dull, humming first sound of 
aortic insufficiency; (2) the closure of the basic 
valves, easily felt by the hand in the pulmonic 
area, which is synchronous with the feeble second 
sound heard at the apex, and in this area often 
unaccompanied by the early diastolic murmur 
audible over the right ventricle, at the base and 
in the axilla; (3) the sudden relaxation of the 
ventricle followed rapidly by a definite shock 
which is coincident with the third sound. In 
some cases this sound is distinct and well defined; 
in other instances, dull and thudding. Just 
about the apex it is often followed, in aortic 
insufficiency, by the humming, echoing Flint 
murmur. In the axilla where the Flint murmur, 
even if present over the ventricle, is often absent, 
the third sound frequently becomes clear, giving 
rise to a distinct protodiastolic gallop rhythm. 
In aortic insufficiency then, the sound varies from 
a loud echoing rumble to a fairly well defined, 
short sound or a slight distant hum more appre- 
30 ciable to the ear as a shock than as an actual 
sound. In other words, it is sometimes exactly 
similar to the third sound heard in normal hearts. 
Cardiograms from cases of aortic insufficiency 
with early diastolic sound and shock show a well 
marked protodiastolic elevation. In the tracings 
from L. B. (Fig. 8) it was found that the onset 
of the elevation occurred 0.15 and the summit 
0.22 second after the shoulder of the cardiogram. 
On the venous tracing the protodiastolic eleva- 
tion corresponds to a part of the katacrotic limb 
of the v wave, the summit occurring usually 
toward the base of the anacrotic limb of an h 
wave, just as was observed in the normal cases. 
(c) In adherent pericardium a third sound is 
frequently associated with a well-marked shock 
occurring in early diastole. This shock, often 
ascribed to a thoracic rebound, has been shown 
by Brauer15 to occur as well when thoracoplasty 
has been performed. As shown in Brauer's 
tracings, the elevation on the cardiogram cor- 
responding to the protodiastolic shock may be 
the most striking feature of the record. In Figs. 
9 and 10 may be seen the cardiogram, carotid and 
jugular tracings from a case of adherent pericar- 
dium with protodiastolic gallop rhythm. The 
period between the second and third sounds in 
this case was notably short. 
The systolic retraction, easily detected by the 
eye and finger, is evident in the tracings. The 
enormous protodiastolic elevation begins shortly 
after the closure of the aortic valve and, when 
31 Fig. 8. Cardiogram and jugular tracing from L. B., a man with aortic insufficiency, early diastolic gallop rhythm 
and Flint murmur, 
c, c wave, v, v wave, h, h wave. 1, ths beginning of systole. 2, approximate end of systole. 3, beginning of proto- 
diastolic elevation. 4, summit of protodiastolic elevation. 
Transmission time may be approximately estimated by measuring the period between it and the beginning of the c wave 
on the jugular curve. 
There is evidently a considerable carotid element in the venous curve. Fig. 9. Cardiogram and carotid tracing from M., a man of about forty, with adherent 
pericardium, early diastolic sound and shock. 
The onset of systole, if Anspannunguzeit and transmission time be allowed for, may be 
seen to precede immediately a depression on the cardiogram. Aortic closure with allow- 
ance for transmission time comes at the bottom of. or just before, the bottom of the 
systolic depression. This is followed by an exceedingly abrupt elevation, the summit of 
which is reached .16 to .17 second after the aortic closure. The marking on the tracing 
which was made to represent the beginning of systole, i. e., that preceding the line 
marked 1, is at least 0.02 too near 1. As much as .10 should be allowed for Anspan- 
nungszeit and transmission. 
Time marked in 1-50 seconds. Fig. 10. Carotid and venous tracing from M., a man of about forty with adherent pericardium, early diastolic 
sound and shock. _ The aortic closure, when allowance is made for transmission time, is followed soon by a 
very sharp depression. The base of this depression corresponds in time to the summit of the protodiastolic eleva- 
tion on the cardiogram. This point falls on the jugular curve just at the base of a very abrupt and high 
wave, the summit of which is marked by the figure 4. allowance is made for transmission, is represented 
on the venous tracing by a marked fall. The 
summit of the protodiastolic elevation, wdiich 
occurs 0.165 second after the dicrotic notch, 
corresponds to the foot of the anacrotic limb of 
an abrupt and lofty elevation of the venous pulse. 
If now we consider that which has gone before, 
the following assertions appear to be justified: 
(1.) In healthy young individuals a third 
heart sound is often audible in the early part of 
diastole. 
(2.) This sound is not infrequently associated 
with a shock which may be not only palpable 
but visible. 
(3.) The sound and shock are evidently closely 
connected with the protodiastolic elevation of 
the cardiogram which was well marked in all of 
our tracings. 
(4.) The onset of this elevation occurred, in 
our tracings, at a period about 0.1, the summit, 
about 0.18 second after the shoulder of the 
cardiogram, or 0.42 and 0.5 respectively from 
the onset of systole in a cardiac cycle, the average 
duration of which was .914, i.e., a pulse of 65 +. 
(5.) The protodiastolic elevation on the car- 
diogram, when allowance is made for trans- 
mission time, corresponds in time to a part of 
the katacrotic limb of the v wave of the jugular 
pulse, its summit reaching, often, a point some- 
what beyond this. 
35 (6.) In five out of six of our cases the v wave 
was followed by an elevation corresponding to 
the h wave of Hirschfelder (the b elevation of 
Gibson), and on some of our tracings the summit 
of the protodiastolic wave would seem to extend 
to a point on the early part of the anacrotic wave 
of this elevation. 
(7.) The summit of the protodiastolic wave 
of the cardiogram appears to correspond closely 
in time, and in its relations to the venous pulse, 
with the shoulder on the ascending limb of the 
cardioplethysmogram, which may be well defined 
in some volume curves of the dog's heart. 
(8.) The phenomena associated with the early 
diastolic sound and shock in normal individuals 
are, apparently, closely analogous to, if not 
identical with, those observed in some forms of 
protodiastolic gallop rhythm. The sound and 
shock are similar in character and in time, and 
are associated with like appearances on the car- 
diogram and in the venous pulse. 
(9.) The " opening snap " in mitral stenosis, 
although usually a somewhat sharper sound, 
may be very similar in character to the normal 
third sound; it occurs at much the same period 
in the cardiac cycle - possibly a trifle earlier - 
and is associated with a well-marked proto- 
diastolic elevation on the cardiogram. 
(10.) This third sound and shock are not 
dissimilar to those observed in adherent peri- 
cardium, which are also associated with a sharp 
protodiastolic elevation on the cardiogram. In 
36 a striking example of this condition the proto- 
diastolic elevation corresponded, on the venous 
tracing, to a sharp depression, the base of which, 
the point corresponding to the summit of the 
protodiastolic wave, was followed by an abrupt 
rise on the curve. 
In view of these considerations it is clear that 
the early diastolic sound sometimes heard in 
normal hearts is an event closely associated with 
the rapid entrance of blood into the ventricles 
at the onset of diastole. How rapid this entrance 
may be is shown by the abrupt ascending limb 
of some cardioplethysmographic curves. 
Now the association of this sound with (a) the 
shock at times felt by the palpating hand; (6) 
the sharp shoulder which may be seen on the 
plethysmogram; (c) the presence in so many of 
these cases of an h wave in the jugular pulse 
following, as it does, immediately on the summit 
of the protodiastolic wave of the cardiogram; 
(d) the observations of the dog's heart in 
which a visible interruption of the dilatation 
of the ventricle was demonstrable, would all 
suggest: 
(1.) That at just this period, early in diastole, 
some structure is thrown into sufficient tension to 
produce audible vibrations. 
(2.) That there is, further, at this period some 
sudden slight, temporary arrest or interruption 
or delay of the rapid dilatation of the ventricle. 
That the sound is due to vibrations of the 
chest wall is ruled out by its presence in the 
37 exposed dog's heart, as well as by its presence in 
the heart after thoracoplasty. 
It is, moreover, fairly evident that the sound 
is usually produced in the left side of the heart. 
It is, as a rule, audible and palpable only at or 
in the immediate neighborhood of the apex, 
while in our three cases in dogs it was heard only 
over the left ventricle - and once in the left 
auricle as well. That a similar sound may arise 
in the right ventricle must, however, be admitted. 
What structures in the left ventricle might be 
thrown into vibration at this period? Eintho- 
ven's suggestion that the third sound is due to 
late vibrations of the aortic valves corresponding 
to waves on the katacrotic limb of the sphygmo- 
gram can hardly be accepted. The character 
of the sound; the position in which it is heard; 
the well-marked shock which may accompany 
it; its various analogies with sounds which are 
unquestionably of other origin,- are sufficient, 
it would appear, to invalidate this explanation. 
Several possibilities suggest themselves: 
(1.) One might fancy that with the sudden 
entrance of a large quantity of blood from the 
left auricle into the dilating ventricle, there is 
produced an appreciable impulse, sufficient to 
cause the protodiastolic wave of the cardiogram; 
that, at the same time, the walls responding to 
their sudden distention may offer a slight momen- 
tary elastic resistance, being thrown at this 
instant into vibrations of intensity sufficient 
to produce the early diastolic sound. The 
38 slight resistance offered at this moment might 
account for the centrifugal h wave of the venous 
pulse, a wave which ought to be more marked 
in the pulmonary veins than in the jugular. 
This is in some respects an engaging hypothe- 
sis. It is true that, in this moment in diastole, 
there is a rise in intraventricular pressure, but 
it is exceedingly slight. There are also several ob- 
jections which may be raised against this idea. In 
the first place, the character of the sound is often 
too sharp and definite to be of muscular origin. 
Again, in mitral stenosis, where, owing to the na- 
ture of the lesion, the first rush of blood into the 
ventricle cannot be as great as under normal cir- 
cumstances, a closely similar, sound and shock are 
met with. J Moreover, the occurrence of the sound 
in the hearts of patients suffering with or con- 
valescent from febrile diseases, as well as in one of 
our experiences with a dog's heart, where it ap- 
peared with apparent dilatation, increased under 
vagus stimulation, and disappeared on the admin- 
istration of strychnine, suggest that the appear- 
ance of the sound may be favored by conditions 
associated with a diminished tonicity of the heart 
muscle. But this would be in contradiction to 
the hypothesis of a muscular sound. For in 
such conditions, the resistance to the first influx 
of blood should be diminished. 
Potain 16 explains the analogous protodiastolic 
t In instances of slight mitral stenosis the heightened auricular 
pressure might more than compensate for the narrowing of the 
orifice, but the presence of the sound in stenosis of a fairly well marked 
degree could hardly be accounted for by sudden tension of the ven- 
tricular walls. 
39 gallop rhythm by the assumption of a suddenly 
arrested diastole dependent, however, on changes 
in the heart muscle. To quote his words: 
" In the different varieties of gallop rhythm in 
diastole the abnormal sound always results from 
the penetration of the blood into the cavity of 
the ventricle. In the normal condition this 
penetration is unaccompanied by any appre- 
ciable sound even in conditions of great circula- 
tory excitement. For a mass of fluid in move- 
ment does not produce a shock except when it 
is arrested by a sudden obstacle. But the 
obstacle which arrests the column of blood 
penetrating the ventricular cavities is the resist- 
ance of the wall, and this resistance is represented 
in the normal heart by the muscular tonicity 
which gives way progressively. On the con- 
trary, the arrest of the column of blood falling 
into the cavity of the ventricle is brusque, sudden, 
and capable of producing a perceptible shock 
for the hand and for the ear whenever, the tonic 
resistance of the myocardium being diminished, 
that of the fibro-connective elements in the wall 
is thrown suddenly into action at the moment 
when filling is accomplished. The state of the 
heart fills the conditions required to give rise to 
gallop'rhythm when its wall is modified in such 
a manner that the resistance of these latter ele- 
ment's is in excess, either because they have 
proliferated more or less considerably, as takes 
place in patients with Bright's disease whose 
hearts are sclerotic, or because the myocardium 
40 has rapidly degenerated, as occurs, for example, 
in typhoid fever. And this explains why the 
same phenomena may be the consequence of 
two conditions of the heart as different as the 
rigidity of the nephritic heart and the extreme 
flaccidity of the heart in certain cases of typhoid 
fever. Moreover, the fibro-connective resistance 
of the wall is brought more certainly into play 
the nearer the heart, constantly dilated, ap- 
proaches the degree of distention at which its 
resistance comes into play. This is the reason 
that in certain patients the gallop rhythm appears 
as soon as they take the horizontal position and 
the increased intra-cardiac pressure brings about 
a notable degree of dilatation. ... It will de- 
pend, therefore, upon the constant pressure, 
that is to say, the more or less considerable 
accumulation of blood in that part of the venous 
system which is near the heart, and also upon 
the more or less complete evacuation of the 
ventricular cavities that the diastolic tension 
of the walls occurs almost at the beginning of 
diastole or only when auricular systole comes 
into play, and that the gallop is therefore proto- 
diastolic or presystolic." 
This hypothesis is interesting but difficult to 
prove, and scarcely applicable to normal cases. 
Moreover, it is difficult to imagine that the limits 
of distention are actually reached so soon. Al- 
though the shoulder of the cardioplethysmo- 
gram, the moment at which the arrest in the 
rapidity of diastole occurs, may be very sharp, I 
41 have never seen an instance in which no further 
dilatation occurred. 
Again, the remarkably small limits of variation 
in the time at which the normal third sound 
occurs would tend to suggest that, as Muller 
and Chauveau hold, it depends on the exaggera- 
tion of a normal phenomenon rather than upon 
causes such as those suggested by Potain. 
(2.) Another possibility which presents itself, 
that which appears to offer the most reasonable 
explanation, is that with the first inrush of blood, 
the mitral and tricuspid valves, especially the 
former, borne up on the entering current toward 
a position of closure, while the ventricular walls 
are rapidly dilating, may be brought suddenly 
into a condition of tension sufficient to cause 
the sound and shock and to give rise to the cen- 
trifugal h wave.§ 
If this hypothesis be correct, one might expect 
to find the sound more frequent pathologically 
in cases where, owing to a diminished muscular 
tonicity, the diastole is more sudden, or where, 
owing to a weak heart muscle, insufficient empty- 
ing of the ventricle and high auricular pressure, 
such an hypothetical early tension of the mitral 
valves might be especially favored. But these 
are, indeed, conditions under which protodiastolic 
gallop rhythm is common. 
Such an hypothesis might well explain its 
appearance in adherent pericardium where dila- 
§ This hypothesis, which, as will be pointed out later on, is essen- 
tially that of Gibson, was advanced quite independently of his work 
and before the appearance of his article. 
42 tation is so common and diastole notably rapid, 
because of the traction exercised upon the ven- 
tricles by the adhesions. 
This explanation also applies peculiarly well 
to the similar phenomena occurring in aortic 
insufficiency. Here there is usually a dilated 
ventricle, often an engorged auricle, as well as 
the added element of regurgitation from the 
aorta, conditions peculiarly fitted to produce an 
early tension and closure of the mitral valves. 
And here, indeed, the sound is often followed by 
the slight vibratory murmur (Flint murmur) so 
analogous to that of mitral stenosis, in all proba- 
bility due to fluid veins arising in the blood as 
it passes through the mitral orifice. 
It is by exactly the same hypothesis that we 
have sought to explain the similar sound in mitral 
stenosis. 
If our hypothesis as to the valvular origin of 
the early diastolic sound be true, one might 
indeed ask why in cases of dilatation with en- 
gorgement of the auricle the valves might not 
be brought, early in diastole, into a position so 
analogous to that which they occupy in aortic 
insufficiency, as to give rise, with the 'further 
passage of blood from auricle to ventricle, to 
fluid veins sufficient to cause a slightly audible 
diastolic murmur. But this was indeed true in 
one of our dogs where, at first, the sound was 
followed by a distinct murmur. Again, as has 
already been said, the'sound in a healthy human 
being is sometimes a slight hum, somewhat 
43 longer than the ordinary phenomenon; and indi- 
cations of such a hum following the sound may 
sometimes be brought out if the patient turn 
upon the left side. In adherent pericardium 
with dilated heart, slight mitral diastolic murmurs 
without valvular disease have also been described. 
Furthermore, I have in one instance met with 
a third sound, a diastolic murmur in the tricuspid 
region, which could only be explained by such 
an hypothesis. The patient was a colored man 
with arteriosclerosis and dilated heart, but 
without valvular disease. There was mitral 
and tricuspid insufficiency due to dilatation of the 
ventricles. To quote one of my own notes, made 
in 1905: " In the fifth space, in about the para- 
sternal line, there is heard a distinct mid-diastolic 
murmur. This begins shortly after the second 
sound with a slight shock exactly like the open- 
ing snap of mitral stenosis, and runs at times 
almost into the first sound. At other times it 
stops just before it. It is slightly rumbling and 
presents all the characteristics of the murmur of 
mitral stenosis with Flint murmur. It is limited 
to an area about the size of the bell of a stetho- 
scope. The murmur seems to be more marked 
during inspiration. No aortic diastolic murmur 
is to be heard." This murmur, always rather 
soft, never very intense, was heard throughout 
the last two years of the patient's life. It wTas 
limited to a small area over the right ventricle; 
never audible at the apex. Its nature "was the 
subject of much discussion, and the only satisfy- 
44 ing explanation which was reached was that with 
diastole, owing to the dilatation of the ventricle, 
the tricuspid valves were brought, with the en- 
trance of the first rush of blood, into a condition 
of tension causing the sound, and thereafter, 
owing to the production of a slight de facto steno- 
sis, the murmur. At the necropsy, both right 
and left ventricles were dilated and hypertro- 
phied; there were no valvular lesions. This is 
the only instance in which I have observed such 
a shock and sound limited to the right ventricle. 
That the phenomenon is due usually to events 
taking place in the left side of the heart would 
well ■ explain the fact that the h wave of the 
jugular pulse is so slight in some cases. 
This hypothesis is similar to that hinted at by 
Hirschfelder17 as an explanation of his h wave.|| 
Henderson18 also assumes that the shoulder of 
the volume curve is associated with the approxi- 
mation of the mitral valves. Furthermore, the 
hypothesis is almost exactly that upon which 
Gibson relies to explain the sound heard in 
association with his b wave. To quote his 
words:19 " By observation on the excised heart 
it can be seen that as the ventricular cavity fills, 
the auriculo-ventricular valves float up and 
close automatically when the ventricle is full,, 
and it is easy to imagine that the inrush of blood 
would be followed by a reaction on the ventric- 
ular walls in proportion to the momentum of 
II Hirschfelder's suggestion, it should be said, relates to the tri- 
cuspid, not the mitral valve. The principle is, however, the same. 
45 the inrush, so that with a rapid and full stream 
the tightening of the valves would be quick and 
strong while with a slow stream the process 
would be more gradual yet in no wise less com- 
plete. The fact that this explanation necessi- 
tates the closure of the valves before the auricular 
beat is no objection; the amount of force neces- 
sary to push open the valves is extremely small, 
and the heart would be the more rather than the 
less efficient pump because of the double closure 
of the valves. The sequence of events in the 
diastolic period would then be as follows: After 
the replacement of the heart which follows 
systole and causes the v wave in the jugular 
pulse, the blood flows into the ventricle, the 
valves float up, gradually wffien the venous 
pressure is low, quickly when it is high, and the 
orifice closes; the auricle is now filled by blood 
from the veins; it contracts and forces the 
greater part of its contents into the moderately 
distended ventricle which then becomes fully 
so, the valves close again from the increase of 
pressure set up in the ventricle by the auricular 
contraction; finally/the ventricular contraction 
keeps the valves closed till the end of systole." 
If this hypothesis be correct, wrhy should the 
sound be heard in some individuals and not in 
others, and why should it be especially common 
in young people? The intensity of the sound 
is often so slight - so near the borderland of the 
audible - that it is not remarkable that it is 
frequently missed. Its apparent frequency in 
46 individuals with a slow, full pulse would appear 
to be in accordance with the last mentioned hy- 
pothesis, and the observation that the sound is 
sometimes louder during the slow beats of ex- 
piration may well be accounted for by the as- 
sumption of a higher auricular pressure during 
this period. 
In connection with the increased intensity of 
the sound in the left lateral decubitus, it should be 
noted that, in this position, a well-marked sys- 
tolic apical murmur may be brought out in cases 
where, in other attitudes, the heart sounds are 
clear. If this murmur be regarded as indicative 
of a functional insufficiency of the mitral valve, 
the third sound may then well be dependent on 
the more sudden distention of the ventricle with 
an increased quantity of blood under higher 
pressure. 
There would, however, seem to be no reason 
to suppose the existence of especially high auric- 
ular pressure or of diminished cardiac tonicity 
in the many healthy young people in whom the 
sound is heard. I have always fancied that one, 
if not the main, reason that the sound was so well 
heard in the young was because of the thinner 
chest walls, the less voluminous lungs, and the 
greater ease with which the heart can be ap- 
proached. 
(3.) There is another possibility with regard 
to the cause of this sound which may be simply 
mentioned. Stewart has shown that there is in 
the normal heart an early diastolic contraction 
47 of the ring of muscle just below the aortic and 
pulmonic valves, a contraction • which serves 
evidently to reinforce the closure of the arterial 
orifices. His work has not yet been published, 
and while one might a priori expect that the 
sound associated with such a contraction, if such 
a sound indeed there be, would occur at a some- 
what earlier period, and that it would be more 
appreciable at the base of the heart than at the 
apex, yet in the absence of positive proof of that 
which we have advanced as the most engaging 
hypothesis, it may be well to bear in mind the 
possibility that the contraction of the aortic 
ring may be a factor in the production of the 
sound, however improbable it may seem. 
SUMMARY. 
In many healthy individuals, especially in the 
young, there is audible at the apex of the heart 
a slight third sound, which occurs in early diastole 
shortly after the second sound. 
This sound is commoner with a slow pulse; it 
is better heard in the recumbent posture and, 
especially, in the left lateral decubitus. It is 
sometimes more clearly audible during expiration. 
The sound is not infrequently associated with 
a shock which may be visible as well as palpable. 
The sound and shock occur synchronously with 
the protodiastolic elevation of the cardiogram 
which is usually prominent in these cases. 
These events cover a period of time represented 
on the jugular pulse by the later part of the kata- 
48 erotic limb of the v wave and, generally, a part of 
the anacrotic limb of an h (Hirschfelder) wave 
(b wave of Gibson), which is usually present in 
these cases. This period corresponds closely to 
that occupied by the shoulder of the ascending 
limb of the cardioplethysmogram. 
Conclusive evidence as to the cause of this phe- 
nomenon is, as yet, wanting. 
From a consideration of the conditions ob- 
served in normal individuals, together with vari- 
ous apparently analogous manifestations occur- 
ring in disease, we are disposed to incline toward 
the hypothesis that the sound is produced by a 
sudden tension of the mitral and, perhaps at 
times, tricuspid valves occurring at the end of the 
first and most rapid phase of diastole. 
In conclusion I wish particularly to thank my 
friend, Dr. Eyster, of the Physiological Depart- 
ment, for valuable assistance. 
REFERENCES. 
1 Trans. Asso. Am. Phys., Phila., 1906, xxi, 52; Am. Jour. Med. 
Sc., Phila., 1907, cxxxiii, 249. 
2 Semaine m<?d., Paris, 1893, xiii, 474. 
3 Johns Hopkins Hosp. Bull., Balt., 1907, xviii, 265. 
4 Arch, fur d. ges. Physiol., Bonn, 1907, cxx, 31. 
5 Lancet, Lona., 1907, ii, 1380. 
6 E. J. Marey: La circulation du sang, 8°, Paris, 1881, Masson. 
7 Am. Jour. Physiol., Boston, 1906, xvi, 325. 
8 Arch, of Int. Med., Chicago, 1908, i, 102. 
9 Allbutt's System of Med., vol. v, p. 1019. 
10 Clinique m^dicale de la Charite. 8°, Paris, 1894, 37, Masson. 
11 Qp. cit., pp. 38 et seq. 
12 Etude cardiographique sur le m<?canisme du bruit de galop. 
Thhse de Paris, 8°, 1902, no. 315. 
13 Munch, med. Wochenschr., 1906, liii, 785. 
14 Ibid.: Op. cit., p. 785. 
15 Verhandl. d. Cong, fur inn. Med., Wiesb., 1904, xxi, 187. 
16 Op. cit., pp 48 et seq. 
17 Op. cit. 
18 Op. cit. 
19 Op. cit., p. 1381. 
49 On Some Relations of the Physician 
to the Public. Duties and 
Opportunities. 
ORATION ON MEDICINE AT THE FIFTY-NINTH ANNUAL 
SESSION OF THE AMERICAN MEDICAL ASSOCIA- 
TION, AT CHICAGO, JUNE 2-5, 1908. 
WILLIAM SYDNEY THAYER, M.D. 
BALTIMORE. 
Reprinted from The Journal of the American Medical Association, 
June 6, 1908, Vol. I, pp. 1877-1883. 
Copyright, 1908. 
American Medical Association. 
One Hundred and Three Dearborn Avenue. 
CHICAGO. On some Relations of the Physi- 
cian to the Public. Duties 
and Opportunities. 
ORATION ON MEDICINE AT THE FIFTY-NINTH ANNUAL 
SESSION OF THE AMERICAN MEDICAL ASSOCIA- 
TION, AT CHICAGO, JUNE 2-5, 1908. 
WILLI AM SYDNEY TRAYEB, M.1X 
BALTIMORE. OxN SOME RELATIONS OF THE PHYSICIAN TO 
THE PUBLIC. DUTIES AND OPPOR- 
TUNITIES. 
ORATION ON MEDICINE AT THE FIFTY-NINTH ANNUAL 
SESSION OF THE AMERICAN MEDICAL'ASSOCIA- 
TION, AT CHICAGO, JUNE 2-5, 1908. 
WILLIAM SYDNEY THAYER, M.D. 
BALTIMORE. 
When, a year ago, you honored me with the invita- 
tion to deliver this address, it was my intention to speak 
on some specific problem in medicine. On further re- 
flection, however, it has seemed wiser to take advantage 
of this occasion to express a few thoughts on some of 
the public relations of the physician-his duties and 
his opportunities. 
The physician has always been and, from the very 
nature of his calling, must be, more or less a public 
character. In the smaller community he is a public 
character in the sense that he is a common source to 
which the citizens repair for advice, not only concern- 
ing their physical and mental but often also their ma- 
terial well-being. In the larger centres of population he 
is a public character in that it is on his direction, on the 
results of his studies and research that the community 
depends for the organization of those more general, 
broader sanitary measures which are demanded to meet 
the exigencies ever arising and multiplying with the 
growth of large urban communities. 
In the early days of this country, when there were 
no large cities, the physician exercised this influence 
individually among his patients, as the family friend 
and adviser. With the growth and development of the 
nation, the great relative increase of the urban popu- 
lation, the multiplying complications of our life on the 
one hand, and on the other, with the enormous advances 
made in the knowledge of the nature and sources of 
disease, of the relations of physiology and pathology to 
other natural sciences, together with the rapid progress 4 
in the art of medicine and surgery-with all this 
growth, this expansion-yes, one may almost say, trans- 
formation, the functions of the physician have con- 
siderably broadened. In the old days the tree of medi- 
cine was a small affair; its roots ran wild and almost 
uncared for, and the physician gathered and used its 
fruits as they grew. The art which he sometimes showed 
in the employment of these fruits, such as they were, 
was indeed, remarkable. Of the tree and its roots which 
contained the sciences of anatomy and physiology and 
pathology, he knew little. But through the years, pa- 
tient students have gained wonderful knowledge of the 
nature of that tree; of the sources from which it draws 
its strength; of the extent and ramifications of its roots; 
of their intimate and intricate entanglement with those 
of almost all the other denizens of the garden of science. 
And with the multiplication of these researches and 
discoveries, the tree, nourished and cared for as never 
before, has undergone a great transformation; it has 
put forth new branches; new shoots have sprung up 
about it; and the fruits which it bears for the art of 
medicine and surgery surpass, almost, that which one 
might have imagined but a few years ago. 
The development of hospitals, of laboratories, of in- 
stitutions for the study of the ever increasing ramifica- 
tions of anatomy, physiology and pathology-ramifica- 
tions leading directly to botanical, physical, chemical 
and indeed, even to mathematical problems-calls for an 
increasing body of students-physicians who accomplish 
their function, and a most important and radical 
function it is, in the study of special scientific prob- 
lems-a life widely different from that of the country 
doctor of old. 
Moreover, the advances and extension of the medical 
and surgical art are such that it has long been impos- 
sible for any one man to develop equal proficiency in 
all its branches. In all large centres of population, 
therefore, certain men have sought to devote them- 
selves to special subjects in order that they may, in this 
manner, acquire a greater proficiency, and do more 
perfect and thorough work. This is natural and 
proper; it is only by the labors of such special workers 
that any art can be perfected. 
At the same time, the crowding together of the popu- 
lation into great cities, a tendency which is to-day es- 5 
pecially striking, lias brought with it new clangers. The 
poisoned well may affect one or two families at most. 
The poisoned water supply of a great city may affect 
thousands. Scarlet fever in the country town has few 
victims and may be more or less readily controlled. In 
congested tenements populated by ignorant and sus- 
picious aliens who do not understand the language of 
the people among whom they live, it is a widely dif- 
ferent problem. These new dangers involving the broad 
questions of public health and prophylaxis, questions of 
drainage, of water, of milk and food supply, of the care 
of contagious diseases - these demand the individual 
attention of men who have had special training. The 
great questions of water supply and of drainage can 
not be attended to properly by the engineer alone, nor 
can the protection of the city from epidemics of infec- 
tious disease safely be entrusted to boards of health 
consisting only of public spirited citizens; both are 
dependent on the advice and assistance of the trained 
sanitarian. 
In almost all large enterprises to-day the aid of the 
physician is sought, as for instance, in the organization 
of the relief departments of great railways and corpora- 
tions and in large department stores. The health and 
comfort of the employe and the profit and success of 
the employer are indissolubly interwoven. But the 
distinctly public duties of the physician are by no means 
confined to exigencies arising in large centres of popu- 
lation. There are, in the history of mankind, examples 
of the gradual or sudden desolation of extensive dis- 
tricts by the insidious influence of diseases which we 
now know to be in great part preventable. 
A recent historian1 has brought forward as an illus- 
tration of the possible influence of a preventable endemic 
disease, the history of the decadence of ancient Greece. 
To-day, as is known, malaria is the scourge of the 
Hellenic peninsula. Endemic throughout the land, it 
saps the vitality, the strength, the virility of the people, 
carrying away, annually, its thousands of human lives. 
Through the shadows of departed years the light of 
ancient Greece shines with undying luster. The lan- 
guage, the poetry, the art, the philosophy, the ideals, 
1. Jones, Ross and Ellett: Malaria. A Neglected Factor in the 
History of Greece and Rome. 12mo. McMillan and Bowers, Cam- 
bridge, 1907; Jones, Janus, Harlem, 1907, xii, 690. 6 
the spirit of beauty, have been for ages and are to-day 
the inspiration of mankind. The sounding hexameters 
of Homer, the breath of 
Him, ^Eschylus, ancient of days, whose word is perfect song,2 
the creative genius of Phidias, the eloquence of Demos- 
thenes, the wisdom of Pythagoras, of Socrates, of 
Plato, of Aristotle, beckon across the centuries to 
remind us that all the wealth of modern worlds has 
given birth to no loftier thoughts, to no higher ideals of 
life and beauty than those which sprang up by the 
waters of the blue yEgean. And to-day as ever, Pallas 
Athene "nee intelligente chez les Grecs heureux"3 
dominates the elect of the world. "The garners of 
Sicily are empty now, but the bees from all climes still 
fetch honey from the tiny garden plot of Theocritus."4 
There is no trace in the literature of the early days of 
ancient Greece of the scourge which has since laid waste 
the land. Malaria appears to have been introduced into 
Attica during the fifth century B. C. Although the 
conditions of the soil and the probable presence of 
anopheles must have been favorable for the spread of 
the disease in the greater part of the Peloponnesus, yet 
the first mention of its occurrence is, apparently, in The 
Wasps of Aristophanes (422 B. C.). But the writings 
of the fourth century B. C. give evidence that the dis- 
ease had gradually spread until, finally, it became 
chronic and endemic, prevailing among the children, 
giving rise to cachexia, conquering the peninsula. And 
step by step with the spread of the disease, the his- 
torian traces the beginnings of that fatal degeneracy 
which marked the fall of the race. A spirit of criticism, 
of jealousy, of pessimism arose; discord, disunion and 
civil strife followed, and in a few centuries the earthly 
abode of the gods was a mere tributary of the Roman 
Empire. Poisoned by the subtle influence of a prevent- 
able disease, the spirit which had produced the science, 
the beauty and the art of ancient Greece faded from the 
world. 
2. Swinburne : The Altar of Righteousness. 
3. France, A. : Discours prononce A 1'inauguration de la statue 
d'Ernest Renan a Treguier, 12mo. Paris. 1903, Calmann-Levy. 40. 
4. Lowell: Harvard University, A Record of the Commemora- 
tion. etc., of the Foundling of Harvard College, 8mo, Cambridge, 
1887. John Wilson & Son. 7 
True or fanciful as this suggestion may be, it is 
hardly an exaggeration of what a preventable infectious 
disease may do. And one can but ask himself what 
might have been saved for the world had we known then 
what we know now? 
To-day, with an educated and specially trained body 
of medical men, assisted by an enlightened government, 
the Italians have reduced the mortality in the fever- 
ridden parts of their neighboring peninsula two-thirds 
in five years; and the task is but begun. Already in 
regions where agriculture was abandoned, work is being 
renewed and a fresh life is springing up. 
There is a modern example which touches us closely, 
of a great undertaking-one of the greatest undertak- 
ings that man has ever essayed-which depends for its 
success largely on the labors of physicians. I refer to 
the digging of the Panama Canal. The French, with 
unexcelled mechanical skill and energy had failed- 
failed largely because of the dreadful and continuefl 
mortality among the workmen. The United States took 
up the work. In the meantime there had come the great 
discoveries of Ross and Grassi and Bignami and Bas- 
tianelli, completing those of Laveran, concerning 
malaria, and the vital and illuminating contributions 
of our own Reed, Lazear, Carroll and Agramonte, with 
regard to yellow fever. And to-day the Panama Zone 
compares favorably, as to sanitary conditions, with the 
more healthy parts of this country. Yellow fever, 
though on all sides, is here unknown. It i's the greatest 
triumph of preventive medicine that the world has 
ever known. 
And to whom is this due? A few months ago I had 
the good fortune to listen to an account by a distin- 
guished foreign physician, of the work at Panama 
whence he had just returned. After speaking with 
warmth of the general conditions, he said impressively, 
"The successful completion of the Panama Canal 
depends on one man " If the measures admirably 
planned and carefully carried out by Colonel Gorgas 
fail, if there is a moment's relaxation, if the old epi- 
demics recur, it will be impossible to find laborers, and 
the work will fail again as it did before. And he did 
not exaggerate. It is on the success of these prophy- 
lactic measures which can be designed and carried out 
only by a specially trained sanitarian, that the com- 8 
pletion of this great undertaking depends. It is to the 
lasting credit of our country that medical men should 
have urged and our President recognized the importance 
of the appointment of a physician on the Panama Com- 
mission. 
There is yet another opportunity for public useful- 
ness in this country for which the training of the 
physician is peculiarly valuable. I refer to the career of 
the legislator. One has but to consider the few examples 
already mentioned of the various ways in which medical 
knowledge and skill are of value to the state, to realize 
how useful the education of a physician may be as a 
preparation for public life. The life of a physician, 
not only prepares a man to treat wisely those more 
specific and practical questions of which we have just 
spoken; more than this, no career brings a man into 
closer connection with his fellowr; no career gives him 
a more intimate knowledge of mankind; no career is 
more fitted to develop those qualities of charity and 
tolerance so vital in our best public servants. It is 
true that medicine and public life are equally jealous 
mistresses, and that few men can serve both as they 
would and should be served; but we have, in this coun- 
try, hardly realized how valuable a preparation for 
public life is the training and career of the physician. 
One has but to look to the prime minister of our sister 
republic in Europe for a most brilliant example of what 
may be accomplished in modern political life by the 
man with a medical training. 
It is doubtless true that the development of the purely 
scientific branches of medicine together with the multi- 
plication of specialties which is everywhere observable 
in our large centers of population, have resulted in a 
relative diminution of the number of family physicians 
in the old sense of the word, and have, in so far, limited 
the public influence which the old fashioned general 
practitioner formerly exerted among his patients. But 
on the other hand, there have developed many wholly 
new problems which are calling the physician more 
directly into public life. If perhaps, the wholesome 
influence of the family doctor is less felt in the com- 
munity than it once was, yet the opportunities for 
public service which are to-day before the physician, 
nay, his public duties, have greatly increased. 9 
The knowledge gained dnring the past forty years has 
taught us that we can accomplish far greater results 
by preventing disease than by attempting to promote 
recovery from that which has already started; it has 
taught us that a large proportion of the gravest mala- 
dies from which humanity suffers are acquired through 
our ignorance and carelessness and unclean habits; 
and with regard to many of these diseases, it has 
given us efficacious methods of prevention. Prophylaxis 
is the watchword of the day. We have in our hands 
the means, not only of delivering ourselves from 
dreaded epidemics of exotic pestilence, but of prevent- 
ing largely the terrible yearly sacrifice to the contagious 
diseases which have for ages been endemic among us. 
But this deliverance can be brought about only through 
the united and conscientious efforts of the medical pro- 
fession. 
This is an age of combination and concentration and 
cooperation - of large associations and undertakings. 
The great growth of this Association which we have 
known of recent years is but a feature of the times. 
Despite the increasing diversification of our interests, 
we physicians have been brought closer together than 
ever before-and to our lasting benefit. For wherever 
medical men come into social contact one with another 
they can not fail to feel a warm pride in their calling- 
they can not fail to be impressed with the earnestness, 
the simplicity, the honesty of the character and aims 
of their fellows-with the realization that, despite dif- 
ferences in natural endowment, in advantages, in sur- 
roundings, in temperament; despite the fact that we 
are all human, and possess our fair share of human 
frailties, we are with singularly few exceptions, all 
working earnestly, as best we can, in the search of 
truth and for the good of humanity. Association and 
acquaintance deliver us from doubt and suspicion and 
jealousy-those all pervading daughters of isolation. 
Our great Association has further enabled us to dis- 
tribute to all parts of the country, an admirable journal, 
which is a monument to its honest, faithful, fearless 
editor, so that the practitioner in the distant rural com- 
munity may reap, at the earliest moment, the benefits 
of the discoveries of the student of the urban laboratory. 
It enables us to lay with greater force before local and 
national legislatures necessary measures of sanitary 10 
reform. It helps us to combat more powerfully the 
many forces of evil which, from time immemorial, have 
battened on the credulousness and superstition of 
the invalid. It is helping us to teach the public with 
greater impressiveness the necessity of high and uni- 
form standards of education for the physician and 
requirements for the license to practice medicine. 
Here we are then, a great body of medical men, united 
in an Association, not for our personal, financial, politi- 
cal or social advancement, but solely in the cause of 
truth and for the benefit of humanity-the deliverance 
of the public from disease. Nevertheless, the work 
before us is unending; the obstacles, great. But why 
should there be obstacles? Why have not' the recom- 
mendations of this Association the force of law? Why 
is it that, when laws themselves exist, all our strength is 
needed to secure their enforcement? 
The main cause, I take it, of all this is the lack of 
comprehension on the part of the public of the nature 
and aims of medicine and of physicians. If the public 
had but a small part of the information which is ours, 
how many thousands of lives might be saved every year! 
The community as a whole, has a very vague under- 
standing of the nature of the medical sciences and arts. 
Under these circumstances can we expect such a public 
to sympathize with and blindly follow all our recom- 
mendations? Surely not. 
In how many ways is this ignorance shown! To take 
but a few examples: 
We know well enough that the one successful way to 
prevent the spread of many contagious diseases in the 
large community is the establishment of well-conducted 
hospitals in which the patients may be isolated as soon 
as possible after the breaking out of the malady. By 
providing for the early segregation of these patients in 
institutions offering to the sufferers the most enlight- 
ened care, the community confers a blessing of incalcu- 
lable value on the families of rich and poor alike. Such 
hospitals, moreover, afford the only opportunity for 
the proper instruction of students of medicine in the 
diagnosis of those contagious diseases, the early recog- 
nition of which is of such vital importance to the public. 
Furthermore, we know that such institutions are abso- 
lutely without danger to the neighborhoods in which 
they are situated. The records of the city of Boston 11 
which possesses a model hospital for contagious diseases, 
shows well what a blessing such an institution may be 
to the community. 
But 1 know another great eastern city where there 
has been, until recently, no provision whatever for the 
care of contagious diseases. More than this, some years 
ago the state legislature passed a law forbidding the 
erection of a hospital for contagious diseases within the 
city limits without a two-thirds majority of each branch 
of the city council, which rendered the erection of 
such a hospital almost impossible. To us this law seems 
wicked and brutal in the extreme-worthy only of sav- 
ages. And yet the measure was passed by men who 
were not inhuman; they were simply ignorant. And it 
is difficult to remedy such ignorance by immediate 
argument. The vehemence which we are too apt to dis- 
play only excites the sensitiveness of the legislator-and 
where passion enters in reason passes out of the door. 
I know again a great city, the water supply of which 
is open to serious contamination. At a period during 
which extensive and radical public improvements were 
under consideration, a meeting wras held of a committee 
appointed to take counsel as to those steps which should 
be taken to improve the water supply. Before this com- 
mittee there appeared a number of medical men and 
sanitarians, including representatives of the state and 
city boards of health-men who had made a careful 
study of such matters. These men urged that steps be 
taken to provide ultimately for a proper system of filtra- 
tion. After they had spoken, a gentleman connected 
with one of the city departments, an engineer, who had 
the last word, made a long address in which he denied 
with passion that the water supply was or could be con- 
taminated. He ridiculed the statements of- the sani- 
tarians and physicians, opposing to them the frequently 
repeated and wholly unfounded-assert ion that they were 
dealing with theories-he with facts. The committee, 
by an overwhelming majority, dismissed, for the time 
being, the question of filtration. The city, fortunately, 
has not yet suffered from the epidemic which may come 
at any time. The men on that committee were not unin- 
telligent; they were simply ignorant of the medical as- 
pect of the question at issue, and were utterly deceived 
by a plausible argument filled with pseudo-scientific 
statements which the orator himself appeared not wholly 
to understand. 12 
A few years ago I happened to meet, on the railway, a 
high official of a large manufacturing concern situated 
in a most malarious district. At that time little had 
been done to protect the employes, who were nearly all 
victims of the disease. "This is a healthy enough place," 
said the official, who lived in a well-netted Imuse in a 
dry part of the town. "The trouble with the people 
here is that they take too much quinin. If they would 
stop taking quinin they would stop having malaria." 
And this was a really intelligent citizen! 
How often again do the trustees of large hospitals 
generously seek to "protect" the patient from what they 
regard as inconsiderate and unnecessary scientific zeal, 
by closing the wards to instruction and denying admis- 
sion to student assistants, thereby blindly cutting off 
from the sufferer the greatest boon that they could offer 
him-the most enlightened observation and care. How 
far are these good men from a comprehension of the 
true significance and value of the hospital to the patient 
and to the public ! 
There could be no more striking example of the ignor- 
ance of a well-meaning part of the community than the 
agitation of the so-called anti-vivisectionists whose pub- 
lications, shocking and wicked and brutal as they are 
misleading, are yet believed by some misguided people. 
But these dreadful publications, inspired for the most 
part, by individuals who probably mean to be honest, 
are but the offspring of fancy and prejudice, born them- 
selves of an utter ignorance and misconception of the 
aims and significance of medical science and of the 
character and ideals of the student. 
These are but a few examples, but they are enough to 
show how little a considerable part of the general public 
-often individuals in whom we might, indeed, expect 
more enlightenment--understand the nature of medicine 
or sympathize with the generous efforts of the physician 
and the investigator. We can hardly expect people with 
ideas such as these to heed the advice of a body such as 
ours. These considerations should bring home to us 
the realization that the education of the public is a most 
vital duty, not only of medical schools and associations, 
but of each separate member of the medical profession. 
On each one of us there rest public duties of the gravest 
import. On the sum of our individual efforts depends 
the success of all the great sanitary reforms of the 
future. 13 
On a few of the opportunities which come to the 
physician of to-day, in his intercourse with his patients 
and his friends, to perform some of these public duties 
I would especially speak. 
Many misconceptions concerning the nature of the 
healing art arise from that strange atmosphere of mys- 
tery which so often surrounds medicine. To physicians 
there is nothing mysterious or supernatural about med- 
icine. We recognize that medicine is a practical art 
resting on a basis of scientifically proved facts; we 
realize that our knowledge amounts to an infinitely small 
part of that which we would know and hope some day 
to know. We know that there is an enormous field for 
study. We practice our art simply on the basis of what 
we have learned from the experience and study of those 
who Irave gone before us, and on what we acquire daily 
from our own study and experience and reason and com- 
mon sense. But from time immemorial the art of medi- 
cine has been connected in the mind of man with the 
supernatural and the divine. Medicine has been re- 
garded rather as a matter of faith than as an art resting 
on a scientific basis. People speak of their "belief" in 
this, that or the other "system" of medicine, and on the 
basis of such "belief" recklessly hand over their bodies 
to some individual who asserts that his practice is based 
on a theory or system revealed as by inspiration to some 
fortunate mortal, perhaps yesterday, perhaps tw-o hun- 
dred years ago. 
This blind faith in systems is not so far removed from 
the faith of the savage in the magic of his medicine man, 
and when we turn to our friends who with such delicious 
innocence and ingenuousness have termed their medical 
faith a "science;" when we see them, as we sometimes 
do, braving with fanatical contempt some dreadful in- 
fection only to find themselves in the end the prey of 
the fatal poison of reality, we seem almost to see the 
medicine man standing with a little group of deter- 
mined warriors in the midst of the circle of fire, breath- 
ing defiance even as he falls, his "invulnerable" mantle 
pierced by a score of deadly bullets.5 
Again, there is a very general idea among people 
that the physician is by practice, if not by nature, 
5. I have seen in the possession of a friend, the "invulnerahle" 
mantle of an Indian medicine man who with a small group of war- 
riors fought until the last man had fallen, although completely sur- 
rounded by troops. The garment was pierced by many bullets. 14 
disingenuous: that while he may be trusted to do 
his duty as he sees it, to his patient, truth is not 
to be expected of him. Scarcely a week goes by that I 
am not asked by the friends of a patient to tell a delib- 
erate falsehood. 
From these misconceptions we physicians can not, I 
fear, be regarded as wholly guiltless. We know how few 
specifics there are in medicine. We know that by simple 
physical and mental means we accomplish our main re- 
sults. But, alas, how easy it is to accomplish these ends 
by misleading means! How easy it is to write the pre- 
scription which we know is of itself of little value, which 
we should never dream of taking ourselves, and to allow 
the patient to believe that it is this that has "cured" him 
of the transitory, self-limited malady! How easy it is 
by assuming an impressive air-and if there be anything 
under the sun that we physicians should pray to be de- 
livered from it is an impressive air-to make the patient 
feel that we possess that mysterious power which has, 
perhaps, come to us from a long line of medical ances- 
tors, the power which enables us at a glance to divine 
that which might never be revealed to our uninspired 
colleague. 
The same results can be achieved without misleading 
the patient one iota. It is perfectly possible to treat 
patients as we would be treated ourselves. It is scarcely 
likely that they would be treated otherwise. It takes a 
little longer; it involves a little more explanation; but 
how much safer and surer is the result! 
The oracular method is easier, but I fear that some 
of us have forgotten that, by a special decree of the 
Olympian Assembly, Asklepius was forbidden to trade 
in oracles.6 That it is necessary for the physician to 
tell untruths is a myth founded on kindness of heart, 
pure and simple-but an unreasonable and a weak, a 
short-sighted and a misguided kindness of heart. Truth 
is as sacred a duty in medicine as anywhere else in life. 
As a matter of policy, as Cabot has pointed out, it is 
almost a necessity, for whatever may be true in other 
spheres of life, the doctor's lie is always detected. 
It is, of course, obvious that truthfulness in medicine 
does not mean that it is always necessary to tell the pa- 
tient that he has a fatal disease if he does not ask you 
6. Lucian : Lucian's Dialogues, translated by Howard Williams, 
12mo. London, 1893. Geo. Bell & Sons. 15 
the direct question. Nor does it forbid the physician to 
seek and keep his eye fixed on the cranny of hope which 
may usually be found, as earnestly and sedulously as 
would the patient himself. Few events in human af- 
fairs are certain. A few years ago I had under my care 
a patient who had had one tuberculous kidney removed 
some years before. She had then bilateral pulmonary 
tuberculosis, tuberculous pleurisy, tuberculous perito- 
nitis and tuberculosis of the remaining kidney. The 
temperature for weeks had been constantly elevated, the 
pulse rapid and feeble. She seemed in extremis. Had 
I been asked, I should have said that she had probably 
a few weeks to live. She asked me calmly if she were 
going to die or whether there was any chance of recovery. 
I answered her truly that she was very ill, that the out- 
look was not good, but that there was always a chance 
for an arrest of the disease, and that it would be wrong 
even to think of giving up the fight. For two years that 
patient has been free from fever, to all outward appear- 
ances well, and to-day she is actually working for her 
living. 
Few patients ask a physician the direct question, but 
when they do they should be told the truth as we should 
tell the truth in every other sphere of life. 
I believe sincerely that most physicians do so, and 
that the annoying general suspicion of the doctor's state- 
ments is ill-founded; but I know a number of good men 
who too often allow their kindness of heart to get the 
better of their good judgment. I know nothing sadder, 
nothing more hopelessly demoralizing, nothing surer to 
upset the mutual confidence of a family than the en- 
trance of the "white lie" into the household or the sick- 
room. Few of us are unfamiliar with the hopeless un- 
certainty of the invalid who comes finally to realize that 
a tissue of falsehood has been spun about him; that on 
no one can he rely. The affection of those about him he 
may not doubt, but of their sincerity how can he again 
be sure? There is no more pathetic picture in the ex- 
perience of the practitioner of medicine. 
The physician has no higher public duties than the 
duty of simplicity, the duty of the avoidance of mystery 
in medicine and the duty of truthfulness. Toward his 
patient I know of no more vital duty than the duty of 
optimism. 14 
disingenuous.; that while he may be trusted to do 
his duty as he sees it, to his patient, truth is not 
to be expected of him. Scarcely a week goes by that I 
am not asked by the friends of a patient to tell a delib- 
erate falsehood. 
From these misconceptions we physicians can not, I 
fear, be regarded as wholly guiltless. We know how few 
specifics there are in medicine. We know that by simple 
physical and mental means we accomplish our main re- 
sults. But, alas, how easy it is to accomplish these ends 
by misleading means! How easy it is to write the pre- 
scription which we know is of itself of little value, which 
we should never dream of taking ourselves, and to allow 
the patient to believe that it is this that has "cured" him 
of the transitory, self-limited malady! How easy it is 
by assuming an impressive air-and if there be anything 
under the sun that we physicians should pray to be de- 
livered from it is an impressive air-to make the patient 
feel that we possess that mysterious power which has, 
perhaps, come to us from a long line of medical ances- 
tors, the power which enables us at a glance to divine 
that which might never be revealed to our uninspired 
colleague. 
The same results can be achieved without misleading 
the patient one iota. It is perfectly possible to treat 
patients as we would be treated ourselves. It is scarcely 
likely that they would be treated otherwise. It takes a 
little longer; it involves a little more explanation; but 
how much safer and surer is the result! 
The oracular method is easier, but I fear that some 
of us have forgotten that, by a special decree of the 
Olympian Assembly, Asklepius was forbidden to trade 
in oracles.6 That it is necessary for the physician to 
tell untruths is a myth founded on kindness of heart, 
pure and simple-but an unreasonable and a weak, a 
short-sighted and a misguided kindness of heart. Truth 
is as sacred a duty in medicine as anywhere else in life. 
As a matter of policy, as Cabot has pointed out, it is 
almost a necessity, for whatever may be true in other 
spheres of life, the doctor's lie is ahvays detected. 
It is, of course, obvious that truthfulness in medicine 
does not mean that it is always necessary to tell the pa- 
tient that he has a fatal disease if he does not ask you 
6. Lucian : Lucian's Dialogues, translated by Howard Williams, 
12mo. London, 1893. Geo. Bell & Sons. 15 
the direct question. Nor does it forbid the physician to 
seek and keep his eye fixed on the cranny of hope which 
may usually be found, as earnestly and sedulously as 
would the patient himself. Few events in human af- 
fairs are certain. A few years ago I had under my care 
a patient who had had one tuberculous kidney removed 
some years before. She had then bilateral pulmonary 
tuberculosis, tuberculous pleurisy, tuberculous perito- 
nitis and tuberculosis of the remaining kidney. The 
temperature for weeks had been constantly elevated, the 
pulse rapid and feeble. She seemed in extrexnis. Had 
I been asked, I should have said that she had probably 
a few weeks to live. She asked me calmly if she were 
going to die or whether there was any chance of recovery. 
I answered her truly that she was very ill, that the out- 
look was not good, but that there was always a chance 
for an arrest of the disease, and that it would be wrong 
even to think of giving up the fight. For two years that 
patient has been free from fever, to all outward appear- 
ances well, and to-day she is actually working for her 
living. 
Few patients ask a physician the direct question, but 
when they do they should be told the truth as we should 
tell the truth in every other sphere of life. 
I believe sincerely that most physicians do so, and 
that the annoying general suspicion of the doctor's state- 
ments is ill-founded; but I know a number of good men 
who too often allow their kindness of heart to get the 
better of their good judgment. I know nothing sadder, 
nothing more hopelessly demoralizing, nothing surer to 
upset the mutual confidence of a family than the en- 
trance of the "white lie" into the household or the sick- 
room. Few of us are unfamiliar with the hopeless un- 
certainty of the invalid who comes finally to realize that 
a tissue of falsehood has been spun about him; that on 
no one can he rely. The affection of those about him he 
may not doubt, but of their sincerity how can he again 
be sure? There is no more pathetic picture in the ex- 
perience of the practitioner of medicine. 
The physician has no higher public duties than the 
duty of simplicity, the duty of the avoidance of mystery 
in medicine and the duty of truthfulness. Toward his 
patient I know of no more vital duty than the duty of 
optimism. 16 
There is another widespread misconception to combat 
which is an important public duty. 1 refer to the too 
common feeling of the public that, with many of us, the 
practice of medicine is purely and simply a trade. 
Viewed in this light the practitioner can but be often 
an object of suspicion. His methods and his word are 
doubted. The best part of his influence is gone. There 
are few, if any, physicians who practice medicine as 
amateurs. The inconveniences which every earnest 
doctor must endure are always considerable. Most 
physicians are obliged to depend on their fees, as most 
clergymen are obliged to depend on their salaries, for 
their daily bread. They must provide, not only for 
themselves, but often for their families. There are 
many men to whom, for more reasons than one, the ma- 
terial gains from practice are an important-a highly 
important-element in life. There are many men, teach- 
ers, scientific workers, men who desire to limit their 
practical activities, as well as men who have achieved 
such position that they are obliged to restrict or select 
from the overwhelming practice which seeks them, who, 
for these very reasons, rightly demand large fees. If 
the public insists on having their services rather than 
those of the many other good men in the profession, they 
should and do understand that they must pay a larger 
honorarium. This is perfectly right and proper. But 
there are very few physicians who enter into the prac- 
tice of medicine with the idea of laying up wealth. 
There are happily exceedingly few to whom medicine is 
a trade. The man to whom the scientific and humani- 
tarian aspects of medicine mean nothing; the man who 
practices solely for what he can make; the man who 
finds no interest in medicine outside of that which he 
puts in his pocket; that man is on a level with the con- 
scienceless quack, and the sooner he leaves the profession 
the better for it and for the public. 
There exists, however, a tendency among some of us- 
men who are, for the most part, honest and honorable- 
which is, it seems to me, below the dignity of our calling. 
I refer to the tendency to regulate one's fees according 
to the means of his patient. It is well that a man should 
have a more or less definite estimate of the value of his 
services, a fixed maximal charge for work of a certain 
character, a charge which, in justice to himself, he 
should always make, unless he has reason to believe that 17 
the patient is not in condition to meet it. He will often, 
with a large proportion of his patients, perhaps, be 
obliged to accept less than the value of his services. But 
that he should speculate on the wealth of the rich, that 
he should demand exceptional recompense from the mil- 
lionaire because of his wealth, is to make medicine a 
trade; is to bring distrust and suspicion and discredit 
on his profession; is to put a serious obstacle in the 
way of all the great reforms which we as physicians and 
sanitarians hope to accomplish. 
Another duty, the grave public import of which comes 
to us with much force to-day, is the instruction of the 
public with regard to the necessary measures of pro- 
phylaxis in connection with infectious diseases. As has 
been demonstrated again and again, general laws and 
sweeping public measures are of themselves insufficient 
to prevent the spread of such diseases as malaria, yellow 
fever, plague, cholera and typhoid fever. It is only 
through the cordial and general cooperation of the 
practicing physician with an enlightened public that 
efficient prophylaxis can be established. It is impos- 
sible here to enter into particulars as one would. We 
can consider but a few examples. The great accomplish- 
ment of the medical, department of our army in eradi- 
cating yellow fever from Havana is fresh in our minds. 
This work was rendered possible by the recognition of 
the fact that the causal element of yellow fever exists 
only in the body of the patient suffering from the disease 
and in the mosquito (Stegomyia fasciata) 'which has fed 
on the blood of the sufferer. The mosquito can acquire 
the infectious agent only from an individual affected 
with the disease, and the human being can acquire the 
disease only through the bite of an infected mosquito. 
Though a great deal can be accomplished by general 
measures directed toward the destruction of mosquitoes 
and the removal of breeding places, it is impossible, by 
these measures alone, to overcome an epidemic. The 
problem, it was realized, could be met satisfactorily only 
by sterilizing, as it were, each individual case of the dis- 
ease. If each case of yellow fever could be successfully 
protected from mosquitoes, one might be sure that, from 
this case at least, there could be no spread of the disease. 
And so, by the cooperation of local physicians with the 
efficient medical corps of the army, every suspected case 
of yellow fever was reported. The houses of patients, 18 
together with those in the immediate neighborhood, were 
promptly netted and the mosquitoes already there were 
killed. In seven months the disease was banished from 
the city. Almost equally brilliant was the work in New 
Orleans, where a dreadful epidemic, already well under 
way, was eradicated by a period at which otherwise it 
would probably have been at the summit of its ravages. 
This problem, it is true, was an essentially simple one, 
once the fundamental knowledge of the manner of en- 
trance and spread of the infection had been acquired. 
In its broader lines, however, the problem is the same in 
connection with many of the gravest and commonest af- 
fections with which humanity suffers. In malaria the 
task of prophylaxis is more difficult because the disease 
is so widespread, and for the reason that, because of its 
very mildness, many cases pass unnoticed. And yet how 
much can be done, and is being done in some parts of 
the world, has already been mentioned. In typhoid fever 
the problem is yet more difficult; in tuberculosis more 
so again. 
But in all these diseases, as soon as the physician, the 
public and the government unite and work hand in hand 
to prevent, so far as possible, the spread of the infection 
from the individual case, enormous inroads can be made 
into the mortality. In all these conditions the infec- 
tious agent dies sooner or later outside of the animal 
body and is disseminated primarily by the infected 
human being and, in the case of tuberculosis, to some 
extent, by cattle. 
To properly combat the spread of preventable infec- 
tious diseases we need: (1) An enlightened public, (2) 
a conscientious and united medical profession ready to 
do its duty as individuals and especially to work in a 
spirit of cordial cooperation, with (3) central and local 
boards of health which are under the direction of trained 
sanitarians. 
The organization of all these measures depends, in 
the end, on the results of our individual efforts as physi- 
cians. The education of the public- can be accomplished 
only by us; and it is our duty privately, publicly, day 
in and day out, to explain to the people the rules of 
self-protection. The faithful performance by us as 
physicians of the necessary measures of prophylaxis in 
every individual case is almost the corner stone of the 
edifice. These duties, it is true, greatly complicate the 19 
life of the physician. The measures which we ought to 
carry out, and which can perfectly well be carried out 
in every case of typhoid fever, are tedious and annoying, 
but they are no more so than the aseptic and antiseptic 
precautions employed daily by the surgeon. They are 
duties which we must recognize unless we are content to 
lose, as we do every year, thousands of the very flower 
of our youth through preventable diseases; unless we 
are content to remain as we are now, one of the few 
nations in which the disgraceful prevalence of typhoid 
fever, a filth disease, is a byword throughout the civil- 
ized world. Isolated, individual effort, however, goes but 
a short way of itself. We must cooperate with one an- 
other and with our boards of health; we must work in 
unison and see to it that, as in the case of scarlet fever 
and measles and diphtheria, so every case of typhoid 
fever and tuberculosis is reported and the proper meas- 
ures of prophylaxis taken. 
And lastly, the character of our state and local boards 
of health, that most vital point depends largely on the 
attitude and efforts of the medical profession. After 
what has been said it is hardly necessary to refer to the 
increasing importance to the community of local and 
central boards of health. It is on these bodies that we 
depend for the organization and direction of the more 
comprehensive measures of prophylaxis, the need of 
which is increasing daily with the greater complications 
of our life and the advances in medical knowledge. 
Moreover, in recent years, departments of health have 
assumed a wholly new significance with the establish- 
ment of diagnostic laboratories. Modern methods of 
diagnosis, microscopical examinations of sputa and of 
the blood, bacteriological examinations of smears and 
cultures from the throat, tests for specific agglutinins in 
the blood in fevers are too complicated and time-absorb- 
ing for the busy practitioner. Much of this work is 
done in private laboratories by specially trained men. 
There are, however, many who can not afford the addi- 
tional expense of such examinations, people who are not 
objects of charity and who can and do bear the ordinary 
expenses incident to their medical attention, as well as 
many who must always be cared for by the benevo- 
lence of the physician or at the public expense. But 
it is absolutely necessary, not only for the sake of the pa- 
tient, but also for the protection of the public, that these 20 
more precise measures of diagnosis be carried out so far 
as possible in all suspicious cases. If they are not car- 
ried out, a vitally important link is removed from the 
chain of our public measures of prophylaxis. And so it 
has come to pass that state and county and city boards 
of health are everywhere wisely establishing laboratories 
in which such examinations are made at the request of 
the attending physician. Now it is clear enough to any 
mind that the direction of such boards should be in the 
hands of men with a special training as public sanita- 
rians, pathologists and bacteriologists. That these facts 
are not wholly appreciated by the general public, that 
the pernicious influence of political favoritism now and 
then plays a part in the selection of such bodies need not 
be mentioned. But I wish to assert and assert emphat- 
ically my conviction that, as a people, we are too fond 
of using the word "political" with a smile of contempt; 
we are too fond of speaking lightly of the conscience and 
honesty of the politician. Few politicians would vol- 
untarily prostitute a branch of the public service which 
is so vitally concerned with the welfare and safety of the 
community. 1 have rarely met men in political life who 
did not pay considerate attention to the judicious and 
tactfully offered advice of conscientious physicians. It 
is for us physicians to set them an example. We know- 
every one in this hall knows-the kind of man who 
should preside over a department of health. And yet, 
what a spectacle do we see with changes of administra- 
tion, in almost any of our cities! Applications from 
busy practitioners; from men who, perhaps, from age 
or infirmity, desire to retire from active work; from 
men who have been unsuccessful in practice and are in 
need of money! How is the politician to know what to 
do if we behave in this manner? We physicians do 
not always realize the responsibilities which rest on us 
in this connection. We ought to act and speak fear- 
lessly and frankly, so that men obviously unfitted shall 
be ashamed to offer themselves publicly for such posi- 
tions. We ought to see to it that the representatives of 
our profession on such bodies are capable and well- 
trained men; men who can give to their work all their 
time, all their thought, all their energy. This again is 
a public responsibility, a public duty which falls upon 
each one of us as a practicing physician. 21 
Another opportunity which comes to us as individuals 
is the opportunity to help forward the movement, nov 
happily started, for better instruction in our schools of 
medicine by increasing the opportunities for practical 
clinical experience. We all know that we improve in the 
art of medicine only by the actual study of disease and 
the observation of the effects of treatment. Rule and 
precept may help; they can not make the physician. 
Where, in our country, has this practical experience been 
offered? In but a very few of our schools have the stu- 
dents had opportunity to follow at the bedside the 
course of the more serious diseases with which they are 
to meet in after life. I myself was never offered the oc- 
casion of following a case of pneumonia or diphtheria or 
typhoid fever from beginning to end. Where then were 
the students of my day expected to gain this experience ? 
Where? Why on the unfortunate human beings who 
might fall into their hands during their early years of 
practice. And why was this so? Simply because stu- 
dents were not allowed in the wards of the hospital ex- 
cept as they followed an occasional visit. Now in this 
country there are hospitals enough and more than 
enough to supply valuable clinical experience to all 
physicians while they are yet in their undergraduate 
days. This opportunity is lost because the public does 
not understand. "What," says the hospital trustee, "do 
you fancy that I want students to attend me or the sick 
men and women under my protection?" "Student" to 
them suggests an irresponsible, inquisitive youth who is 
conducting perilous experiments. And the student is 
excluded from the wards. They do not understand that 
the student, as a clinical clerk in the ward, is nothing 
more than a trained assistant. They do not realize that 
the presence of such students is not an experiment; that 
the system of clinical clerks has been in existence for 
years in England to the great advantage of physicians 
and community. The student is excluded from the 
wards; and what is the result? The "protected" pa- 
tient enters the hospital, where he is under the direct 
charge of an interne, a recent graduate from a school 
where he has been denied the clinical advantages which 
he is now for the first time enjoying. He is, however, 
now in a position of considerable responsibility, for his 
busy chief can spare at the most an hour or two for his 
daily visit. He has many patients to care for, and little 22 
help in emergencies. lie does his best, and in the midst 
of his multifarious duties the early symptoms of the 
typhoid perforation are perhaps unobserved, or probably, 
as he has never seen a case before, unrecognized. The 
dreadful reality comes upon him when it is too late. The 
young physician has learned something that he will 
never forget; but the patient? The patient is dead- 
his one chance, that of an early operation, lost; sacri- 
ficed to the well-meaning charitable ignorance of the 
public. Suppose, on the other hand, that the patient 
enters a ward in which there are a number of medical 
students on duty as clinical clerks and presided over by 
a similar young physician, a recent graduate, but one 
who, in his school days, has had some months of practi- 
cal experience at the bedside. Under the watchful eye of 
the student who has but a few patients to follow, who is, 
as has been said, but an extra assistant, a trained assist- 
ant, the first suspicious symptoms are noted. The at- 
tention of the interne is excited. The blood is care- 
fully examined from hour to hour. The surgeon, early 
notified, joins in watching every change, and by a timely 
operation, the patient is saved. What a different picture! 
"Fancy," one may say? No. Experience; personal 
experience. How, under these circumstances, can the 
public object to the presence of the student? Solely be- 
cause of a word, because of the word "student," which 
means to them an irresponsible observer. As a busy, ac- 
tive assistant under the direction and orders of a trained 
superior officer, would the public object to his presence? 
The question is too absurd to ask. 
In these matters we as physicians must teach our non- 
medical friends. When they realize that the hospitals 
need medical students as trained assistants, as a part, 
really, of the staff; when they realize that the students 
need hospital experience to make them capable physi- 
cians; when they realize that they owe this training to 
the physician in order to protect themselves and the 
public; then and then only will the old opposition to 
the instruction of students in the wards of hospitals 
disappear. The prejudice against ward teaching is 
largely a matter of words, of one word, the awful word, 
"student," in its absurdly perverted popular meaning. 
And while, incidentally, praying to be ourselves deliv- 
ered from the tyranny of words, let us strive, each one 
as he can, to educate the public in this important mat- 23 
ter, to help forward the movement- which has already 
begun toward the more complete utilization of school 
by hospital and hospital by school. 
The mention of these few opportunities for public 
service, opportunities which come to us all as physicians, 
should but impress on our minds the thought with which 
these remarks opened, namely that the physician is, 
from the very nature of his calling, essentially a public 
character. And however modest may be our field of 
work, our responsibility should always be before us. On 
our learning, on our progressiveness, on our alertness, on 
our honesty, on our fearlessness, on our perseverance, 
hang not only our own welfare, but that of the general 
public, in other words, that of our country, in much 
higher degree than we often realize. It is a heavy re- 
sponsibility. Of much in the past we may be proud. 
There is much in the present on which we could improve. 
And the future? What shall that be? The answer lies 
with us. 
406 Cathedral Street. Snljn ©uttnn 
1868-1908 Minute Adopted at the Annual Meeting of the 
Interurban Clinical Club 
APRIL, 1909 
At the last annual meeting of the International Clinical Club 
John Dutton Steele was unanimously elected a member. He was 
the first addition to the six original members of the organization 
from Philadelphia. The happy anticipation with which we wel- 
comed him to our little group of fellow students was ended but 
a few weeks later by the news of his untimely death. 
John Dutton Steele was born in Sterling, N. Y., on Feb- 
ruary 21st, 1868. He was an exceedingly delicate child, acquiring 
early the cruel malady which left him with a permanent defor- 
mity- But it was soon manifest that he possessed unusual quali- 
ties of mind. He graduated from Williams College in 1888, and 
in 1893 from the medical department of the University of Pennsyl- 
vania, where he led his class and was awarded the alumni medal. 
After a service as interne at the Philadelphia Hospital he studied 
for a period in Germany and Austria. On his return he was 
made assistant demonstrator of anatomy, then instructor in medi- 
cine and finally Associate in Medicine in the University of 
Pennsylvania. He was clinical pathologist and later visiting 
physician to the Presbyterian Hospital. Always delicate, ham- 
pered by physical difficulties which might have discouraged many 
a man, Steele showed a courage, an enthusiasm, a persistence in 
his work, a never failing devotion to the highest ideals, which 
were most inspiring to his students and his associates, and enabled 
him to accomplish in his short life more than his share of good 
work- 
He was a member of the Philadelphia County Medical Society ; 
of the Medical Society of the State of Pennsylvania ; of the Ameri- 
can Medical Association ; of the Philadelphia Pathological Society. 
In 1905 he was made an associate member of the Association of 
American Physicians, and finally, on the thirteenth of May, 1908, 
he was elected a full member of the Association. But the malady against which he had so long contended had at 
last gained the upper hand. He was at this time a very ill man 
and died four days later at Wayne, Pennsylvania, on the seven- 
teenth of May, 1908. 
The value of Steele's life to the world is not to be measured by 
his work alone, good as it was ; it depends largely upon the influ- 
ence which, as a man, he exerted on all those with whom he was 
brought into contact. 
Steele possessed in high degree that peculiar gentleness and 
refinement and sweetness of character which is sometimes met 
with in those who have borne bravely and cheerfully a cruel 
physical defect or misfortune. The suffering that he must have 
endured, the difficulties that he had to overcome, served but to 
purify and refine and sweeten his character, to elevate his ideals, 
to sharpen his ambition. 
No student could have been more devoted, more wholly devoid 
of pettiness or jealousy, more generous or open in his work ; and 
those of us who knew him best can never forget the singular 
transparency and frankness and happiness of his countenance. 
No one could have failed to feel the inspiration which emanated 
from such a character. That Steele has left such memories as 
these to his friends and students is perhaps his greatest service. 
The story of his life and the tragedy of his death is told in a 
few words in a letter from one who knew and loved him well : 
"He was a very frail child, even up to the time that he spent 
at Williams College ; all this being due to his tubercular hip. 
They thought for many years, in his early and middle childhood, 
that he could not live. As he grew older, however, he gained 
rapidly in strength, and throughout it all, he was always as cheer- 
ful and optimistic as could be. As soon as he was able to do so, 
he went to work hard- Though he was always facing, in his own 
mind, the danger of a renewed outbreak, he was too devoted to 
the better kind of ideals to permit danger to stand in the way of 
his doing an amount of work that was, as he perfectly well knew, 
dangerous to him, and really ultimately took his life. In other 
words, he deliberately sacrificed himself upon the altar of his 
ideals / because he was not happy with the prospect of doing 
lesser things." To those who were nearest and dearest to him we/who had 
hoped to learn to know him better, desire to express oxir deepest 
and most heartfelt sympathy. 
His main publications are as follows : 
Tricuspid, mitral and aortic stenosis. Univ. Med. Mag., Phila., 
1896-'97, 200-202. 
(and J. H. Musser). A case of aneurysm of the abdominal aorta with 
thrombosis of the right renal artery. Internal. Med. Mag., Phila., 
1896-'97, V. 506-509. 
(and F. A. Packard). A case of sarcoma of the lungs with symptoms 
of Addison's disease with involvement of the suprarenal capsules. 
Med. News, Phila., 1897, LXXI, 329-333; also Tr. Coll. Phys. 
Phila., 1897, s. 3, XIX, 140-148. 
A case of renal tuberculosis. J. Am. M. Ass., Chicago, 1897, XXIX, 
325-327. 
A review of the literature of Koch tuberculin R. Internal. Med. Mag., 
Phila., 1897, VI, 756-761. 
(and Cattell, H. W.) Aneurysm of the right posterior aortic sinus of 
Valsalva with rupture. Internal. M. Mag., Phila., 1897-'98, VI, 
258-263. 
Echinococcus cyst of the liver. Tr. Path. Soc., Phila., 1897-'98, n. s. 1,106. 
Rupture of the aorta with flap-like deflection. Tr. Path. Soc., Phila., 
1897-'98, I, 241. 
(and J. H. Musser). The myocardium. Tr. Path. Soc., Phila., 1897-'98, 
n. s. I, 116-122. 
Anaemic and haemorrhagic infarct of kidney and spleen. Tr. Path. 
Soc., Phila., 1898, XVIII, 296-297. 
Some observations on the cortical nerve cells in pathology. Tr. Path. 
Soc., Phila., 1898, XVIII, 352-360. 
(and Musser, J. H.) Aneurysm of the abdominal aorta with thrombo- 
sis of the right renal artery. Tr. Path. Soc., Phila., 1898, XVIII, 
191-196. 
(and Eshner, A. A.) Tuberculous pericarditis. Tr. Path. Soc., Phila., 
1898, XVIII, 199. 
Glandular carcinoma of the stomach and peritoneum. Tr. Path. Soc., 
Phila., 1898, XVIII, 73. 
Obliteration of the gall bladder. Tr. Path. Soc., Phila., 1898, XVIII, 71. 
Localized intestinal hepatitis of syphilitic origin. Tr. Path. Soc., 
Phila., 1898, XVIII, 114. 
Some observations upon the lesions of the cortical nerve-cell in diph- 
theria. Tr. Path. Soc., Phila., 1898, XVIII, 352-360. Pleuritis in the newborn infant with the report of a case. Phila. 
Med. J., 1898, II, 557-562. 
Abscess of the liver and ulceration of intestine. Tr. Path. Soc., 
Phila., 1898, XVIII, 115. 
A case of renal tuberculosis. Tr. Path. Soc., Phila., 1898, XVIII, 
324-326. 
Tuberculosis of the supra-renal capsules ; pigmentary changes in the 
skin. Tr. Path. Soc., Phila., 1898, XVIII, 422-424. 
(and Arnoldt, J. P.) Masses of fibrin from the intestine. Tr. Path. 
Soc., Phila., 1898-'99, n. s. 2, 629. 
Two cases of chronic tuberculosis of the kidney. Tr. Path. Soc., 
Phila., 1898-'99, n. s. 2, 21-25. 
A critical summary of the literature on retroperitoneal sarcoma. 
Am. J. Med. Soc., 1900, CXIX, 311-326, 2 fig. 
(and J. H. Musser.) Some cases of dilation of the stomach. Am. J. 
M. Soc., Phila., 1900, CXIX, 125-140, 3 fig. 
Pathology of acquired heart disease in children. J. Am. M. Ass., 
Chicago, 1900, XXXIV, 1603-1607. 
The association of chronic jaundice with gastroptosis. Report of a 
case. Univ. M. Mag., Phila., 1901, XIII, 837-845. 
The present aspect of the antitoxin treatment of diphtheria. Thera- 
peutic Gazette, 1901, 3 ser. XVII, 439. 
The relation of the pancreas to diabetes. Phila. M. J., 1902, IX, No .5, 
suppl. 23-25. 
Gastroptosis and gastric motor insufficiency. St. Louis M. a. S. J., 
1902, LXXXII, 60-81, and Phila. M.J., 1902, IX, 174-181. 
A case of chronic interstitial pancreatitis, with involvement of the 
islands of Langerhans in a diabetic. Am. M. J. Soc., Phila., 1902, 
CXXIV, 71-76. 
An analysis of seventy cases of gastroptosis. J. Am. Med. Assoc., 
1902, XXXIX, 1173. 
Experimental evidence of biliary obstruction in floating liver. Univ. 
Penn. M. Bull., Phila., 1902-03, XV, 424-433. 
(and A. P. Francine.) The result of a year's observation of gastropto- 
sis. Penn. M.J., Pittsburg, 1903-4, VII, 464-468. 
(and A. P. Francine.) Two years' experience in gastroptosis. Univ. 
Penn. M. Bull., Phila., 1903-4, XVI, 350-362. 
Retroperitoneal sarcoma. Am. J. M. Soc., Phila., & N. Y., 1904, 
CXXVII, 939-966. 
Two cases of scarlatina morbili and one case of the so-called scarla- 
tiniform serum-eruption in diphtheria. Medicine, Detroit, 1904, X, 
409-516. Pleural effusion in heart disease. J. Am. M. Ass., Chicago, 1904, 
XLIII, 927-933. 
The tests for occult blood in the feces and their clinical significance. 
Penn. M.J., Pittsburg, 1904-5, VIII, 274-276. 
Additional observations upon retroperitoneal sarcoma. Tr. Coll. Phys., 
1904, XXVI, 26-39. 
(and Butt, W. R.) Occult blood in the feces and its clinical signi- 
ficance. Am. J. M. Soc., Phila. & N. Y., 1905, n. s. CXXX, 36-51. 
The detection of functional disturbances of digestion by the examina- 
tion of the feces. Med. News., N. Y., 1905, DXXXVII, 1158-1163. 
The therapeutical and prognostic value of occult haemorrhage in the 
stools. New York M.J. (etc.) 1906, LXXXIII, 125. 
Hyperesthesia of the gastric mucous membrane and its treatment. 
Therap. Gaz., Detroit, 1906, 3. s., XXII, 11-14. 
Hyperesthesia of the gastric mucous membrane and its treatment. 
Proc. Phila. Co. M. Soc., Phila., 1905-'06, XXVI, 403-408. 
Notes upon the clinical examination of the feces. Univ. Penn. M. 
Bull., Phila., 19O6-'O7, XIX, 109-112. 
Hyperesthesia of the gastric mucous membrane and its treatment. 
Medicine, Detroit, 1906, XII, 519-522. 
The relation of excessive gastric acidity to gastric symptoms. J. Am. 
M. Ass., Chicago, 1906, XLVH, 496-500. 
The nucleus test in pancreatic disease, Univ. Penn. M. Bull., 1906-'07, 
XIX, 235-240. Also Tr. Ass. Am. Phys., Phila., 1906, XXI, 346-358. 
Notes upon the clinical examination of the feces. Tr. Ass. Am. Phys., 
Phila., 1906, XXI, 796-803. 
Occult bleeding in typhoid fever. Tr. Ass. Am. Phys., Phila., 1906, 
XXI, 799-803. 
The etiology and treatment of chronic constipation. Internal. Clin., 
Phila. and Bond., 1906, 16. s , IV, 53-63. 
A case of poor digestion of muscle fibre due to reflex intestinal irrita- 
tion from chronic appendicitis. Tr. Ass. Am. Phys., Phila., 1906, 
XXI, 796-799. 
The method of determining the total amount of the fecal bacteria by 
weight and its clinical significance. J. Am. M. Ass., Chicago, 1907, 
XLIX, 647-649. 
Experimental observations upon the value of intestinal antiseptics. 
Tr. Ass. Am. Phys., Phila., 1907, XXII, 200. 
On the relation of pernicious anaemia to the digestive tract. Penn. 
M.J., Athens, 1908, XI, 680-682. NOTE ON PELLAGRA IN MARYLAND. 
By William Sydney Thayer, M. D., 
Associate 'Physician, Johns Hopkins Hospital. [From The Johns Hopkins Hospital Bulletin, Vol. XX, No. 220, 
July, 1909.] 
NOTE ON PELLAGRA IN MARYLAND.* 
By William Sydney Thayer, M. D., 
Associate 'Physician, Johns Hopkins Hospital. 
The recent recognition of pellagra in the United States, 
nay, the discovery that the disease is widespread in many parts 
of the South, would appear to justify a note on two character- 
istic cases of this disease which have apparently arisen in 
Maryland, the first that have been described here. Inasmuch 
as there are not many in the audience who have met with pella- 
gra, a few words as to the history, distribution and nature of 
the malady may be pardoned. 
The disease was apparently first recognized in the Asturias 
in Spain by Gaspar Cazal. Thierry,1 physician to the Duc de 
Duras, ambassador of France at Madrid, in a letter to the dean 
of the faculty of medicine at Paris in 1755, describes the 
malady as it appeared then in the Asturias, where it was 
known as mal de la rosa and acknowledges that much of the 
.information has been given to him by Cazal. 
Frapolli2 in 1771 refers to this affection in Lombardy where 
it was commonly known by the peasants as pellagra (pell'agra 
= rough skin). Pellagra was soon recognized in many parts 
of Northern Italy, while in France it was descried in " Les 
Landes " by Hameau.3 Although prevalent during the first 
half of this century in various parts of France, it has now in 
great part disappeared. The disease exists in many other re- 
[193] 
* Observations made at a meeting of the Johns Hopkins Hospital 
Medical Society, May 17, 1909. 
1 Description d' une maladie appellee mal de la rosa. Recueil 
periodique d' observations de medecine, de chirurgie, et de phar- 
macie, 2e edition, June, 1755, II, Paris, 1783. 
3 Animadversiones in morbum vulgo pellagram. 8°, Mediolani, 
1771. 
3 Cited by Gaucher. Maladies de la Peau. Brouardel et Gilbert. 
Nouveau Traite de Medecine et de Therapeutique. Fasc. XIV, 8°, 
Paris, 1909. Bailliere, p. 41. 
1 [198] 
gions-in Northern Portugal, the Austrian Tyrol, Dalmatia, 
Croatia, Bosnia, Turkey, Greece, Bessarabia, Kherson and 
Poland. It is said to have been recognized in Africa by 
Pruner in 1847. Sandwith4 in 1898 described the disease in 
Egypt. In the Western Hemisphere it exists in Mexico, 
Brazil, Argentine Republic, and is said to occur in the Barba- 
does and New Caledonia. Finally, within the last two years 
the occurrence of the disease in the United States has been 
recognized. The first mention of this malady in America is by 
Harris of Atlanta,5 who, in 1902, reported a case of uncina- 
riasis which presented symptoms simulating pellagra, a case 
which was unquestionably a complication of the two diseases. 
In 1907 Searcy6 reported an epidemic of acute pellagra in the 
insane asylum at Mt. Vernon, Alabama. In the same year 
Merrill,7 of Colorado, Texas, reported a case, and later J. W. 
Babcock 8 published an important note on the existence of the 
disease in the South Carolina State Asylum for the Insane. 
Since this time confirmatory reports as to the existence of 
the disease have been published by J. McCampbell,9 N. M. 
Moore,10 King,11 S. Leach 12 and Randolph.13 
[194] 
4 Pellagra in Egypt. J. Trop. M., Lond., 1898-9, I, 63-70, 1 Pl. 
5 Anchylostomiasis in an individual presenting all of the typical 
symptoms of pellagra. Am. Medicine, 1902, IV, 3, 99. 
' Epidemic of acute pellagra. J. Am. M. Ass., Chicago, 1907, 
XLIX, 37. 
7 A sporadic case diagnosed as pellagra. J. Am. M. Ass., Chicago, 
1907, XLIX, 940. 
8 Babcock. J. W., et al. What are Pellagra and Pellagrous In- 
sanity? Does such a Disease exist in South Carolina, and what 
are Its Causes? An Inquiry and Preliminary Report. Report to 
South Carolina Board of Health, 8°, Columbia, S. C., Dec. 30, 1907. 
9 Some observations on pellagra in this country with special 
reference to pellagrous insanity. Charlotte (N. C.), M. J., 1908, 
LVIII, 83-86. 
10 Pellagra: report of case, with remarks on etiology. J. Am. 
M. Ass., Chicago, 1908, LI, 1076. 
11 Pellagra with report of cases. South. M. J., Nashville, 1908, 
I, 289-293. 
12 A case of pellagra. Tr. M. Ass., Alabama, Montgomery, 446- 
452. 
13 Notes on pellagra and pellagrins: with report of cases. Arch. 
Int. M., Chicago, 1908-9, II, 553-568, 1 Pl. 
2 In October, 1908, a conference on pellagra was held under 
the auspices of the State Board of Health of South Carolina 
in Columbia, at which papers were read by N. M. Moore, E. J. 
Moore, J. J. Watson,14 J. L. Thompson, J. H. Taylor, John 
McCampbell, I. M. Taylor, H. E. McConnell, D. B. Frontis, 
G. A. Neuffer, B. A. Lancaster, M. Ray Powers, H. H. Griffin, 
E. M. Whaley and J. W. Babcock. These papers, most of 
which were published in the Journal of the South Carolina 
Medical Association, Vol. IV, November, 1908, have been col- 
lected in pamphlet form.15 Through the kindness of Hrs. Bab- 
cock, Watson, Williams and others I have recently had the 
privilege of observing a remarkable group of cases of this dis- 
ease in the State Hospital at Columbia as well as several in- 
stances from the surrounding country. 
The symptoms of this remarkable malady are so distinct 
that although there are probably many larvate cases, a charac- 
teristic example of this disease can scarcely be confounded 
with any other affection. 
Pellagra is characterized by symptoms of three main classes: 
(1) Those related to the alimentary tract. 
(2) The cutaneous manifestations. 
(3) The nervous and mental symptoms. 
Among the symptoms related to the gastro-intestinal tract 
are nausea, indefinite symptoms of dyspepsia, often vomiting, 
but especially diarrhoea which is more marked in the morning 
hours and often obstinate. 
One of the most characteristic symptoms is the stomatitis 
which may be extremely severe. The mucous membrane of 
the mouth is of a fiery red color. Eating and swallowing are 
extremely painful. Aphthous ulcers develop and often extend 
over large areas, patches of white macerated epithelium ex- 
foliating and leaving a raw, velvety, fiery red surface beneath. 
Salivation may be distressing. 
[1941 
141 have recently, through the kindness of Dr. J. J. Watson, 
had the privilege of reading the manuscript of a communication 
read by him before the Chester Co. Medical Society last fall, in 
which he discusses the disease on the basis of the study of one 
hundred cases in Italy and South Carolina. 
13 Conference on Pellagra, etc. 8°, Columbia, S. C., 1909, The 
State Co., Printers. 
3 [194] 
The cutaneous symptoms are highly characteristic. These 
begin with an erythema on the backs of the hands and, in those 
who go bare-foot, on the dorsa of the feet. The palms and 
soles are rarely affected. At the outset the manifestations 
consist simply of a slight blush which rapidly assumes a bril- 
liant red color like sunburn. The outlines of the patches are, 
however, as I have seen in several instances, rather sharply 
defined, more so than is usually the case with sunburn. This 
manifestation is always symmetrical. There may be a slight 
swelling of the affected areas. The blush, at first brilliant red, 
becomes soon of a deeper, more cyanotic color and may extend 
downward to the proximal interphalangeal joint, and upward 
to a point just above the wrist where it ends abruptly. The 
surface of the skin in these affected areas soon becomes dry, 
harsh and scaly, finally exfoliating in flakes or scales of con- 
siderable size or sometimes, especially about the edges, in finer 
bran-like particles. This dry exfoliating skin often becomes of 
a deep brownish color; cracks and fissures form. In severer 
cases, over the greater part of the backs of the hands there 
develop shallow bulls, containing serum or pus or sometimes 
blood. Large masses of epithelium exfoliate, leaving a raw, 
red surface. After exfoliation the denuded skin has a thin, 
atrophied appearance. It has often a glistening, shiny aspect 
with slight superficial wrinkles and cracks and a deep red 
color, looking somewhat like the first skin which is formed 
after a burn. In some cases the brownish discoloration of the 
exfoliating skin is considerable. Often the cracks and fissures 
are deep and haemorrhagic. In marked cases the skin over the 
dorsa of the last two phalanges becomes dry and of a deep 
brownish-red color, while the formation of bullae and exfolia- 
tion may extend even to these regions. Similar changes occur 
on the dorsa of the feet in those who go bare-foot, and in 
marked cases like manifestations may also be seen over the 
malar prominences, extending across the bridge of the nose so 
as to give rise to a butterfly or mask-like appearance. Occa- 
sionally, similar cutaneous changes may be seen about the neck 
as a collar. 
There can be no doubt that the rays of the sun have an 
influence in the production of pellagrous erythema, but while 
4 the protection of certain parts may control the appearance of 
these manifestations or change the shape of the patches of efflo- 
rescence, yet it can in no way be mistaken for an ordinary sun- 
burn. These changes appear at a time of the year when the 
rays of the sun are not particularly intense, and, again, 
Neusser16 has pointed out that in Roumania, the Gypsy chil- 
dren, who run about entirely naked, show a distribution of the 
lesions which is exactly the same. 
Nervous and mental manifestations are almost always pres- 
ent. Vertigo is common. The graver nervous symptoms are 
mainly referable to the spinal cord and point to varied and 
combined lesions. In severe recurrent cases there may be a 
general increase in the deep reflexes, especially, however, in the 
lower extremities. Well marked spastic symptoms may occur 
and in some instances disturbances of sensation and paralysis 
of the sphincters. In other cases the reflexes of the lower ex- 
tremities may be lost; those of the upper extremities increased. 
Anatomically, sclerotic changes are found, especially in the 
lateral columns of the dorsal cord, but lesions of the posterior 
columns are also not uncommon, and Sandwith 17 has described 
degeneration of posterior roots. An excellent account of the 
nervous manifestations of pellagra may be found in the 
" Referat " of Tuczek.18 
The mental phenomena of the disease are exceedingly inter- 
esting and are well summarized by Neusser.19 In the begin- 
ning of the disease there is, as a rule, confusion, weakness of 
judgment and will, feelings of anxiety, disorientation as to 
time and place, disturbances of the patient's disposition all 
the way from a slight depression to hypochondriacal fancies 
and suicidal tendencies. The patient is often silent; his ex- 
pression is dull and serious; he looks, as Dr. Watson has ex- 
pressed it, as if he had forgotten how to smile. There may be 
[1941 
[195] 
18 Die Pellagra in Oesterreich und Roumania. 8°, Wien, 1887. 
17 Three fatal cases of pellagra with examination of the spinal 
cord. J. Path. & Bacteriol., Edinb. & Lond., 1900-1901, VII, 460-464. 
18 Ueber die nervbsen Erscheinungen der Pellagra. Verhandl. d. 
Gesellschaft deutsch. Naturf. u. Aerzte, 1905, Leipz., 1906, I Theil, 
283-300. 
19 Das Krankheitsbild der Pellagra. Verhandl. d. Gesellsch. 
deutsch. Naturf. u. Aerzte, 1905, Leipz., 1906, I Theil, 251-269. 
5 [195] 
self-depreciation, delusions of persecution, self-accusation, re- 
fusal of nourishment. Often maniacal symptoms are observed 
in that the previously depressed and stuporous patients become 
suddenly emotional and restless. After such excitement the 
worn-out sufferers fall into an apathetic condition with, often, 
kataleptic phenomena. Hallucinations of sight and hearing 
are common. Mutism is apparently frequent. In the final 
stages the defects of intellect progressively increase, the mem- 
ory is lost and the patients become profoundly demented. In 
chronic and recurrent cases dementia is a common result. In 
Italy it is estimated that one-tenth of the cases become per- 
manently insane. 
The disease is met with hi two main forms; (1) as an acute 
typhoidal condition; (2) as a milder chronic, and commonly 
recurrent malady. 
In the first form the disease is acute and fatal, running its 
course in a few weeks with active delirium, fever and uncon- 
trollable diarrhoea. 
In the second form the disease may run a chronic course 
with relapses lasting, in some cases, as long as 25 years. The 
severer cases run, however, a much shorter course. With each 
relapse emaciation, anaemia and debility increase, and with the 
progression of severe nervous and mental symptoms the patient 
becomes profoundly cachectic, demented and bed-ridden, 
partly, as Neusser has said, because of weakness, partly 
because of changes in the cord. For an excellent discussion of 
the disease I would refer to the articles of Neusser (Op. cit.), 
Tuczek (Op. cit.) and Sturli,20 in the "Proceedings of the 
German Society of Naturalists and Physicians for 1905 " as 
well as to the " Precis " of Dr. Lavinder.21 A good account of 
the disease may also be found in Gaucher's fasciculus on dis- 
eases of the skin (Brouardel et Gilbert's "Nouveau Traite de 
Medecine et de Therapeutique. Ease. XIV. Maladies de la 
Peau." Paris, 1909. Bailliere). 
20 Ueber die Aetiologie der Pellagra. Verhandl. d. Gesellsch. 
deutsch. Naturf. u. Aerzte, 1905, Leipz., 1906, I Theil, 269-283. 
21 Pellagra. A Precis. U. S. Treasury Dept. Public Health and 
Marine Hospital Service. 8°, Washington, 1908. Government 
Printing Office. 
6 One of the most remarkable features of pellagra is its pecu- 
liar seasonal relations. The onset is generally in the spring 
months. In Italy this occurs in the early spring; during the 
summer the condition tends to improve with an occasional re- 
lapse or exacerbation in October, after which the symptoms 
ameliorate to disappear entirely by the new year. The patient 
may then seem apparently well, but in the succeeding spring 
another recurrence follows. This probably continues indefi- 
nitely, unless the conditions of living are changed for the 
better. 
In Italy, where the disease has been best studied, the num- 
ber of cases is really considerable. Pellagra exists, however, 
-only among the poorer classes. In Lombardy where the dis- 
ease is still very prevalent the number of cases in 1907 was 
estimated to be as large as from 3200-3500 out of a population 
of 543,961, i. e., one case in every 160-170 of the population, 
while the mortality from pellagra in 1907 for this province 
was 18.2 per 100,000 inhabitants. In Padova the death rate 
from pellagra in 1907 was 36.6 per 100,000 inhabitants which 
indicates an enormous number of cases in comparison to the 
population, especially when one considers that the mortality 
from the disease is only about 2.5 per cent. But the general 
■conditions in Italy are improving greatly under vigorous and 
well planned preventive and curative measures which have 
been directed toward (1) the exclusion of spoiled corn; (2) 
the education of the peasant in improved methods of agricul- 
ture; (3) the introduction of artificial dessicating plants for 
CQrn; (4) the erection of public store houses; (5) the estab- 
lishment of rural bakeries which furnish well-made wheaten 
bread to the peasants; (6) the establishment of corn exchanges 
where mouldy corn may be exchanged for good; (7) the 
founding of local hospitals and sanitaria; dispensaries and 
■economic kitchens for the distribution of proper food. 
There are in Italy 22 special hospitals (Pellagrossari) for 
the care of patients suffering from the disease." 
[195] 
231 have recently had the privilege, through the kindness of 
Dr. Babcock, of reading a remarkable and most valuable account 
of Pellagra in Italy-a report to the Dept, of State by W. Bayard 
Cutting, Jr., U. S. Vice and Deputy Consul. It is greatly to be 
7 [196] 
Many hypotheses have been advanced as to the nature of 
this remarkable malady. I can here only refer you to the 
abundant literature upon the subject. Especially valuable are 
the various articles of Lombroso to which full references may 
be found in the Index Catalogue of the Surgeon General's 
Library, while the recent article of Sambon23 contains many 
interesting considerations. 
Marzari24 in 1810 first called attention to the fact that the 
disease prevails especially among those whose main articles of 
diet are the products of Zea mats-Indian corn. Since this 
observation it has been shown clearly enough that there is a 
striking relation between the consumption of corn and the 
prevalence of pellagra. In those regions in Italy in which the 
disease is especially frequent the peasants live largely on a sort 
of corn mush called polenta and on soggy, heavy corn bread. 
The corn of which the meal is made is often harvested too 
early and stored under such conditions that it becomes com- 
monly spoiled or mouldy. There is good reason to believe that 
the prevalence of the malady is in some way connected with 
the consumption of spoiled or mouldy corn. In Italy the dis- 
ease is strictly limited to the poor; it is unknown among the 
ivell-to-do who exclude corn from their diet. While notable 
instances and small groups of cases have been reported in in- 
dividuals where the consumption of corn has not been proven, 
yet that there is a relation between the consumption or at least 
the culture (Sambon) of corn and this disease is accepted by 
the great majority of observers. Nevertheless, two active 
schools still exist, the Zeists, who believe that the disease is 
due directly to the consumption of maize, and the anti-Zeists, 
who deny this relation. Sambon (Op. cit.) who is inclined 
to doubt the relation of normal or diseased corn as an article 
hoped that this document may be published for the benefit of the 
public. I am indebted to Mr. Cutting's report for the figures above 
quoted. 
23 Brit. M. J., 1905, II, 1272-1275. 
24 Saggio medico-politico sulla Pellagra 1810, Venezia, presso 
Parolari. Reference taken from Osservazioni del Dr. Cerri, etc., 
intorno al saggio medico-politico sulla pellagra del Signor G. B. 
Marzari. Milano, 1811. 
8 of diet to this disease, suggests that, as it is the field laborer 
who is especially subject to pellagra, and as his neighbor in 
the city who lives under the same conditions is usually free 
from the disease, it may be that it is in the maize field that the 
peasant comes in touch with the specific agent of pellagra. 
The common belief is, however, that the disease is acquired by 
eating corn which, having been harvested too early and stored 
under conditions which favor the development of parasitic 
growths, has become contaminated with some organism or or- 
ganisms which, either through their own toxic products or 
through poisons produced by the decomposition of the maize, 
or both, gives rise in the consumer to the symptoms of pella- 
gra. The results of the campaign against pellagra in Italy, 
already referred to, tend strongly to support the general con- 
tention of the Zeists. 
Of the theories which have been advanced as to the nature 
of these poisons it will be impossible here to speak. Suffice it 
to say, that some, as for instance, Neusser,2' have suggested 
that poisons might arise from changes in healthy maize in the 
process of digestion; others, for example, Lombroso,2b believe 
that the poisons are chemical substances arising from the de- 
composition of the corn before its ingestion; others, to the 
products of changes produced by various special micro-organ- 
isms, and bacteria (Majocchi and Cuboni)27; or by moulds 
(Ballardini,28 Gosio and Ferrati,29 Ceni,30 Fossati31). 
Various observers believe that they have produced pellagra 
in human beings and in animals by the introduction of dif- 
[196] 
23 Die Pellagra in Oesterreich und Roumanien. 8°, Wien, 1877; 
Untersuchungen uber die Pellagra. Wien. med. Wchnsch., 1887, 
XXXVII, 132-135. 
26 Sull'eziologia e sulla cura della pellagra. Lav. d. Cong, di 
med. int., 1892, V, Milano, 1898, 160-186; for the complete refer- 
ences to Lombroso's numerous works on the question see Index 
Catalogue of the Surgeon General's Library. 
27 Referred to by Sambon (Op. cit.). 
28 Referred to by Sambon (Op. cit.). 
29 Sull'azione fisiologica del veleni del mais invasi da alcani 
ifomiceti; contribute all' eziologia della pellagra. Riv. d'ig. e 
san. pubb., Roma, 1896, VII, 961-891. 
30 Referred to by Sambon (Op. cit.). 
81 Referred to by Sambon (Op. cit.). 
9 [196] 
f erent products and extracts of diseased corn or of-organisms 
which have developed upon it, but most of these experiments 
would appear to be inconclusive. 
Before passing on to the report of my two cases let me pre- 
sent several photographs. The first (Photograph 1) is of a 
case of Italian pellagra in Lombroso's clinic, which was taken 
for Dr. J. J. Watson, of Columbia, who has most kindly al- 
lowed me to reproduce it. The general expression and the 
changes in the hands and face are rather striking. The sec- 
ond and third (Photographs 2 and 3) are of a remarkable case 
which Dr. Watson was good enough to show me several days 
ago. The man, an inmate of the almshouse, was a most strik- 
ing example of the disease, showing a marked stomatitis with 
salivation, a persistent diarrhoea, cutaneous changes on the 
hands and face of a high degree, as are beautifully shown in 
these pictures. The patient was exceedingly weak; the gait, 
spastic. There was a great increase in the deep reflexes in both 
upper and lower extremities; there was a double ankle clonus 
and dorsal flexion of the great toe on plantar stimulation. The 
patient was dull; the expression, serious and fixed; he an- 
swered questions slowly and in a peculiar monotone; but with 
these exceptions, there had been no definite mental symptoms. 
If now you will compare the brief description of the disease 
and these photographs with the account of the two cases which 
follow and the photographs of the second patient, whom I had 
hoped to present to you this evening, the identity of the con- 
ditions will, I think, be clearly evident. 
(1) On November 27, 1905, in skimming over a number of 
medical journals I happened to come across an article on pella- 
gra which I read with considerable interest. On the following 
day, with this article fresh in my mind, I was called to see 
Mrs. X., living about fifty miles from Baltimore. The patient 
was a lady 57 years of age, well-to-do and living in the best 
general circumstances. The history, exactly as I wrote it at 
the time, is as follows: 
Mrs. X. Aged 57. November 18, 1905. 
Family History.-Parents dead. On the mother's side there is 
an extremely bad history from the mental standpoint-all but one 
1 of her mother's brothers and sisters committed suicide following 
melancholia. In her own immediate family there have been no 
[197] 
10 cases of this sort. She has had five children; easy labors, and has 
always herself been a healthy woman with the exception of a 
very severe case of scarlet fever when a child and typhoid fever in 
1884. The daughter says that all her life she has been one 
who was rather susceptible to cold, living in a very hot house 
and fearing exposure. For six or eight years her daughter says 
that she has had a curious tendency to go to sleep, sometimes 
during conversation, often when she was playing cards writh her 
friends, and during the last two years her color has changed from 
a pink and white complexion to an extremely sallow, pale color. 
One year ago, she consulted a dentist, who refused to fill a tooth 
because he thought from the patient's appearance that she was 
" in the last stages of Bright's disease." 
Present Illness.-A year ago last June, she began to suffer with 
diarrhoea in the morning; would be waked up early in the morn- 
ing by a desire followed by very watery stool. Sometimes this 
was the only stool in the day, sometimes there would be several 
more. They were unassociated with pain. At about the same 
time she began to develop an aphthous stomatitis. Dr. Y. says that 
the appearances were characteristic, though the aphthous ulcers 
were rather numerous. At the same time the whole skin became 
rather dry, the backs of her hands especially, as her daughter 
expresses it, became " scaly just like the back of a fish." They 
did not burn and there was no other complaint excepting of 
soreness and cracking of the skin. After two or three weeks the 
condition of the skin of the hands and of the mouth cleared up 
and associated with this, the diarrhoea stopped and the patient 
was in tolerably good condition until October of the same year 
when a similar attack came on again. At that time the patient 
developed rather well marked mental symptoms, was depressed 
and at the same time rather hysterical. The diarrhoea was more 
serious; the hands were discolored, purplish brown, not exactly 
like an ordinary eczema; they were very dry and scaly. The 
mouth again became very sore and the whole attack lasted five or 
six weeks. By Christmas the patient was almost well and re- 
mained well up to the onset of the present attack. 
The present attack began six weeks ago (about October 1), the 
patient first becoming rather indifferent and manifesting a lack of 
interest in conditions about her, after which the mouth began 
to be very sore and burning again, the hands became scaly, red 
and rough on their backs and finally cracks and fissures appeared 
as well as large rather loose blebs containing pus, which ruptured 
spontaneously or on slight rubbing. The diarrhoea, which was 
sharp at first, lasted about two weeks since when it has dis- 
appeared, the patient having now normal movements, one a day. 
With this attack, however, the mental condition of the patient 
has grown steadily worse. She has been dull and drowsy and, at 
[197] 
(11) 1197] 
times, confused, talking at random and rather incomprehensibly 
to herself, and of late showing curious jerky twitching move- 
ments from time to time. 
Dr. Y. has examined the urine repeatedly and found it free from 
albumin, of a specific gravity averaging about 1015 or 1016. 
Micturition not especially frequent. The appetite up to the illness 
was good: since then it has been fair but she has been unable to 
eat as she would because of the great pain and burning on any 
attempt to take food. 
Status Prwsens.-The patient was seen at about quarter past 
nine in the morning; in bed lying on the right side. She was 
somewhat restless, moving her jaw frequently as if chewing and 
nervously moving her hands about under the bed clothes. The 
patient is of medium size, fairly well nourished, of a remarkably 
pale, sallow complexion with a mere suggestion of color in the 
cheeks. Lips and mucous membranes, rather pale, though not as 
pale as the color of the skin would suggest. The face has a 
remarkable expression; the forehead is wrinkled much of the 
time; the eyes, which are rather heavy, are often nearly closed 
in such a manner as to suggest that there is photophobia although 
at other times the patient looks directly out of the open window. 
There is slight lacrimation. There is no fulness above the 
clavicles. The face has a strangely cretinoid aspect. The skin 
is dry, ichthyotic in appearance especially over the trunk, rough 
to the feel; no sign of moisture anywhere. The hair is rather 
remarkably dry but not exactly lustreless. The patient talks to 
herself unintelligibly, at frequent intervals, and is confused and 
wandering, though now and then she answers sharp questions 
well. There are occasional sudden twitchings of the arms and 
trunk; the hands move about under the bed clothes much of the 
time. There was a curious tremor, somewhat like the movements 
one sees in Friedreich's ataxia. Pupils, equal. (I find unfortu- 
nately no note about the reflexes.) 
Pulse, 22 to the quarter, of moderate size; rather soft; regular. 
Respiration, 24. Lungs, perfectly clear on auscultation ahd per- 
cussion. No apparent enlargement of the heart; no accentuation 
of the second aortic sound. The abdomen is greatly and uniformly 
distended and everywhere tympanitic. Neither liver nor spleen 
is palpable. 
On the back of each hand the skin is dry, hard, cracked and 
scaly; in many places reddish-brown in appearance; in places 
discolored by old dry haemorrhage. In other places there are 
areas where the skin is white and loose, evidently the remains of 
recent bullae. This condition is uniform on both hands and 
extends down to the proximal inter-phalangeal joint. The deep 
redness of the skin, however, extends a little further down the 
phalanges. It does not extend above the wrist. The mouth shows 
(12) a high degree of stomatitis. There is a foul pungent odor to the 
breath. The lips all along the inner surface, show a layer of 
macerated loose white epithelium, and a similar layer covers the 
greater part of the tongue and the cheeks. On the hard palate 
the condition is much less marked. The mucous membrane is of 
a deep red color though not nearly as fiery red, according to the 
doctor, as it has been. Along the left leg in particular there are 
masses of exfoliated epithelium. There is no oedema. The legs 
are well developed, though not unduly thickened or large. 
In the region of the thyroid between the sternomastoids there is 
a hollow. There is no sign of thyroid either on inspection or 
palpation. 
I was immediately struck by the extraordinary similarity 
between this case and the description and picture of pellagra. 
The condition, as I remarked to the physician in charge, was 
indeed apparently identical. There was but one atypical fea- 
ture about the case, namely, the October relapse without a 
spring relapse in the same year. There were, however, several 
peculiar features in the history of the patient-namely, the 
striking change in the complexion, the drowsiness, the chilli- 
ness, the remarkable facies which had led the dentist to assume 
that she was " in an advanced stage of Bright's disease." 
These features taken in connection with the impalpability of 
the thyroid and the dryness of the skin suggested the possi- 
bility of hypothyroidism. It was accordingly determined to 
start treatment with thyroids, beginning with three 2-gr. 
(0.13 gm.) doses of dessicated thyroids a day. The change in 
the patient's condition was immediate and remarkable. I did 
not see her again, but the attending physician tells me that on 
the very day that the treatment was begun the patient passed 
for the first time a quiet night. For several weeks she con- 
tinued with this dose and then for several months took from 
four to five grains (0.26-0.33 gm.) daily. The improvement 
was rapid, the mental, cutaneous and gastro-intestinal symp- 
toms entirely cleared up, and since then she has remained quite 
well. The doctor, however, assures me that the patient has 
found that whenever she has tried to stop the thyroids, of 
which she is now taking two grains (0.16 gm.) a day, a sense 
of heaviness and'dulness has returned, so that he and she are 
convinced of the necessity of continuing the treatment.32 
[197] 
[198] 
32 " In regard to the present condition of the skin. The whole 
(13) [198] 
From the effects of the thyroid together with the symptoms 
above referred to it is not impossible that this is an instance of 
hypothyroidism; the mental symptoms might well be asso- 
ciated with this condition; but the cutaneous, the buccal, the 
gastro-intestinal manifestations were so striking that it was 
difficult to discard the suspicion of the existence of pellagra. 
This suspicion was strengthened upon the recognition of the 
disease in the South, and now, since I have become familiar 
with the disease, I have no hesitation in presenting the report 
of this case as a characteristic instance of pellagra. 
The patient, it should be said, ate the products of maize no 
more frequently than does any ordinary individual in this re- 
cutaneous surface is quite normal, and the harshness and dryness 
entirely gone. The hands are particularly soft and pliant. There 
is no discoloration or efflorescence. Her hands are rather smaller 
than they were five or six years since. This change in the skin 
began immediately with the improvement of the other symptoms 
and within five or six weeks they had entirely disappeared, the 
dryness and the efflorescence, and skin normal. 
There has never been any return of the stomatitis or diarrhoea. 
I am not sure that Dr. Thayer was fully impressed with one 
symptom that long preceded the others, was continuous with late 
developments, diarrhoea, stomatitis, trophic skin changes and dis- 
appeared synchronously with these and has never returned,-and 
that is her very notable somnolence. This was observed by many 
of her friends and neighbors. If she was playing cards she would 
frequently have to be wakened up when it came time for her to 
play. She would go to sleep in a crowded room, doze at the 
table-fall asleep at any and all times. 
In many respects her character is changed. She is more alert 
than I ever knew her and mentally active. Always having a sense 
of humor, she has developed some reputation for witticisms. She 
is very independent and rather aggressive. 
No statement can exaggerate the marvelous disappearance of 
her symptoms. She was apparently moribund when Thayer first 
saw her and I had abandoned all hope of her survival of more 
than a few hours. At 4 p. m. of that day she took 2% gr. of 
powdered thyroids. Her restlessness ceased at once-that is in 
two hours. She slept for ten hours and her intelligence fully 
returned in the morning. 
She has never been without the thyroids for more than a week. 
She fears to go longer, as she thinks the nervous symptoms begin 
to reappear."-(Quotation from a letter to me about this patient 
from Dr. Y., dated June 1, 1909. Editor.) 
(14) gion. May it perhaps be that the hypothyroidism rendered 
her unduly susceptible? Or may it be that in thyroids we 
have a valuable therapeutic agent. With regard to the latter 
question, Dr. Babcock tells me that he has used this substance 
in several cases without effect. The question as to the predis- 
posing effect of hypothyroidism is interesting. It is not im- 
possible that an affirmative answer may be justified. 
Ever since my observation of this case I have been on the 
lookout for further instances of the disease. It remained, 
however, for my colleague Dr. Finney to direct my attention 
to the second case, the first which has appeared at the Johns 
Hopkins Hospital, a patient who came to the Surgical Depart- 
ment on Friday, May 14, 1909. 
Case II.-M. J. S., Gen. No. 65,580, married, 35 years old, a 
driver. The patient comes to the Surgical Department of the 
Dispensary with the complaints that he "can't swallow"; that 
"it hurts to talk"; that his mouth and throat and hands are 
" sore." 
Family History.-Father died of tuberculosis, at 38; mother, of 
" inflammation of the stomach," at 37; two sisters and one 
brother are well; two brothers and a sister died in infancy. 
Has been married sixteen years. Wife living and well; three 
children living and well; five died "of marasmus" under three 
years of age. 
Past History.-The patient says he has always been delicate 
but never seriously ill. Chills and fever ten years ago. Appetite 
and digestion have always been good. Gonorrhoea at the age 
of 17, and, at the same time, a sore on the penis which was not 
followed by secondary symptoms. At one time he used to drink 
a great deal of beer; now, several glasses of gin a day. Smokes 
cigarettes constantly. Lives a rather irregular life, driving a 
whiskey wagon. The work is light; he takes care of horses and 
" drives a few orders a day." Two weeks ago he gave his horse 
several feedings of " chops " with which he mixed medicine' to 
make the horse " slick." This he mixed with his hands and to 
this act he ascribes his present illness. He denies eating corn 
bread, corn flakes or hominy. 
Present Illness.-Two weeks ago at about the beginning of May, 
about three days after feeding the horse with the medicated 
" chops," his hands became, as he expressed it, " chapbed," and 
several days later he applied a salve which he obtained from the 
druggist. Two or three days after this the hands " broke out in 
blisters " which broke, leaving the present condition. Three days 
after his hands became affected the lips and tongue became sore 
[198] 
(15) [1981 
and this soreness has spread back into his throat and is worse now. 
For six days it has been difficult to swallow. Since the onset 
of his illness he has vomited several times daily, often nothing 
but saliva, but he has been very nauseated and since his throat 
became sore it has been difficult for him to eat or drink. At the 
time when first seen the patient was rather thin but, in the 
main, a healthy looking man. There was a very marked stoma- 
titis; the tongue, lips and palate were fiery red as also were the 
gums and the mucous membrane of the mouth, where, in many 
places, over small and large areas, greyish-white masses of 
macerated epithelium were exfoliating. The hands showed a 
remarkable condition. The dorsa of the hands were of a deep 
brownish-red color covered with masses of dry scaly exfoliating 
skin; in some places evidently the remains of old bullae. The skin 
beneath was of a deep red color. This process extended to a point 
just above the wrists where it ended sharply, and to the proximal 
interphalangeal joint. Below this, over the phalanges, the skin 
showed a deep brownish-red pigmentation and in places a sug- 
gestion of the beginning of the formation of bullae; it was harsh 
and dry. The differences, however, in the stage and the degree 
of the process on the fingers below the proximal interphalangeal 
joint and the changes on the back of the hand were striking. The 
knee kicks were fairly active but not exaggerated. The patient, 
on questioning, stated also that he had had several movements of 
the bowels each day which were rather loose; he did not regard 
the condition as diarrhoea. The picture appeared to me to be 
typical of pellagra and the patient at his own request, was ad- 
mitted to the hospital. 
On entrance the temperature was 99.8° F.; pulse, 111; respira- 
tions, 20. At night the temperature rose to 101.7° F.; falling the 
next morning to 99° F. and rising to 100.8° F. on the evening of 
the 15th, to fall again to 99.5° F. on the morning of the 16th. 
The blood pressure was 115. The blood showed nothing re- 
markable in the appearance of the fresh specimen. The count 
showed red corpuscles, 3,864,000; leucocytes, 6400; haemoglobin, 
84 per cent (obviously a wrong estimate). 
Dr. Selling noted that the patient's face was sunburned and 
that his lips were reddened and bleeding in one or two spots. On 
removing some of the greyish macerated epithelium from the 
inner surface of the lips a raw red bleeding surface was left, 
and the whole area of the buccal mucous membrane was covered 
with similar patches varying in size from a pin head to a 
centimetre. The mucosa visible between these areas was very 
red and in places bleeding. The tongue showed, similar areas 
with marked pyorrhoea alveolarium. The lid slit of the right eye 
was a little wider than the left. Pupils, equal; reacted to light 
and accommodation. Posterior cervical glands were moderately 
[199] 
16 enlarged. Both epitrochlears were palpable, about the size of 
beans. Physical examination of the chest and abdomen showed 
nothing abnormal. There were no scars on the extremities, no 
nodes on the shins. Ophthalmoscopic examination was negative. 
On May 15, Dr. Sladen dictated the following description of his 
hands and mouth: " The patient's two complaints are the condi- 
tion of his hands and that of his mouth and throat. The hands 
are symmetrically affected and only on the dorsa where in a 
distribution as shown by the photographs, the skin is dry and 
desquamated, leaving as a remnant a smooth pink skin which is 
cracked in several places, particularly on the wrist and knuckles, 
and covered by haemorrhagic crusts. They look like skin after 
scalding. No particular pain is associated with them. On the 
dorsa of the fingers where desquamation has not taken place, 
the skin is thick, dry and raised in blisters, one of which is 
haemorrhagic. 
Mouth.-The lower lip is chapped and over the surface of the 
gums and soft palate the mucous membrane is fiery red and 
mottled with irregular patches of greyish-white membrane. These 
are on the under surface of the tongue also. As well as can be 
seen the pharynx and pillars present the same condition. There 
was well marked arteriosclerosis, the radials and brachials tor- 
tuous and thickened. Knee kicks were active; abdominal reflexes, 
present; the cremasteric also; the deep reflexes of the upper 
extremities were active. Mentally he was perfectly clear, rational 
and well oriented." 
The urine was yellow; slightly turbid; acid; specific gravity, 
1020; a trace of albumin, the sediment showing many pus cells 
and one granular cast. 
The patient had three stools the first day and two on the 
second. These were loose, of a brownish color separated into two 
layers, the upper fluid, the lower of semi-fluid, rather coarsely 
granular material. Nothing remarkable on microscopical ex- 
amination. 
Dr. Boggs on the morning of the 16th of May noted that there 
was " no induration about the margins of the lesions on the hand 
and very slight pigmentation about the upper edge. The horny 
layer of the skin is detached to the base of the nail of every finger 
and there is a slight haemorrhagic exudation. This layer is not, 
however, separated beyond the second joint of the finger except 
on the thumb where it extends almost to the nail and on the right 
side not quite so far. The palmar surface of the hands is 
perfectly free. The tongue is very smooth as though the super- 
ficial layers of epithelium were loose, of a bright red color " 
I came into the patient's room just as Dr. Boggs was leaving 
and, after describing the conditions on entry, made the following 
note: "... .The patient is in bed. Fairly healthy but rather 
[199] 
(17) (199] 
tired looking man; rather sparely nourished. Color of the lips 
and mucous membranes, good. Tongue and mucous membranes 
of the mouth are of an intense fiery red color. On the hard palate, 
buccal mucosa and gums there are everywhere masses of white 
macerated epithelium which in some places are hanging loose. 
The intense redness of the mucosa is very characteristic. There 
is a marked seborrhoea sicca of the scalp. The skin of the 
neck, face and trunk shows in other respects nothing remarkable, 
and the feet and legs are perfectly clean. The condition of the 
hands has changed considerably in the last two days. Much of 
the dry, brown superficial skin has exfoliated and to-day the dorsa 
of the hands show a deep red dry surface covered with thin 
glistening wrinkled scales and many deep, haemorrhagic fissures. 
These are especially marked at the left wrist and over the thumb 
on the same side but there are also deep bleeding fissures on the 
right, especially on the back of the wrist and over the metacarpo- 
phalangeal joint of the third finger. The exfoliative changes stop 
in great part at the first (proximal) interphalangeal joint, but 
on the left little finger over the second phalanx there is some 
dry exfoliating skin, and a loose bulla, in part haemorrhagic, on 
the third finger. On the index finger of the same hand the skin 
is raised by a slight, loose, wrinkled bulla. On the other fingers 
the skin is dry, hard, slightly reddish-brown in color. The 
palms of the hands are perfectly clean and the process on the 
dorsum is limited by a sharp line between the metacarpal bones 
of the little and third fingers, although outside this, the skin is 
dry and harsh and exfoliating in smaller bran-like scales. The 
deep redness is here not present. On the radial side of the hands 
the process stops a little beyond the middle of the thumb. 
The thorax is symmetrical; costal angle, under 90. Movements, 
aparently equal. Respiration perfectly clear. 
Heart.-Point of maximum impulse in the fifth space, just 
within the mamillary line. Sounds, clear. Aortic second a little 
louder than pulmonic second. 
Abdomen, natural. Spleen, not palpable. Liver, just below 
costal margin in the mamillary line, indefinitely felt. No special 
glandular enlargements although an occasional small soft gland 
is felt in the neck on both sides There is a slight reddening 
at the right elbow joint, probably from resting upon the elbow; 
the skin not harsh. There is no increase in the deep reflexes of 
the arms or legs; plantar stimulation is followed by plantar 
flexion of the great toe. Radial arteries rather thickened and 
distinctly palpable." 
While making this examination it was noted that the patient 
was somewhat restless, and appeared apprehensive, often raising 
his head from the pillow during the examination. When, toward 
the end of the examination something was said about bandaging 
18 his hands, he suggested that that be done immediately as he was 
obliged to go home on the following morning. When asked 
why he had to go, he said he must look after his horse. He 
was asked if some one else could not attend to this for him, to 
which he answered that his son who was there, could do it if he 
were there to tell him what to do, but that he should be obliged 
to go home for a few hours on the following day, after which 
he promised to return. He then suggested again that his hands 
should be bandaged now and that he could take off the bandages 
when he reached home, a suggestion which seemed rather point- 
less. He had a distinctly apprehensive look and his whole con- 
versation suggested slight mental confusion. 
Immediately after I left he was dressed in order that his photo- 
graph might be taken. He soon became exceedingly impatient, 
insisting that he must leave the hospital immediately and becom- 
ing very much excited. While the photograph was being taken 
he was exceedingly nervous and irritable, refusing to remain 
quiet, and immediately thereafter he insisted on leaving without 
further delay. After reaching home the patient talked wildly. 
He tried to find some liquor and accused his wife of taking it. 
He said that he had been maltreated in the hospital and that one 
of his friends had committed suicide with a cap pistol. He 
showed disorientation as to time, fancying that he had been at 
home once before during the morning. He was so obviously out 
of his mind that his brother tried to persuade him to go back 
to the hospital which he refused to do, but he was persuaded to 
go to St. Joseph's Hospital. I have learned since that he entered 
St. Joseph's Hospital in the evening. During the night he was 
delirious, got out of bed frequently, threatened other patients and 
was so noisy and obstreperous that he was put in a cell. He 
was very noisy and maniacal all night. On the following day 
when Dr. Hayward saw him he was very much confused. He 
did not know his name, nor did he realize where he was and 
seemed to think that he was at a place called " St. Michael's." 
The case was not regarded as a fitting one for a general hospital 
and he was taken home by his friends. On the afternoon of May 
25, I visited him at his house. He was then lying on a couch, 
looking perhaps a little thinner than when I last saw him. He 
had the same dull, rather sad expression. He spoke little but 
answered questions clearly though he -had rather a suspicious 
look. The stomatitis was somewhat better. The tongue was dry, 
very red but not quite as fiery as when last seen. The patches 
of exfoliating epithelium were less marked. The hands were 
bandaged so that I could only see the last two phalanges where 
[199] 
[2001 
19 [2001 
the skin had become of a much deeper brown color like that of 
the backs of the hands before its exfoliation. On the right malar 
prominence in a small area the skin was dry and harsh and a 
little brownish. 
In this instance the lesions of the hands and mouth, the 
diarrhoea, the mental symptoms form a picture too characteris- 
tic to admit of serious doubt as to the nature of the disease. 
Nothing could be more typical of pellagra than the whole com- 
plex of symptoms. 
The existence of pellagra in Maryland is no more than one 
might expect in view of the considerable number of cases wihch 
have been reported through the South. One important ques- 
tion naturally arises with regard to the recent recognition of 
pellagra in this country. Has the disease existed for a consid- 
erable period of time, or has it appeared for the first time 
within the last few years? The testimony of the physicians 
and nurses in charge of the State Hospital for (he Insane at 
Columbia, South Carolina, is perfectly definite upon this point. 
The disease has existed there for at least 18 years, and it is 
therefore probable that it must have existed unrecognized else- 
where. It would seem, however, very probable that the fre- 
quency of the malady has been increasing in the last few years. 
It is hardly likely that so many cases could have been passed 
by unnoticed. I feel quite sure that I myself have never seen 
a marked case of the disease before meeting with the first in- 
stance here reported. 
It is needless to suggest here that the appearance of pellagra 
is of very grave significance. The prevailing idea is that the 
disease is due to the consumption of spoiled or mouldy corn. 
The disease is really wide-spread in this country. It is ap- 
parently increasing. The products of corn are a most impor- 
tant element in the diet of all classes of society in this country. 
Is there not then perhaps reason to fear a serious increase in 
the prevalence of this malady? One interesting point is al- 
ready evident. In Italy where corn is eaten only by the lower 
classes the disease is absolutely limited to the poor. In this 
20 country I have heard within the last year of several acute fatal 
cases of the disease in individuals living under the best social 
and hygienic conditions as in my first case. It is most impor- 
tant that every one of us should be on the lookout for fresh 
cases of pellagra and further investigations into its prevalence 
and cause should immediately be undertaken. 
[200] 
21 1. A case of Italian pellagra in the clinic of Professor Lombroso at Turin. 
Observe the facial expression, the eruption on the hands and face. Photo- 
graph kindly lent me by Dr. J. J. Watson, of Columbia, S. C., for whom the 
photograph was taken. THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1909. 
2. A case of pellagra under the care of Dr. J. J. Watson, of 
Columbia, S. C. Note the facial expression and the eruption on 
the hands and face. 
PLATE XVI. 3. The hands of the patient in Plate 2. 
4. Case 2. Pellagra arising in Baltimore. Observe the facial 
expression and the eruption on the hands. THE JOHNS HOPKINS HOSPITAL BULLETIN, JULY, 1909. 
5. Hands of Case 2. The pigmented skin has in great part exfoliated. Observe 
the sharp outlines of the cutaneous changes and the deep fissures with haemorrhage. 
PLATE XVII. 
6. Larger photograph of hands in Case 2. Vol. XXIV 
Number 4 
POST-GRADUATE STUDY. 
389 
A point we have frequently noted is the coincidence of uterine 
retroversion, especially those cases with adhesions, and urethritis. 
We do not believe that the urethral and bladder condition is a 
result of the retroversion, but that the two are most frequently 
due to a gonorrheal infection. Anteflexion, per se, has not been 
considered a cause of this condition. 
In young women complaining of frequency of, or pain on, 
urination, without a history of instrumentation, or suspicion of 
gonorrhea, the thought of tuberculosis of the urinary tract should 
be considered. 
The frequency of neurotic or diabetic polyuria is to be dif- 
ferentiated from that due to local causes. 
In the treatment of chronic urethritis, the patients are given 
some alkali, as potassium acetate or citrate, tincture of hyos- 
cyamus, and often oil of sandal wood or copaiba. They are 
instructed to abstain from stimulating food and drink; to take 
quantities of water; and to forego sexual indulgence. Irriga- 
tions and instillations of the medicaments in general use, (po- 
tassium permanganate, boric acid solution, silver nitrate, etc., 
protargol and argyrol, etc.,) improve these patients to some 
extent, but a point is soon reached beyond which such treatment 
is of no benefit. We have had the best results from topical 
applications of silver nitrate 3% and 5%, every five to eight days, 
applied through a Kelly cystoscope, with the patient in the 
knee chest posture. The patient afterwards assumes the 
lateral, or dorsal position, when a catheter is introduced into 
the bladder to allow of the escape of air, and to instill two 
ounces of argyrol 15%, or protargol 2%. 
THE NECESSITY OF POST-GRADUATE STUDY. 
WILLIAM S. THAYER, M.D.* 
Professor of Clinical Medicine, Johns Hopkins Medical School, Baltimore. 
Mr. President and Gentlemen:- 
My position at this moment reminds me somewhat of that of 
a patient who last year consulted a good friend of mine, an 
oculist. My friend was testing his eye-sight, moving to and fro 
before his eyes on a graduated rod, a card upon which a cutting 
from the newspaper had been pasted, and asking him from time 
* Remarks made at the Annual Banquet of the Faculty of the New 
York Post-Graduate Medical School and Hospital, January 20, 1909. 390 
POST-GRADUATE STUDY. 
Post-Graduate 
Apr., 1909 
to time whether he could read the cryptic legend. Finally the 
patient who had repeatedly answered " No," started and 
replied with some vigor, " Yes, I can but it isn't true." " What 
do you mean," asked the doctor? " I mean what I said," said 
the patient; "■ I can read it but it isn't true." The doctor 
thereupon adjusted his glasses. Now I fancy you have all 
noticed that most oculists wear extraordinary glasses. The 
spectacles of this particular oculist contain a pair of large con- 
vex glasses which look like the head lights of an engine, and 
from the strange distortion of his eyes apparent to the observer 
who regards them from without, one is constantly invited to 
speculate as to what the appearance of the ordinary object 
must be to his unaided vision. The doctor adjusted his 
glasses and read, with some surprise, the following words. " It 
is time to pay * * *." But there is one essential difference 
between the position of this patient and that in which I now 
find myself. He denied the truth of the allegation, while I 
acknowledge the obligation in full, and, though painfully con- 
scious of its extent, I desire here to announce that not until I 
am driven to the last ditch shall I seek the protection of the 
bankruptcy act. 
It is a great pleasure to meet this evening the Director ..nd 
Faculty of one of the first bodies to recognize the value and 
importance of affording in America full opportunities for post- 
graduate work. Thirty years ago there were relatively few 
opportunities for the graduate who wished to pursue advanced 
study, or for physicians practising in distant rural districts who 
desired to come back to the city to refresh their minds and to 
learn of the advances in medicine. Men of the former class went 
for the most part to Europe, while those of the latter were too 
often regarded as more or less in the way, obstructions to the 
regular functions of the hospital and the medical school. How 
different are the conditions to-day! It is a matter of special 
pride to us in Baltimore that the Johns Hopkins University 
should also have recognized so early the importance of post- 
graduate instruction. When I first went to Baltimore, nearly 
twenty years ago, I found Osler and Welch and Halsted and 
Councilman and Kelly hard at work, surrounded by a group of 
active, enthusiastic post-graduate students. Of what value 
this post-graduate work has been, will be evident enough when Vol. XXIV 
Number 4 
POST-GRADUATE STUDY 
391 
I mention the names of a few of my colleagues during the first 
year or two that I was in Baltimore. There were Flexner and 
Barker and Howard of Cleveland, Clark of Philadelphia and 
Camac of New York, Blumer of New Haven and my dear 
friend, Lazear who gave up his life on the Yellow Fever Com- 
mission. But there were other men, men who had already been 
in practice in regions often far removed from laboratories and 
large clinics who had come back to prove themselves the superiors 
of many a man who had entered upon the study of medicine 
under far more promising auspices. I need only mention Walter 
Reed. 
But such an institution as yours has in the past and does now 
perform a much larger function than the mere instruction and 
help of individuals. It helps materially to remove the old idea 
so firmly fixed in the mind of the public as well as alas, in that of 
some medical men, that when a student receives his degree of 
" Doctor of Medicine " and passes his state examination he has 
reached a turning point in his career; he has ceased to be a 
student; he has become a physician. There could be no more 
false or fatal fancy than this. The graduation from college, the 
passa"0 of the stafe examination are merely mile stones in the 
life v l a student of medicine. When the turning point does come 
and alas, it does sometimes come, the point at which he ceases 
to be a student, it is but the inevitable beginning of a sure and 
progressive degeneracy. The physician must of necessity be a 
student all the days of his life and should keep his eye constantly 
open for the chance or the opportunity which may allow him to 
turn his back on the routine of his daily work and make the 
acquaintance and study the methods of new men. 
Again nothing is more damaging to the physician himself or 
to the medical community than the Chauvinism which is ever 
ready to arise and spread among a group of men who live and 
associate together. And the only way to prevent this is to mix 
among one's colleagues. A most valuable opportunity for this 
mixing is offered by the great post-graduate medical schools. 
I am sure that you gentlemen have found here in New York as 
we have in Baltimore, that the advantages of post-graduate 
instruction are as great to the instructor as to the student. 
Every year there come to us men who bring ideas and inspiration 
which to us are of inestimable value. One never knows from 
what country town another Robert Koch may emerge. 392 
THE ESSENTIALS OF SUCCESS. 
Post-Grad uatb 
Apr., 1909 
In conclusion, gentlemen, let me raise my glass to the long 
life and success of the New York Post-Graduate Medical School. 
May it ever serve as an inspiration to higher and better work, 
and may it continue to bring more closely together the phy- 
sicians of this and bther countries. 
THE ESSENTIALS OF SUCCESS IN A POST-GRADUATE 
SCHOOL.* 
BY J. GEORGE ADAMI, M.D., LL.D., F.R.S., MCGILL UNIVERSITY, 
MONTREAL, CANADA. 
You of the Post-Graduate Medical School of this city, the pio- 
neer institution of this order on either continent, may well 
gather enthusiasm by looking backward and seeing what you 
have accomplished during the last six and twenty years. You 
may well gather courage when you consider the difficult en- 
trance of your body into the w'orld, the precarious days of its 
infancy, and its present ripe maturity, with its huge body of 
earnest teachers, its imposing array of those taught, its build- 
ings and their environment, its status and the service it is ren- 
dering to the profession. And, most justly, may you pride 
yourselves when you look round and receive on this continent,, 
in Germany and in England that sincerest form of appreciation 
and flattery-imitation. 
During the last few days, knowing that I was to appear before 
you, I have been inquiring into the causes of your undoubted 
success, and, let me frankly admit it, our equally undoubted fail- 
ure at McGill in post-graduate work. What I shall have to- 
say regarding the results of the inquiry will be familiar enough 
to you, but by the recapitulation may be of some service in 
strengthening you to continue along the same good lines. We 
have abundant clinical material at Montreal, and our Faculty 
for now close on eighty years has so controlled the large gen- 
eral hospitals that there is no city on this continent in which 
the students have freer and more constant access to the wards, 
it is, indeed, that freedom of access and the abundant bedside 
study and instruction that has given to our graduates whatever 
standing they have attained. We, havediad a succession of able 
clinical teachers, sound physicians and sound surgeons'. We 
* Remarks made at the Annual Banquet of the Faculty of the New- 
York Post-Graduate Medical School and Hospital, January 20. 1909. FURTHER OBSERVATIONS ON 
THE THIRD HEART 
SOUND 
W I L L I A M S Y I) N E Y T HAYE R, M.D. 
BALTIMORE 
Reprinted from The Archives of Internal Medicine 
October, 1909, Vol. lh pp. 297-305 
CHICAGO 
American Medical Association 
Five Hundred and Thirty-five Dearborn Avenue 
1909 FURTHER OBSERVATIONS ON THE 
THIRD HEART SOUND 
WILLIAM SYDNEY TH A YE It, M.D. 
BALTIMORE FURTHER OBSERVATIONS ON THE THIRD HEART SOUND * 
WILLIAM SYDNEY THAYER, M.D. 
BALTIMORE 
At the last meeting of the Association of American Physicians1 I 
made a few remarks concerning the frequency, especially in young people, 
of a third heart sound heard in early diastole somewhere between one- 
tenth an d'tATwo*Hw uT\ > mTton^^f a second after the second sound of 
the heart, causing a characteristic protodiastolic gallop. This sound is 
especially common in the recumbent and left lateral postures and is more 
frequent in young individuals. It was pointed out that it was often 
associated with a palpable and sometimes even with a visible impulse, 
and this impulse was shown to be identical with the normal early dias- 
tolic elevation of the apex cardiogram. Further analogies were pointed 
out between this sound and that which characterizes the early diastolic 
gallop rhythm heard under various pathological conditions, especially in 
aortic insufficiency, in mitral stenosis and in adherent pericardium. Car- 
diograms and jugular tracings showed that the ascending limb of the 
protodiastolic elevation of the cardiogram corresponds with the descend- 
ing limb of the v wave of the jugular pulse, but when allowance is made 
for transmission time the apex of the protodiastolic elevation falls often 
on a slight rise described first by Hirschfelder as the h wave; this wave 
was present or indicated in a surprising proportion of my cases. 
During the past six months Dr. Peabody and I have endeavored to 
accumulate records of different forms of pathological gallop rhythm 
as well as of these instances of third sound in normal individuals with 
the view, if possible, of determining, first, the frequency of this phe- 
nomenon in the healthy man, and, second, its relation, if any, to the 
pathological protodiastolic gallop rhythm. While I am not ready at the 
present moment to enter into an extended discussion of the pathological 
gallop rhythms, there are certain points with regard to our observations 
which seem to me worth bringing up to-day. 
* Read before the Association of American Physicians in May, 1909. 
1. Thayer, W. S.: The early diastolic heart sound (the so-called third heart 
sound). Boston Med. and Surg. Jour., 1908, clviii, 713; Tr. Assn. Am. Phys., 
1908, xxiii, 326. 4 
I. THE FREQUENCY OF A THIRD SOUND IN NORMAL INDIVIDUALS AND THE 
CONDITIONS UNDER WHICH IT IS OBSERVED 
We have studied a limited number of healthy patients who had 
entered the hospital for trivial surgical complaints, a number of normal 
boys and girls of different schools, as well as a series of physically healthy 
individuals at the city jail.2 These observations have been in some 
respects rather surprising. I have examined altogether 231 consecutive 
individuals; in 65 per cent, of these subjects under the age of forty the 
third heart sound was present. This sound, however, is rarely audible in 
the erect posture; it is present commonly in the dorsal decubitus and is 
almost always clearer in the left lateral position, where the apex impulse 
is more evident. Its frequency varies in an interesting manner accord- 
ing to the age of the individual. The frequency with which the third 
sound was heard in these 231 individuals when arranged according to 
decades is shown by the accompanying table and chart (Fig. 1). 
Table Showing the Frequency of the Third Heart Sound in Two Hundred 
and Thirty-one Normal Individuals 
Decades- 
- 1 
2 
3 
4 
5 
6 
Cases 
39 
90 
55 
26 
14 
7 
Percentage of cases with 
third sound.. . 
58.9 
84.4 
50.9 
42.3 
14 
0 
It may then safely be asserted that the early diastolic or third sound 
is a normal phenomenon in a large proportion of young individuals. 
A further analysis of these cases shows that in every decade except 
the fifth, in which there were but 14 cases, the average pulse rate was 
somewhat slower among the cases in which the third sound was audible 
than among those in which it was not heard. 
Cardiographic and jugular tracings have been taken in a number of 
cases. In all instances these show a rather marked protodiastolic eleva- 
tion on the cardiogram. They do not, however, show as constant an h 
wave as was indicated in my early tracings. 
It may then safely be asserted that the early diastolic or third sound 
is a normal phenomenon in a large proportion of young individuals. 
II. WHAT IS THE CAUSE OF THIS PHENOMENON ? 
While these observations do not justify positive conclusions on this 
point, they have on the whole strengthened me in the feeling that was 
expressed last year that the sound is probably the result of a sudden ten- 
sion of the mitral valve occurring with the first inrush of blood at the 
2. For the privilege of examining these prisoners I am indebted to the courtesy 
and kindness of Dr. G. L. Wilkins. 5 
beginning of diastole. As has been previously shown, this sound is 
unquestionably coincident with the impulse associated with the first inrush 
of blood from auricle to ventricle; it is especially frequent in cases in 
which this impulse is unusually marked. 
One might, therefore, expect the sound to be audible in normal indi- 
viduals : 
Decades 1 2 3 4 5 6 
No. of Cases (39) (98) (55) (26) (14) (7) 
Percent. 
10.) 
90 
80 
70 
60 
50 
40 
30 
20 
10 
0 
Fig. 1.-Chart showing occurrence of a third heart sound' in normal indi- 
viduals. The uppermost line (A-A) indicates percentage of cases in which the 
sound was heard; the second (B-B) line, the percentage of cases in which the 
sound was heard in the dorsal decubitus; the lowest line (C-C), the percentage of 
cases in which the sound was heard in the erect posture. 
1. In positions in which the apex is especially accessible. 
2. Under circumstances in which the quantity of blood in the left 
auricle is large. 
But when we consider the conditions under which the sound is heard 
in normal individuals we find that it is best audible: 6 
1. In positions in which the apex is especially accessible-i. e., on the 
back and left side. 
2. With a rather slow pulse, which means a larger volume of blood. 
3. During the first slow beats of expiration where, beside the influ- 
ence of rate, we have the presence of more blood as a result of the 
increased aspiration into the lung during inspiration. 
Fig. 2.-Third heart sound (protodiastolic gallop). Normal heart. The 
upper tracing is from the jugular vein; the middle tracing is the apex cardio- 
gram; the lowest tracing is from the brachial artery. The timer registers tenths 
of seconds. 
Moreover, in pathological conditions one might expect the diastolic- 
impulse and sound to be more marked: 
(a) In conditions in which the quantity of blood entering the ven- 
tricle in diastole is exceptionally large. 
(b) Where the filling of the ventricle is unusually rapid. 
(c) Where the ventricle, owing to changes in the walls or a dimin- 
ished vascular tonus, is unusually distensible or dilated. 
Now (a) the conditions under which an increased quantity of blood 
enters the ventricle in diastole are especially aortic and mitral insuffi- 7 
ciency. In the former condition the third sound is present in most 
cases. 
With regard to mitral insufficiency I have been struck this winter by 
the frequency with which a slight dull sound is heard in early diastole, 
especially in those cases in which the heart's action is slow. Figures 4 to 
6 show the marked protodiastolic impulse in cases of gallop rhythm in 
aortic and mitral insufficiency. 
Figure 3.-Third sound (protodiastolic gallop). Normal heart. The upper- 
most tracing is from the jugular vein; the middle tracing is the apex cardiogram; 
the lowest tracing is from the brachial artery. 
Adherent pericardium (b) is the striking example of a condition in 
which the filling of the ventricle might be expected to be especially rapid ; 
but here the early diastolic sound and shock are characteristic. 
With regard to conditions (c) in which the tonicity of the ventricle 
is low and the walls might be easily distensible, as in patients after acute 
infections, it may be said that a diastolic gallop is generally regarded as 
common under these circumstances. I can not say that I have been as 
much struck with its frequency here as under some other circumstances, 
but it may well be that its absence in hospital cases in which the patients 8 
have been long in the recumbent posture is due to the fact that a large 
amount of venous blood has accumulated in the splanchnic vessels. 
In cases of dilatation of the left ventricle, which are commonly asso- 
ciated also with a relative mitral insufficiency, the condition is, as is well 
known, especially common. In all these conditions, with the presence of 
gallop rhythm, the protodiastolic elevation on the cardiogram is marked. 
With regard to mitral stenosis, in which, as is well known, a third 
sound is very common, the condition is not always analogous. In some 
Figure 4.-Protodiastolic gallop rhythm. Mitral insufficiency. The uppermost 
tracing is from the jugular vein; the middle tracing is the apex cardiogram; the 
lowest tracing is from the brachial artery. 
cases associated with insufficiency, in which the stenosis is not of high 
degree, the conditions, as has been pointed out, are such that similar 
manifestations might be expected, and this is the case. In others an 
opening snap, occurring apparently rather early, is audible without a 
definite protodiastolic shock. In cases of extreme stenosis it is possible 
that the tension of the valves giving rise to the sound may occur as 
a result of pressure from above in association with the diastolic relaxation 
of the ventricle, as was suggested by Potain. With this exception, how- 
ever, it seems highly probable that the normal and pathological early dias- 9 
tolic sounds are due to a similar phenomenon, at least in the great ma- 
jority of cases. This is borne out by the similar character of the sounds 
and their relation to the cardiogram and the jugular pulse. 
III. WHY IS IT THAT THE SOUND IS SO MUCH BETTER HEARD IN THE 
RECUMBENT POSTURE AND ON THE LEFT SIDE? 
Is it simply because of the greater accessibility of the apex? This 
seems to me hardly possible. If, however, we adopt the working hypothe- 
Figure 5.-Protodiastolic gallop rhythm. Mitral insufficiency. The uppermost 
tracing is from the jugular vein; the middle tracing is the apex cardiogram; the 
lowest tracing is from the brachial artery. 
sis that the sound is due to a sudden early diastolic tension of the mitral 
valve its greater frequency in the recumbent posture might easily be 
explained by the increased quantity of blood which must reach the left 
heart in this position owing to the more favorable conditions for venous 
flow. In connection with this question I have the distinct impression 
that the sound is more marked in individuals who have been in the erect 
posture and who lie down for the examination than in those who have 
been longer in the recumbent posture. In these cases the venous flow to 
the heart may well be increased on the first change of position owing to 10 
the elevation of the extremities, an increase which, after a time, might 
disappear as a result of the accumulation of blood in the abdominal ves- 
sels. In a few cases 1 have compared the heart sounds of patients in the 
dorsal decubitus with those heard when the legs and arms were held by 
attendants in an elevated position. The elevation of the extremities has 
seemed to me distinctly to increase the intensity of the sound. 
Figure 6.-Protodiastolic gallop rhythm. Mitral and aortic insufficiency. The 
uppermost tracing is from the jugular vein; the middle tracing is the apex cardio- 
gram; the lowest tracing is from the brachial artery. 
IV. WHY SHOULD THE SOUND BE MORE MARKED IN THE LEFT LATERAL 
POSTURE ? 
The answer to this would seem to be simple enough. The slight and 
almost constant difference between the frequency with which the sound 
is heard in this position and in the dorsal decubitus may well be accounted 
for by the greater accessibility of the apex and by the fact that the 
entrance of blood into the ventricle does not in this position take place 
against gravity. 
In addition to this it may be that the apex systolic murmur so com- 
monly heard in young individuals in the recumbent and especially in the 11 
left lateral posture, in perfectly normal hearts, may represent, in some 
instances, a slight functional mitral insufficiency, in which case the 
greater frequency of the sound in these positions would be easily 
explicable. 
In conclusion, these observations would seem to justify the following 
assertions: 
1. The third heart sound is present in the majority of young indi- 
viduals in the recumbent and left lateral posture. 
2. This sound may well be due, as first suggested by Hirschfelder and 
later, independently, by Gibson and myself, to the sudden tension of the 
auriculoventricular valves as a result of the first rush of blood from 
auricle into ventricle in diastole. 
3. Pathologically, the sound is especially frequent in conditions in 
which the quantity of blood entering the ventricle from the auricle is 
especially large; in which the diastole is unusually rapid; in which there 
is a lowered ventricular tonus or dilatation of the ventricle. The most 
striking examples of these conditions are aortic and mitral insufficiency, 
some instances of slight mitral stenosis combined with insufficiency, 
adherent pericardium, myocardial weakness and dilatation of the ven- 
tricle. 
4. A protodiastolic gallop, therefore, is not per se a pathological 
manifestation. 
400 Cathedral Street. REMARKS ON THE OCCASION OF THE DEDICA- 
TION OF THE NEW HALL OF THE COLLEGE 
OF PHYSICIANS OF PHILADELPHIA. 
By William Sydney Thayer, M. D., 
Associate Physician, The Johns Ho plcins Hospital, Baltimore. [From The Johns Hopkins Hospital Bulletin, Vol. XXI, No. 226, 
January, 1910.] 
REMARKS ON THE OCCASION OF THE DEDICA- 
TION OF THE NEW HALL OF THE COLLEGE 
OF PHYSICIANS OF PHILADELPHIA. 
By William Sydney Thayer, M. D., 
Associate Physician, The Johns Hopkins Hospital, Baltimore. 
To bring the greetings of the Medical and Chirurgical Fac- 
ulty of Maryland to its older sister, The College of Physi- 
cians of Philadelphia is an honor and a pleasure. But 
perhaps, after all, Tis not as a sister that it should greet you 
but rather as a child. For a large number, more than a 
quarter of the one hundred and one founders of our Faculty 
gained their inspiration in Philadelphia from study with 
men who were founders or members of this honorable insti- 
tution. And from that day to to this, we in Maryland have 
ever sought refreshment from the quickening current which 
has flowed from the lips of your students and philosophers 
and poets.. 
Among the charter members of our Society was John 
Archer who, in the year 1768, received from the College of 
Medicine of Philadelphia the first medical diploma awarded 
in America after a course of study; and Tis a significant fact 
that in the one hundred and ten years of the life of our 
Society nearly one-half of its honorary members have received 
their medical education in Philadelphia. 
In another sense Tis with a feeling of peculiar pride that 
one enters the abode of this most distinguished and repre- 
sentative body. Nowhere has the physician, from the begin- 
ning, occupied so important a position in the community as 
here. In the past the title Doctor of Medicine has had, in 
many regions, an humble significance. In Philadelphia, 
however, from the earliest times, the social sphere of the 
[11] 
(1) [ill 
physician has been larger and fuller than in almost any other 
spot in the world; and few, if any cities can point, among 
the annals of their practitioners and teachers and students, 
to so long a line of men of broad general culture, who have 
not only contributed to the advance of the science and art of 
medicine, but have been scholars in a larger sense and true 
leaders of men. 
Here in Philadelphia more than in almost any other city, 
physician has been synonymous with gentleman and scholar. 
And who more exemplifies what the physician may be, how 
many sided and diverse may be his interests and his influence, 
in science, in culture and in letters, than your honored 
member to whose fine words we listened but a few months 
ago in Osler Hall? 
The foundation of a body such as this in 1787 is a striking 
evidence of the character of the medical profession in Phila- 
delphia over one hundred and twenty years ago. How much 
this college has done to elevate and uphold the standards of 
medicine needs no comment. 
The library early became an important feature of your 
organization and the influence which this admirable collec- 
tion has had upon medicine not only in this city but in the 
country at large, is not to be overestimated. Next to the 
Surgeon General's Library, this institution is probably mainly 
to be thanked for a most honorable and I think one of the 
most characteristic features of the better American Medical 
Literature. I refer to that broad familiarity shown, almost 
always, by the investigator with the contributions to litera- 
ture of students from all parts of the world. The facilities 
offered for the study of the original communications of 
foreign authors by the accumulation of libraries such as this, 
and especially by the establishment of that inestimable bles- 
sing the Surgeon General's Library, have been of incalculable 
benefit to American medicine. It is largely through the 
opportunities afforded by these institutions and through the 
foundation of the Index Catalogue and the Index Medicus, 
that the American student has learned so well how and where 
to seek for the literature upon any question in which he is 
interested; and this knowledge and these opportunities have 
2 gone far toward delivering us from vain contentions as to 
priority as well as from that medical Chauvinism which is 
so dangerous an enemy of the cause of truth. 
At one of the earliest meetings of this college Benjamin 
Rush speaks thus of the benefits which may follow its founda- 
tion : " By stated meetings as a college we may promote 
enquiries and observations upon the prevailing diseases of 
the city. Here the timid may be encouraged and the san- 
guine may be taught to doubt." (What a happy phrase!) 
" Here the young practitioner may profit by the experience 
of the old, and the old by the boldness of enquiry, and modern 
improvements of the young. Here uniformity in principle 
and practice in medicine will gradually insinuate themselves. 
Nor will the advantages of our conferences end in the acqui- 
sition of knowledge. The heart will naturally interest itself 
in the pursuits of the head. Here friendships will be con- 
tracted and cemented, and occasional and unavoidable sus- 
picions or disputes may be accommodated by explanation or 
mediation. By these means we shall become not only the 
guardians of the honor of the profession, but likewise of 
each other's character." 
What words could better describe the advantages of a 
college of physicians! How well have the hopes of the 
speaker been fulfilled! 
What the physician was so early in this community, what 
this college has helped him to be in the century which has 
passed, that he is coming to be all over the world to-day. 
Bound by no " human creed," by no blinding faith or pre- 
judice of tradition, given over wholly to the search for truth 
and its application to the promotion of the welfare of man- 
kind, no human interest is foreign to the true physician. 
A broad sympathy born of a knowledge of the errors of the 
past and a full appreciation of the will-o'-the-wisps that 
beset us to-day, a devotion to the cause of justice and liberty, 
a tolerance full of pity for ignorance and the ills moral and 
physical which it bears, a hatred of superstition and intol- 
erance and an abhorrence of all influences which fetter or 
pervert the free moral and intellectual development of his 
fellow, these are sentiments which must animate and guide 
rm 
[12] 
(3) [12] 
him who devotes his life to the search for truth. And so it 
has come to pass that the physician who, in the past, was too 
often the humble servant of the ruling influences in the com- 
munity, social, political, religious, occupies to-day a position 
in the front rank not only of the army of students of the 
natural sciences, but of every great movement for liberty, for 
justice, for the elevation and emancipation of the masses- 
careless as ever of his life in the presence of pestilence, or of 
his worldly reputation in the face of entrenched prejudice 
and intolerance. What wonder is it that men whose lives are 
given over to such ideals should become leaders as well as 
servants of mankind! What wonder is it that among them 
there should develop now and again the rare powers of im- 
agination and expression which mark those great physicians 
whom we call poets! What wonder is it that out of our 
body should come a Holmes and a Weir Mitchell! 
This college has been in the past one of the noblest nurs- 
eries of searchers for truth, of men who have followed con- 
sistently the wise admonition of our poet: 
Take from the past the best its toil has won, 
But learn betimes its slavish ruts to shun. 
Pass the old tree whose withered leaves are shed, 
Quit the old paths that error loved to tread, 
And a new wreath of living blossoms seek, 
A narrower pathway up a loftier peak; 
Lose not your reverence, but unmanly fear 
Leave far behind you, all who enter here! 
May it ever serve to broaden and extend the horizon of 
the physician, to stimulate his love of beauty and truth and 
justice and liberty and tolerance, to bring him nearer to his 
fellow man, to give to the world wise and fearless counsellors 
and leaders! 
(4) ON THE THIRD HEART SOUND 
by 
W. S. Thayer 
Professor of Clinical Medicine, Johns Hopkins 
University, Baltimore. 
In their studies on gallop rhythm various obser- 
vers, notably Chauveau (Etude cardiographique sur 
le mecanisme du bruit de galop. These de Paris, 
8, 1902, No. 315) and Fr. Muller (Munch. Med. 
Wochenschrift 1906, LIII. 785), express the opinion 
that the elevations on the cardiogram, associated with 
the appearance of the sounds which characterize the 
so-called gallop rhythm are but pathological exagger- 
ations of waves which are present in the normal trac- 
ing - that the sounds which are associated with the 
presence of these exaggerated elevations are, there- 
fore, dependent on a pathological accentuation of 
normal phenomena. 
That the wave on the cardiogram which is char- 
acteristic of presystolic gallop rhythm is coin- 
cident with the jugular wave of auricular contrac- 
tion ( the "a" wave of Mackenzie) is a well known 
fact. Some observers have doubted that a sound 
could be associated with auricular contraction. 
Of the occurrence at times of such a sound there 
can, however, be no question. I have heard over 
the heart, a perfectly distinct sound in association 
with each auricular contraction in three cases of of auriculeventricular dissotiation, cases as to the 
nature of which there could be no possible doubt. * 
As to the cause of the protodiastolic elevation 
of the cardiogram, and the sound which is so often 
heart in conditions where this wave is exaggerated 
(protodiastolic gallop) there is more uncertainty. 
The opinion is, however, not uncormon that this form 
of gallop rhythm is indicative of graver cardiac changes 
than the presystolio gallop. 
My own observations lead me to agree with the views 
of Chauveau and Muller that the elevations of the car- 
diogram which are so evident in gallop rhythm represent 
the accentuation of normal incidents in the cardiac 
cycle. 
That, however, which I would emphasize particularly 
is that one form of gallop rhythm, namely, the proto- 
diastolic is, under given conditions, a normal phenomenon. 
To call attention to the fact that a proto-diastol- 
ic gallop rhythm is a common and normal phenomenon in 
young people is the main object of the few remarks 
which I shall make today. 
As has been set forth in previous publications. 
I have for years called attention to the fre- 
quency of a slight sound in early diastole in normal 
young people* 
1° This sound varies from a hardly perceptible 
soft thud, of lower pitch than the second sound, to 
a clear distinct sound nearly as loud as the second sound of the heart. It follows the second sound after 
a pause of somewhere between 0, 1 and 0, 21b seconds. 
It is always later than and distinct from the sec- 
ond part of a split second sound. 
2° It is, as a rule, audible only at the apex of 
the heart and just at this point; it is not to be heard 
at the base and rarely over the right ventricle. 
3° It is rarely audible in the erect posture. 
4° In the dorsal decubitus, however, it is extreme- 
ly common in voung people. 
5° It is, as a rule, best heard in the left later- 
al decubitus; in this position'the apex impulse is 
usually much more distinct* In individuals in whom the 
sound is present in the recumbent posture, it is often 
accentuated on turning into the left side, while, in 
some instances, it is audible only in this position. 
6° It has seemed to me that the sound is more 
readily heard in individuals who, having been in the 
erect posture, lie down for the examination, than in 
those who have been for sometime in the recumbent posture. 
7° In some cases, also the elevation by attendants 
of the arms and legs of an individual in the recumbent 
posture has a^peabed to increase or even to bring out 
this sound. 
8° The frequency of this third heart sound is re- 
markable, as may be appreciated by the following table 
which is based on the examination of 231 consecutive 
healthy individuals. Table showing the Frequency of Occurrence of 
the Third Heart Sound. 
Decades, 
1 
2 
3 
4 
5 
6 
'Cases, No., 
39 
90 
55 
26 
x4 
1 
Third Sound, 
58,9 
34,4 
50,9 
42,3 
14 
0 
If one may rely on these figures, the sound is 
then audible in over 50^ of healthy individuals under 
the age of thirty. It is especially frequent in 
healthy vigorous boys in the second decade. 
9° The sound is associated often with a palpa- 
ble, sometimes with visible shock, which corresponds 
on the cardiogram, to a well marked proto-diastolic 
elevation. 
10° The summit of this early diastolic eleva- 
tion corresponds on the simultaneously taken jugu- 
lar pulse, to a point toward the base of the cata- 
crotic limb of the "v" wave (Mackenzie}, or, when, 
allowance is made for transmission time, to a point 
a little beyond the base of this limb. 
11° The jugular pulse in these cases shows, 
often a slight elevation following the base of the 
catacrotic limb of the "V" wave. This elevation 
was first described by .Hirschfelder, (Johns 
Hopkins Hosp. Bull. Balt., 1907, XVIII, 265) and 
shortly afterwards, independently, by A. J. Gibson 
(Lancet, London, 1907, II, 1380.). The summit 
of the protodiastolic wave of the cardiogram which 
is coincident with the third sound, corresponds 
approximately to the beginning of the "h" wave. 12° The Third Heart sound has been described 
by Hirschfelder (op. Cit.) who at first regarded it as 
of right ventricular origin, and by Gibson (op. Cit. ). 
Both of these observers were struck by its association 
with the above mentioned "h" wave ("b",Gibson) in the 
jugular pulse. 
To what is this sound due? 
The cardio-plethysmographic studies of Yandell 
Henderson (Am. Jour. Physicol. Boston, 1906, XVI, 325) 
have shown that a greater part of the filling of the 
ventricles in diastole occurs rapidly immediately 
upon the opening of the auriculo-ventricular valves; 
this is clearly demonstrated by the diastolic curve 
of the cardio-plethysmogram which begins by a steep 
ascending limb followed by a more or less definite 
shoulder, after which the distention of the ventricle 
is often relatively slight, as is shown by a gently 
rising plateau followed by a moderate, abrupt elevation 
which coincides with the auricular contraction, and 
precedes immediately the steep descending limb of 
ventricular systole. So striking indeed, in this 
course of events that Henderson (op* Cit.) has sug- 
gested the division of the long pause of the heart 
into two periods, diastole and diastasis. 
Now the shoulder of the cardio-plethysmogram and 
the proto-diastolic elevation of the cardiogram corres- 
pond in time to approximately the same point on the 
t 
tracing of the jugular pulse i.e. a point near the foot of the catacrotic limb of the "v" wave. In other words, 
this point corresponds in time to the end of the rapid 
ventricular diastole. 
It has, accordingly, seemed to me that the most 
reasonable hypothesis for the explanation of this 
sound was the assumption of a tension of the mitral 
valves brought back into a condition of approximate 
closure as a result of the rapid filling of the ventri- 
cle, a tension sufficient to give rise to an audible 
sound. This hypothesis reached by me independently, 
was expressed previously by both Hirschfelder and 
Gibson, who ascribe the "h" ("b") wave of the jugular 
curve to a slight centrifugal impulse in association 
with a sudden tension of the tricuspid valves. 
The fact that conditions which ought to increase 
the auricular pressure such as the assumption of the 
recumbent posture and elevation of the extremeties, 
favor the appearance of the sound, as well as the 
circumstance that the phenomenon is especially well 
marked with slow action of the heart and during the 
first slow beats of expiration, would appear to sup- 
port this hypothesis. 
Several important questions immediately suggest 
themselves. • 
I. »'hy is the third sound so frequently heard in 
young individuals? ' 
2. Is 'this sound precisely analogous to that 
characteristic of proto-diastolic gallop rhythm in individuals whose hearts are obviously diseased? 
3. the hypothetical explanation equally 
satisfactory in these pathological conditions? 
With regard to the first question it has seemed 
to me that the greater frequency of the sound in the 
young was probably due to the greater accessibility of 
the apex of the heart, which, favouring auscultation 
renders this sound which is often of very moderate 
intensity, more readily appreciable. With regard to 
the second question it may be said that so far as 
our observations have gone, we have been unable to 
detect any essential difference between proto-dias- 
tolic gallop rhythm in normal and in pathological 
conditions, and that I am at present inclined to 
regard them as analogous phenomena. 
In connection with the third question it must 
be acknowledged that there is still need for 
careful clinical studies as to the exact conditions 
under which the different forms of gallop rhythm 
are found. At the present moment however the 
working hypothesis -which has been advanced above 
would seem to amply to the pathological conditions 
under which gallop rhythm occurs, as well as to 
the conditions existing in the normal individual . 
But it is not toward the hypothetical explanation 
of this phenomenon, a question which is more parti- 
cularly discussed in another communication (Further Observations on the Third Heart Sound. Paper 
now in press, to appear in Archives of Int. 
Med., Chicago, and in Trans. Ass. An. Phys. Phila., 
1909) that these remarks have been especially directed* 
That which it is desired especially to set forth may 
be summed up in a few sentences: 
I. A third heart sound, occurring shortly after 
the second sound and constituting a characteristic 
proto-diastolic gallop is heart with great frequency 
in young people in the recumbent and left lateral pos- 
tures. 
This sound is the rule rather than the exception 
in the first three decades of life. (Of the subjects 
examined in the first decade only one was under three 
years of age.) 
2. The sound is associated with a marked proto- 
diastolic elevation of the cardiogram which corresponds 
in tracings of the venous pulse, to a point near the 
base of the catacrotic limb of the "v" wave a point 
which coincides also in time with the shoulder on the 
ascending limb of the cardio-plethismogram of the dog. 
3. The most satisfactory hypothesis for the ex- 
planation of this sound would seem to be that advanced 
independently by Hirschfelder, Gibson and myself, name- 
ly the assumption that, as a result of the rapid ven- 
tricular diastole, the mitral valves, brought toward 
a position of closure, are thrown into a condition of 
tension such as to give rise to audible vibrations. It would seem on the whole probable that the 
sound heard in proto-diastolic gallop rhythm in 
obviously pathological conditions is due to a 
similar cause. This point, however, needs further 
investigation. 
4. It should, however, especially be emphasized 
that protodiastolic gallop rhythm is not per se a 
pathological manifestation. 
* Whether this sound is of muscular origin or 
whether it may, perhaps, be due to tension of the au- 
ricula-ventricular valves following a sudden increase 
of intra-ventricular pressure due to the auricular 
contraction, is a question which can not here be 
discussed. In this connection, however, it may 
be mentioned that in presystolic gallop rhythm the 
first heart sound is usually dull, prolonged and 
more or less devoid of that which is sometimes called 
a valvula quality. 
1° Tran. Ass. Am. Phys., Phila., 1906, XXI, 52; 
also, Am. J. M. Sc., Phila., 1907, CXXXIII, 249.- 
2° Boston M. S. J., 1908, CLVIII, 713-726 also, 
Trans. Ass.Am. Phys., Phila., 1903, XXIII, 326.- 
3° Archives Int. Lied., Chicago, 1909, now in print. 
Further Observations on the Third Heart Sound. 
o 
The summit of the protodiastolic elevation 
with vrhich this sound is apparently coincident, 
occurs usually about 0, 18 seconds after the shoul- 
der of the carefully recorded cardiogram. 3e Annee - N° 3. 
Mars ^910. 
ARCHIVES 
I) ES 
MALADIES Dll CIE UR 
DES VAISSEAUX 
ET DU SANG 
PUR LI EES SOUS LA DIRECTION DU 
D H. VAQUEZ 
Professeiir agrege A la I''acull6 <le Medecine de Paris, Medecin de I'hopilal Saint-Antoine. 
Redaction : D' Ch LAUBRY, D1 Ch. AUBERTIN, D1 Jean HEITZ 
EXTRAIT 
Quelques remarques 
sur le troisieme bruit du coeur 
PA K 
WILLIAMS THAYER 
Professeiir de clinique medicare a la John's Hopkins University, 
Baltimore, 
PARIS 
L1BBA1R1E J.-B. BAILL1EKE et FILS 
19, RUE IIAUTEFEU1LLE, 19 
19 10 QUELQUES REMARQUES SUR LE TROISIEME 
BRUIT DU CCEUR (1) 
PAR 
WILLIAMS THAYER, 
Professeur de clinique medicale & h John's Hopkins University, Baltimore. 
Au cours de leurs travaux sur le bruit de galop, quelques 
auteurs, et notamment Henri Chauveau (2) et F. Miiller (3), onl 
emis 1'opinion que les soulevements du cardiogramme, associes 
avec la presence des bruits qui caracterisent les soi-disant bruits 
de galop, n'etaient que des augmentations palhologiques d'ondu- 
lations existant sur les traces normaux. Ils en deduisaient 1'opinion 
que les bruits percus au moment de ces soulevements n'etaient 
eux-memes que 1'expression d'accentuations pathologiques de 
phenomenes essentiellement normaux. 
On est d'accord pour expliquer 1'un de ces soulevements, celui 
qui precede la systole ventriculaire, par la contraction auriculaire, 
celie-ci se presentant sur la courbe du pouls jugulaire an meme 
moment que ce soulevement (J. Mackenzie). Certains auteurs 
se sont demande si la systole auriculaire pouvait donner lieu a 
un bruit, et il semble bien que 1'existence de ce bruit du a la 
systole auriculaire ne soil pas douteuse. Il nous est arrive, 
dans trois cas de dissociation auriculo-ventriculaire (maladie de 
Stokes-Adams), d'entendre distinctement a 1'auscultation du 
coeur un bruit qui se repetait regulierement avec chaque contrac- 
tion auriculaire. 
Ce n'est pas ici le lieu d'aborder la question de la nature de ce 
bruit, de discuter s'il est d'origine musculaire, ou s'il est simple- 
ment 1'expression d'une mise en tension des valvules auriculo- 
ventriculaires a la suite de 1'augmentation soudaine de la pression 
intraventriculaire que determine la systole auriculaire. C'est tout 
au plus si I'on peut faire observer que, dans le bruit de galop 
presystoiique, le premier bruit du coeur a generalement un ca- 
(1) Communication faite au Congers international de medecine de Budapest, 
sept. 1909. 
(2) Etude cardiographique sur le mecanisme du bruit de .galop. These de 
Paris, 1902, n° 315. 
(3) Munch. med. Wochenschr., 1906, Bd. LI 11, 785. 2 
WILLIAMS THAYER 
ractere sourd, prolonge, et depourvu de ce qu'on a appele quel- 
quefois la qualite valvulaire. 
Pour ce qui est du soulevement proto-diastolique du cardio- 
gramme et du bruit qui accompagne si souvent Tang-mentation 
de ce phenomene (bruit de galop proto-diastolique), nous n'avons 
pas la m^me certitude. 11 y a cependant des observateurs qui 
envisagent le bruit de galop proto-diastolique comme un signe 
clinique d'une signification plus grave que le bruit presystolique. 
Disons de suite que nous sommes d'accord avec Henri Ghau- 
veau et avec Muller, et que nous considerons comme eux les 
soulevements du cardiogramme qui caracterisent le galop 
comme dus a 1'accentuation d'incidents normaux du cycle car- 
diaque. Il y a pourtant une consideration sur laquelle je vou- 
drais insisler ici, a savoir que I'unedes formes de bruit de galop, 
et precisement la forme proto-diastolique, nous apparatt, dans 
certaines conditions donnees, comme un phenomene normal, et 
e'est pour altirer 1'attention sur ce fait que le bruit de galop 
proto-diastolique est un phenomene normal et frequent dies les 
jeunes sujets, que nous avons ecrit ces lignes. 
Depuis plusieurs ann6es, comme nous 1'avons deja signale dans 
d'autres travaux (i), nous avons ete frappes, enauscultant le coeur 
de jeunes sujets, de lafrequence d'un leger bruit supplementaire 
qui se presentait au commencement de la pause diastolique. 
l.Cephenomenese presente dans les cas les moins marques sous 
la forme d'un bruit sourd, a peine perceptible, d'une tonalite plus 
basse que celle du deuxieme bruit du coeur. Chez d'autres sujets, 
cependant, il est tres distinct et atteint quelquefois une intensite 
presque aussi grande que celle du second bruit, qu'il suit a une 
distance d'environ 18 centimetres de seconde (2). 
2. Generalement, on ne 1'entend qu'a la pointe du coeur et 
exactement a la pointe. 11 n'est perceptible ni a la base ni au 
ventricule droit. 
3. On 1'entend rarement en examinant les individus debout. 
4. Il est, au contraire, tres frequent chez les jeunes sujets, 
auscultes couches sur le dos. 
(1) Trans. Ass. Am. Phys., Phila., 1906, XXI, 5 ; also Am. J. m. Sc., 
Phila., 1907, CXXXIII, 249. - Boston, med. and surg Journ., 1908, GLVI1I, 
713-726 ; also Trans. Ass. Am. Phys., Phila., 1908, XXIII, 326. - Further obser- 
vations on the thrid heart sound (Arch. int. Med., Chicago, 1909, IV, 297, and 
Trans. Ass. Am. Phys., 1909, XXIV, 71). 
(2) Le sommet du soulevement proto-diastolique du cardiogramme, synchrone 
de ce bruit, se trouve generalement suivre d a peu pres dix-huit centiemes de 
seconde le debut du plateau du cardiogramme, c'est-a-dire le moment approxi- 
matif de la cloture des valvules sigmo'ides. Il siege done a une periode telle 
qu'on ne peut le confondre avec le deuxieme son d un d^doublement du 
second bruit du coeur. QUELQUES REMARQUES SUR LE TROISIEME BRUIT DU ClEUR 
3 
5. Generalement, on le percoit le mieux quand le sujet se 
couche sur le cote gauche, position dans laquelle la pointe du 
coeur se rapproche de la paroi. Quand on remarque le phenomene 
chez un individu en decubitus dorsal, le bruit devient souvent 
plus distinct lorsque le sujet se tourne sur le cote gauche. 
Quelquefois meme on ne 1'entend que dans cette position. 
6. Il nous a semble que, lorsqu'on examinait les sujets, d'abord 
debout, puis ensuite couches sur le dos, le bruit etait percu plus 
frequemmentet aussi plus dislinctement que chez ceux qui etaient 
restes couches depuis un temps assez long. 
7. Dans quelques cas, 1'elevation, par un aide, des extremites 
d'un sujet en decubitus dorsal a paru augmenter ou meme 
faire apparaitre le phenomene. 
8. La frequence de ce troisieme bruit du coeur est assez grande 
comme on le verra par le tableau suivant, base sur 1'examen 
consecutif de 231 sujets bien portants. 
Tableau indiquant la frequence du troisieme bruit du coeur. 
Ages 
1 a 10 
10 i 20 
20 a 30 
30 5 40 
40 a 50 
50 a 60 ans. 
Sujets examines 
39 
90 
55 
26 
14 
7 
Frequence du 3® bruit. 
58,9 «/0 
84,4 •/. 
50,9 •/. 
42,3 •/. 
14 o/e 
0 •/.. 
D'apres ce tableau, le bruit supplementaire serait perceptible 
chez plus de la moilie des sujets bien portants au-dessous de la 
trenlaine. On le constaterait avec un maximum de nettete chez 
les garcons bien portants et vigoureux de dix a vingt ans. 
9. Le bruit est accompagne souvent d'un choc perceptible a la 
palpation, quelquefois meme visible, et qui se traduit toujours par 
un soulevement prolo-diaslolique marque sur le cardiogramme. 
10. Le sommet de ce soulevement proto-diastolique correspond, 
sur les traces du pouls jugulaire, a un point situe sur la 
descente catacrotique de I'ondulation v (Mackenzie), ou, si nous 
tenons compte du temps de la transmission, a la base ou meme 
un peu au dela de la base de cette derniere. 
11. On remarque d'ailleurs souvent sur les traces du pouls 
jugulaire de ces sujets un petit soulevement qui suit immediate- 
ment te~.de but de la descente catacrotique de I'ondulalion v. Le 
pied de ce soulevement correspond approximativement au som- 
met de I'ondulation proto-diastolique du cardiogramme, c'est-a- 
dire a la periode ou se manifesto le troisieme bruit du coeur. 
12. Ge bruit a ete egalement note dans des conditions nor- 
males par Hirschfelder (1), qui a pense d'abord qu'il prenait 
naissance dans le ventricule droit, etpar A.-G. Gibson (2).Ghacun 
de ces observateurs a decrit, independamment 1'un de 1'autre, 
(1) John's Hopkins Hospital Bull., Balt., 4907, XVIII, 265. 
(2) Lancet, Lond., 4907, II, 4380. 4 
WILLIAMS THAYER 
I'association du bruit proto-diastolique avec un meme soulevement 
remarquable du pouls jugulaire, ondulation h (Hirschfelder), 
ondulation b (Gibson). 
A quelle cause peut-on attribuer ce bruit proto-diastolique ? 
Fig- 1- - Troisieme bruit du cceur chez un sujet normal. Temps marque en dixiemes de seconde. 
Le trac6 sup^rieur est celui du pouls jugulaire ; le trac6 moyen, celui de la pointe du coeur; le trace 
inf^rieur, celui de l'artere brachiale. 
a = ondulation a; c = ondulation c; v - ondulation v; fl = ondulation h; P = soulevement proto- 
diastolique. 
Les etudes cardio-plethysmographiques de Yandel Hen- 
derson (1) montrent que le ventricule se dilate avec une grande 
rapidite au moment de 1'ouverture des orifices auriculo-ventricu- 
laires. La courbe diastolique du cardio-pl^thysmogramme se 
(1) Am. Jour. Physiol., Boston, 1906, XVI, 325. QUELQUES REMARQUES SUR LE TROISIEME BRUIT DU CCEUR 
5 
pr^sente sous forme d'une elevation tres rapide, presque verti- 
cale. Puis la dilatation du ventricule n'augmente plus que lente- 
ment et se traduit sur la courbe par un plateau tres legerement 
incline, etquise termine par une petite elevation qui correspond 
a la contraction auriculaire. Cette succession de phenomenes est 
si frappante que Henderson a eu 1'idee de diviser la pause du coeur 
en deux parties distinctes : la diastole et la diastase. 
Mais lemlateau de la courbe diastolique du cardio-plethysmo- 
Fig. 2. - Troisieme bruit du coeur chez un sujet normal. Temps marqu& 
en dixiemes de seconde. 
Le trace sup&rieur est celuidu pouls jugulaire ; le trace inoyen, celui de la 
pointe du coeur; le trac6 inf^rieur, celui de l'artere brachiale. 
a = ondulation a; c = ondulation c; v = ondulation v. 
gramme el le sommet du soulevement proto-diastolique du 
cardiogramme se rapportent approximativement au meme point 
du trace jugulaire, c'est-a-dire a la base de la descente catacrotique 
de Tondulation v. En d'autres mots, cette ondulation marque la 
fm de la premiere periode ou periode rapide de la diastole du 
ventricule. 
En partant de ces faits, il nous parait que 1'hypothese la plus 
plausible pour 1'explication du troisieme bruit du coeur est la 
suivante : le remplissage rapide du ventricule ^plie les valvules 6 
WILLIAMS THAYER 
mitrales, peut-etre aussi les tricuspides, encore-forme ee, d'ou 
mise en tension, laquelle serait assez brusque dans certains cas 
pour produire des vibrations sonores. 
Cette hypothese, a laquelle nous sommes arrives sans connaitre 
les travaux anterieurs, coincide d'ailleurs avec celle de Hirschfel- 
der et de Gibson. Ces auteurs regardent 1'ondulation 4(ou b pour 
Gibson) comme 1'expression d'une impulsion centrifuge precise- 
Fig. 3. - Cardio-plethysmogramme d'un chien (methode de Yandell Hen- 
derson) avec traces auriculaires (methode de Fredericq) et carotidiens. 
CP = cardio-plethysmogramme ; J = trace auriculaire droit ; C = trace 
carotidien; a = ondulation a;c = ondulation c; v = ondulation e; P = sou- 
Idvement proto-diastolique. 
ment due a une mise en tension soudaine des valvules auriculo- 
ventriculaires droiteS. Le fait que 1'intensite du troisieme bruit 
augmente par les influences qui peuvent accroitre la pression 
intra-auriculaire, telles que la position couchee et 1'elevation des 
extremites, le fait aussi que ce bruit se trouve plus marque 
lorsque le coeur bat lentement, et surtout qu'il se ralentit a la 
premiere phase de 1'cxpiration, constituent autant d'arguments 
qui paraissent hitter en faveur de cette hypothese. 
Voici cependant quelques questions qu'on pourrait se poser : 
1. Pourquoi observe-t-on ce troisieme bruit du coeur avec une 
telle frequence chez les jeunes gens? QUELQUES REMARQUES SUR LE TROISIEME BRUIT DU CCEUR 
7 
2. Ge bruit est-il bien vraiment celui qui caracterise le bruit de 
galop proto-diastolique observe chez des sujets souffrant d'une 
inaladie du coeur? 
3. Enfin cette hypothese explique-t-elle aussi les faits patho- 
logiques? 
Pour ce qui est de la premiere question, il semble qu'on 
pourrait expliquer la frequence de ce bruit chez les jeunes gens 
par les rapports intimes que presente chez eux la pointe du coeur 
avec laparoi, rapports qui, en facilitant 1'auscultation, permettent 
la conslatation d'un bruit quelquefois tres leger. 
Surle second point, je puis dire que, jusqu a present, ilnem'est 
pas arrive de pouvoir faire une distinction nette entre le bruit de 
galop proto-diastolique normal et le meme bruit pathologique. Je 
dirais meme que, pour le moment, j'incline a croire que ce sont 
la des phenomenes analogues en principe. 
En reponse a la troisieme question, il faut reconnaitre que nous 
manquons d'etudes cliniques precises nous renseignant sur les 
circonstances exacles dans lesquelles on rencontre chaque forme 
de bruit de galop. On parle d'habitude des bruits de galop en 
masse. Pour le moment toutefois, 1'hypothese avancee ci-dessus 
paraits'appliquer aussi bien aux bruits de galop proto-diastoliques, 
qui se presentent dans les conditions pathologiques, qu'a ceux 
qu'on rencontre chez 1'individu normal. 
Sans insister d'ailleurs ici sur le fondement de cetle hypothese, 
question deja abordee autre part (1), nous voudrions insister seule- 
ment sur les quelques considerations suivantes : 
1. Ghez les jeunes sujets bien portants, examines en decubitus 
dorsal^sur le cote gauche, on entend avec une grande frequence 
un troisieme bruit du coeur. Ge bruit suit de pres le deuxieme 
bruit, de maniere a constituer un bruit de galop proto-diastolique 
bien caracterise. 
2. La presence de ce bruit jusqu'a la trentaine est la regie 
plutot que 1'exception (2). 
3. Ce bruit est associe avec une exageration du soulevement 
proto-diastolique du cardiogramme. Sur la courbe jugulaire, il 
correspond a un crochet situe au pied de la descente catacrotique 
de 1'ondulation r, crochet qui est egalement synchrone duz 
plateau de 1'elevation diastolique du cardio-plethysmogramme. 
4. L'hypothese qui explique ce phenomene de la facon la plus 
satisfaisante parait etre celle d'abord emise par Hirschfelder et 
ensuite, independamment 1'un de 1'autre, par Gibson etpar^moi- 
(1) Trans. Jss. Am. Phys., 1909. XXIV, 11. 
(2) Parmi les sujets examines au-dessous de la dixieme ann^e, ce bruit 
n'existait que chez un seul enfant, de moins de trois ans. 8 
WILLIAMS THAYER 
mdme : a savoir qu'il s'agirait d'une mise en tension de la valvule 
mitrale, mise en tension qui se produit a la suite de la dilatation 
rapide du ventricule au commencement de la pause diastolique. 
5. Il n'est pas impossible que le bruit qui caracterise le galop 
proto-diastolique dans les etats manifestement pathologiques soit 
du a la meme cause. La solution de cette question demande 
cependantdes recherches plus precises. Il faut toutefois admettre 
que le bruit de g-alop proto-diastolique ne doit pas etre consi- 
dere d'emblee comme ph^nomene pathologique. 
9922-10. - Cobbkil. Iniprimerie GbStiI. ON THE COMMONER TYPES OF FUNCTIONAL 
CARDIAC MURMURS 
BY 
W. S. THAYER, M.D. 
BALTIMORE 
From the 
Transactions of the Association'of American Physicians 
1910 Reprinted from the Transactions of the Association of the American Physicians, 1910 
ON THE COMMONER TYPES OF FUNCTIONAL 
CARDIAC MURMURS. 
By W. S. THAYER, M.D., 
BALTIMORE. 
The question as to the significance of cardiac murmurs is often 
one of the gravest which is brought before the physician-and the 
surgeon. Examiners for insurance companies, medical boards of 
the army and navy, school physicians, surgeons on the eve of an 
operation, meet daily with individuals in whom there are detected 
cardiac murmurs of varying character unassociated with evidences 
of functional disturbance. And if, in the course of the examination, 
the patient gain knowledge that he has a cardiac murmur, the ques- 
tion as to its nature and significance is often referred to one or more 
colleagues of the original examiner. The experienced clinician, 
meeting with many such cases, learns soon to pass almost uncon- 
sciously over the commoner and more obviously unimportant of 
these murmurs, making, perhaps, no comment on them even in his 
private records-and is genuinely surprised to find that his younger 
and less experienced colleague is unfamiliar with that which to him 
is too obvious to mention. He forgets that it is only long clinical 
experience that brings confidence in such matters, and that under 
the imperfect methods of clinical instruction which have prevailed 
in the past, and, unfortunately, still prevail to a considerable extent 
in America today, a large proportion of physicians enter their pro- 
fession with a very limited practical experience. 
Upon the subject of "functional," "accidental," "anaemic," or 
"haemic" murmurs, as they may chance to be called, there is a large 
literature rich in observation, but especially rich in hypothesis. In 
many of the studies the hypothetical considerations have over- 
shadowed the clinical description. 2 
THAYER: FUNCTIONAL CARDIAC MURMURS 
It cannot be denied that there are many cases in which the sig- 
nificance of a murmur can be determined only by time and obser- 
vation. That, however, which seems to us to have been hardly 
enough emphasized is that there are certain clinical pictures of 
functional cardiac murmurs which are really rather easily recog- 
nizable. To consider some of these commoner pictures is the main 
object of the present communication. 
What is the significance of a cardiac murmur in general? By 
what mechanism are cardiac murmurs produced? Rather broad 
questions, one may say, and yet the questions may, for the most 
part, be answered in a relatively simple manner. The overwhelm- 
ing majority of cardiac murmurs are probably the result of fluid veins 
arising beyond a point of constriction, or just beyond a more or less 
fixed point, through which the blood passes into a vessel of consider- 
ably larger size, or capable of greater distention. At such points it 
is obvious from the simplest physical consideration that murmurs 
should arise the more readily, the more rapid the current, and the 
less viscous the fluid; and, moreover, that they should be transmitted 
in the course of the current. 
Nothing is simpler than the illustration of these points to a class 
by means of rubber tubes attached to a water tap. The character of 
the murmurs which arise with stenoses or insufficiencies of the four 
cardiac orifices are familiar enough to all, and the explanation of 
their manner of origin and conduction is simple enough. The man- 
ner of origin and the conduction of all the ordinary cardiac murmurs, 
with the exception of stenoses of the auriculo-ventricular orifices, 
may be illustrated remarkably well in the living dog's heart tube, 
and few demonstrations are more illuminating than the production 
of an artificial mitral insufficiency, where one may hear, on ausculta- 
tion, a soft systolic murmur at the apex of the left ventricle, while in 
the left auricle, immediately beyond the valves, there is a marked 
thrill and a murmur of the very highest degree of intensity. 
If it be easy to see why, in disease, murmurs arise, it is difficult, 
indeed impossible, to explain why, at certain points in the heart, 
murmurs are not always present in the normal individual. That, 
under ordinary circumstances, no murmur should be produced by 
the entrance of blood from auricle to ventricle, is perhaps not re- THAYER: FUNCTIONAL CARDIAC MURMURS 
3 
markable when one reflects upon the large size of the orifice-so 
large, after all, that auricle and ventricle represent in diastole prac- 
tically one cavity-and the relatively low pressure under which the 
blood passes from auricle to ventricle. But when one considers the 
normal emptying of the ventricle, the structure of the aortic and 
pulmonic rings, and that of the vessel beyond, the wonder is not 
that systolic murmurs at pulmonic and aortic orifices often occur, 
but, as has been well said before, I think by Dr. Broadbent, that 
they are not always present. A ventricle contracting with consider- 
able force, throwing a large quantity of blood through the fibrous 
ring at the root of the aorta or pulmonary artery, a ring which is 
practically indistensible, into a vessel beyond capable of great dila- 
tation-here we have elements which one might well fancy should 
produce always a relative stenosis sufficient to result in fluid veins 
beyond the point of relative constriction, i. e., the normal ring. 
That with a dilatable aorta, an unusually large quantity of blood 
thrown out of the ventricle with greater force through a normal 
ring may produce murmurs, and loud murmurs, is clearly shown in 
aortic insufficiency, especially in young individuals. How often, in 
such cases, a mistaken diagnosis of aneurysm is made is familiar to 
all clinicians. But, as we all know, there is a variety of conditions 
in which, without disease of the valves or muscle of the heart, 
murmurs are audible. Certain of these functional murmurs are 
so constant in their character as to be immediately recognizable. 
There are, it seems to me, at least three such clinical pictures. 
1. The basic, commonly called "pulmonary" systolic murmurs. 
These murmurs, which are usually rather soft in character, and 
generally associated with an element of the first sound, are best audi- 
ble in the third left interspace, but are often heard with less intensity 
all over the heart. If heard at the apex, they are usually limited to 
the recumbent position, disappearing when the patient stands up, 
while even at the base they are of considerably less intensity and 
may disappear in the erect posture. As pointed out by Janeway,1 
these murmurs are greatly intensified, often becoming loud and 
rough on forced expiration. On inspiration, however, they become 
- Trans. Assoc. Amer. Phts., 1896, xxi, 61. 4 
THAYER: FUNCTIONAL CARDIAC MURMURS 
feebler, and when the breath is held after a deep, full inspiration, 
the murmur usually vanishes. Such murmurs, absent at all other 
times, may be brought out in a considerable number of individuals 
by forced expiration. They are common in young people, and are, 
as a rule, unassociated with any other form of cardio-vascular abnor- 
mality. This phenomenon forms a fairly definite clinical picture, 
and may be recognized readily. 
2. Systolic murmurs limited to or heard with greatest intensity at 
the apex, but audible only in the recumbent posture. 
Murmurs such as these are very common in healthy young men 
and women. They are commoner, perhaps, in nervous or thin, 
emotional people, but are often found' in robust youths and girls. 
The murmurs may be very slight and feeble, or they may be fairly 
loud; they do not replace the first sound which in itself, is distinct, 
sometimes well defined, sometimes prolonged. The murmur may 
be transmitted for some little distance into the axilla, and is com- 
monly accentuated on the left lateral posture; indeed, it is not infre- 
quently heard only in this posture. On standing up, or sitting, the 
murmur entirely disappears. There is no further evidence of cardio- 
vascular defect. Such murmurs may be heard all over the cardiac 
area-sometimes they are loudest in the pulmonary area. In the 
erect posture, however, they clear up at the apex, leaving only the 
pulmonary systolic which, as has been said, disappears on inspira- 
tion. 
3. Cardio-respiratory murmurs. 
As is well known, there has been much discussion as to the fre- 
quency of murmurs arising in the respiratory tract, but dependent 
upon cardiac action, and suggesting, on cursory examination, a true 
endocardial sound. 
Potain1 sought to explain all non-organic heart murmurs by the 
cardio-pulmonary hypothesis. 
To the careful observer the existence of cardio-pulmonary mur- 
murs can hardly be a question of doubt. They form, however, a 
definite class and are usually easily recognizable. They are com- 
monly systolic in time, but rather late, occurring an instant after a 
1 Clinique m^dicale de la Charite, 8*, Paris, 1894, Masson. THAYER: FUNCTIONAL CARDIAC MURMURS 
5 
clear-cut first sound. They are often short and of a character 
different, on analysis, from that of the ordinary soft intracardiac 
murmurs. The important point is that they are limited to one 
phase of the respiration, disappearing, as a rule, when the breath is 
held. The commonest form is that which is heard with the several 
beats occurring during inspiration. In these cases careful attention 
reveals clearly that the murmur is simply an intensification of the 
respiratory murmur, and sharply limited to the period of ventricular 
systole. These murmurs are often more intense on effort with 
rapid, forceful, cardiac action, and on deep breathing. 
What is of special importance is the fact that they are often heard 
u'ith great intensity in the back. 
Cardio-respiratory murmurs are by no means limited to inspira- 
tion. They may occur at other phases of the respiration as well, 
and sometimes may be noticeable when the breath is held. In 
many instances, no matter at what phase of the respiration it may 
be present, a cardio-respiratory murmur may be recognized by a 
distinct difference between its timbre and that of the usual endo- 
cardial murmur-its superficial, short, rustling character, and espe- 
cially its lack of direct association with one of the cardiac sounds, 
which it accompanies rather than modifies. This may be appreciated 
by making a young individual take vigorous exercise and listening 
when his heart is beating rapidly and forcibly and the respiration is 
accelerated. Here, a short post-systolic whiff is riot uncommonly 
heard, usually during the middle of inspiration-a sound which, on 
careful study, is obviously of pulmonary origin. Familiarity with 
the commoner post-systolic cardio-respiratory murmurs may not in- 
frequently bring comfort and assurance to the examiner who meets 
with similar sounds at other phases of the respiration. 
One fact which again should especially be emphasized is that 
cardio-respiratory murmurs are not infrequently audible in the 
back, and may here give rise to serious misapprehension by the 
unskilled observer. 
Now, in addition to these three more definite types, there are 
observed in healthy individuals many cardiac murmurs which expe- 
rience and time may and do justify the clinician in regarding on the 
first or on later examinations as of functional character. The 6 
THAYER: FUNCTIONAL CARDIAC MURMURS 
judgment as to the significance of many of these sounds must be 
formed in the individual case. Such decisions are often of the most 
delicate and important duties which fall to the physician. 
In a general way, murmurs which are limited to a single phase of 
the respiration may be regarded as of no pathological significance. 
Soft systolic murmurs which occur at the apex as a slight whiff, after 
a first sound which seems clean-cut and of a normal character, in 
hearts which are of a normal size and without undue accentuation of 
the pulmonic second sound, may, as a rule, be regarded as func- 
tional, even if they do persist in the erect posture and on full inspira- 
tion. These cases, however, do not form a definite recognizable 
clinical picture, as in the three groups above mentioned. 
Again, there are instances in which systolic functional murmurs 
at the apex are present in the erect posture alone and absent in the 
recumbent posture. This condition, on which Potain insists, is, in 
the experience of the author, rare. In general, however, it may be 
said, with considerable assurance, that heart murmurs limited to a 
single phase of the respiration, or heard in one position of the body 
alone, are, in the great majority of cases, quite devoid of patho- 
logical significance. 
There are, however, other murmurs unassociated with essential 
and incurable cardiac lesions, which are commonly considered in the 
same class as those already mentioned. This does not seem to the 
writer fitting. He prefers to consider them apart, as they are, after 
all, associated with definite, though perhaps not serious, disease. 
Among these are: 
1. Those murmurs associated with anaemias of all sorts. These are, 
on the one hand, (a) soft systolic murmurs heard at the base, more 
commonly at the pulmonic than at the aortic orifice, but frequently at 
both. In these individuals the pulse is often large and soft, and the 
throbbing of the arteries is generally noticeable. (&) Systolic mur- 
murs at the mitral and tricuspid orifices: These murmurs are also 
soft and blowing, sometimes, however, largely replacing the first 
sound. They are not infrequently transmitted to the axilla, or even 
to the back, and the second pulmonic may be somewhat accentu- 
ated, while commonly the heart is slightly large. 
2. Systolic apical murmurs occurring especially in the course of 
an acute infectious disease (acute rheumatism, and typhoid fever THAYER: FUNCTIONAL CARDIAC MURMURS 
7 
especially), where, however, there may be relatively little anaemia. 
In these patients the first sound is usually dulled and may be wholly 
replaced by the murmur. Here, again, there is generally a slight 
cardiac enlargement; the murmur may be transmitted to the axilla 
and the second pulmonic may be slightly accentuated. These two 
conditions have been considered in a separate class because, al- 
though there may be no valvular disease, yet the slight enlargement 
of the heart, the enfeeblement of the first sound, the accentuation of 
the second pulmonic, the behavior of the heart on exertion, justify 
one in assuming the existence of a true weakness of the heart muscle 
with dilatation of the orifices and secondary mitral, and perhaps 
tricuspid insufficiency. The general condition of cardiac weakness 
and secondary mitral and tricuspid insufficiency form a picture per- 
fectly distinct from that presented by normal individuals with cardiac 
murmurs of the three first mentioned types with which we are con- 
cerned. 
Systolic murmurs are not uncommon at the apex in exophthalmic 
goitre. But here, again, there is generally a distinct cardiac en- 
largement, and there is much evidence to lead one to believe that 
these murmurs are the result of true insufficiency of the mitral ring 
dependent upon dilatation. 
Transient Aortic and Pulmonic Insufficiency. Before discussing 
the raison d'etre of these various functional murmurs, it may be well 
to say a word as to the occurrence of murmurs indicating aortic and 
pulmonary insufficiency in the absence of disease of the valves. 
Aortic insufficiency of muscular origin is only to be recognized by 
prolonged observation of the case. The writer has, however, met 
with a number of cases sufficient to convince him of its actual occur- 
rence. 
In two instances after typhoid fever he has seen the development 
and disappearance, with complete convalescence, of a characteristic 
murmur of aortic insufficiency, associated with slight cardiac enlarge- 
ment and a noticeably collapsing quality of the pulse. 
He has also met with a similar condition in two cases of exoph- 
thalmic goitre. Both of these cases are sufficiently remarkable to 
deserve a brief note. 
The first case was that of a trained nurse who, showing marked 8 
THAYER: FUNCTIONAL CARDIAC MURMURS 
symptoms of exophthalmic goitre, consulted me with regard to oper- 
ation. As there was evidently double mitral valvular disease, to- 
gether with an aortic insufficiency, operation was not advised. The 
wise patient, however, took matters in her own hands, and repaired 
to Dr. Olmsted, of Hamilton, who performed a thyroidectomy, 
which resulted in complete recovery. On examining the patient 
some six months later, I was surprised to find that all traces of aortic 
insufficiency had disappeared. This nurse has since then been doing 
active work for ten years. Last year I had the privilege of examining 
her again, and found evidence of old, double mitral disease in perfect 
compensation, but no signs of an aortic insufficiency. 
The second case was that of Mrs. S., aged thirty-eight years, who 
first entered the hospital in March, 1901, with distinct symptoms of 
exophthalmic, goitre. No cardiac abnormality was noted. She re- 
turned in June, 1905. At this time there was some irregularity of 
the heart and a slight systolic murmur all over the area. The cardiac 
apex impulse was 10 cm. from the median line. The urine showed 
a trace of albumin and a few hyaline and finely granular casts. 
Two years later, in November, 1907, the patient was seen again. 
Dyspnoea and oedema of the feet had come on nearly a year before 
and had been gradually increasing. She was anaemic; the pulse was 
collapsing and rather irregular, about 100. The heart was large, 
the apex impulse 12 cm. from the median line. There was a sys- 
tolic murmur heard all over the cardiac area, loudest at the base 
and transmitted upward into the carotids. A slight diastolic mur- 
mur was distinctly heard along the left sternal margin. The second 
pulmonic sound was accentuated. 
The patient entered the hospital, where she remained for nearly 
three months. Rest was followed by but little improvement. The 
heart increased in size, the apex impulse being recorded as 145 cm. 
from the median line. The urine showed a trace of albumin and 
a few hyaline and granular casts. 
In December and January a large part of the thyroid was re- 
moved in two operations. This was followed by some improvement, 
but the oedema never wholly disappeared. At the end of February 
she left for home, improved but in a condition far from satisfactory. 
At the time of departure the apex impulse was 145 cm. from the THAYER: FUNCTIONAL CARDIAC MURMURS 
9 
midsternal line. The systolic murmur was still heard all over the 
area, but the diastolic murmur was no longer audible. 
About nine months later the patient was again seen in Atlanta. 
She had improved in many ways, was able to walk about, and was 
free from oedema. The heart was somewhat irregular-about 100. 
There were no cardiac murmurs, but there was a slight proto- 
diastolic gallop at the apex. In October, 1909, a year later, she 
walked into my consulting room, apparently well. Her pulse was 
still a little rapid-about 100-and somewhat irregular. The apex 
was 2 or 3 cm. nearer the median line (11.5 to 12). There was a 
soft basic systolic murmur, barely audible, but no murmur at the 
apex and no trace of a diastolic murmur at the base or along the 
sternal border. The patient was seen again in June, 1910, after 
the reading of this paper; she remained in good condition. 
A most interesting case of similar character, following tonsillitis 
and polyarthritis, came under the observation of the author last 
year. J. L., a colleague and friend, consulted him on September 3, 
1909. He had been in bed for two weeks with polyarthritis following 
tonsillitis. He looked pale and worn out. The pulse was slightly 
abrupt, and the heart a little large. The apex impulse was in the 
fifth space, 9 cm. from the median line, and the dulness extended 
4.2 cm. to the right. There was a slight diastolic murmur in the 
aortic area and along the left sternal border, although the second 
aortic sound was fairly sharp. A year before, the writer had ex- 
amined the heart, finding no abnormalities. An endocarditis was 
feared. A month later, however, the heart was somewhat smaller. 
The pulse no longer collapsing, and the aortic murmur was wholly 
gone. Six months after this he was in good general condition. The 
apex was 8 cm. from the median line; a soft systolic murmur was 
heard all over the cardiac area in the recumbent position, disap- 
pearing at the apex in erect posture and at the base on deep inspira- 
tion. The diastolic murmur had remained absent. 
The observations of Hugh Stewart (unpublished observations) 
have proved the importance of the part played by the ring of muscle 
below the aortic valves in the closure of the orifice. And just as 
Stewart has been able to produce an aortic insufficiency by mechan- 
ical injury to this ring of muscle without lesion of the valves, so, in 10 
THAYER: FUNCTIONAL CARDIAC MURMURS 
some cases, it is but natural that a weak and diseased heart muscle 
should result in aortic as well as mitral insufficiency. 
Pulmonary insufficiency independent of valvular disease is also a 
condition commoner than has been generally recognized. It is met 
with, as Graham Steele has pointed out, in connection with cases of 
dilatation of the right ventricle usually following old mitral disease, 
and is associated with a soft diastolic murmur heard along the left 
sternal margin, in much the same area as that occupied by the mur- 
mur of aortic insufficiency; the murmur has also a similar character. 
One may suspect the nature of such a murmur by the absence of 
other signs of aortic disease (character of the pulse and of the second 
aortic sound at the base and in the carotids), the presence of marked 
dilatation of the right ventricle, and sometimes by the disappearance 
of the sound with improvement in the patient's condition. That 
such murmurs may be associated with dilatation of the pulmonic 
orifice in absence of aortic changes has been proved frequently by 
necropsy. Two cases of this character have already been demon- 
strated at our clinical and pathological conference during this term. 
It goes, however, without saying that these murmurs are indicative 
of pathological changes in the heart muscle-changes from which 
there may be improvement, and perhaps, indeed, actual recovery, 
as in some cases of exophthalmic goitre, or after acute infections. 
They do not, however, represent purely functional murmurs in nor- 
mal individuals. 
To return to the commoner forms of truly functional murmurs in 
normal individuals, viz.: 
1. The basic "pulmonary" systolic murmurs. 
2. The apical systolic murmurs disappearing in the erect posture. 
3. The cardio-respiratory murmurs. 
From careful observation we know that these murmurs have 
practically no pathological significance. Can we explain their 
appearance? 
As to the first form-the basic systolic murmurs over the conus 
or pulmonary artery-there are various possibilities. As has been 
said, the structure of the pulmonary artery and orifice, as w'ell as 
that of the aorta-a practically indistensible fibrous ring with a 
highly distensible vessel beyond-is such that it is remarkable that 
systolic murmurs are not always present. THAYER: FUNCTIONAL CARDIAC MURMURS 
11 
McCallum and the writer1 have observed that in dogs it is 
extremely easy to produce a systolic murmur just beyond the pul- 
monic ring, following haemorrhage. Here the excursions of the 
pulmonary artery were generally very large; in other words, the 
vessel was relaxed or the volume of blood thrown into the vessel 
with each systole was large. This was also true in cases where, 
after haemorrhage, salt solution had been infused. Under these 
circumstances also the ventricular action appeared to be rather 
abrupt. Now, in anaemia in general there is a rather low' blood 
pressure. Furthermore, the changes in the blood itself might be 
expected to favor the appearance of murmurs (diminished specific 
gravity and viscosity). Especially important, however, are the 
observations of Plesch,2 w'ho has shown that in anaemia the rate of 
blood flow7 per minute is greatly increased; more than this, the 
volume of blood thrown into the vessels with each ventricular con- 
traction is larger than under normal circumstances. The conditions, 
then, which are present in anaemia-increased quantity of blood 
thrown with each systole through the aortic and pulmonary rings, 
which, as has been said, are more or less indistensible, the changes 
in the blood itself, and the relaxed condition of the vessels-are 
exactly those which one might postulate for the production of basic 
systolic murmurs. 
The explanation, then, of many systolic murmurs in aortic and 
pulmonic areas in anaemia is simple enough. 
It is a question, how'ever, whether any of these conditions play a 
part in the production of the basic murmurs so common in healthy 
young individuals. It is significant that these murmurs are heard 
best on the left side of the sternum, and in the third space, rather 
below the pulmonary orifice. It is also remarkable that they are 
increased or induced by expiration, and diminished or obliterated by 
inspiration. These facts suggest another explanation. 
Now, McCallum and the writer observed that in dogs with an 
exposed heart it is extremely easy to produce a murmur by very 
1 Experimental Studies on Cardiac Murmurs, Amer. Jour. Med. Sci., Philadelphia and New 
York, 1907, cxxxiii, 249. 
2 Sauerstoffversorgung und Zirculation in ihren Kompensatorischen Wechselbeziehungen, 
Verhandl. d. XXVI Kong. f. inn. med., Wiesb., 1909, 299; also, Bestimmung des Herzsch- 
lagvolumens, Deutsche med. Wochenschrift, 1909, xxxv, 239. 12 
THAYER: FUNCTIONAL CARDIAC MURMURS 
slight pressure on the conus arteriosus with the bell of the stetho- 
scope. Such pressure resulted in a thrill and murmur beyond this 
point. May it not be, then, that the pressure exerted by the chest 
wall against the pulsating conus arteriosus may often be sufficient 
to result in such a murmur? With inspiration the interposition of 
a cushion of air-containing lung equalizes the pressure, removes the 
cause, and the murmur ceases. With age and increased volume 
of the lungs the murmur is less frequent. This hypothesis, while 
unproved, has seemed to me that which is most applicable to the 
condition. Janeway,1 in a discussion of our paper, calls attention 
to the frequency of expiratory systolic murmurs at the base, and 
suggests pressure as a cause. 
The cause of the cardio-respiratory, inspiratory systolic murmurs 
is obvious enough. The reinforcement of the inspiratory murmur 
with each systole is due to the accentuation of inspiration during 
ventricular contractions, and the sound dependent on this ought 
to be more marked, the more forcible and abrupt the contraction and 
the larger the quantity of blood expelled. As has been said, exercise 
may and often does exaggerate this phenomenon. 
As to the cause of the systolic apical murmurs heard in the 
recumbent and left lateral posture, the writer can only express an 
opinion in agreement with that of Henschen,2 but unsupported by 
experimental evidence. He has always regarded these murmurs as 
indicative of a true mitral insufficiency because of the location in 
which they are heard, because of their occasional transmission out- 
ward, and because of the general similarity of the sound to that heard 
in true mitral insufficiency. Such a mitral insufficiency dependent 
on position alone, if it be a mitral insufficiency, is, however, a per- 
fectly normal phenomenon. 
Whatever the cause of these phenomena, it seems to him that these 
three forms of murmurs-(a) the basic systolic murmurs increased 
on expiration, (6) the apex systolic murmurs limited to the recumbent 
posture, (c) the cardio-respiratory, inspiratory systolic murmurs- 
form three clinical pictures which are fairly distinct and apparently 
of no pathological significance. 
1 Trans. Assoc. Amer. Phys., Philadelphia, 1906, xxi, 61 
2 Ueber systolische functionelle Herzgerausche C. r. XVI Cong. int. de m6d., Budapest, 
1909, vi, M^d. interne, fasc. I, 221. THAYER: FUNCTIONAL CARDIAC MURMURS 
13 
Frequency. How frequent are these murmurs in normal indi- 
viduals? Basic systolic murmurs are, as is known, extremely com- 
mon. It would be interesting to know how often it might be possible 
to produce these murmurs by forced expiration in a given number of 
individuals. The writer, however, has no figures to offer based on 
any large number of observations. 
Cardio-respiratory Murmurs. Cardio-respiratory murmurs, of the 
kind of which we have spoken, are not rare, but by no means as 
frequent as the last mentioned class. 
A point of particular interest and importance is the frequency with 
which systolic apical murmurs of undoubtedly functional character 
are audible in practically normal individuals. 
Last year the writer had occasion to examine a large number of 
healthy young people in connection with studies of the third heart 
sound. In all these individuals special note was made as to the 
presence of systolic murmurs disappearing in the erect posture. Of 
218 cases in the first four decades of life, 73, or about one-third, 
showed systolic murmurs at the apex in the recumbent posture, 
murmurs which disappeared in the erect attitude. As a rule, these 
murmurs were heard all over the cardiac area, but loudest at the 
base in the pulmonic area. 
The following table illustrates their frequency by decades: 
Table Showing the Frequency of Apical Systolic Murmurs in Healthy Individuals. 
Decades 
... 1 
2 
3 
4 
Cases 
. . . 391 
98 
55 
26 
Murmurs present . . . . 
... 22 
35 
12 
5 
It^will be seen that in the first decade 56 per cent, of these indi- 
viduals showed systolic apical murmurs in the recumbent position; 
35 per cent, in the second decade; 21 per cent, in the third; 19 per 
cent, in the fourth. These murmurs were, of course, usually asso- 
ciated with the common basic systolic murmur, of the presence of 
which no special note was made. 
Especially interesting are the statistics of the examination of 
thirty robust boys who were studied at one of the best conducted 
of schools, situated in the country just outside of Baltimore. These 
* No cases under three years of age were examined. 14 
THAYER: FUNCTIONAL CARDIAC MURMURS 
boys were all in the second decade and in apparently excellent 
physical condition. In none of them was there the slightest sub- 
jective or objective evidence of cardiac involvement. 
Eighteen of these thirty boys, however, showed cardiac murmurs 
of one sort or another. 
In thirteen a soft systolic murmur was heard all over the cardiac 
area when in the recumbent or left lateral posture. 
Three showed basic systolic murmurs disappearing on full inspi- 
ration. 
One showed a basic systolic murmur present in the recumbent 
posture alone. 
One showed a basic systolic with no evident change on respiration. 
This, from its character and position, and from the absence of any 
other suggestion of cardiac involvement, was regarded as certainly 
functional. 
To many, perhaps, these considerations may seem altbekanntes, 
and yet the number of men who are refused by insurance and mutual 
benefit organizations, whose career is cut short in army and navy 
because of a lack of appreciation by over-conscientious examiners, 
of just these points, is really large. 
In one year the writer had had occasion to examine fourteen 
young men between the ages of eighteen and twenty-four, the con- 
dition of whose hearts had been questioned by the careful examiners 
of applicants for a certain well-conducted organization. In one of 
these subjects there were marked extra-systolic irregularities. One 
was a nervous young man with a rather rapid heart. All the others, 
twelve in number, showed various forms of the three types of func- 
tional murmurs of which we have spoken, without other serious 
evidence of cardiac defect. 
Such experiences emphasize the fact that it is important to realize 
that cardiac murmurs are, in many instances, normal phenomena, 
that under some circumstances and conditions they are to be 
expected in normal individuals, and that certain of these truly 
functional murmurs are not difficult to recognize and to account for. 
It is also important to distinguish these true functional murmurs 
from those other murmurs to which the same term is often applied, THAYER: FUNCTIONAL CARDIAC MURMURS 
15 
murmurs which depend on valvular insufficiencies due to pathological 
weakness of the heart muscle. 
Lastly, it is well to remember that it is only when murmurs occur 
in certain localities or in more or less definite relation to the heart 
sounds, or when they are associated with evident anatomical or 
functional derangement, that they are necessarily of pathological 
significance. 
In conclusion, then, the writer would urge: 
1. That a cardiac murmur is but one, and sometimes an unim- 
portant one, of the links in the chain of evidence leading to the 
recognition of disease of the heart. 
2. That certain cardiac murmurs are present normally in a large 
proportion of healthy young people. 
3. That the commoner forms of these murmurs are: (a) The 
basic systolic murmurs heard best in the third left interspace arid 
often all over the area in the recumbent posture, and disappearing on 
full inspiration. (&) The systolic murmurs sometimes limited to the 
apex, sometimes heard all over the cardiac area in the recumbent 
posture-disappearing in the erect posture, (c) The cardio-respira- 
tory, inspiratory murmurs. 
4. That the truly functional murmurs-those heard in healthy 
individuals-should be carefully distinguished from those other 
murmurs which may arise at various orifices without actual valvular 
disease, but nevertheless, as a result of pathological changes in the 
heart muscles or in the blood-i. e., the anaemic murmurs, the 
murmurs, systolic and diastolic, dependent upon weakness of the 
heart muscle. 
5. That a familiarity with the cardiac murmurs common in the 
normal individual is at least as important as an acquaintance with 
those murmurs which are associated with cardiac disease. ON TWO CASES OF INTRA- 
THORACIC TUMOR. 
W. S. THAYER, M. D., 
Baltimore, Md. 
Reprinted from 
The Old Dominion Journal of Medicine and Surgery, 
Vol. xi., No. s, November, 1910. 
Richmond: 
Old Dominion Publishing Corporation 
1910 ON TWO CASES OF INTRA-THORACIC 
TUMOR. 
I. Large Thoracic Aneurysm Extending into and Com- 
pressing the Left Lung and Leaking into the Left 
Pleural Cavity, with Remarkably Little Cardiac 
Displacement. 
II. Mediastinal and Pulmonary Sarcoma with Visible 
Thoracic Pulsation and Tracheal Tug. 
The two following cases of intra-thoracic tumor, one an 
aneurysm, the other a neoplasm, have seemed to the author wor- 
thy of a brief note. 
The first case was discussed by Dr. McCallum and the author 
at their Friday Clinical and Pathological' Conference.* 
In view of the interesting features of this case, the notes 
are here presented exactly as they were read at the Conference. 
The second patient, seen by the author in consultation, was 
of such interest that he dictated a full discussion of the condi- 
tions at the outset. Because of certain similarities and points 
of contrast between this case and Case I., this discussion is here 
reproduced as it was written, excepting a few abbreviations. 
Case 1.-Man, 36. Large aneurysm of the aorta, filling the whole up- 
per left chest and completely compressing the left lung, with gradual ooz- 
ing of blood into the lower part of the pleural cavity. Clinical picture at 
one time simulating neoplasm. Final rupture into the left pleural cavity. 
* The histories and discussions as io diagnosis of the cases presented at 
these conferences are prepared in writing before the author is aware of 
the results of the necropsy and read from manuscript. The results of the 
necropsy are then set forth by the pathologist, and the specimens 
dettionstrated. 2 
INTRA-THORACIC TUMOR 
D. T., aged 36, a colored stevedore, was admitted to the hospital on 
April 6, 1909. Family history, unimportant. He had had measles and 
whooping-cough as a child. In '93, he suffered from what was apparently 
an arthritis of his right elbow. No history of lues. Urethritis, ten years 
ago. Lumbago, two years ago. Has always been a hard worker and has 
been an excessive drinker of coffee. A little over three months ago, he 
began to h^ve pain behind both shoulder blades, sharp and shooting. These 
lasted every night for a week and a half and were followed by a bad 
cough which came in paroxysms not especially at night. Scanty whitish 
expectoration; hoarseness. The cough gradually became what he calls 
"a big, barking, severe cough," and he had, at one time, after taking medi- 
cine, a burning pain in his chest as if his chest would split; palpitation; 
severe dyspnoea. The cough continued. In February, his face, eyelids and 
neck became swollen, the swelling lasting from two to three or four 
weeks. At this time he lost his voice completely. There was also marked 
orthopnoea. Occasional edema of the legs for a day or so at a time. 
The appetite was poor and he felt weak. The cough has been steadily 
growing worse and he is obliged sometimes to sit up all night because of 
coughing. 
On February 9th, in the dispensary, a tracheal tug was detected. A 
fluoroscopic examination was made, the report upon his dispensary history 
stating that a thoracic aheurysm was found.* No more definite note. 
On entry, the patient was a large, well-developed man, with a 
high-pitched voice and a brassy cough. Considerable cyanosis of lips 
and finger tips; slight enlargement of the cervical, axillary, inguinal 
and epithrochlear glands. The right side of the chest moved more than 
the left, which looked rather full, measuring 1% cm. more than the 
right. The veins in the left side of the neck were greatly distended but 
did not appear to pulsate. During a severe paroxysm of coughing, the 
patient raised a little dark-red blood. On percussion, there was a slight, 
wooden tympany at the apex of the left lung, but almost complete flat- 
ness below. There was tubular respiration throughout the left lung 
and there appeared to be a small paravertebral triangle of dullness on 
the right side. Dr. Peabody detected cardiac dullness as much as 7 cm. 
to the right of the sternum; heart sounds clear, excepting a soft systolic 
murmur. There was a slight edema over one ankle. 
Blood: 
Red blood corpuscles, . . . 3,568,000 
Colorless corpuscles, . . . 8,120 
Haemoglobin, . . . . . . .53% 
Dr. Boggs was struck by the fullness of the left side of the neck and 
swelling of the left arm. He noticed an area in the lower left back. 
* The author was unaware of this note and examination until after 
the death of the patient. INTRA-THORACIC TUMOR 
3 
where there was slight tympanitic resonance, and also a similar area in 
the interscapular region in the other back. He also noted an inspiratory 
retraction in the tympanitic area in the left back. 
Fluoroscopic examination by Dr. Baetjer showed that the entire lung 
was obscured by an uniform shadow as if practically all lung tissue were 
obliterated. In the mediastinal region there was a dense mass projecting 
to right about the size of aii orange. "Edge very sharp, showing that 
we are dealing with a mass not connected with vascular system. The 
The denseness of the shadow would indicate that we are dealing with £ 
solid mass, probably carcinomatous glands and the uniform density of 
shadow in left thorax probably indicates that the shadow is caused by 
thickened pleura and not lung, indicating that we are probably dealing 
with an extension of the process to the pleura. The lung may also be 
involved." The note as to the previous fluoroscopic examination was 
not discovered until after the patient's death. 
, The writer saw the patient on the 15th of April, and was struck by 
the extreme dullness on left side; there was, however, slight resonance 
throughout the back, especially at the apex. There was an area in the 
right back within the scapular line in which there was slight dullness. 
There was tubular respiration everywhere on the left, and also, to a' 
certain extent, in the dull area on the right. There were, however, ab- 
solutely no adventitious sounds. The heart did not seem to be pushed 
far to the right; the apex impulse was a little inside the mamillary 
line. Sounds, clear, excepting a soft systolic murmur in first space and 
over the manubrium. The writer was struck by the systolic lift of the 
whole manubrium with each beat and the remarkably distinct tracheal 
tug. 
Dr. Barker saw the patient on the succeeding day and dictated the 
following note: "* *, * Findings indicate solidification in the left 
thorax, involving pleura and probably lung, with pressure on veins, ob- 
structing outflow of blood from left upper extremity. Adhesions between 
left bronchus and aorta bailsing tracheal tu'g; injury to left recurrent 
laryngeal nerve. In differential diagnosis one must consider 
•(1) Mediastinal neoplasm with involvement of lung; 
(2) Primary pulmonary and pleural neoplasm with glandular in- 
volvement; ■ ul -A 
(3) Hodgkins' disease; ' . , 
(4) Extensive tuberculosis of lung with glandular involvement; 
(5) Sypholoma with glandular involvement and aneurysm formation. 
Fluoroscopic examination Supports View that this is neoplasm, but 
the fever makes one think of tuberculosis, syphiljs and Hodgkins' disease." 
■ Laryngoscopic examination shpwed complete paralysis of left vocal- 
cord. 
As Dr. Sladen thought he heard Isomewhat nasal voice sounds in the 
lower left back, a needle was introduced below the angle •,of the left 4 
INTRA-THORACIC TUMOR 
scapula and 15 cc. of turbid bloody fluid withdrawn. Cultures were 
negative. 
Differential count: 
Lymphocytes, 63% 
Endothelial cells, ...... 28% 
Polymorphonuclears, . . . . . 7% 
Large mononuclears, ..... 2% 
The needle did not seem to pass through or into solid tissue. 
The writer saw the patient on 19th of April. The temperature had 
ranged between 97.8° and 101.6°, remaining as a rule slightly elevated. 
Sputa, scanty; mucous, occasionally streaked with bjood. Once or twice 
a little elastic tissue was found, and on several occasions, clots of blood. 
Once, numerous eosinophiles were noted. The amount was never more 
than 30 cc. in the day. 
There was almost stony flatness throughout the left front and dull- 
ness over the manubrium, reaching well to the right. There was no para- 
vertebral triangle of dullness. In the supraspinous fossa there was more 
resonance than below. Vocal fremitus was not wholly absent. There 
was rather remarkable tubular respiration on the left; compensatory 
puerile respiration on the right. The heart was not essentially displaced 
and sounds were best heard in about the normal position. Very distinct 
pulsation over manubrium, involving the whole upper chest; marked 
tracheal tug. Shock of second sound at base palpable. 
Wassermann reaction, negative. 
Blood count: 
Red blood corpuscles, .... 3,800,000 
Colorless corpuscles, .... 8-10,000 
Haemoglobin, ...... 59-63% 
On the 4th day of May, the patient who had been coughing a great 
deal and raising considerable sero-mucous expectoration, was seized with 
a sudden and violent fit of coughing and choked to death in a few min- 
utes. Fresh blood escaped from the mouth with the final paroxysm of 
coughing. 
After death, the right lung was resonant throughout, except for a 
small area in the right interscapular region, where the note was dull. 
The left was flat throughout. 
In summary then, a man of thirty-six began, four months 
before death, to suffer from pain in his scapular regions, fol- 
lowed by cough, dyspnoea, loss of voice, swelling of the legs, loss 
of weight and anaemia. Expectoration, scanty and mucoid, 
showing occasionally a little blood. The left side of the chest 
was somewhat fuller than the right, and almost, though not en- INTRA-THORACIC TUMOR 
5 
tirely flat throughout. Vocal fremitus, diminished but present, 
especially in the back. Respiration, tubular throughout without 
adventitious sounds; not so loud at the apex in front as usual, 
but of fair intensity at the base. Evidence of marked intra- 
thoracic pressure; heaving of the manubrium, tracheal tug; 
paralysis of the left recurrent laryngeal; venous engorgement 
and swelling of the left shoulder and arm; 15 c. c. of bloody 
fluid obtained on puncture from the left chest showed an excess 
of small mononuclear cells. The needle apparently did not enter 
the lung substance. The heart was not essentially displaced. 
"The picture presented by this case was most remarkable. 
From a purely physical standpoint, a solidified lung with a 
somewhat thickened pleura might present the signs observed 'a 
the left chest on auscultation and percussion. There must have 
been some connection between the aorta and the trachea or the 
bronchial tree in order to produce so marked a tracheal tug. 
The solidification of the lung could scarcely have been tubercu- 
lous because of the entire absence of rales. Fluid in the left 
chest seems most improbable because of the absence of more 
marked displacement-of the heart. 
One might account for most of the symptoms by assuming 
that the condition was a neoplasm arising at the root of the lung 
or in the mediastinum and extending throughout the left lung. 
Such a growth might be a carcinoma arising in the bronchi 
near the root of the lung, involving the entire lung and pleura 
and, through involvement of the mediastinal glands, causing 
pressure. But it would be very remarkable to have so exten- 
sive a pulmonary involvement. The same argument might be 
used against the assumption that the condition was a sarcoma 
arising in the mediastinal glands. The complete absence of 
secondary glandular enlargements in the neck is notable. Again, 
the pulsation over the manubrium was more marked than is 
usually seen in a new growth. 
I have never seen so extensive a tracheal tug with anything 
but an aneurysm. Moreover, we have a distinct note on the 
fluoroscopic examination of February stating that there was an 6 
INTRA-THORACIC TUMOR 
aortic aneurysm. This note I was not aware of when I first 
made a diagnosis of neoplasm. 
"One finds himself obliged to ask whether an aneurysm 
might have accounted for all of the symptoms ? One could per- 
haps imagine an aneurysm of the transverse arch which had 
leaked into the left pleural cavity and resulted in a gradual 
accumulation of blood so marked that complete dulness was pro- 
duced; the tubular respiration might have been transmitted as 
in the case of fluid. But in this case the heart would certainly 
have been displaced. On the whole, when one considers the 
fluoroscopic note of the 9th of February, I should be inclined 
to regard the case as one of neoplasm-either a mediastinal sar- 
coma with extension or a cancer starting at the root of the lung 
with infiltration, in association with an aneurysm of the arch 
of the aorta." 
The necropsy, made by Dr. McCallum twenty-one hours after death, 
showed arteriosclerosis ; aneurysm of the arch of the aorta; invasion and 
compression of the left lung; complete atelectasis with aspiration of 
blood into the right lung from haemorrhage occuring just before death; 
oozing of blood into the pleural cavity; horseshoe kidney. 
On opening the abdomen, the organs were found to be pushed down- 
ward, the liver extending 13 cm. below the ensiform cartilage and 11 
below the costal margin in the mammillary line. 
The diaphragm on the left side reached the 6th space; on the right, 
the 5th. On removal of the sternum, the right lung was found to be 
very prominent and to extend across the middle line. The left pleural 
cavity was obliterated by a rather gelatinous-looking mass through which 
the knife passed into a ragged cavity which apparently contained a 
mass of blood clot. The upper part of the mediastinum was filled by 
a firm mass. The pericardium was pushed over so as to be about divided 
by the median line. The apex of the heart reached only about 4% cm. 
to the left of the median line. The pericardial cavity contained about 
100 cc. of clear fluid. The pericardium was adherent to the mass in the 
left pleura so that it stood open after the heart was removed. The 
mediastinum above this was filled with a hard mass. The trachea was 
compressed antero-posteriorly but not eroded. 
On opening the aorta behind, there was found to be a large orifice 
occupying the front of the arch. This orifice measured 6% cm. in trans- 
verse diameter, and from it there bulged an enormous blood clot. The 
l^ft sub clavian and carotid arteries opened outside the orifice of this 
sack. The arteries on the right opened apparently from another sack 
which was not very large. It had rather a thin wall and contained no INTRA-THORACIC TUMOR 
7 
•clots. The portion of the aorta which lay directly against the trachea 
was not a part of the aneurysmal sack but was greatly thinned and 
covered with a thin clot. 
The left lung was greatly compressed. The bronchi contained only 
a little frothy fluid. The left pleural cavity, on being cut into, was found to 
contain an enormous mass of blood clot which was apparently fresh. 
Over the upper part of the lung, the clot was apparently much older and 
showed a brownish color. The lung itself was completely airless, com- 
pressed into a pasty, flabby thin mass of tissue. The whole lung showed 
this same condition. It was grayish and dull-looking. In the upper 
portion, there projected a large aneurysmal sack which was completely 
filled with thombus. It was hardly walled from the lung substance. The 
wall was so thin and friable as to be scarcely noticeable. 
Section of the contents of the left pleura showed that the pleural 
cavity contained a great quantity of blood in various stages of coagu- 
lation; old discolored clots, as well as fresh, newly-formed clots and some 
fluid blood. There is possibly 1% litres altogether in the pleural cavity. 
The left lung is cut through so as to show a sack projecting into it. It 
was found that the lung substance was greatly compressed; it was com- 
pletely airless, of a dark color, pasty, not even moist; the bronchi seemed 
also to be much compressed. The sack was very much larger than was 
suspected at first. From side to side, it measured 15% cm. and 12% cm. 
from above downwards. The right side of the sack was filled with a 
laminated decolorized clot, while the left side, which *is projecting actually 
into the lung, is filled with a fresh clot. The aneurysmal wall is exceed- 
ingly indefinite and very friable. Just behind the hilum of the lung, the 
aneurysm approaches the surface of the lung, and consequently the pleura, 
and evidently there has been a rupture there, for turbid, bloody fluid 
squeezes out into the pleural cavity from the sack. At a point, a short 
distance below the line of section, the probe passes easily from the 
aneurysmal sack into the pleural cavity. Evidently, therefore, the leak- 
age of blood is at this point. The costal pleura was very adherent over 
all this uppermost part of the lung where the compression was most 
striking. None of the bronchi in the left lung are actually eroded. The 
blood contents that are found may well have leaked in from elsewhere. 
The right lung was extremely voluminous and in many areas showed red 
patches due to the inhalation of blood. 
In a word then, the autopsy revealed the existance of an enor- 
mous saccular aneurysm of the arch of the aorta pressing op the 
trachea so as to cause the tracheal tug, filling the mediastinum 
so as to cause the dulness and the shadow to right, extending 
into the left lung which was adherent to the parietal pleura in 
the upper part in such a way as completely to compress it, to ren- 
der it wholly airless, perforating the pleura and allowing the 
leakage of blood, exceedingly gradual at first, as shown by the old 8 
INTRA-THORACIC TUMOR 
decolorized clots, more rapid in the end as shown by the man- 
ner of death, the quantity of fresh blood and the final displace- 
ment of the heart as found at necropsy. The aneurysm itself, 
compressing the lung wholly-leaving some bronchi alone open, 
and the blood which had escaped into the lower part of the 
pleural cavity and there clotted, account satisfactorily for the 
marked dulness and tiibular respiration without adventitious 
sounds, i. e., conduction of the respiratory murmur from the root 
of the lung. 
The most remarkable feature of the case was the absence of 
marked cardiac displacement during the greater part of the 
period in which the patient was under observation. This must 
have depended upon the adhesions in the mediastinum and the 
upper left chest which held the pericardium in position. The 
dulness in the right interscapular region was clearly due to the 
aneurysmal mass through which also slight tubular respiration 
was transmitted. 
As one looks back at this case, one cannot but feel that had 
we been familiar at the outset with the first fluoroscopic note, 
the idea of a possible neoplasm would not have occupied so 
prominent a place in the minds of those who observed the 
patient. It is interesting that in the later stages the outlines of 
the shadow should have been so sharp and the pulsation so slight: 
as to have misled so1 accurate an observer as Dr. Baetjer. 
The differential diagnosis between thoracic aneurysm and 
neoplasm may be exceedingly difficult-indeed impossible-for 
a considerable period after the onset of symptoms. At the time 
of the observation of Case I., the author had never seen a dis- 
tinct tracheal tug excepting in the presence of thoracic aneu- 
rysm. That a tracheal tug must sometimes be present in con- 
ditions resulting in adhesions between the aorta and trachea or 
bronchial tree, he has always been convinced. The possibility 
of such an event is illustrated by Case II. . 
Case II.-Man 59. Mediastinal and pulmonary sarcoma causing tho- 
racic pulsation and tracheal tug so as to simulate aneurysm of the aorta. 
X, 59 years of age, consulted the author on January 8, 1910. He had INTRA-THORACIC TUMOR 
9 
always been a strong, well man but a heavy drinker, although never to 
immediate excess. His physician says that there is a suggestive history 
of lues some years ago. For several years he had had a tendency to 
bronchitis during the winter. Last summer, he was at times at very 
high altitudes, and while there, he took a great deal of exercise. 
About a month ago, the patient began again to suffer from a cough 
which did not apparently begin with a cold in the head; expectoration, 
scanty and mucoid. This cough has been growing gradually worse, and 
last night there was a little blood in the expectoration. He has had a 
good deal of flatulence and has complained much of eructations. Has 
been losing weight. A relative stated that he felt that the patient was 
an ill man. 
The patient was lying on the couch in his room. Face, rather pale, 
with a rather drawn and ill look. The color of the mucous membranei 
was fair. The tongue was slightly coated. The pulse was much larger 
on the right than on the left, regular; pressure, not remarkable; rate, 
not' essentially accelerated. The right upper chest moved more than the 
left, which looked perhaps a trifle smaller. In the left second space there 
was distinct pulsation, not very striking, but evident. Heart: Apex im- 
pulse, not felt. Sounds, clear. The second sound was louder on the left 
than on the right, but loudest over the pulsating area in the second left 
space. 
Lungs: Well marked dullness at the left apex, more marked near the 
sternum in the first and second spaces, but extending outwards to a con- 
siderable distance, and reaching upwards into the supra-clavicular fossa. 
There was but very slight dullness posteriorly. The vocal fremitus was 
not essentially modified. The respiratory sounds were remarkably tubu- 
lar. Elsewhere the respiration was clear. There is a fairly well marked 
tracheal tug. The cup contained a little mucoid sputa with several small 
masses of blood, not a teaspoonful in all. A fluoroscopic examination was 
made by Dr. Erving. The left upper front was filled with a large shadow, 
which came out directly above the base of the heart. The lower part of 
the outline was sharp and rounded and apparently pulsated (?). Above 
and to the left, the outlines of the mass faded off rather more gradually 
than is common in aneurysm, and to the right it did not pass to the right 
sternal margin. 
A plate* was also taken. This showed an outline, roughly like that 
drawn upon the chart. The plate was not large, so that the entire out- 
line of the mass was not seen. 
The shape of the lower border of the mass and its relation to the 
base of the heart was very suggestive of an aneurysm. It was striking, 
however, that the shadow did not extend beyond the right of the sternum. 
January 9th.-The patient was seen this morning. He was in bed 
and a rather more satisfactory examination could be made. There was 
apparently a slight diminution of the size of the left upper chest. Well- 
marked pulsation in the second left space about two or three fingers' 
* This plate unfortunately disappeared before photographs could be 
made. 10 
INTRA-THORACIC TUMOR 
breadths from the sternum extending also farther out. There was a 
distinct area of maximum pulsation about two fingers' breadths to the 
left of the sternum. On palpation, the impulse was rather lifting and 
strong, but there was no shock of the second sound. On percussion, the 
area of the heart could be made out, essentially normal in size and posi- 
tion. It is striking that, on careful percussion, dullness extended above 
the clavicle, and although the dullness fades off markedly as one passes 
(This Diagram was Made after the Loss of the Plate ) 
C A St 737 
Cask II. Diagram of Area of Dulness, Tubular 
Respiration and Pulsa tion. 
outwards, the lower border is rounded and sharply defined, suggesting a 
rounded mass to the left of the sternum. The dullness extends about to 
the mid-sternum. There is but little dullness in the left supraspinous 
fossa. Everywhere in the dull area there is a tubular modification of the 
respiration, pure tubular above, nearly so below, gradually fading away 
as one passes outwards, much more suddenly as one passes downwards. 
There is a well-marked tracheal tug, palpable but not visible. 
The temperature has been slightly above 99° at night. 
In a small bottle was a little expectoration with purulent masses and INTRA-THORACIC TUMOR 
11 
a number of fresh streaks of blood. Twice during examination of the 
patient he coughed and brought up a little expectoration of the same 
character. This was clearly from below, not from the throat. In the 
spittoon there were mummular masses of blood, t*ae largest perhaps as 
large as one's little finger nail, which he had expectorated during the 
night. The sputa showed no tubercle bacilli. 
Blood: 
Red corpuscles, ..... 5,400,000 
Leucocytes, ...... 15,00(0 
Haemoglobin, . . 105% (Dare) ; 80-90 (Tallquist) 
Urine shows nothing remarkable. 
Rest, mild, general massage and iodine of potassium in small doses 
were advised. 
Discussion.-The following discussion was dictated at this 
time for the author's record: 
Three main possibilities are suggested in this case: 
(1) Aneurysm of the arch of the aorta; 
(2) Neoplasm of the lung, starting at the root and extending 
outwards with communicated pulsation from the aorta. 
(3) Chronic fibroid tuberculosis of the left apex with com- 
munication of aortic pulsation. 
To take up the last possibility. There is no definite history 
of continued cough or expectoration or fever at any time in the 
patient's life. A colleague who examined the patient last sum- 
mer, tells me that he was unable to make out any abnormal signs 
at his left apex. The slight fever and loss of weight might sup- 
port this idea. 
The outline of the condensed area shown by percussion and 
by the radiograph, is very unlike that which one sees with a 
retracted apex. A sharp convex rounded outline below is most 
unlike that which one sees ordinarily in such conditions. To 
the right, however, and above, it should be said the outline of 
the mass faded rather gradually. The diminution in the volume 
of the left upper chest might support the view that the condition 
was a chronic fibroid tuberculosis, and one might account for 
the pulsation through the hypothesis of mediastinal adhesions, 
while the fact that the mass is entirely limited to the left side 12 
INTRA-THORACIC TUMOR 
would also be in harmony with this idea. But the difference be- 
tween the pulse on the two sides is rather striking, and I have 
never seen a tracheal tug in such a condition, although always 
recognizing the possibility of its existence. 
Lastly, it would seem very remarkable that an old fibroid 
tuberculosis could exist without adventitious sounds, particu- 
larly a fibroid tuberculosis of such extent, where as recently as 
last summer, a good clinician was unable to detect physical signs. 
Again the expectoration is not at all like that of tuberculosis 
and contains no tubercle bacilli. 
% 
(2) Neoplasm-The loss of weight and rather cachectic ap- 
pearance and the age of the patient would not be against this 
supposition. The dyspnoea upon exertion and the slight fever 
would both be in harmony with such an idea. 
The character of the expectoration is not unlike what one 
might see in neoplasm. Again, the mass with rather indefinite 
outlines to the left and above, extending outwards from the 
mediastinum; the marked dulness with a nearly pure tubular 
respiration, without adventitious sounds-these are all condi- 
tions such as are not uncommon in pulmonary neoplasm. The 
pulsation might be due to adhesions with the aorta. The absence 
as yet of palpable glands may well be regarded as strongly 
against this supposition. The apparent pulsation of the lower 
border of the mass on fluoroscopic examination is too uncertain 
to be regarded as definitely against this supposition. 
I have, however, never seen a well marked tracheal tug in 
thoracic neoplasm. That there is no more anaemia may well 
be regarded as an argument against neoplasm. 
(3) Aneurysm-The history of a cough coming mj two 
months ago which has not disappeared and the dyspnoea on 
exertion are not unlike what one might expect wit han aneu- 
rysm. The fever, loss of weight and general cachectic appear- 
ance would be against it. The gradual development of the pro- 
cess in the last two months, and the suggestive history of lues 
earlier in life would not be against aneurysm. 
The character of the expectoiation is not unlike what one INTRA-THORACIC TUMOR 
13 
might expect wich an aneurysm pressing upon a bronchus. The 
character and position of the pulsation, the position of the heart 
and its relation to the outlines of the dulness in the upper chest 
on percussion, the diminution in the size of the left radial pulse, 
the well-marked tracheal tug, the sharp outline of the lower part 
of the mass upon fluoroscopic examination and its apparent pul- 
sation, all seem to me strongly in favor of aneurysm. 
On the other hand, the age of the patient, as emphasized by 
a distinguished consultant, was rather against aneurysm, as 
well as the extent of the dulness at the apex of the lung, the 
rather indefinite outline of the mass towards the left, the 
absence of the pulsation of the aorta on fluoroscopic examina- 
tion, to the right of the sternum, and the rather remarkably 
loud tubular respiration all over the dull area, the last being 
the most strinking point against aneurysm. To these might 
be added the fact that the second sound over the mass is 
not so accentuated as it often is. The second sound, however, is 
fairly loud at the point of maximum impulse in the second left 
space. The outline of the mass to the left, although not so sharp 
and distinct as it sometimes is, might well occur in the case of 
an aneurysm which had already become associated with rather 
marked changes in the surrounding lung, while the feebleness 
of the pulsation on fluoroscopic examination might be accounted 
for by thrombi in the aneurysmal sac. The loud, clear, tubular, 
lespiration is perhaps the strongest point against aneurysm, but 
the entrance of the air into this area is slight, and it is conceiv- 
able that with an atelectatic lung, the sounds may be conducted 
entirely from the bronchi. Such rather loud sounds I have seen 
with aneurysm pressing on the lung. 
On the whole, then, I should be inclined to place aneurysm 
first on the 'list of probabilities-a saccular aneurysm starting 
probably from somewhere in the descending arch and extending 
out into the left lung, causing maiked atelectasis, and associated 
with a good deal cf thrombosis in the sac. The small left radial 
pulse would be due to pressure on the left subclavian. The 
tubular respiration, in a great part conducted from the large 
bronchi at the root of the lung. 14 
INTRA-THORAC1C TUMOR 
Second, I should put neoplasm; and lastly, tuberculosis. 
Finally, one must remember the possibility of a neoplasm 
of unusual character, such, for instance, as a dermoid cyst, of 
which I have seen one example several years ago, a case in the 
service of Dr. Barker" 
The author did not see this patient again, but the subsequent 
history has been kindly given him by the attending physicians. 
There was rapid loss of weight and strength and increasing 
dyspnoea. An haemorrhagic effusion developed in the left pleu- 
ral cavity and finally, a few hard glands appeared above the left 
clavicle, one of which, on removal, showed evidence of sarco- 
matous invasion. There was urgent dyspnoea. The effusion, 
although frequently evacuated, recurred rapidly and in the lat- 
ter part of March, the patient died. No necropsy was allowed. 
The tracheal tug was not evident in the latter days of the 
patient's life. 
Here then, a pulmonary or mediastinal neoplasm causing 
adhesions doubtless, between the aorta and trachea or bronchial 
tree, resulted in a well-marked systolic tracheal tug-a tug so 
distinct as to materially influence the differential diagnosis, 
especially when considered in connection with the visible pulsa- 
tion and difference in size of radials. 
In conclusion, it may be well to emphasize again the two 
points of special interest brought cut by these cases: 
(1) The presence in Case I. of a large aneurysmal sac in 
the mediastinum and left chest resulting in the gradual escape 
into the lower part of the left pleural cavity of a large amount 
of blood without essential cardiac displacement owing, doubt- 
less, to the existence of old adhensions. 
. (2) The occurrence in Case II. of a well-marked tracheal 
tug with a pulmonary and mediastinal neoplasm. ADDRESS DELIVERED BEFORE THE 
GRADUATING CLASS IN THE 
U. S. MEDICAL SCHOOL 
IN MAY, 1909. 
WILLIAM SYDNEY THAYER, M. D., 
Baltimore, Md. 
Reprinted from 
The Old Dominion Journal of Medicine and Surgery, 
Vol. xi., No. 6, December, 1910. 
Richmond: 
Old Dominion Publishing Corporation 
1910 ADDRESS DELIVERED BEFORE THE GRADUATING 
CLASS IN THE U. S. NAVAL MEDICAL 
SCHOOL IN MAY, 1909. 
WILLIAM SYDNEY THAYER, M. D. 
Baltimore, Maryland. 
At the outset of the few remarks which I shall make this 
morning, I want to express my sincere appreciation of the 
honor conferred on me by the invitation to speak to you. My 
attention has been called in the last year or so to the great pro- 
gress which has been made in the equipment of your service. 
I have visited several times the beautiful hospital at Annapolis 
and have been struck by the opportunities there offered and 
the character of the work done, and it is unnecessary to say 
how much I have been impressed by this admirable institution. 
I am not unaware that many of these improvements are due to 
the energy and wisdom of your distinguished Surgeon-General, 
to whom I believe I owe the honor of the in w Nation to address 
you to-day. 
Rather at a loss at first as to what phase of medicine I 
should touch upon in my remarks this morning, I have found 
the consideration of the opportunities offered by the career of 
a naval surgeon a most interesting field for reflection, and so I 
have concluded to express without attempt at elaboration, some 
of these thoughts as they have come to my mind. 
Few fields offer a broader prospect to one who starts out in 
life than that into which he is led by the study and practice 
of medicine. Every sphere of activity offers to the man who 
has his share of natural optimism and enthusiasm, objects of 
interest-the mere pleasure of doing anything well is a satis- 
faction. But there are, it seems to me, few careers that are so 
many sided, that offer so many opportunities closely connected 
with one's daily life and occupation for the satisfaction of one's 2 
Address Before Graduating Class 
intellectual and moral nature, as that of the student or prac- 
titioner of medicine. 
To one type of man the social and psychological side of 
medicine-practice in its narrower sense-is especially attrac- 
tive and stimulating. The consciousness of the growth of one's 
power and influence over one's fellows, the ever increasing real- 
ization that one can throw into his patient his own healthy 
mindedness, his own optimism-that he can really bear his 
patient across the valley that he has to traverse; the conscious- 
ness that the community about one is coming to look upon him 
as its guide and its support, and the sense of responsibility 
which this brings with it-this sort of experience-and it is a 
common one to the general practitioner, is immensely broaden- 
ing to the man; it is a rich reward and a great goal for the 
individual whose human and social instincts are especially de- 
veloped. Many a man who has not possessed, in a striking de- 
gree, the quality of a scientific mind has left a noble record in 
this broad field. 
Again, for the technician, for the man skilful with his 
hands, and of an inventive, mechanical mind, the career of a 
surgeon has always possessed much charm, and, as in the case 
of the general practitioner of medicine, the social and human 
qualities of the man count for much in his success, so with the 
surgeon, technical genius and skill is ever a vital part of the 
work. And although the genial and warm-hearted and mag- 
netic man may be a poor doctor if he lack a scientific interest 
in his profession, and although a skilful technician alone is a 
poor surgeon in the broader sense of the word, yet few men can 
excel in all branches, and there will always be a field for him 
who possesses real technical genius, even if the studious and 
scientific side of his nature fall below the level of that of some 
of his colleagues. It is the even balance of these qualities that 
makes perfect, but an even balance is hard to find, and real ex- 
cellence in one quality, if the others be not too deficient, will 
generally bring success. 
To the man who is, essentially, a student every step in the Address Before Graduating Class 
3 
study and practice of medicine has its charm and its attrac- 
tion-I might almost say, its dangers. Are we not all anat- 
omists at the outset of our medical studies ? Have we not all 
in the crowded, prescribed course that we have had to pursue 
in the American medical school of to-day-have we not all neg- 
lected some important branch for the study of that which has 
demanded for the moment our special interest ? 
In institutions which are in the transitional period in which 
some of our American schools find themselves, where an attempt 
is made to encourage self-reliance and independence of thought 
and action in the student of medicine, where the experiment 
is being- tried of an elective system in the midst of a regular 
four years' course of medicine with annual examinations for the 
whole class, the fascination to the student of special branches of 
study are really a danger. In the school with which I am con- 
nected, we meet occasionally with able men who become so in- 
terested in special problems of anatomy, physiology, chemistry, 
pharmacology, that they are actually in danger, in other 
branches, of failing to pass the examinations requisite for pro- 
gression in their course. 
In every branch of medical science or art there is oppor- 
tunity for the student; this is almost as true in the busy life of 
the country practitioner as at the desk of the worker in the 
research laboratory. And as has been emphasized again and 
again, the physician must of necessity be a student from the 
beginning to the end of his career. This constant opportunity 
to contribute something new to the science or art of medicine 
is one of the greatest charms of study and practice. 
But the medical profession is crowded; the expenses of life 
are great; and many a man well equipped for scientific work, is 
obliged by grinding necessity to sacrifice most valuable oppor- 
tunities for study and progress and self-development. Many a 
poor man's career is marred by the most sordid and hateful of 
all influences which poison one's spontaneity and ardor-finan- 
cial anxiety. 
It is undeniably true that in the past the career of the naval 4 
Address Before Graduating Class 
surgeon has not offered especial attraction to the student, and 
yet, as one looks at the development of recent years, and as one 
thinks of the life and opportunities of the surgeon in the navy 
to-day, it is difficult to resist the thought that it is especially to 
the man with studious and scientific tendencies that the career 
of a surgeon in the navy should appeal. The man with inde- 
pendent means, the man to whom exceptional advantages for 
study and research are offered at the beginning of his career 
would hardly be attracted by the navy. But to the man with 
insufficient means, with a studious turn of mind, the oppor- 
tunities offered by a service in the navy or the army are by no 
means small. And I have been struck of late by the fact tha 
many men of this type are realizing that the advantages of 
service such as is now offered by the navy and the army is more 
satisfying to their ambition than positions which promise a 
much more speedy financial return. 
What are the advantages that a naval service would seem to 
offer ? 
Certain material attractions are obvious. They have always 
existed. 
(1) The first is that such a service brings with it a fixed, 
though moderate income which means the absence of financial 
anxiety. The importance of this to the impecunious man of a 
studious temperament cannot be over estimated, for it means 
a mind free to study those problems which interest him in so 
far as the opportunity offers. Again it means a pension for 
one in his old age and some provision for his family. 
(2) Moreover, such a service offers to many, opportunities 
for travel and for the acquisition of foreign languages which 
are exceptional. But more than this, it should mean for the 
student of an inquiring mind an opportunity to meet new men, 
to inspect other institutions and to study foreign methods. For 
some years it has been to me a matter of interest to observe the 
surgeons from foreign navies whose ships have happened to visit 
Baltimore; and among these men, although they vary, I have Address Before Graduating Class 
5 
met with students who were profiting fully by their oppor- 
tunities. One especially, had been a rich contributor to scien- 
tific medical literature. 
These, after all, used to be the main advantages of a service 
in the navy. But the study and the practice of medicine and 
surgery have greatly changed in the last twenty-five years, and 
the opportunities offered in the navy to-day are vastly different 
from what they used to be. 
(3) One of the first that comes to one's mind is the oppor- 
tunity offered by this school. Here men who enter the navy 
are afforded the advantages of a post-graduate course such as 
would be open to few outside. It not only gives them an ex- 
cellent equipment but it must bring to the notice of those in 
authority the special attainments and tastes and abilities of 
the various men, and it must thus give the chance to the ambi- 
tious student to show his special qualifications for those branches 
of the service toward which his aspirations lead him. This 
cannot fail to help the really strong man toward the attainment 
of his ambitions. 
There are probably few courses in tropical medicine better 
than that which is offered here under the direction of Dr. Stitt. 
And the advantages of close association with such men as Stiles 
and Rosenau and others who are so soon to work close by in the 
laboratories of the Public Health Department, cannot easily 
be overestimated. The intimate connection of your excellent 
hospital with teaching and experimental laboratories such as 
you have here is admirable. What more tempting goal could 
there be for a man of scientific instinct than an assignment to 
work or teach in such an institution as this ? 
(4) The time is fast coming when the naval surgeon can 
no longer complain of lack of opportunities for work with the 
best of modern equipment. The character of your hospitals and 
the establishment of hospital ships, offer all that could be asked 
to those whose good fortunes or, perhaps, one might better say, 
attainments bring the desired assignment. 6 
Address Before Graduating Class 
(5) The great advances in recent years of our knowledge 
of the nature of tropical diseases have brought forward many 
problems, and have imposed new duties and responsibilities on 
the naval surgeon; but these responsibilities are associated with 
greater opportunities. A service in the navy offers to some an 
unusually good chance for the study of exotic disease. Espe- 
cially interesting in this connection are the all-important ques- 
tions of prophylaxis with which every naval surgeon must 
of necessity deal. In these fields there are excellent openings 
for research and discovery. Much of this, of course, applies 
equally well to a service in the army. In the past, indeed, the 
opportunities for work have been greater in the army than for 
the navy, and what advantage has been taken of these oppor 
tunities by the members of your sister service need not be em- 
phasized. One has only to mention the names of Beaumont, 
Woodward, Billings, Sternberg, Reed, Lazear, Carroll, ami 
Gorgas- one might name many ethers. To-day, however, the 
navy offers advantages for scientific work equal to those of irs 
sister service. It is interesting to reflect upon the prominent 
position which has been taken by me mbers of the naval and 
military service of other countries in the great discoveries of the 
past twenty or thirty years. Laveran, the discoverer of the 
malarial parasite, was an army surgeon. Kelsch, a most im- 
portant writer on tropical diseases, was an army surgeon. Ross, 
the discoverer of the method of transmission of malaria, was an 
army surgeon. Ziemann, the first to confirm his. work and that 
of the Italians, was a naval surgeon. Normand and Bavay, who 
first described Cochin China diarrhoea and its parasite, strongy- 
loides stereoralis, were naval surgeons; Calmette, whose con- 
tributions to medical science are familiar to us all, began his 
scientific work as a naval surgeon; and so on. One might make 
a long list. 
There are, of course, drawbacks to a service in the medical 
corps of the navy. Various objections may be raised. One of 
these objections which has, certainly, considerable foundation, 
is that the surgeon is surrounded for much of his time by a Address Before Graduating Class 
7 
body of exceptionally healthy men-that there is small occasion 
to meet with the graver diseases which are so important in the 
practice of the ordinary physician. It is true that the naval 
surgeon has less opportunity than other men to study the serious 
maladies incident to age, but, on the other hand, he is in an 
unusually favorable position to observe the development and 
spread of those epidemics of simpler mild infectious diseases 
which, for the very reason of their mildness, have often been 
studied insufficiently. 
(6) There is one point on which I would especially insist, 
namely: that this very position of the naval surgeon, in intimate 
association with a large body of unusually healthy young men. 
is one which offers certain really valuable opportunities for re- 
search. Let me suggest a few examples. There is no new 
chemical or biological test of urine or sputa or blood which does 
not need control. It is scarcely an exaggeration to say that 
whenever the announcement of such a test is made, that which 
is most urgent is a patient, careful control made on a large 
series of normal individuals, and it is very rare that such con- 
trols are made before a great mass of over-enthusiastic and mis- 
guided observations are published broadcast. Nowhere could a 
better opportunity be offered for such controls tnan in navy or 
army. Many of these tests may be too elaborate to be properly 
carried out on shipboard, but others are relatively simple in 
their nature. 
There is yet another sort of observation for which the naval 
surgeon has exceptional opportunities. I refer to questions re- 
lating purely to physical diagnosis. It is a matter which has 
come very closely home to me in the last several years in study- 
ing various questions relating to the cardio-vascular system. 
To take a series of examples: The study of various instruments 
for the measurement of the blood pressure which has a real 
value in clinical research, always calls for normal controls, and 
the greatest difficulty with which I have met is in obtaining a 
sufficient number of normal individuals under normal condi- 
tions. The relation of blood pressure to exercise; the delicate 8 
Address Before Graduating Class 
questions as to the functional capacity of the heart; as to the 
possibility of acute dilatation of the normal heart as a result of 
exercise; the study of the cardiogram, of the venous pulse; 
such simple questions of physical diagnosis as the variability of 
the position of the cardiac apex in different postures; of the 
palpability of the normal arteries at different ages; such a ques- 
tion as that in which I am now especially interested, as to the 
frequency of the third heart sound; all these are questions the 
elucidation of which depends largely on the study of a con- 
siderable number of normal individuals, and it is exceedingly 
hard to bring together a sufficient number of such individuals 
in private practice or in the hospital. 
I can easily imagine that the attempt on the part of the 
naval surgeon to study such questions might be attended with 
difficulties, but I do not believe that these difficulties would be 
insurmountable, and I am sure that with the increase of the 
scientific output of the corps and with the growing enthusiasm 
of the individual members, the opportunities themselves will in- 
crease. 
There are, of course, dangers in the life of a naval surgeon 
which are really considerable. The pleasures of travel and 
change, the seduction of the charming social conditions which 
often surround the naval officer, the lack at times, of other than 
routine duties of small significance are only too likely to wean 
one from habits of study and work, and the very fact that the 
service affords a fixed salary, a fact which has before been re- 
ferred to as a distinct advantage, might, I can well imagine, 
operate in quite a contraiy manner. Indeed, it seems to me 
immensely creditable io the personnel of the army and navy 
that the medical corps has always been so efficient, when in life 
in general, a living income is, in the majority of cases, a deadly 
blow to productive activity. To the enthusiastic student, the 
ambitious physician, it stems inconceivable that the competence 
for which he sighs should be his ruin, and yet one can almost 
count on his fingers the rich men who have had careers in medi- 
cine. With some, no doubt, the freedom from financial respon- Address Before Graduating Class 
9 
sibility acts as a damper to ambition, but many of those who 
have failed in the past to do all that for which their natural 
abilities might have fitted them, might have been stimulated to 
most useful service by the opportunities which are offered to- 
day. Financial independence, however modest the income, has 
unquestionably its dangers as well as its blessings, but these 
dangers are likely to lose much of their force if associated with 
stimuli such as are now offered by the character of the corps and 
the standard set by your naval school. 
Other objections which I have heard raised against a ser- 
vice in the naval medical corps are the lack of opportunity for 
advance, and again a feeling that has existed that.the position 
of the surgeon in the service is not perhaps equal to that of the 
line officer-that in a certain sense he is looked down upon and 
perhaps discriminated against. These objections which may 
or may not have had some foundation in the past have, I take 
it, little ground to-day. 
The legislation of recent years has, I fancy, afforded mate- 
rial relief to the first condition. 
The second consideration is no new story. But the situa- 
tion is one which is in no way peculiar to service in the navy; 
it applies as well to all practitioners of medicine, and it has 
various causes. 
In England, and on the continent, the social standing of the 
physician was, in old times, far from the highest; this was, in 
part, dependent on the fact that the average medical man 
did not represent a very high type of social culture. But times 
have changed. The art of medicine rests to-day on a scientific 
basis, and with modern requirements and conditions, there is no 
class of professional men for whom a broader, general educa- 
tion is required. The time was when the sureogn might pre- 
sent himself for his entrance examinations after one or two 
years' cramming which had secured him the degree of M. P. 
at a medical school where the requirements for admission were 
little more than the ability to read and write. Such men. 
though often worthy and earnest workers, were probably some- 10 
Address Before Graduating Class 
times individuals whose social qualifications were scarcely equal 
to those of the line officers who had had the advantages of the 
excellent training afforded by the Academy at Annapolis. But 
to-day no one can graduate from the better medical schools with- 
out having a general education, at least equal to any which is af- 
forded to the line officer. If occasionally there may be some 
sense of annoyance at an apparent failure to appreciate the 
value and dignity of the medical corps, it may be of interest to 
you to know that the overseers of the old University from which 
1 graduated in both arts and medicine are still elected by the 
votes of the graduates of the academic and philosophical depart- 
ment alone. The graduates of a department of which the Uni- 
versity has such just cause to be proud as that of medicine-a 
department which now requires, as a condition for entrance, the 
possession of a degree of Bachelor of Arts-the Doctors of Med- 
icine-are still denied the franchise as unsafe and dangerous 
characters. This depends largely on the survival of the ancient 
prejudice founded on the memory of the character of some of 
the graduates of the medical school in the days of a two years' 
course with few or no requirements for entrance. But these 
are the last vestiges of an old tradition which has no founda- 
tion in the conditions of to-day. 
It seems to me, then, that a naval service should offer real 
attractions to young men entering upon their career in medi- 
cine, and particularly, perhaps, to those of a studious and con- 
templative character. 
And now, if I may be permitted, I should like to express a 
thought or two that have come to my mind as to the relations 
between the naval surgeon and the general profession. It has 
always seemed to me especially desirable that the associations 
between the medical corps of the army and navy and the gen- 
eral profession should be as close and familiar as possible. I 
cannot but feel that the ties which have been established be- 
tween the several members of the army and navy medical corps 
who have been detailed for special work in the laboratories or 
wards of the hospital with which I have been associated, and Address Before Graduating Class 
11 
the staff and students at that institution have been of real value 
to us all. The fine character and brilliant attainments of many 
of those men have given us a warm and lively interest in the 
service, and have resulted in a cordial and continued exchange 
of ideas. I have been struck in Germany by the frequency 
with which staff officers of the army and navy are found at 
work in the great laboratories and clinics, and by the close re- 
lations which exist between them and the general profession. 
The establishment of a medical reserve corps in the army and 
the judicious execution of the provisions of the bill by which 
this body was created by the late Surgeon-General and his suc- 
cessor, will, I think, be of great value in bringing together more 
closely the army surgeon and the medical profession throughout 
the country. It is an encouraging sign that an army surgeon 
should to-day be president of the American Medical Associa- 
tion ; that a naval surgeon-Dr. Beyer-should have taken so 
prominent a part in the recent International Congress for Tu- 
beiculosis; that your own Dr. Stitt should be an officer of the 
Society of Tropical Medicine. It is a most hopeful sign of the 
times that officers of the Marine Hospital Service should occupy 
important positions in the sections of the American Medical 
Association and take such an active part in the promotion of 
the hygienic welfare of the South. It is good that you have 
given me this opportunity to be among you to-day. Any meas- 
ures by which the medical profession in and outside the service 
may be brought more closely together can only prove of mutual 
benefit. 
It is to you in the army and navy that we in the general 
profession look for information as to the nature of and means 
of protection from many of those exotic scourges which the 
ever closening relations with foreign parts are bringing closer 
and closer to our doors, and on these and other problems we 
should work hand in hand. 
These are the main thoughts that I have wished to express 
to you to-day, and in conclusion I can only thank you warmly 
again for the privilege of being here. I wish that I might come 
again as a member of your entering class. The author desires to disclaim responsi- 
bility for the form in which this publication 
appears. Various changes from his manu- 
script, such as the omission of diphthongs, 
the elimination of the final "al" from certain 
adjectives, the changing of the terminal "re" 
to "er", the running together of compound 
words and the omission of the final "e" from 
other words, were made against his express 
protest. THE AMEBOID ACTIVITY OF MEGALOBLASTS 
W I L LI A M SYDNEY T II A Y E B, M.D. 
BALTIMORE 
Reprinted from the Archives of Internal Medicine 
Feb., 1911, Vol. 7, pp. 223-225 
CHICAGO 
American Medical Association 
Five Hundred and Thirty-five Dearborn Avenue 
1911 THE AMEBOID ACTIVITY OF MEGALOBLASTS 
WILLIAM SYDNEY THAYER, M.D. 
BALTIMORE 
In the study of the blood and blood-forming organs so much attention 
has been given to methods of fixation and staining that the careful exam- 
ination of the fresh specimen or tissue is too often neglected. Certain 
biological characteristics of the cells, such, for instance, as ameboid activ- 
ity, may easily be overlooked. 
In the study of the blood of a case of Addisonian anemia of a chronic 
course, I have observed characteristic ameboid movements in a megalo- 
blast. Phylogenetically, it is not remarkable that a megaloblast should 
possess the powers of ameboid activity; indeed, one might expect that 
this should be so. Inasmuch, however, as the present observation is appa- 
rently the first of this nature, it would appear to be worthy of record. 
History.-R., aged 39, a patient of Dr. G. A. Hartman, consulted me on 
Sept. 27, 1905. His family, personal history and habits were excellent. Two 
years previously he had had several "spells" of faintness which occurred about a 
week apart. These were associated with a slight feeling of confusion. He never 
actually fell, the attacks lasting but a minute. Shortly after this, his ankles 
and legs began to swell. He became more and more short of breath after 
exertion. There were periods of diarrhea; no blood in the stools. Somewhat 
over two months before consulting me he had been obliged to give up work on 
account of great weakness and diarrhea. 
Physical Examination.-The patient was a rather sparely nourished man, 
with marked yellowish pallor of the face, lips and mucous membranes; conjunc- 
tivae were subicteric; slight arcus senilis. Pulse in the recumbent posture 
28 to the quarter. There was nothing remarkable on examination of the 
lungs or the heart, except a soft systolic murmur heard all over the cardiac area 
in the recumbent posture, which almost disappeared at the apex in the erect 
posture. The abdomen was a little full. Hepatic flatness began at the sixth rib 
above, border palpable 2 to 3 cm. below the costal margin in the mammillary 
line. In the median line, by percussion, it extended to a point about 5 cm. above 
the umbilicus. The spleen was palpable; knee-jerks active; deep reflexes in the 
arms very lively. On the left side there was a distinct ankle-clonus. Sensation 
appeared to be good in the legs, both of which were bandaged because of edema. 
Blood: Fresh specimen showed a very marked poikilocytosis; numerous very 
large elements; color of the individual corpuscles apparently good. Leukocytes 
were scanty, the proportion of whites to reds being apparently rather high. 
Red blood cells 1,464,000 
White blood cells 4,000 
Hemoglobin 30 to 35 per cent. 
A differential count of the leukocytes showed: _ ~ , 
Per Cent. 
Polymorphonuclears 71.9 
Small mononuclears 17.3 
Large mononuclears 4.8 
Eosinophils 3.0 
Myelocytes 1.6 2 
During the differential count one megaloblast and three normoblasts were 
seen. 
Oct. 10, 1905: Examination of Stool: A large liquid stool, with a few 
small formed particles, yellowish-brown in color. Microscopically, much granular 
detritus; numerous muscle cells and vegetable cells; few triple phosphate and 
many Charcot-Leyden crystals; very large number of cercomonads; no eggs of 
parasites. 
Rest and arsenic in increasing doses were prescribed. The patient remained 
at home under the care of his physician, Dr. Hartman, and improved slowly. 
Jan. 7, 1906: Red blood cells, 1,692,000; white blood cells, 4,500; hemo- 
globin was 55 per cent. No eosinophils were found; there was an increased per- 
centage of small mononuclears. 
Feb. 18, 1906: Red blood cells, 2,394,000; white blood cells, 4,000; hemoglobin 
amounted to 58 per cent. 
May 16, 1906: Red blood cells, 2,584,000; white blood cells, 6,500; hemo- 
globin amounted to 65 per cent. 
Nov. 15, 1906: The patient has been steadily improving. Color looks much 
better. Has gained twelve pounds in weight. Hemoglobin 80 to 90 per cent, by 
Tallquist. 
The patient was not seen again for a year and a half. He consulted me 
again on May 30, 1908. Since the winter, he had been failing. A morning 
diarrhea had set in during the winter which had exhausted him greatly, obliging 
him to give up work. There had been a slight purpuric eruption on his legs; 
three weeks previously, nose-bleed. There was marked pallor, slightly subicteric; 
pulse of rather low pressure, rapid at the beginning of examination; slight 
protodiastolic gallop at the apex; a soft systolic murmur all over the cardiac 
area. The abdomen was a little full; liver about one and one-half fingers' breadths 
below the costal margin, soft and smooth. The spleen was readily palpable and, 
on quiet breathing, visible about two fingers' breadths below the costal margin. 
Knee-jerks were active. 
Blood: On examination of a fresh specimen, the following note was 
made: "Corpuscles on the average very large; great difference in size; 
marked poikilocytosis. Leukocytes, scanty. One megaloblast seen in the 
fresh specimen. 
"Under observation, this megaloblast shows typical ameboid move- 
ments. Small round pseudopodia are projected into which the colored 
protoplasm flows in much the same manner seen with the ordinary 
intestinal amebas. Slight changes in shape occur at times in the nucleus. 
The movements of the cell are marked, strikingly like those in leukocytes, 
and entirely unlike the gradual changes of shape sometimes seen in red 
blood corpuscles in the fresh specimen. The pseudopodia that are pro- 
jected are exactly like those seen in the movements of a polymorphonu- 
clear leukocyte; that is, on the edge of the cell there appear sometimes 
very small round buds, several at a time, which coalesce and form larger 
processes. The absolute homogeneity of the protoplasm does not allow 
one to observe the rolling motion so clearly as in the case of Amoeba coli 
or a leukocyte containing granules. At times, however, the movement is 
really rather active as shown in the few drawings that I have made. The 
change is so distinct that in the course of five minutes the whole picture 
is different." Megaloblasts in a case of Addisonian anemia showing true ameboid movements. The 
outline drawn by the author from the fresh specimen represents eight successive phases of the 
movement of the cell. The original drawings were elaborated in detail and colored by Mr. 
Herrman Becker under the supervision of the author from a similar megaloblast selected from 
the bone-marrow of a new-born infant. 
On the left and above is seen a normal red blood corpuscle. Figs. 1 to 8, Ameboid move- 
ments of the megaloblasts. 3 
The accompanying illustration shows six successive phases of this cell 
which I drew from the fresh specimen. The picture was so remarkable 
that I demonstrated the specimen to my neighbor, Dr. Hamman. By the 
time Dr. Hamman had arrived, the movements had become very sluggish, 
but the projection of one pseudopod, into which the protoplasm grad- 
ually flowed, was clearly observed. Red blood cells, 1,488,000; hemo- 
globin, Tallquist, 30 per cent. 
The patient was not seen again for over a year. On Nov. 1, 1909, however, 
he consulted me again, stating that he had picked up during the summer of 1908, 
but in the spring of 1909, had begun to fail again, recovering remarkably, how- 
ever, under atoxyl. The general appearance of the patient was very much better. 
He was still a little pale and looked rather thin, but the great pallor which he 
had shown before had almost entirely disappeared. 
The fresh blood showed a remarkable change in appearance. The corpuscles 
were rather deeply colored, and, on the average, of rather large size. There was 
little poikilocytosis, but occasional pear-shaped and saucepan-shaped cells were 
observable. The leukocytes were obviously diminished. No nucleated reds were 
seen in the fresh specimen. There were occasional microcytes. Red blood cells, 
3,600,000; hemoglobin, 87 per cent. 
The patient was seen again on Aug. 24, 1910. He was rather pale, but on the 
whole in fairly good condition. The physical examination showed nothing remark- 
able. The liver and spleen were of about the same size as on the last note. Red 
blood cells numbered 2,207,000; white blood cells, 3,350; hemoglobin was 62 per 
cent. The fresh specimen showed considerable difference in the size of the 
corpuscles; there was a number of microcytes, but macrocytes were especially 
numerous; there was considerable poikilocytosis; leukocytes were very scanty. 
Vital staining by Vaughan's and Widal's methods showed very few corpuscles 
with intracellular staining. Little polychromatophilia. The corpuscles showing 
vital staining were certainly fewer than 1 to 100. Differential count of the 
leukocytes showed: lymphocytes, 38.6 per cent.; large lymphocytes, 0.6 per cent.; 
large mononuclears, 2.8 per cent.; eosinophils, 0.4 per cent.; unclassified, 1.2 
per cent. There were no myelocytes, basophils or nucleated reds seen in counting 
250 white corpuscles. The reds were of good color. There was well-marked 
anisocytosis and poikilocytosis. The resistance of the red blood corpuscles to 
solutions of sodium chlorid showed the onset of hemolysis at 0.325 per cent.; 
complete hemolysis at 0.275 per cent. 
SUMMARY 
In a typical instance of Addisonian anemia, ameboid movements were 
observed in a characteristic megaloblast. These movements were alto- 
gether analogous to those seen in polymorphonuclear leukocytes. 
In the early stage of development represented by the megaloblast, the 
red blood corpuscle is then, probably, a cell with powers of active 
progression. 
In conclusion, it may be well to urge the more frequent study of the 
behavior of the various elements of the blood and blood-forming tissues, 
wherever they may be obtained sufficiently early, in the fresh state under 
conditions as nearly approaching the normal as may be. TWO CASES OF CONGENITAL HaEMOLYTIC JAUN- 
DICE WITH SPLENOMEGALY. OBSERVATIONS 
ON HaEMOLYTIC JAUNDICE. 
By William S. Thayer, M. D., 
Professor of Clinical, Medicine, Johns Hopkins University, 
AND 
Roger S. Morris, M. D., 
Associate in Medicine, Johns Hopkins University. [From The Johns Hopkins Hospital Bulletin, Vol. XXII, No. 240, 
March, 1911.] 
TWO CASES OF CONGENITAL HAEMOLYTIC JAUN- 
DICE WITH SPLENOMEGALY. OBSERVATIONS 
on haemolytic jaundice. 
By William S. Thayer, M. D., 
Professor of Clinical, Medicine, Johns Hopkins University, 
AND 
Boger S. Morris, M. D., 
Associate in Medicine, Johns Hopkins University. 
In 1900 Minkowski reported the history of a group of indi- 
viduals belonging to one family, all of whom showed a remark- 
able syndrome characterised by chronic acholuric jaundice, 
splenomegaly and urobilinuria. The appearance of these 
symptoms could be traced through three generations affecting 
at least eight members of the family. The general health of 
these individuals was not essentially impaired and no impor- 
tant changes were observed in the blood. 
Bettmann, in the same year, described a similar case in 
which the jaundice displayed marked variations in intensity, 
deepening after exercise, food, drink and excitement, esp^ia1 d 
anger, and also after exposure to cold. An experimental 
haemoglobinuria might be produced in this case by the appli- 
cation of cold. 
Pick (1903) and von Kranhals (1904) reported like cases, 
the latter having observed a family of which nine members in 
three generations showed a chronic congenital splenomegalic 
jaundice. In all instances the stools were of normal color. 
The urine which was of a dark color, was free from albumen, 
blood and hgemoglobin; it showed constantly the presence of 
urobilin, but never of bile. The number of red corpuscles was 
below normal, 2,300,000 and 3,500,000 respectively, in the 
[851 
[861 
1 186] 
men, and, on one occasion, as low as 1,000,000 in one of the 
women. The haemoglobin ranged between 55% and 65%. 
The red blood corpuscles were irregular in contour and varied 
in size from 6 to 10 /z. There were no nucleated reds but well 
marked polychromatophilia. 
Minkowski was fortunate in obtaining a necropsy of one of 
his patients. No especial changes were found in the liver, and 
the bile passages were quite clear. A small pigment stone was 
found in the gall bladder. The spleen was enlarged, and 
microscopically there were simple hyperplasia and hyperaemia. 
The kidneys showed a brownish discoloration produced by a 
granular pigment deposit in the epithelial cells of the convo- 
luted tubules. Not only did this pigment give an intense re- 
action for iron, but there was a large amount of material 
united with proteids which gave the reaction only after boil- 
ing with ammonium sulphide. From but one kidney about 
0.95 grammes of pure iron was obtained. Similar pigmenta- 
tion did not appear in any other organ. 
Minkowski regarded the condition as dependent on an 
anomaly of the blood pigment transformation, perhaps conse- 
quent upon a primary change in the spleen. 
The clinical picture was not a new one. Similar observa- 
tions had been made before by Murchison (1883), Wilson 
(1890) and Le Gendre (1897), and the syndrome appears to 
be similar to the Chronic Simple Jaundice with Splenomegaly 
of Gilbert and the Chronic Infectious Jaundice of Hayem 
Q898). It was, however, Minkowski's observation and 
necropsy report that first brought this condition sharply before 
the medical world. During the seven years following Min- 
kowski's original communication, a considerable number of 
similar observations found their way into the literature: 
Chauffard (1901); Barlow and Shaw (1902); Mason 
(1902); Widal and Ravaut (1902); Arkwright (1903); 
Lortat-Jacob and Sabareanu (1904) ; Caporali (1905) ; Claus 
and Kalberlah (1906) ; Strauss (1906); Benjamin and Sluka 
(1907). 
These cases seem to bear a striking resemblance one to 
another and suggest a common cause. The absence of evidence 
of hepatic disease and the existence of extensive siuerosis. es- 
(2) pecially of the kidney, in some respects analogous to that seen 
in Addisonian anaemia, on which Hunter especially has in- 
sisted, point to an increased blood destruction as a primary 
cause of the disease-an hypothesis adopted by most of these 
authorities. 
In 1907 Chauffard made an interesting contribution to 
the study of this syndrome by the discovery in a similar case, 
of a marked fragility of the red blood corpuscles on exposure 
to hypotonic solutions of sodium chloride according to the 
method of Vaquez and Ribierre. This observation he was 
able to confirm in two patients presenting a similar syndrome 
in the wards of his colleague Widal. Thus, while with the 
normal red blood corpuscles haemolysis begins at .42%-.44%, 
and is complete at .32%, in these three cases the beginning 
and end of haemolysis were respectively .62% and .36%, .66% 
and .34%, and .52% and .18%. The average size of the red 
blood corpuscles was somewhat diminished. 
Widal and Philibert on further study, were unable to de- 
monstrate the presence of any haemolytic properties in the 
serum of their own patients, either with regard to their own 
corpuscles or those of other individuals. This fragility of the 
red blood corpuscles, so marked toward hypotonic salt solu- 
tions, was also evident in respect to other haemolytic sub- 
stances. The diminished resistance of the red blood cor- 
puscles has been a constant feature in the considerable number 
of cases of this malady which have since then been reported. 
A few months later Chauffard described another interesting 
haematological feature which he had observed in all cases of 
this disease which had come under his observation, namely: 
the presence, on vital staining of a peculiar basophilic granu- 
lation of the red blood corpuscles. Chauffard's first studies 
were made by staining freshly made and fixed smears of blood 
with Pappenheim's (pyronin and methyl-green) solution. 
Many of the red blood corpuscles which are of a slightly grayish 
color and barely visible, having lost their refractiveness with 
their haemoglobin, show a fine granulation of a bright red 
color. These dots, generally arranged about the periphery, are 
sometimes scattered throughout the cells in the form of a defi- 
nite granulation. The granular corpuscles are usually some- 
[86] 
(3) [86] 
what larger than their neighbors; they may be demonstrated 
well by the method of vital staining of Widal, Abrami and 
Brule. 
Four to six drops of blood are allowed to fall into a test tube 
containing 10 drops of a basic coloring matter which is quite iso- 
tonic and contains in addition oxalate of potassium to prevent the 
coagulation of the blood. 
Oxalate of potassium, 20%, 2 cc. 
Unna's polychrome methylene blue, 100 drops 
A = - 0.60 
The fresh corpuscles are allowed to remain for 10 to 20 minutes 
in contact with the solution, after which the mixture is centrifu- 
galized, the supernatant fluid is removed, and the corpuscles 
drawn up with a pipette and placed upon slides upon which they 
are spread as an ordinary drop of blood; the covers are then dried 
and fixed by heat. Such preparations may be preserved indefi- 
nitely. 
The distribution of the granules is irregular. Sometimes 
scattered, they are usually collected in groups of two and 
three. Sometimes they are arranged in the form of a wreath 
or crown at the periphery of the corpuscle; they are generally 
distributed in such a manner as to suggest filaments wound 
around within the cell and showing frequent varicosities; they 
are unequal in size and of irregular form. Not infrequently 
this granular net-work is gathered together toward the pe- 
riphery or near the centre of the cell in such a manner as to 
suggest grossly a nucleus. 
Sabrazes has called these corpuscles " granulo-reticulo-fila- 
mentous." The apparent reticulum is very adherent to the 
red blood corpuscle. If a dried and stained specimen be washed 
with pure water the corpuscles lose their blue color, while the 
granular filamentous appearance remains. Indeed, in some 
cases the reticulum may be found outside the corpuscle, lying 
between other well preserved elements. Widal, Abrami and 
Brule have thought that the polychromatophilia which is pres- 
ent to a certain extent in these cases, bears a close relation to 
the presence of granular corpuscles, but this does not appear 
to be an absolute rule. 
It is exceedingly interesting to see how closely these observer 
agree in their descriptions of this granulation with the careful 
studies of Vaughan (1903). Although originally described by 
[87] 
(4) Pappenheim,* the first careful studies upon the vital staining I 
of the red blood corpuscles were made by Vaughan, who found 
that this granulation was present in somewhat under 1% of 
the red blood corpuscles of normal individuals. In the new- 
born, where they are most frequent, the highest percentage 
with but one exception (7%) was 4%. In pernicious ansemia 
with active regeneration, they were found in great numbers 
(once as high as 18%). In congenital icterus with splenomeg- 
aly the percentage is usually over 10%, and figures as high 
as 40% have been reported. Chalier, however, in his excellent 
monograph, is inclined to regard these figures as excessive, 
asserting that he, himself, has never seen a percentage above 
20. This granulation, it is needless to say, is quite distinct 
from the basophilic granulation of Grawitz and others. The 
granules are different in shape and arrangement and are not 
to be stained in the fixed specimen. They are, of course, quite 
distinct from the remarkable Schiiffner's granules which ap- 
pear with Romanovsky's stain in certain parasitiferous cor- 
puscles in tertian and sestivo-autumnal malaria. 
It is probable that this phenomenon is simply an indication 
of active blood regeneration (Vaughan, Ferrata), but there are 
apparently few conditions in which the frequency of these 
granular corpuscles compares with that in congenital jaun- 
dice-a fact which seems to give them a real diagnostic 
value. 
These observations have been confirmed by a considerable 
number of observers, and the picture of this disease, which 
Chauffard has called haemolytic jaundice, is sufficiently definite 
to be regarded as a distinct clinical entity. 
The patient often belongs to a family other members of 
which have suffered from the same condition. Early in life, 
sometimes immediately after birth, but in other cases later, 
perhaps not until puberty, a jaundice appears. This jaundice 
is usually of a moderate degree varying from a pale lemon hue 
to a well marked golden yellow. It is remarkably variable, 
[87] 
* This subject is well discussed by Ferrata who, however, in 
common with every continental author, ignores Vaughan's excel- 
lent work. 
(5) [87] 
increasing often under physical effort or emotional excitement. 
The stools are of normal color or pleiochromic, especially 
under those conditions associated with increase in jaundice. 
The urine is of rather high color, often of a brownish almost 
mahogany hue, but free from bile. Urobilin is usually demon- 
strable. The blood shows an anaemia of moderate degree, 
generally between 3,000,000 and 4,000,000 red corpuscles, al- 
though in one case a blood count of under 2,000,000 is re- 
ported. There is usually considerable anisocytosis, but little 
or no poikilocytosis. The average size of the corpuscles is 
sometimes rather below the normal, a point upon which Chauf- 
fard particularly has insisted. The color index is somewhat re- 
duced. Polychromatophilia is usually well marked. On vital 
staining the granulation described by Pappenheim, Vaughan, 
Sabrazes, Chauffard and others is present in a large number 
of corpuscles. The percentage of granular elements is usually 
above 10% and may be as high as 20%, or even more. The 
serum is of a clear, yellowish color, and the test for bilirubin is 
positive. Urobilin is generally undemonstrable. The leuko- 
cytes are usually of normal number or slightly increased. The 
differential count shows nothing remarkable beyond evidences 
of increased marrow activity as manifested by a high per- 
centage of eosinophiles and the occasional presence of myelo- 
cytes and nucleated red cells-normoblasts. 
The serum shows a rather high degree of hypertonicity. 
Starkiewicz regarded this condition as a mechanism of defense 
on the part of the organism to protect the fragile red cor- 
puscles. Troisier, however, believes it to be the result of 
exosmosis of the corpuscular salts as a result of the fragility 
of the red cells. 
The remarkable feature of this interesting condition is that 
subjective symptoms are usually absent despite the constant 
anaemia. The patients are generally unconscious of any dis- 
ability. They appear to adapt themselves so well to their con- 
dition that it is only occasionally that a complaint is elicited. 
There is a complete absence of all the ordinary phenomena of 
biliary intoxication: there is no bradycardia; no pruritus; no 
tendency to haemorrhage; no xanthelasma. The patients are, 
indeed, as Chauffard has gracefully said, " a peine des mal- 
(6) ades-plutot des icteriques que des malades "-barely pa- 
tients, rather icterics than patients. 
There is one exception to this rule. Many of these indi- 
viduals suffer from attacks of abdominal pain suggestive of 
biliary colic. These pains, localized in the epigastrium and in 
the region of the gall bladder, are often accompanied by fever 
and by an aggravation of the jaundice. In a number of 
instances they have been so severe as to lead to operation. In 
many cases it is probable that the attacks are due to the pres- 
ence of small pigment stones in the gall bladder, such as have 
been found in four of the six cases of congenital jaundice that 
have come to necropsy-every instance but one in which the 
gall bladder was examined. 
In the last several years the authors have had the oppor- 
tunity of observing two striking cases of congenital haemolytic 
jaundice which appear to be worthy a note of record. 
Case I.-Miss X., 16 years of age, a school girl, consulted one of 
us (W. S. T.) on the 30th of May, 1906, with a complaint of jaun- 
dice. Her father and mother were well and strong. She has one 
sister, younger than herself, who is perfectly well, and the family 
history in other respects, is good. 
Her mother states that as an infant the patient used to have 
slight attacks of jaundice for which they were accustomed to 
give her calomel, but as she grew older the attacks became more 
frequent until, finally, the jaundice became permanent. The yel- 
low color has varied in intensity from time to time, but the 
mother is not sure that it has ever been wholly absent. It has 
been deeper as a rule at the time of menstruation, and worse after 
exertion and bad colds, or with any indisposition. Six years ago 
the patient had a febrile attack which was regarded as typhoid 
fever, in other respects she has been a strong healthy girl, taking 
part in all the out-of-door games of her companions. She is not 
conscious of having been short of breath. 
Eight months ago she began to have occasional attacks of pain 
in the right side of the epigastrium, lasting from ten to twenty 
minutes. Of these attacks she has had several. Three weeks ago 
she had a paroxysm of sharp, cramp-like pains in the same posi- 
tion, so sharp that at times while at school she had to lie down; 
there has been no fever with any of these attacks, but in the last 
three weeks she has had more or less pain, usually every other 
day. Lately the jaundice has been worse, but it is the pain that 
has excited the attention of her parents. 
[87] 
[88] 
(7) [88] 
In other respects she had felt perfectly well and only recently, 
since she has grown older, she has been somewhat annoyed by 
the consciousness of her jaundice. 
On examination there was a distinct jaundice although in other 
respects the color of the patient was that of a healthy girl; the 
tongue was clean; pulse 19 to the quarter, regular, not remarkable. 
Examination of heart and lungs negative. 
Abdomen, natural; no tenderness on pressure in the region of 
tne gall bladder; palpation, negative, although, on light percus- 
sion, there is possibly a very slight suggestion of dulness in the 
region of the gall bladder. The spleen in readily palpable, de- 
scending on deep inspiration at least 4 cm. below the costal 
margin. 
Widal reaction, negative. 
Blood: 
R. b. c 3,680,000 
W. b. c 800,500 
Hb 70-71% 
Dried and stained specimens showed the red blood corpuscles of 
about normal size with but slight variation in diameter; the 
color is good; no marked polychromatophilia. Their contour is 
fairly regular, but there is some distortion, a few elliptical and 
dumbell shapes being found. No nucleated reds. 
Differential count: 
Polymorphonuclear neutrophiles 72.5 % 
Small mononuclears 18.0% 
Large mononuclears 7.5 % 
Transitionals 1.5 % 
Eosinophiles 5 % 
The case was regarded as one of chronic, congenital jaundice 
with splenomegaly of the type described by Minkowsky. There 
was a question as to the existence of gall stones, but, in the ab- 
sence of severe symptoms, operation was not advised. Blaud's 
pills to be continued through long periods of time, were pre- 
scribed. 
Three years later, having become familiar with the work of 
Chauffard, Widal and others, the writer requested the parents of 
the patient to allow him to see her again. She was accordingly 
seen on the 20th of March, 1909. Jaundice had been present for 
the greater part of the preceding three years, although the patient 
had grown and developed normally and was a perfectly healthy 
looking girl. The mother says that after long periods in the 
house she becomes more jaundiced and that dancing, violent ex- 
ercise and bad colds make it worse. It is worse at the catamenial 
(8) periods, better just afterwards. The author's note on this occa- 
sion reads: 
" Strong, healthy looking girl; color good; tongue clean. 
There is a distinct slight jaundice of the skin and conjunctiva. 
Pulse 22 to the quarter, regular, not remarkable in quality. 
Heart sounds, clear at the apex and base. 
Abdomen: natural in appearance. Spleen, readily felt just be- 
low the costal margin, descending on deep breath 3 or 4 cm. below. 
It seems smaller than when last seen. The liver descends just 
below the costal margin on deep breathing; flatness above at 
about the 6th rib, extending to the costal margin. Gall bladder, 
not felt. 
Blood: 
R. b. c 3,200.000 
Hb 75% 
w 
Resistance of the red blood cells: 1 cc. of blood was collected in 
9 cc. of 1% aqueous sodium fluoride solution, and the corpuscles 
were subsequently washed three times in 0.85% NaCl solution. A 
5% suspension of the red corpuscles in 0.85% salt solution was 
prepared. The corpuscles were then placed in solutions of NaCl of 
varying strength and the first trace of haemolysis (minimal re- 
sistance) and complete haemolysis (maximal resistance) noted. 
The results showed: 
Minimal resistance 0.68% NaCl. 
Maximal resistance 0.45% " 
After centrifu°-alizing the blood-sodium fluoride mixture, the 
supernatant fluid was found to be of a canary yellow color; it 
was pipetted off and tested for urobilin and bilirubin. Neither 
pigment could be demonstrated, using the technique described by 
Conner and Roper. 
Urine.-Fresh specimen March 20, 1909. Brownish yellow, 
clear, acid, sp. gr. 1.014; albumen and sugar absent; bile: foam 
white; tests with yellow nitric acid negative. Trousseau's test 
(tincture of iodine) negative. Urobilin: marked green fluorescence 
on treating the amylic alcohol extract with 1% ZnCL in ammo- 
niacal alcohol; also positive on spectroscopic examination. 
On the 4th of April, after taking Blaud's pills gr. V, t. i. d. for 
two weeks, the patient allowed us to make another examination of 
the blood: 
R. b. c 3,800,000 
W. b. c 5,200 
Hb 84% (Dare.) 
Vital staining of fresh blood with Unna's polychrome methylene 
blue, according to the method of Vaughan, showed 149 red cells 
[88] 
(9) [88] 
with basophilic granulations out of 1228 cells examined, or about 
12.1% (normal = 0.5% to 1.8%.-Vaughan). 
Differential count of 564 cells with Ehrlich's triacid stain: 
Lymphocytes 18.6% 
Large mononuclears and transitionals.... 3.5% 
Polymorphonuclears, neutrophilic 73.0% 
Polymorphonuclears, eosinophilic 1-2% 
Polymorphonuclears, basophilic 0.7% 
Myelocyte, neutrophilic 0.17% 
Degenerated 2.6% 
Wilson's stain (Romanovsky) and the triacid stain were used 
in studying the red cells. There was moderate anisocytosis, no 
poikilocytosis. The red cells were of good color and no polychro- 
matophilia, basophilic granules, nuclear particles, Cabot's ring 
bodies, or nucleated reds were seen. The blood platelets were 
rather few in number in the stained specimens. 
Resistance of the red blood corpuscles: 
Minimal resistance 0.72% NaCl. 
Maximal resistance 0.42% " 
The blood plasma-sodium fluoride mixture was again of a bril- 
liant canary yellow color. Using the methods recommended by 
Conner and Roper, bilirubin was demonstrated; tests for urobilin 
were negative. 
Urine.-Fresh specimen, April 8, 1909. Yellowish brown, clear, 
acid, sp. gr. 1.024; albumen, sugar and bile, absent. Urobilin: 
marked positive reaction, both chemical and spectroscopic. Micro- 
scopical examination showed a few squamous epithelial cells; 
otherwise negative. 
Stool.-Dark brown, small, constipated stool. No blood, pus or 
mucus. Microscopical examination: a few muscle fibers without 
striations, many yeast cells. No ova or parasites. Schmidt's test 
(concentrated corrosive sublimate) positive for urobilin, negative 
for bilirubin. 
Blood.-The average diameter of 500 red corpuscles in dried and 
stained specimens (Wilson's modification of Romanovsky) was 
7.45 /j.. The variations were between 5 and 9.4 g-essentially nor- 
mal measurements. 
In July of the same year the patient was seen in Europe. At 
that time she seemed perfectly well but showed, as always, a dis- 
tinct slight jaundice of the skin and conjunctivae. 
The general appearance of the patient was very remarkable. 
Without observation one would have picked her out as a perfectly 
healthy girl; her cheeks were red and her expression bright, the 
general nourishment good and it was a matter of great surprise to 
[89] 
(10) find so marked an anaemia. She had never been short of breath 
and complained of no subjective symptoms of anaemia. 
The second case was seen in the wards of Prof. Barker, to 
whose courtesy we are indebted for the privilege of reporting 
the case. 
Case II. (Med. No. 23623).-F. B., single, age 27, a manicurist, 
was admitted to the hospital on January 22, 1909, complaining of 
jaundice. The family and personal history are good. No other 
member of the family is jaundiced. The patient has had measles 
at 9, mumps at the same age and whooping-cough at 12. During 
the last twelve years there have been occasional attacks of major 
hysteria, usually following mental shock. There has been chronic 
constipation. The patient has been jaundiced since she was three 
days old; the jaundice is variable, sometimes very deep and 
again scarcely noticable. Since the age of 16 she has complained 
of what she called bilious spells about twice a month. While 
dressing in the morning she becomes nauseated, vomiting one or 
two ounces of fluid, at first like water and then almost pure. bile. 
A few minutes after vomiting she feels relieved and is able to go 
to work. 
There is no history of pain in the region of the gall bladder, or 
of haematemesis. The patient has not passed acholic or bloody 
stools to her knowledge. She has had no abdominal pain. In 
July cholecystostomy was performed by Dr. John D. Blake. No 
gall stones were found. 
About two months ago the patient began to have a " dead, 
aching pain " a little below the right scapula; the pain seldom 
shifted. There has been slight pain occasionally above the left 
nipple. Her average weight is 138 lbs.; in the last three months 
she has lost 13 lbs. 
Status presens. (Dr. Boggs).-The patient is well nourished. 
There is a marked icteric tint to the entire skin, the sclerae and the 
mucous membranes. No xanthoma. The lungs are negative. 
Heart : Apex is just felt in the 4th interspace 9.5 cm. to the left 
of the median line. Relative cardiac dulness extends 10.5 cm. to 
the left in the 5th, 3.5 cm. to the right in the 3rd interspace, and 
above to the 3d rib. There is a soft systolic blow at the apex, 
transmitted to the axilla. Pulmonic second sound accentuated. 
There is a blowing systolic murmur over the conus. 
Abdomen: Spleen extends 4 cm. downward and forward beyond 
the costal margin. Liver not palpable. No haemorrhages noted. 
Jan. 29. (Dr. Thayer). Perfectly healthy looking woman with 
yellowish type of jaundice. Tongue clean. Abdomen slightly 
more prominent on left. Spleen readily palpable. Liver not en- 
larged. 
[89J 
(11) [89] 
Feb. 5. (Dr. Hanes). Since admission the patient's only com- 
plaint, jaundice, has varied very markedly from a light yellow to 
a deep lemon color. The sclerae are constantly yellow and do not 
vary as much as the skin. The heart is as noted before,-the 
systolic blow is very faint and is not transmitted to the axilla. 
Spleen still enlarged, edge firm and sharp. Patient discharged. 
During the patient's stay in the hospital, her blood pressure 
(systolic) varied between 100 and 118 mm. Hg. The temperature 
was between 97.6° and 100.2° F. Pulse 60 to 83, respirations 18 
to 20. 
Blood examinations: 
Jan. 23. R. b. c 3,800,000 
W. b. c ' 8,900 
Hb 70% 
In the fresh blood the red cells appear normal in color and 
shape. No nucleated reds or parasites. 
Jan. 26. Wasserman reaction negative. Coagulation time, 5 min. 
Jan. 27. Blood count practically the same as on the 23d. 
Jan. 28. (Dr. Hanes). The patient's blood serum is of a golden 
yellow color, and the HN03 test for bile is positive. 
Jan. 29. (Dr. Rous). "Resistance of the red blood cells to 
hypotonic salt solution. Into a series of tubes containing 1 cc. 
each of dilute salt solution 20 mm. of the patient's whole blood 
were dropped. The dilutions comprised a series from 0.85% to 
0.10% NaCl. As control, the blood of S., who had about the same 
number of cells per cm., was taken. The corpuscles of S. showed 
complete haemolysis at a dilution of 0.30% and those of the 
patient at 0.40%. (This is an immediate observation). After 24 
hours the reading showed a trace of haemolysis at 0.55% for S., 
and about the same at 0.75% for the patient." 
Differential count of 400 cells showed: 
Lymphocytes 47.0 % 
Large mononuclears and transitionals... 5.25% 
Polymorphonuclear neutrophiles 46.0 % 
Polymorphonuclear eosinophiles 0.5 % 
Mast cells 0.25% 
Unclassified 0.75% 
Feb. 3. R.b. c 3,700,000 
W. b. c 10,500 
Hb 76% 
Viscosity 4.1 (in terms of distilled water). 
Stool examinations were made on Jan. 27 and 29 and on Feb. 3. 
Schmidt's test showed only hydrobilirubin. Microscopically noth- 
ing of importance was found. 
Urine was examined on six different days. Sp. gr. 1.018 to 1.030. 
(12) There was no albumin or sugar. No bile or bilirubin was demon- 
strated. Urobilin was tested for apparently only on Feb. 4th, 
when the report says, " Schlesinger's urobilin test negative. 
Spectroscopic examination inconclusive." The color of the urine 
was described as brownish yellow and orange. 
It is rather unfortunate that more careful tests for urobilin 
were not made; it must have been present. 
All attempts to communicate with the patient since her dis- 
charge from the hospital have failed. 
These cases are typical examples of this condition. Al- 
though both patients showed a well-marked jaundice, in 
neither was there the slightest disturbance in the shape of 
itching; in neither was there bradycardia. The complaint of 
the second patient bore apparently no relation to her jaundice. 
The extraordinary manner in which these individuals adapt 
themselves, as it were, to their anaemia, is strikingly illus- 
trated by both of our patients, especially by the first, whose 
appearance and history were not of a delicate but rather of a 
robust, strong girl. 
A striking peculiarity in the observations made upon this 
case is the remarkably high point of concentration of the 
solutions of sodium chloride at which complete haemolysis 
appears, .42% and .45%, a concentration equal to or above 
that at which, in the normal individual, haemolysis begins. 
Acquired Hcemolytic Jaundice.-1This remarkable syndrome, 
chronic acholuric pleiochromic jaundice without the usual 
symptoms of biliary intoxication, associated with anaemia, 
enlarged spleen, and siderosis of the viscera is not, however, 
always of congenital origin. Soon after Chauffard's first 
observations, Widal and Abrami, Chaufiard and Troisier, Le 
Gendre and Brule, von Stejskal, Oettinger, Parkes-Weber and 
others reported a series of interesting observations in which a 
similar train of symptoms came on without apparent cause in 
adult life. The onset of the jaundice in these instances fol- 
lowed various different accidents-an ischio-rectal abcess 
(Widal and Abrami), haemorrhage following a miscarriage 
(Widal and Abrami), severe nervous shock (Chauffard and 
Troisier), acute gastro-enteritis (Le Gendre and Brule). In 
other instances, such as the two cases of von Stejskal, that of 
Oettinger, and that of Parkes-Weber, the process seems to 
[89] 
[901 
(13) [90] 
have appeared without striking initial symptoms. Again, in 
a considerable group of cases a jaundice of a transient char- 
acter presenting similar haematological phenomena-an 
anaemia with signs of regenerative activity of the bone mar- 
row, granular corpuscles on vital staining and a marked 
fragility of the red cells, has been observed in the course of a 
variety of conditions, cancer of the stomach (Chalier) ; cirrho- 
sis of the liver (Chalier and Le Play); malaria (Sacquepee, 
Chalier) ; repeated haemorrhages in cancer of the bladder 
(Widal and Joltrain) ; streptococcus infection (Sacquepee) ; 
uncinariasis (Barre) ; syphilis (Gaucher and Giroux) ; pul- 
monary tuberculosis (Landoiizy); jaundice of the new born 
(Sabrazes and Leuret; Cathala and Daunay). 
This acquired haemolytic jaundice, as it has been called by 
Widal and Abrami, who described the first cases, does not 
constitute a definite disease picture to the same extent as does 
congenital splenomegalic jaundice, but rather an interesting 
syndrome. Acquired haemolytic jaundice may be divided, as 
suggested by Brule, into apparently primary and secondary 
cases. The former arise either without apparent cause or 
during the course of some acute transient malady, after which 
they persist with seeming independence. Secondary hemo- 
lytic jaundice is observed in a transient manner associated 
with acute infections or poisons, or as a terminal phenomenon 
in the course of some chronic disease. 
One essential difference exists between most of the cases of 
acquired haemolytic jaundice and the congenital malady, 
namely: the existence in the former of an anaemia sufficiently 
grave to occupy a prominent position in the clinical picture. 
The anaemia may, indeed, be intense and is associated with the 
usual subjective symptoms. There are often striking varia- 
tions in the intensity of the jaundice and the grade of anaemia. 
Sudden paroxysms of fever associated with painful swelling 
of the spleen and extremely rapid fall in the number of red 
corpuscles have been described. 
A patient of Widal and Abrami's showed, on the 19th of 
May, 2,600,000 red blood corpuscles; ten days later, while in 
apparently good condition, there appeared severe headache, 
dyspnoea, marked exacerbation of the jaundice, and in a day 
(14) or two the blood count showed but 850,000 red elements. In 
one of von Stejskal's cases the blood count rose in eighty days 
from 640,000 to 4,000,000. 
The blood picture is often very similar to that in pernicious 
anaemia; marked oligocythaemia; a high color index; anisocy- 
tosis ; poikilocytosis; often an increase in the average corpuscu- 
lar diameter. There are almost always marked evidences of 
marrow activity in the shape of nucleated red blood corpuscles, 
among which megaloblasts are often found. Contrary to what 
one sees in pernicious anaemia, the leukocytes are usually 
somewhat increased, and, occasionally, there is a well-marked 
leucocytosis, which, on differential count, shows a considerable 
proportion of myelocytes and a large percentage of eosino- 
philes. Granular corpuscles are present on vital staining, as 
in the congenital form of the disease; sometimes, however, 
these are not so numerous. 
There are two striking points of difference in the haemato- 
logical picture between acquired and congenital haemolytic 
jaundice. The corpuscular fragility, so evident in the former 
condition, is often very slight in the acquired disease when the 
test is made with unwashed corpuscles. 
Widal and Abrami showed early that in acquired haemolytic 
jaundice the corpuscular fragility may, indeed, be almost in- 
appreciable if the test be made with the whole blood. With 
deplasmatized corpuscles, however, the resistance is distinctly, 
sometimes very markedly, diminished. These authors showed 
that this increased fragility of the deplasmatized red cor- 
puscles is common to both congenital and acquired varieties 
of the disease with the essential difference that while in con- 
genital haemolytic jaundice the fragility is usually demon- 
strable with the whole blood, in the acquired condition the 
resistance of the whole blood may be normal, while that of the 
deplasmatized corpuscles may show a very marked reduction. 
The deplasmatized red blood corpuscles of acquired haemolytic 
jaundice show also a distinct diminution in resistance toward 
other haemolytic substances, such as anti-human sera of all 
sorts and leech extract. 
In normal blood the resistance of the deplasmatized cor- 
puscles does not differ essentially from that of the whole blood. 
[90] 
(15) [90] 
While it is difficult to avoid the conclusion that this in- 
creased corpuscular fragility has a definite association with 
the haemolysis which occurs in these cases, yet it should be 
remembered that no direct parallelism can be drawn between 
the'degree of fragility and the extent of the anaemia. The 
conditions existing in congenital and acquired haemolytic 
jaundice form an interesting paradox, as has been pointed out 
by Brule; on the one hand a marked corpuscular fragility 
associated with a moderate anaemia, on the other a moderate 
fragility and an intense anaemia. " It is impossible to draw a 
direct conclusion as to the fragility of the red blood corpuscles 
in the organism from their fragility in vitro." 
This diminution in tbe resistance of the deplasmatized cor- 
puscles may be restored if they be brought into contact again 
with their plasma. Although there is a slight difference be- 
tween the resistance of the corpuscles according to the manner 
in which they are separated from their plasma (IscoVesco, 
Salignat), yet these differences are so slight that they need not 
be considered; in fact the quantity of serum necessary to 
restore the resistance of separated corpuscles is so large that, 
practically, it is unnecessary to wash the corpuscles deplas- 
matized in an oxalate solution. The anti-haemolytic power of 
the serum is not restricted to that of the patient himself. It 
is present in other and heterologous sera. Heating to 56° C. 
for a considerable period of time does not remove the power. 
There would then appear to be no evidence of the existence of 
a specific anti-haemolytic substance. Widal, Abrami and 
Brule believe that the anti-haemolytic power is dependent on 
some special physical property or properties of the serum. 
The blood of some individuals with acquired haemolytic jaun- 
dice possesses one characteristic which, for the moment, 
appears to be rather special, and is not observed in the con- 
genital forms, namely, an auto-agglutinative power of the 
serum. The test is a relatively simple one; it is thus de- 
scribed by Brule. 
" One lets fall into a watch glass 10 drops of the patient's serum 
and then a drop of red blood corpuscles isolated by centrifugation: 
the mixture is shaken up and then allowed to rest. Soon the cor- 
puscles are seen to gather at the bottom, sometimes appearing to 
form little masses. But if there is no auto-agglutination, we need 
[91] 
(16) but to shake the glass slightly to restore the mixture to its pre- 
vious homogeneity and to disperse the corpuscles in the serum. 
If the auto-agglutination be positive, one sees after a period vary- 
ing according to the intensity of the phenomenon, from one to 
twenty minutes, a collection of the corpuscles into little granules 
easily perceptible by the naked eye, which give the emulsion an 
aspect comparable to brick dust; violent and prolonged shaking 
cannot dissociate these corpuscles. Little by little the agglutina- 
tion increases, the corpuscles gather at the bottom of the watch 
glass where they form an homogeneous pellicle, the supernatant 
serum becomes limpid, and shaking no longer dissociates the 
hsematic pellicle. If at the beginning of the phenomenon one 
examines a drop of the serum microscopically it may be seen that 
the corpuscles, instead of disposing themselves in rouleaux as 
normally, gather in little islands, between which there float a few 
isolated corpuscles." 
This phenomenon has been found in a number of instances 
of acquired haemolytic jaundice. In others, such as the cases 
of Widal and Joltrain, and that of Parkes-Weber, auto- 
agglutination has been absent. The phenomenon is interest- 
ing and may be of considerable diagnostic value. It is not 
present in congenital haemolytic jaundice, although the patient 
of Benech and Sabrazes, whose jaundice is believed by the 
authors to have been acquired from a wet nurse, might be 
regarded as belonging to this class. It has, however, been 
observed in one instance of hepatogenous jaundice by Brule. 
It should be said that it has not as yet been studied sufficiently 
to justify far-reaching conclusions as to its diagnostic value 
or significance. 
Attacks of pain in the region of the gall bladder associated 
with fever and exacerbation of the jaundice are very common. 
Indeed, the first three reported cases (Widal and Abrami; 
Chauffard and Troisier) were all operated upon for suspected 
gall stones. In one of these cases a little bile sand was found; 
in the other instances the gall bladder was quite clear. 
Acquired haemolytic jaundice presents itself in a variety of 
forms. The most important are: 
1. Those cases simulating cholelithiasis. 
2. Those simulating pernicious anaemia with jaundice. 
3. Those simulating a chronic infectious cholangitis, chron- 
ic, infectious, splenomegalic jaundice (Hayem). 
[91] 
(17) [91] 
4. It has also been observed in some of those conditions in 
which the most striking symptoms, anaemia and splenomegaly, 
leave one in doubt as to whether the case should be classed 
clinically as Banti's disease or a cirrhosis of Hanot's type. 
Recent studies by Chauffard and Troisier, as well as by Ar- 
mand-Delille and Feuille, suggest strongly the possible rela- 
tionship between some so-called splenic anaemias and haemolytic 
jaundice. Attention has also been called to this point by 
Parkes-Weber. 
In other instances the condition may manifest itself under 
the symptoms of an icterus gravis (Roque and Chalier). 
The syndrome is, however, sufficiently definite and easily to 
be recognized if carefully studied, by the absence of bile in the 
urine, its presence in the blood serum, the urobilinuria, the 
presence of a large percentage of granular corpuscles on vital 
staining, by the fragility of the red corpuscles, especially mani- 
fest with the deplasmatized elements, and by the commonly 
present auto-agglutinative power of the serum. 
It is important to remember that in Addisonian anaemia 
and in cholelithiasis the corpuscular resistance is at least 
normal; indeed, as a rule, it appears to be increased. In one 
of my cases of pernicious anaemia haemolysis began at only 
.325%, and was complete at .275%, a greatly increased 
resistance. 
In obstructive jaundice Vaquez and Ribierre have also 
shown that the resistance of the red corpuscles is as a rule 
distinctly increased, an observation which we have been able 
to confirm. 
Pathological Anatomy.-Several individuals presenting the 
syndrome of haemolytic jaundice have come to necropsy 
(Vaquez, Giroux and Aubertin; Oettinger; Gandy and Brule; 
Widal and Joltrain; Roque and Chalier; Micheli; Moller; Wil- 
son; Tileston and Griffin). The cases of Vaquez, Giroux and 
Aubertin, Gandy and Brule, Wilson, and Tileston and Griffin, 
were apparently of congenital origin; the others, probably 
acquired. In all cases, however, the essential features appear 
to have been general evidences of an haemolytic process as 
manifested by a siderosis of liver, spleen and kidneys. The 
autopsy in the case of Vaquez and Giroux is of especial interest 
[92] 
(18) as it occurred in a congenital case in which death followed 
splenectomy, so that complications with other terminal pro- 
cesses were ruled out. The lesions which have been confirmed 
in the later eases, were as follows: 
A marked congestion of the spleen especially confined to the 
pulp, the engorgement of which was in rather striking con- 
trast to the relative emptiness of the sinuses. There were few 
macrophages in the splenic pulp, more in the sinuses. The 
endothelial cells were stuffed with iron containing pigment. 
The liver showed no evidence of biliary obstruction, no 
angio-cholitis. Many of the liver cells, especially in the 
centro-lobular zones, were, however, stuffed with large gran- 
ules of ochre pigment. 
There was moderate siderosis of the cells of the convoluted 
tubules of the kidney, and marked hyperplasia of the marrow. 
These observations have been confirmed, in great part, in 
all cases which have come to necropsy, affording thus abundant 
evidence of the haemolytic character of the process. The 
siderosis of the kidney, which is usually present, has, however, 
been very moderate in some instances, and was apparently 
absent in Gandy and Brule's case of congenital haemolytic 
jaundice, where death occurred in the course of a pneumonia 
as well as in Micheli's instance of the acquired form of the 
disease. In no instance was there evidence of biliary obstruc- 
tion. 
Pathogenesis.-The pathogenesis of this remarkable syn- 
drome is by no means clear. The evidence of a chronic 
haemolytic process is not so very different, indeed, from that 
which one sees in various other conditions, such especially as 
Addisonian or bothriocephalus anaemia, conditions in which 
chronic jaundice is not uncommon. The clinical picture in 
some of the acquired forms of the disease with crises of ag- 
gravation of the malady, may almost resemble paroxysmal 
haemoglobinuria. Here, as Donath and Landsteiner have 
shown, there is in the serum a true auto-haemolysin. But in 
paroxysmal haemoglobinuria there is no evidence of a dimin- 
ished resistance of the red blood corpuscles.* In Addisonian 
1921 
* It is true that Meyer and Emmerich believe that they have 
been able to demonstrate a diminished resistance of the red cor- 
(19) [92] 
anaemia, as has already been said, the resistance of the red 
blood corpuscles is usually increased. 
On the other hand there is no evidence of a specific haemo- 
lysin in these instances of jaundice associated with corpuscular 
fragility, so that one has been tempted to separate an haemo- 
lysinic jaundice, such as the jaundice with pernicious anaemia 
or that seen with paroxysmal haemoglobinuria, from the jaun- 
dice associated with corpuscular fragility, to which the name 
haemolytic has come to be applied-a deplorable complication 
of terms. 
This is, however, not to say that the primary causal element 
in some of the instances of so-called acquired haemolytic jaun- 
dice may not be the presence of toxic haemolytic substances in 
the organism. Indeed, there is some reason to believe that this 
may be the case. Troisier, for instance, in his recent thesis 
advances various arguments in support of the hypothesis that 
the fragility of the red corpuscles in these cases of haemolytic 
jaundice is dependent upon the fact that they have already 
become sensitized by union with an haemolytic amboceptor. 
However this may be, we are in the presence of a remarkable 
clinical syndrome-acholuric, pleiochromic, jaundice, anaemia, 
corpuscular fragility, granulation of the red corpuscles on 
vital staining, post-mortem evidences of blood destruction in 
the form of siderosis of the liver, spleen and kidneys, absence 
of evidence of the presence of haemolytic substances in the 
serum. 
Several questions naturally suggest themselves. 
1. Where does the haemolysis take place? 
2. Where does the bilirubin circulating in the blood find its 
origin ? 
3. What is the primary cause of this condition ? 
1. As to the manner and seat of the haemolysis there have 
been varying opinions. Some (Minkowski, Chauffard, Vaquez) 
fancy that, gathered in the pulp of the spleen which, as has 
been seen, is always markedly engorged, the abnormally fragile 
puscles in paroxysmal hemoglobinuria against changes of tem- 
perature, dilute acids and saponin. Meyer and Emmerich: Ueber 
paroxysmale Hemoglobinurie. Deutsches Arch. f. klin. Med., 
Leipsig, 1909, XCVI, 287-327. 
(20) corpuscles are there destroyed. Others (Widal and his pupils) 
are inclined to believe that the destruction occurs in the general 
circulation, the debris accumulating as it always does in the 
spleen, and accounting thus for the symptoms and manifesta- 
tions on the part of that organ. One observation, as pointed 
out by Castaigne, is strongly in favor of the circulatory origin 
of the haemolysis, namely, the siderosis of the kidneys, which 
is often demonstrable. Otherwise no important evidence can 
be adduced in support of one or the other of these views which, 
in the end, are essentially the same, excepting in so far as they 
bear upon the second question. 
2. The Cause of the Jaundice.-Most observers have be- 
lieved the jaundice to be immediately hepatic in origin due 
to the over-production of bile by a liver overstocked, so to 
speak, with the products of blood destruction. The old idea 
that this was, in a sense, after all, an obstructive jaundice 
owing to the inspissation of the bile and the engorgement of 
the intra-hepatic bile passages, or to a diffuse intrahepatic 
cholangitis, must, however, be abandoned as a result of the 
clinical and pathological observations of some of these cases. 
If the hepatic origin of the jaundice be accepted, we must fall 
back upon the assumption of Minkowski, that the overworked 
hepatic cell gives off a part of the excess of bile which it 
produces into the capillaries, as well as into the bile passages. 
Widal and his pupils, however, advance another hypothesis, 
which is in many ways inviting. Pointing out the rapidity 
with which jaundice follows experimental blood destruction 
in animals, they call attention to the lack of evidence of any 
inspissation of the bile, referring especially to one of their 
patients on whom a cholecystostomy was performed for sus- 
pected stone. The gall bladder and ducts were empty, and 
the bile which was discharged from the fistula in large quanti- 
ties, was of normal character, and strikingly fluid. On the 
other hand they observe that Langhans and Quincke have 
demonstrated bilirubin in the seat of old haemorrhagic foci, 
that Sabrazes and Muratet have observed the presence of 
urobilin in cerebro-spinal fluid after cerebral haemorrhage, 
and that Froin has shown that haemoglobin may be changed 
into biliary pigment in haemorrhagic exudates in the meninges 
[92] 
[93] 
(21) [93] 
and in the pleura, observations which have been confirmed by 
Guillain and Troisier, Widal and Joltrain and others. The 
urobilin which various observers have demonstrated in the 
serum they believe to be due to a direct transformation from 
haemoglobin through bilirubin such as has been shown to occur 
in haemorrhagic exudates (Troisier: These). They point to 
the fact that in cases presenting the syndrome of which we 
have been speaking, despite the long-continued jaundice, there 
is no evidence of the ordinary symptoms of biliary retention, 
symptoms which they believe to be due to the action of biliary 
salts, namely, pruritus, bradycardia and emaciation. Bile acids 
have never been found in blood or urine. Nor do the red 
corpuscles show the increased size and heightened resistance 
to hypotonic salt solutions which Rist and Ribadeau-Dumas 
believe to indicate an acquired tolerance for intoxication by 
taurocholate of sodium. Everything, they think, points to the 
existence of a purely pigmentary cholaemia which, theoretically, 
might easily arise in the blood itself. This is a conceivable 
and seductive hypothesis. The objections based upon the ab- 
sence of haemoglobin in the circulation, which have been 
raised against this idea are answered by Widal by the assump- 
tion of a destruction of the corpuscles so gradual that the 
quantity of haemoglobin is too small to be recognizable. It 
cannot be said, however, that the symptoms of ordinary biliary 
intoxication are never present, rare though they be, for itching 
has been observed in one or two instances. On the other hand 
the argument that the absence of these symptoms is evidence 
of the purely pigmentary character of the jaundice is based 
upon a false assumption, for King and Stewart have shown 
that it is, in fact, upon the bile pigment, that bradycardia 
depends. 
It is at the moment impossible to form a definite opinion 
upon this question. While all recognize the haemolysis as the 
remote cause of the jaundice, the majority of observers still 
cling to a point of view similar to that of Vaquez and Auber- 
tin, which has been well summarized by Chalier. According 
to this the condition represents " a lesion of the blood of 
unknown cause terminating in destruction of the red blood 
corpuscles, in secondary splenic hyperplasia with the forma- 
(22) tion of an excess of iron-containing pigment and an over- | 
production of bile by the liver as a result of the superabun- 
dance of pigment to transform, and, consecutively jaundice." 
In their own words (Vaquez and Aubertin), " .... if the 
primary cause of haemolytic jaundice is in an alteration of the 
blood, its immediate cause is without doubt an increased func- 
tional activity of the liver cell: there may exist, indeed, a 
biliary over-activity of the liver just as there exists a glyco- 
genic over-activity of the liver, and haemolytic icterus would 
then be an icterus through hepatic over-activity (' ictere par 
hyper-hepatie Their idea as to the manner in which the 
bile pigment enters the blood is' doubtless similar to that ex- 
pressed by Leuret, " With the blood pigment modified by the 
spleen the hepatic cell proceeds to produce an excess of bili- 
rubin to a degree such that in certain cases it overflows and 
secretes bile at both poles: whence hepatogenous icterus "-es- 
sentially the idea of Minkowski. The question must be re- 
garded as still open, and there is much that would attract one 
to the haematogenous hypothesis of Widal, the argument in 
favor of this point of view being set forth strongly in the 
thesis of Troisier. 
3. As to the third question, the primary cause of the cor- 
puscular fragility, a positive answer cannot be given. 
In congenital haemolytic jaundice it has generally been 
assumed that the fragility of the red blood corpuscles is an 
inherited defect. The red cell, it might be fancied, has here 
failed to acquire those powers of resistance which are ordi- 
narily gained in the first days of extra-uterine life, retaining 
permanently its original fragility. In the acquired forms of 
the disease the question is, however, by no means so simple. 
Widal, Abrami and Brule, by intra-peritoneal injections of 
toluylendiamin, have produced in animals a jaundice with 
clinical and pathological phenomena similar to those observed 
in haemolytic jaundice in the human being. According to 
the dose, the process was more acute and severe, or slower and 
more gradual and persisting for a long period after the last 
injection of the poison. No haemolytic properties could be 
found in the serum. On the other hand the red blood cor- 
puscles showed a markedly diminished resistance to hypotonic 
[93] 
(23) [93] 
saline solutions as well as a granulation on vital staining, while 
evidences of increased marrow activity were striking. The 
urine in some of these cases, however, contained bile pigment. 
Obstructive jaundice in animals results neither in anaemia, 
granular corpuscles, nor increased fragility. Indeed, the re- 
sistance of the red blood corpuscles is always normal or in- 
creased. Here, then, is a similar phenomenon produced pri- 
marily by a soluble toxic substance, and while in many in- 
stances in the human being, no such cause is apparent, in 
other cases, such as those occurring in malaria, syphilis and 
uncinariasis, the primary action of some circulating toxic 
substance would appear to be certain. It may be, as suggested 
by Widal, that the marrow, constantly called upon, ends by 
producing corpuscles less resistant than the normal. But 
under such circumstances we must fancy that some poisons 
have acted primarily on blood or marrow. What these may be 
we know not. The fever associated with paroxysmal aggrava- 
tions in some cases of acquired haemolytic jaundice is suggest- 
ive of an infection. 
It is possible, then, that the corpuscular fragility as well as 
the granular corpuscles, the main stigmata of the syndrome, 
may sometimes be secondary to the action of some circulating 
toxic substance or substances. 
Treatment.-Various essays have been made in the treat- 
ment of both congenital and acquired haemolytic jaundice. 
Widal and his pupils have shown clearly that the persistent 
administration of iron is the one method from which good 
results may be obtained. In the severe acquired forms rest 
in bed and the other adjuvants suitable for the treatment of 
any grave anaemia should be adopted. In congenital haemo- 
lytic jaundice recovery is unknown, but a temporary improve- 
ment in the anaemia may be obtained by persistent treatment 
with iron. In acquired haemolytic jaundice long continued 
treatment may result in apparent, perhaps, indeed, in com- 
plete recovery (Widal, Abrami and Brule). This is a very 
important fact when one reflects upon the futility of treat- 
ment with iron in Addisonian anaemia, a malady which may so 
closely resemble this syndrome. 
[94] 
(24) The studies, then, of the last several years have brought out 
a fairly definite clinical syndrome, that of acholuric jaundice 
associated with splenomegaly and fragility of the red blood 
corpuscles. In its purest form this group of symptoms is 
manifested in a sharply defined disease picture, congenital, 
often familial splenomegalic jaundice. It is probable that 
many of Gilbert's cases of chronic simple jaundice with sple- 
nomegaly as well as of Hayem's infectious splenomegalic jaun- 
dice are examples of the disease. 
A similar condition is, however, not infrequently met with 
in adult life. In these so-called acquired cases the symptoms 
are usually considerably more acute and severe than in the 
congenital malady. 
The syndrome has, moreover, been found in a variety of 
other instances of non-obstructive jaundice associated with 
various infections or poisons. 
What the essential primary element in these cases may be 
is not at present clear. 
Most important for the moment is the recognition of those 
apparently idiopathic examples of acquired haemolytic jaun- 
dice simulating pernicious anaemia, cholelithiasis, the so-called 
splenic anaemias, or, indeed, icterus gravis-most important 
because of the fact that the recognition and persistent treat- 
ment of some of these cases with iron may bring about a great 
improvement, and, perhaps, a permanent recovery. 
The recognition of this syndrome has opened up again, and 
in an interesting manner, the question as to the possibility of 
a purely haematogenous jaundice. 
The methods of studying the corpuscular resistance neces- 
sary for the diagnosis of such cases are, of course, too delicate 
for use by the busy practitioner, but they may be carried out 
easily in any well-equipped laboratory. One may hope that a 
re-investigation of some of the many instances of non-obstruc- 
tive jaundice by means of these methods of study may help to 
shed further light upon an interesting field of medicine. 
L94] 
LITERATURE. 
Abrami, P. 
Nouveau cas d'lctfere Mmolytique congenital et familial. Bull, et m£m. 
Soc. med. d. hOp. de Par., 1908, 3. s., xxvi, 329-335. 
Arkwright, J. A. 
Family group of cases of enlarged liver and spleen with jaundice. 
Edinb. M. J., 1903, n. s., xiii, 52-54. 
(25) [94] 
Armand-Delille et FeuilliIL 
Anomie spienomegallque avec fragility globulalre. Bull, et m6m. Soc. 
med. d. h6p. de Par., 1909, 3. s., xxvli, 266-271. 
Barlow, Sir T., and Shaw, B. 
Inheritance of recurrent attacks of jaundice and of abdominal crises 
with hepato-splenomegaly. Trans. Clin. Soc., Bond., 1902, xxxv, 155- 
163; also Med. Press and Circular, 1902, Ixxiil, 564. 
Barton, W. M. 
Acquired haemolytic ictero-anaemla; Widals' syndrome. Am. J. M. Sc., 
1910, cxl, 239-246. 
Basile, G. 
Gli Itterl emolltici e 1'lnfezione sifilitica. Il Policlinlco, 1909, xvl, sez. 
prat., 1291. (Summary of the article of Gaucher and Giroux.) 
BfiNECH, E., et SABRAZfeS, J. 
IctSre hemolytlque chronique avec spl6nomegalie. Gaz. h6bd. d. Sc. 
mM. de Bordeaux, 1909, xxx, 469-472. 
Benjamin, E., and Sluka, E. 
Uber eine chronlsche mlt Ikterus einhergehende Erkrankung des Blutes. 
Berl. kiln. Wchnschr., 1907, xliv, 1065-1069. 
Bernard, L. 
A propos de 1'orlglne syphilltique des Icteres spienomegallques. Bull, 
et mem. Soc. med. d. hflp. de Par., 1908, 3. s., xxv, 158. 
Bernard, L., et Troisier, J. 
Sur un cas d'intoxication saturnine avec meninglte, anomie et IctSre. 
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Brul£, M. 
Les Icteres hemolytiques acquis. These de Paris, 1909, n° 88 (with 
full table of references). 
Bu6, V. ' 
Les ict?res du nouveau-n6. Gaz. d. mal. Infant, (etc.), Par., 1908, 
x, 185-190. 
BURGERHOF. 
Congenitale famllialre icterus. Geneesk. Bl. u. Klin, en Lab. v. de 
prakt. Haarlem, 1907-8, xiii, 241-266. 
Cade. 
Une famille d'icterlques; choiemie familiale et icteres hemolytiques. 
Bull, et mem. Soc. med. d. h6p. de Par., 1908, 3. s., xxv, 421-429. 
Cade and Chalier. 
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Campani, A., e Ferrari, G. 
Sopra un caso d'ittero cronico Infantile. Clin. Med., ital., 1908, xlvll, 
394-407. 
Caporali, L. 
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Le foie et le fer. Leurs rapports A 1'etat pathologique. Presse med.. 
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Les icteres hemolytiques avec siderose pigmentaire du foie. Bull, et 
mem. Soc. med. d. hop. de Par., 1907, 3. s., xxiv, 1211-1216. 
Chronique. J. med. frang., 1910, iv, 95. 
Les icteres hemolytiques. J. med. frang., 1910, iv, 101-109. 
Cathala et Daunay. 
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pendant les premiers jours. Compt. rend. Soc. de biol., Par., 1908, 
Ixiv, 801-803. 
Recherches sur le sang et i'ictere simple du nouveau-ne. Obstetrique, 
Par., 1908, n. s., 1, 561-604. 
(26) Chalier, J. 
Les ict&res h6molytiques. 8°, Lyon, 1909. ThSse. (With an admirable 
table of references to the literature.) 
Chauffard, A. 
Maladies du foie, in Tralte de m6d. (Charcot, Bouchard, Brissaud), 
Par., 1892, iii. 
IctSre chronique dyspeptique avec cholurie minlme et intermittente. 
Choluries sans ictere. Bull, et mem. Soc. m6d. d. hOp. de Par., 1901, 
3. s., xviii, 444-449. 
Pathogenie de i'ictbre congenital de 1'adulte. Semaine m6d., Par., 1907, 
xxvii, 25. 
Chauffard et Rendu. 
La resistance globulaire normale chez 1'adulte. Presse med., Par., 1907, 
xv, 345. 
Chauffard et Fiessinger, N. 
IctSre congenital h6molytique avec lesions globulaires. Bull, et mem. 
Soc. med. d. hOp. de Par., 1907, 3. s., xxiv, 1169-1184. 
Recherches experimentales sur les rapports entre l'h6molyse et les 
hematies granuleuses. Bull, et mem. Soc. med. d. hOp. de Par., 3. s., 
xxiv, 1367-1373. 
Nouvelles recherches sur la gen^se des h6maties granuleuses. Compt. 
rend. Soc. de biol., Par., 1907, Ixiii, 672. 
Chauffard, A. 
Les ictferes hemolytiques. Semaine med., Par., 1908, xxviil, 49-52; 
also Rev. gen. de clin. et de therap., Par., 1908, xxii, 84. 
Ikterus hsemolyticus. Allg. Wien. med. Ztg., 1908, lili, 462. 
Chauffard, A., et Troisier, J. 
Deux cas d'ictfere h6molytique. Bull, et mem. Soc. med. d. hOp. de 
Par., 1908, 3. s., xxv, 411-420. 
Contribution a 1'etude des hemolysines dans leur rapport avec les 
an6mies graves. Bull, et mem. Soc. med. d. hOp. de Par., 1908, 3. s., 
xxvl, 94-105. 
Des rapports de certaines anemies spienomegaliques avec 1'lctere 
hemolytique congenital. Bull, et m6m. Soc. med. d. hOp. de Par., 1909, 
3. s., xxvii, 293. 
Claisse et Socquet. 
Insufflsance mitrale traumatique. Asystolie. Gangrene des membres. 
Ictfere hemolytique. Bull, et mem. Soc. med. d. hop. de Par., 1908, 
3. s., xxv, 769-773. 
Claus und Kalberlah. 
fiber chronischen Ikterus. Berl. kiln. Wchnschr., 1906, xliil, 1471-1474. 
Cocking, W. T. 
A case of persistent jaundice of fifty years' standing. Quarterly Med. 
J., Sheffield, 1903, xi, 104. 
Conner, L. A., and Roper, J. C. 
The relations existing between bilirubinemla, urobillnuria, and uro- 
bilinemia. Tr. Ass. Am. Phys., Phila., 1908, xxiil, 222-245. 
Darr6, H. 
Sur un cas d'an6mie ankylostomiasique avec fragilitie globulaire et 
IctSre hemolytique. Bull. Soc. path. exot. Par., 1909, li, 97-101. 
Ehni et Alexieff. 
De la resistance des globules deplasmatisees dans 1'anemie. Compt. 
rend. Soc. de biol. Par., 1908, Ixiv, 1101. 
Etienne, G. 
Sur un cas probable d'ictSre hemolytique. Rev. m6d. de 1'est., Nancy, 
1909, xli, 548-551. 
Ferrata, A. 
fiber die klinische und morphologische Bedeutung der vitalfarbbaren 
Substanz und die basophile Punctirung der Erythrocyten. Fol. hsema- 
tolog., Leipz., 1910, lx, I Th., 253-277. 
Feuilli^, E. 
H6molyse, flux leucocytaires et ictere. Compt. rend. Soc. de blol., Par., 
1908, Ixv, 626-628. 
Fiessinger, N., et Abrami, P. 
Les hematies a granulations; procedes de coloration, valeur s6m- 
eiologique. Revue de med., Par., 1909, xxix, 1-40. 
194] 
[95] 
(27) [95] 
Froin, G. 
W-12 at°lySe anoimaIe- Compt. rend. Soc. de blol., Par., 1906, Ixviil, 
Gandy et Brul6, P. 
Ictfere hemolytique congenital, autopsle. Bull, et mem. Soc med. d 
hOp. de Par., 1909, 3. s., xxviil, 369-375. 
Gaucher et Giroux. 
Note preilminalre sur 1'ictere h6molytlque de la syphilis secondalre. 
Ann. d. mal. ven., Par., 1909, iv, 481-482. 
Gaucher, E., et Joltrain. 
Purpura chronique de l'angioscierose. Urobiligenie hemolytique locale. 
Urobillnhemie et urobilinurie. J. de med. int., Par., 1909, xil, 275-277. 
Gerhardt. 
Die Pathogenese des Ikterus. Muench, med. Wchnschr., 1905, 111, 889- 
Gilbert, Lereboullet et Herscher. 
Les trols choiemles congenitales. Bull, et mem. Soc. med. d. hOp. de 
Par., 1907, 3. s., xxiv, 1203. (With abundant references to the liter- 
ature.) 
Gilbert et Lereboullet. 
La choiemie simple famlliale. Son importance en pathologic. J. med. 
franq., Par., 1910, iv, 110. 
Gougerot et Salin, H. 
IctSre hemolytique acquis general et purpura avec ictere hemolytique 
local, au cours d'une Infection indetermin6e. Arch. d. mal. du coeur 
(etc.), Par., 1910, ill, 720-729. 
Guillain, G., et Troisier, J. 
Physiologie pathologique de l'h6matome pleural traumatlque. La 
biligenie hemolytique locale. Semaine med., Par., 1909, xxix, 133. 
Contribution ft. retude des ict£res hemolytiques locaux. Rev. de med., 
Par., 1909, xxix, 459. 
Hawkins, C. P., and Dudgeon, L. F. 
Congenital family cholaemia. Quart. J. Med., Oxford, 1908-9, 11, 165-177. 
Hayem, G. 
Sur une variete partlculiere d'lctere chronique, Ictere infectleux chro- 
nique spienomegallque. Presse med., Par., 1898, vi, 121-125. 
Nouvelle contribution ft 1'etude de 1'ictftre infectieux chronique spieno- 
megalique. Bull, et mem. Soc. m6d. d. hOp. de Par., 1908, 3. s., xxv, 
122-138. 
Hutchison, R. 
Family jaundice. Clin. J. Lond., 1909, xxxlv, 241-244. 
Hutchison, R., and Panton, P. N. 
A contribution to the studv of congenital family choleemla. Quart. 
J. Med., Oxford, 1908-9, 11, 432-437. 
Iscovesco, H., et Salignat. 
La fragillte globulaire varie-t-elle suivant que 1'on op£re sur le sang 
deflbrine, fluore ou exalte? Compt. rend. Soc. de biol., Par., 1907, 
Ixlii, 778. 
Jacob, F. H. 
Acholuric Jaundice. Proc. Roy. Soc. Med., 1910, Hi (Clinical Section), 
157. . si 
Jacob et L^vy-Valensi. 
Un nouveau cas d'lctftre hemolytique congenital. Bull, et m6m. Soc. 
med. d. hOp. de Par., 1909, 3. s., xxvl, 219. 
Jona, G. 
Ittero emolitico della tuberculosl e funzlone emolltlca del fegato. Riv. 
veneta di sc. med., Venezia, 1909, 1, 3-19. 
King, J. H., and Stewart, H. A. 
Effect of the injection of bile on the circulation. J. Exper. Med., N. Y., 
1909, xl, 673. 
V. Kranhals. 
Uber congenitalen Icterus mit kronlschen Mllztumor. Deutsches Arch, 
f. klin. Med., Leipz., 1904, Ixxxi, 596-612. 
28 Landouzy, L. 
Anbmie et ictbre hhmolytiques tuberculeux. Bacillo-tuberculose hbmo- 
lysante, anbmie grave et subictbre. par fragility globulaire chez un 
phthlsique pulmonaire. Presse med., Par., 1910, xviii, 761. 
Le Gendre, P. 
Ictbre urobilinique chronique (durant depuis douze ans) chez un jeune 
homme de dix huit ans. Bull, et mem. Soc. mbd. d. h6p. de Par., 1897, 
3. s., xxlv, 457-459. 
Le Gendre et BrulE. 
Deux observations d'ictbres hbmolytlques, 1'un congenital, 1'autre acquis. 
Bull, et mbm. Soc. mbd. d. hOp. de Par., 1909, 3. s., xxvl, 112-124. 
Lemierre, A., et Abrami, P. 
L'ictbre pneumococcique. Presse mhd., Par., 1910, xviii, 82. 
Le Play, A. 
Cirrhose hypertrophique alcoolique avec ictbre hbmolytique et hbmor- 
rhagies intestinales ft evolution aigue, examen nbcroscopique. Bull. 
Soc. anat., Par., Ixxxiv, 552-556. 
Leuret, E. 
Etude sur quelques cas d'ictbre des nouveaux-n6s. Thbse de Bordeaux, 
1904. 
Remarques sur la pathogbnie de 1'ictbre des nouveau-nbs. Phgnombnes 
d'hbmatolyse. Folia haematol., Berl., 1906, iii, 81. 
Etude sur la resistance globulaire nouveau-nb envisagSe spdcialement 
dans ses rapports avec i'ictbre idiopathique. Gaz. hebd. d. Soc. med. 
de Bordeaux, 1908, xxix, 147-150. 
Etat du s6rum sanguin chez le nouveau-nd ft i'btat normal, dans 
1'lctbre idiopathique et dans 1'ictbre biliphbique. Compt. rend. Soc. 
de biol., Par., 1908, Ixiv, 691-692. 
A propos de la pathogbnie de i'ictbre du nouveau nh. Obstetrique, 
Par., 1909, xiv, 142-146. 
Etude anatomo-pathologique compare de 1'ictbre hbmolytique du nou- 
veau-nb et de 1'hbmolyse provoqude. Nature hbmolytique de 1'ictbre 
post-chloroformlque. Arch. d. mal. du coeur (etc.), Par., 1910, iii, 
236-253. 
Lortat-Jacob, L., et SabarEanu, G. 
Deux observations de i'ictbre chronique familial. Rev. de mbd., Par., 
1904, xxiv, 810-818. 
Marchiafava, E., et Nasari, A. 
Sugii itteri emolitici. Bull. d. r. Accad. med. di Roma, 1909, xxxv, 
152-161. 
Mason. 
Case of congenital jaundice in a girl aged 13. Quart, med. J., Sheffield, 
1902-3, xi, 40-41. 
Massaglia, A., et Tarabini, L. 
Contributo alia patogenesi dell'ittero da emolisl. Gazz. d. osp., Milano, 
1908, xxix, 1655-1657. 
Micheli, F. 
Note istologiche su di un caso di splenomegalia con ittero acholurico 
cronico acquisito. Gior. d. r. Accad. di med. di Torino, 1909, 4. s., 
xv, 213-220; also Path. rev. quindicen., Genova, 1908-9, i, 517-522. 
Minkowski. 
Uber eine hereditare, unter dem Bilde eines chronischer Ikterus mit 
Urobilinurie, Splenomegalie und Nierensiderosis verlaufende Affection. 
Verhandl. d. Cong. f. inn. med., Wiesb., 1900, xviii, 316. 
Ikterus u. Leberinsufficienz. Deutsche Klinik, Berl. u. Wien, 1905, 
v, 651-686. 
Moller, S. 
Uber chronischen acholurischen Ikterus mit Splenomegalie. Berl. kiln. 
Wchnschr., 1908, xlv, 1639-1643. 
MOUSSOUS, A. 
De la pathogbnle de 1'ictbre Idiopathique du nouveau-nb (grythrodermie 
ictbrogbne). Provence m6d., Par., 1908, xix, 227-230. 
Murchison, C. 
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[95] 
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Sur un cas d'ictere d'origine hemolytique non congenital; etude des 
lesions anatomiques. Bull, et mem. Soc. med. d. hOp. de Par., 1908, 
3. s., xxv, 391. 
Parsons, L. G., 
Congenital acholuric jaundice. Proc. Roy. Soc. Med., 1910, iii, Section 
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PliiJU, G. 
Icteres familiaux et leur mecanisme morblde. Loire med., St. Etienne, 
1908, xxvll, 117-125. 
Pick, A. 
Uber hereditiiren Ikterus. Wien. kiln. Wchnschr., 1903, xvl, 493. 
Plehn, A. 
Famlliiire Mllz- und Leber-vergrosserung mit Anaemle und gutartigen 
Verlauf. Deutsche med. Wchnschr., 1909, xxxv, 1749-1751. 
Pollak, R. 
Fall von chronischen familiilren acholurischen Ikterus. Mitth. d. 
Gesellsch. f. inn. Med. u. Klnderhellk. in Wien, 1908, vii, 92-94. 
Poynton, F. J. 
A clinical lecture on congenital family cholsemia or recurrent family 
jaundice. Lancet, 1910, 1, 153-156. 
Quenu, E., et Kuss, G. 
Notes sur les icteres postchloroformiques. Bull, et mem. Soc. de chir. 
de Par., 1908, n. s., xxxlv, 1108-1110. 
Renaux, E. 
Un cas d'ictbre hemolytique congenital. Presse med. Beige, Brux., 
1909, Ixi, 711-713. 
[96] Ribierre, P. 
L'hemolyse et. la mesurc de la resistance globulaire. Application it 
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Rist, E., et Ribadeaux-Dumas, L. 
La spienomegalie liee st 1'ictere et rimmunite acquise contre 1'intoxi- 
catlon biliare. Tribune med., Par., 1905, n. s., xxxvlii, 421-425. 
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Ictere hemolytique acquis. Prov. med., Par., 1909, xx, 367-368. 
Roque, G., Chalier, J., et Nov6-Josserand. 
Ict£re hemolytique acquise h type ictere grave. Lyon med., 1909, 
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Rosenfeld, R. 
Uber familihren Ikterus. Deutsche med. Wchnschr., Leipz. u. Berl., 
1909, xxxv, 616-621. 
Rossi, G. 
Contributo alia conoscenza degll itterl congenitl emoliticl. Tommasl, 
Napoli, 1909, iv, 197-201. 
SABRAZfeS, J., et Leuret, E. 
Hematies granuleuses et polychromatophilie dans 1'ictere des nouveau- 
n6s. Gaz. hebd. d. soc. med. de Bordeaux, 1908, xxlx, 123. 
Sabraz^s, J., et Muratet, L. 
Cellules endotheiiales hemato-macrophages dans le liquide cepnalo- 
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SACQUfiPfiR, E. 
Icteres hemolytiques d'origine paludeene. Bull, et mem. Soc. med. d. 
hop. de Par., 1908, 3. s., xxvi, 361-369; also Bull, med., Par., 1908, 
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Ictfere grave streptococcique; formule sanguine des icteres hemolytiques 
acquis, avec reaction granuleuse retarde. Bull, et mem. Soc. med. 
d. hOp. de Par., 1909, 3. s., xxvi, 164-171. 
30 Starkiewiez, W. 
Sur la pathogenic de Picture acholurique congenital. Rev. de m6d., 
Par., 1909, xxix, 61-75. 
de Stefano, S. 
Un caso de itterizia congenita. Pediatria, Napoli, 1909, 2. s., vii, 
217-221. 
v. Stejskal. 
uber haemolytischen Ikterus und fiber das Auftreten haemolytischer 
Vorgiinge bei diesem und bei pernicibser Anaemie. Wien. kiln. 
Wchnschr., 1909, xxii, 661-667. 
Mitt. d. Gesellsch. f. inn. Med. u. Kinderheilk. in Wien, 1908, vii, 221- 
229. (Brief note.) 
Strauss, H. 
fiber erworbene Formen des chronischen acholurischen Ikterus mit 
Splenomegalie. Berl. klin. Wchnschr., 1906, xliii, 1590-1593. 
(Remarks a propos of Moller's case.) Berl. klin. Wchnschr., 1908, 
xlv, 1643. 
Tileston, W., and Griffin, W. A. 
Chronic family jaundice. Am. J. M. Sc., Phila., 1910, cxxxix, 847-869. 
(With excellent table of references.) 
Tixier, L. 
Ictdre d'origine hemolytique. Resistance des hematies deplasmatisees 
sensiblement normale. Compt. rend. Soc. de biol., Par., 1908, lxiv, 
43-44. 
Reactions de la moelle osseuse dans uns cas d'ictbre hemolytique. 
Compt. rend. Soc. de biol., Par., 1908, lxiv, 108-109. 
Treves, F. 
A case of jaundice of sixteen years' standing. Practitioner, 1899, 
ixii, 18-20. 
Troisier, J. 
Ictbre et urobilinhemie hemolytiques au cours de la pneumonie. Compt. 
rend. Soc. de biol., Par., 1909, Ixvii, 46-47. 
Urobilinhemie d'origine hemolytique. Compt. rend. Soc. de biol., Par., 
1909, Ixvi, 739-740. 
Physiologie pathologique de 1'hematome pleural traumatique; la bili- 
genie hemolytique locale. Semaine med., Par., 1909, xxlx, 133-138. 
R61e des hemolysines dans la genhse des pigments biliaires et de 1'uro- 
biline, 4°, Par., 1910. These. 
Vaquez, H. 
Des modifications du volume des hematies au cours de I'ictSre. Compt. 
rend. Soc. de biol., Par., 1902, liv, 975-977. 
Vaquez, H., et Ribierre, P. 
De la resistance du sang au cours de i'ictfere. Compt. rend. Soc. de 
biol., Par., 1902, liv, 1074-1076. 
Vaquez, H., et Giroux. 
IctSre chronique acholurique avec spienom6galie. Ses relations avec 
l'anemie hemolytique. Bull, et m6m. Soc. med. d. h6p. de Par., 1907, 
3. s., xxiv, 1184. 
Vaquez, H., et Aubertin, Ch. 
Sur l'anatomie pathologique de 1'ictbre hemolytique. Arch. d. mal. 
du coeur (etc.), Par., 1908, i, 609-623. 
Vaughan, V. C., Jr. 
On the appearance and significance of certain granules in the erythro- 
cytes of man. J. Med. Research, Bost., 1903-4, x, 342-366. 
Weber, F. Parkes. 
Acquired chronic acholuric jaundice, with a blood picture at one 
time resembling that of pernicious anaemia. Am. J. M. Sc., Phila., 
1000 n s cxxxviii 24 
Congenital' familial splenomegaly with chronic acholuric jaundice, 
Proc. Roy. Soc. Med., Lond., 1909, ii, Pt. I, Clin. Sec., 117. 
Weber, F. P., and Dorner, G. 
Congenital acholuric so-called haemolytic jaundice in one family. 
Lancet, Lond., 1910, 1, 227 ; also Vier Faile von congenitalen achol- 
urischem (sogenanten haemolytischen) Ikterus in einer Familie. Fol. 
haematolog., Leipz., 1910, ix, I Th., 528-533. 
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31 196] 
Widal, F., et Ravaut, P. 
Ict&re chronique acholurique congenital chez un homme de 29 ans. 
Augmentation passagfere et leg&re du foie et de la rate. Parfait etat 
de sante g4n6rale. Bull, et mem. Soc. med. d. h6p. de Par., 1902, 
3. s., xix, 984-990. 
Widal, F., et Philibekt, A. 
La fragilite globulaire chez certains icteriques congenitaux. Gaz. d. 
hOp., Par., 1907, Ixxx, 1275. 
Widal, F., Abrami P., et Brul£, M. 
Types divers d'ictSres hemolytlques. La recherche de la resistance 
globulaire par le procede des hematies deplasmatisees. Bull, et 
mem. Soc. m6d. d. hbp. de Par., 1907, 3. s., xxiv, 1127. 
Differentiation de plusieurs types d'icteres hemolytlques par le procede 
des hematies deplasmatisees. Presse med., Par., 1907, xv, 641. 
Hemolyse par fragilite globulaire et hemolyse par action plasmatique. 
Compt. rend. Soc. de biol., Par., 1907, Ixlii, 346-349. 
Widal, F., et Abrami, P. 
Types divers d'ictSres hemolytlques non-congenitaux avec anemie. Re- 
cherche de la resistance globulaire par le procede des hematies de- 
plasmatisees. Tribune med., Par., 1907, n. s., xxxlx, 711. 
Widal, F., Abrami P., et Brul£, M. 
Pluralite d'origine des ictSres hemolytiques. Bull, et mem. Soc. med. 
d. hOp. de Par., 1907, 3. s., xxiv, 1354-1367. 
Diversite de types des hematies granuleuses; procedes de coloration. 
Compt. rend. Soc. de biol., Par., 1908, Ixiv, 496-499. 
Les ictferes d'origine hemolytique. Arch. d. mal. du coeur (etc.), Par., 
1908, 1, 193. 
Auto-agglutination des hematies dans 1'ictere hemolytique acquis. 
Compt. rend. Soc. de biol., Par., 1908, Ixiv, 655-657. 
Retrocession des symptomes cliniques et des troubles hematiques au 
cours des IctSres hemolytlques acquis. Bull, et mem. Soc. med. d. hOp. 
de Par., 1909, 3. s., xxviii, 73-85. 
Widal, F., et Joltrain. 
Ictfere hemolytique devellope au cours d'une anemie post h6morrhaglque. 
Bull, et mSm. Soc. med. d. hdp. de Par., 1908, 3. s., xxv, 468-474. 
Biligenie hemolvtique locale dans 1'hemorrhagie meningee. Compt. 
rend. Soc. de biol., Par., 1909, Ixvl, 927-930. 
Widal, F., and Benard. 
Biligenie hemolytique localis6e A la peau sur de larges plaques d'ery- 
theme noueux sans extravasation sanguine. Compt. rend. Soc. de biol., 
Par., 1909, Ixvl, 950. 
Wilson, C. 
Some cases showing hereditary enlargement of the spleen. Trans. 
Clin. Soc., Lond., 1890, xxlii, 162. 
Wilson, C., and Stanley, D. 
Sequel to some cases showing hereditary enlargement of the spleen. 
Trans. Clin. Soc., Lond., 1893, xxvi, 163-171. 
32 A Study of Two Cases of Adams-Stokes' 
Syndrome With Heart-Block 
W. S. THAYER, M.D. 
BALTIMORE 
AND 
F. W. PEABODY, M.D. 
CAMBRIDGE, MASS. 
Reprinted from the Archives of Internal Medicine 
March, 1911, Vol. 7, pp. 289-31,7 
CHICAGO 
American Medical Association 
Five Hundred and Thirty-five Dearborn Avenue 
1911 A STUDY OF TWO CASES OF ADAMS-STOKES' SYNDROME 
WITH HEART-BLOCK 
W. S. THAYER, M.D., and F. W. PEABODY, M.D. 
BALTIMORE 
CAMBRIDGE, MASS. 
Despite the numerous observations of recent years on the subject of 
auriculoventricular dissociation there is much that remains unexplained. 
Two cases of heart-block, which came under our observation during the 
past year, have presented features of such unusual interest as to justify 
special consideration. 
CASE 1 
Adams-Stokes' syndrome; partial and complete auriculoventricular dissocia- 
tion without essential lengthening of the a-c time; striking relief of certain phases 
of partial block of atropin; recovery. 
A man, aged 53, consulted one of us on Nov. 28, 1908. His father 
died at 65 of angina pectoris. In other respects there was nothing of note in the 
family history. He had been a man of excellent habits, was in active business 
and had always been well and strong. As a young man he had what was probably 
typhoid fever. He was married and had had two children. There was no history 
of venereal disease. He did not drink, but had been a rather heavy smoker 
(pipe and cigarettes) and had been in the habit of taking very active physical 
exercise (bicycle riding). For the last two years he had been rather more easily 
tired than previously. This had not, however, interfered with his work. 
Present Illness.-Nine days before consulting me he awoke in the morning 
with a feeling of nausea. Shortly afterward he heard some one call, "Did you 
fall?" and found that he was on the floor. He realized that he must have 
fainted. On the following morning, while in the bathroom he again lost con- 
sciousness and fell to the floor. Dr. Earnshaw,1 who was summoned immediately, 
found that his pulse was exceedingly slow and irregular. The patient was put 
to bed. The pulse remained slow and irregular. Attempts to move or rise were 
followed by slight, general convulsive seizures, of which the patient was quite 
unconscious. Several of these occurred during the day. These were accompanied 
by sensations of impending death, as if, as the patient expressed it, he "was 
just going off;" they began with a sinking feeling, as if "something were going." 
There were frequent attacks of vomiting throughout the day, and the sensations 
of flushing and sinking lasted for two days. There was at no time any pain. 
The urine showed a slight trace of albumin. Since that time he has felt a little 
weak, but reasonably well. 
Physical Examination (W. S. T.)-This showed a healthy-looking man, of 
good color. The pupils were equal, responding quickly to light and accommoda- 
tion. The pulse was 66, the radial just palpable, slightly more so on the left 
than on the right, probably a little thickened. The rhythm was regular, although, 
while feeling the pulse off and on for about two minutes, one intermission which, 
at the time, was regarded as an extrasystole, was felt. The pulse showed the 
normal respiratory variations; it was accelerated by deep inspiration, slower at 
1. An excellent account of the features of this remarkable case observed by 
Dr. Earnshaw may be found in Am. Jour. Med. Sc., 1910, 503. 2 
the beginning of expiration. Pressure (Janeway) : maximum, about 150; mini- 
mum, apparently between 110 and 120. 
Thorax: Symmetrical; costal angle, about 90. Heart: Point of maximum 
impulse not visible or distinctly palpable when patient was in the dorsal 
decubitus. On percussion the dulness extended to a point in the fifth space just 
outside the mammillary line, about 11 cm. from the median line, to the right, 3.7 
cm. from the median line. The first sound was heard loudest at about the point 
of outermost dulness. The first sound began fairly sharply, and was continued 
into a blowing systolic murmur of moderate intensity which, however, was lost 
before the midaxilla. The murmur was a little louder in the aortic area than 
elsewhere, and the aortic second sound was a little sharper than the pulmonic 
second. The same systolic souffle was heard rather louder in the xiphisternal 
notch. In the erect posture the murmur was not audible in the back, and was 
heard with diminished intensity at the apex, but remained of about the same 
intensity at the base. Lungs: Resonance and respiration everywhere clear. 
Abdomen: Natural. Liver: Not distinctly felt, the dulness extending about a 
finger's breadth below the costal margin in the mammillary line and, in the median 
line, a little below the xiphoid. 
Cardiographic and sphymographic tracings were taken on the same day. 
They showed the pulse to be regular, at the rate of 63 to the minute. The jugu- 
lar tracing (Tracing 1) showed a well-marked a wave, followed by c and v 
waves. The a-c time averaged 0.18 second. 
Course of Disease.-The patient was advised to lead a careful life and to 
avoid excitement or overexertion. He remained perfectly well up to the last week 
in December, when there was a recurrence of attacks similar to those from which 
he had previously suffered. From Dec. 27, 1908, until May 15, 1909, the patient 
has been under constant observation in Bryn Mawr under the care of Dr. Earn- 
shaw, or under our care at the Johns Hopkins Hospital. 
During this time there have been three periods in which he has had attacks 
of bradycardia, often associated with syncopal attacks or convulsions. In the 
intervals between these periods the pulse has been for the most part regular and 
of a normal rate, and the general condition has been in the main satisfactory. 
The first recurrence of attacks lasted from December 27 until January 16: 
these attacks were more severe than those which occurred during the later periods. 
During sixteen days there were two hundred and three hours in which there was 
distinct evidence of partial or complete heart-block. The longest individual attack 
lasted continuously for ninety-six hours. During the second period, which lasted 
from March 15 to March 29, there were seventeen hours of heart-block on six of 
the fifteen days. During the third period, from April 11 to 19, there were sixteen 
hours of block on five of the nine days. A fourth period, lasting from June 
until August, occurred while the patient was under the care of Dr. Earnshaw of 
Bryn Mawr, Pa. These have been described by Dr. Earnshaw.1 Since August 
the patient remained in good health until the latter part of February, 1910. 
when, while walking on the street in Philadelphia, he suddenly fell to the ground. 
There was a momentary loss of consciousness. By the time his physician saw 
him his pulse was regular and of normal rate. In May the patient again sud- 
denly lost consciousness and for nearly a week the pulse was very slow and 
irregular and numerous syncopal and convulsive attacks occurred. Since then 
he has been apparently well. 
The general characteristics of the attacks were similar. They always 
began with a sudden fall in the rate of the pulse, often to about 30 beats 
to the minute. The onset was usually without apparent cause. Some- 
times, however, it seemed to follow overexertion or exhaustion. During 
GENERAL CHARACTER OF THE ATTACKS Tracing 1.-Case 1; Nov. 28, 1908 Right jugular and brachial. Normal rhythm; a-c time under 0.2 second. 4 
the attacks the lieart's action was usually very irregular, the rate ranging 
from 10 to 49. Occasionally, during a short attack, the rate was regular 
at about 30 or 35, but usually there were several beats at more or less 
regular intervals, shorter or longer, followed by complete cessation of the 
ventricular contractions, lasting from a few seconds up to as much as 
twenty-five seconds. Toward the end of the longer pauses the patient 
often fell into a slight, momentary, partial or general convulsion. 
The onset of these attacks was rather characteristic. With the longer 
pauses in the ventricular contractions the pallor of the lips increased 
the pupils dilated, the eyes rolled slightly upward, and the face, hands 
and legs showed clonic twitchings which sometimes became general. This 
was followed usually by a flush which coincided with the return of the 
patient's radial pulse. The convulsion ceased and the patient broke into 
a rather profuse perspiration. At the end of each long pause there 
occurred usually one or two very forcible heart-beats, followed by a series 
of much more rapid beats. During these attacks the auricular pulsation 
was easily visible in the veins of the neck. The rate was usually 100 or 
above, once as high as 130. The respiration was slow, often as slow as 
eight or ten to the minute. During the long intermissions in ventricular 
contractions, there were periods of apnea as long as thirty-five seconds. 
The onset of the attack was always noticed by the patient, who com- 
plained of "weak, sinking feelings" at the beginning of a pause in ven- 
tricular contractions, and always experienced a feeling of well-being when 
the ventricular contractions returned. Except occasional sensations of 
blurring or yellow spots before the eyes, subjective symptoms were, for 
the most part, absent. There was never a distinct aura. During the 
attacks there was frequent vomiting, and all paroxysms were marked by 
sweating, which came in successive outbursts with the resumption of pul- 
sations of the ventricles after long pauses. The output of the urine was 
generally decreased. 
There was, almost invariably, a tendency to constipation and flatu- 
lence. The end of the attacks came almost always suddenly and without 
warning, but occasionally the pulse-rate gradually increased up to about 
60 or 70. 
At the end of each of the three long periods of bradycardia the patient 
was much exhausted, and from each attack the convalescence was slow. 
During the convalescence the pulse-rate of the patient usually ranged 
from 60 to 80, and was regular, except for occasional intermissions. The 
intermissions were noticed usually between two and three in the morning, 
and were rarely associated with subjective discomfort; but his nurse, Miss 
Dewey, who watched him with unusual care, often reported that, for a 
series of eight or ten beats, there appeared to be a distinct weakening in 5 
the force of the pulse, and sometimes an apparent intermission. On 
several occasions one of us (F. W. P.) saw the patient during the night 
and was able to observe these periods during which the pulse seemed to 
become peculiarly small, but we were never able to obtain records which 
permitted us to determine the exact character of the occasional intermis- 
sion described bv the nurse. 
CLINICAL NOTES ON SPECIFIC ATTACKS 
The patient was seen by one of us (W. S. T.) on Jan. 2, 1909, in 
consultation with l)rs. Earnshaw, Stengel and Pepper, during one of the 
severest attacks. The following description was made from notes taken 
at the bedside. 
Tracing 2.-Case 1; March 1, 1909. Right jugular and brachial. Normal 
rhythm; a-c time averages 0.2 second. 
At that time the patiert was lying in bed, exceedingly pale, so pale 
that at times he looked as if he were actually dead. He appeared to be 
very weak, spoke but little, and then but a few words at a time. Any 
effort to speak was, as a rule, followed by a convulsion. As one observed 
the patient, who lav motionless, with his eyes closed, the pallor seemed to 
increase until the face was almost absolutely colorless, the respiration 
ceased and the appearance became truly that of a corpse. The breathing 
was slow and irregular, somewhat suggestive of the Cheyne-Stokes type; 
long pauses with occasional deep breaths between. The respiration seemed 6 
to have no effect on the radial pulse. At times several short respiratory 
movements, not particularly deep, followed one another in rather rapid 
succession. Twenty-three respirations were counted in three minutes. 
There were at times very long periods of apnea, which were usually asso- 
ciated with the long intermissions between ventricular contractions. The 
pulse was very irregular, often, indeed usually, occurring in groups of 
three beats, one or two strong beats followed by one or two feebler beats 
occurring in rapid succession, as if one, at any rate, of these beats were an 
extra-systole. There were between 20 and 30 beats to the minute. During 
four successive minutes there were 28, 25, 28, 23 beats, respectively. 
After unusually long pauses, sometimes amounting to as much as twenty 
seconds, during which there was often apnea, the patient turned his head 
slightly to the right, rolled his eyes upward, became rigid and showed 
slight convulsive movements as described above. Shortly after the begin- 
ning of the convulsive movements there was usually a general flushing, a 
deep breath and profuse sweating. The flush apparently coincided with 
the return of the radial pulse. The same flushing, sweating and deep 
respiration were associated with the return of pulsations after shorter 
periods of intermission and apnea, periods which had not been followed 
by convulsive movements. On this date Drs. Stengel and Pepper had 
taken several tracings of the radial and jugular pulse which showed, 
apparently, complete heart-block, the jugular pulsating at a rate of about 
a hundred and the radial showing no evident relation to the jugular beats. 
A week later, Jan. 9. 1909, one of us (W. S. T.) saw the patient again 
in consultation with Dr. Earnshaw, when the following note was made: 
"The patient has been on the whole better. The pulse at times has 
been fairly regular, between 50 and 60 to the minute, and the convul- 
sions have been fewer. He has been able to take more food and there 
has been no vomiting. The condition to-day is entirely different from 
that of a week ago. He looks much better. His color is better and the 
rate of the pulse is now, at times, as high as 40 to the minute; at times, 
however, only 20 or 30. It occurs in groups of 6 to 10 beats at regular 
intervals with pauses amounting, sometimes, to as much as fifteen sec- 
onds. The auricular pulsations can be seen perfectly well in the neck. 
They cannot be heard either in the neck or over the heart. They occur 
regularly, or nearly so, at a rate of from 59 to 60 to the minute. With 
the hand on the apex impulse of the heart, or on the wrist, and the eye 
fixed on the jugular in which the a and c waves are easily distinguishable, 
it is clear that the ventricular beats nearly always follow the auricular 
contractions-that is, the impulse would appear to come through the 
auriculoventricular bundle. It is not an independent ventricular rhythm. 
The auricular impulses are so clearly defined in the neck that it is pos- 
sible to see with certainty that during the period of observation, lasting Tracing 3.-Case 1; March 15, 1909. Right jugular and brachial. Normal rhythm; a-c time averages 0.19 
second. 8 
perhaps half an hour, there were scarcely any ventricular beats that were 
not preceded by an auricular contraction. The only exceptions were 
occasional apparent extrasystoles which, however, were fewer than they 
were last week. The pallor developed in the same way as it did a week ago 
after longer pauses in the ventricular pulse, but it was not so marked. 
The resumption of the beats, after pauses which commonly amounted to 
as much as ten or fifteen seconds, were often preceded by a deep inspira- 
tion; but deep inspiration was not always followed by ventricular con- 
traction, nor did swallowing affect the condition.'' 
From this time the patient giadually lecovered; the pulse intermis- 
sions became shorter and less frequent, and on February 2, the patient 
was removed from Philadelphia to Ba'timoie without ill effect. Here he 
remained at the .Johns Hopkins Hospital under our observation until 
May 15. 
The treatment consisted of rest, a light general diet, restricted in 
amount, and general massage with graded resistance movements. The 
patient was given small doses of atropin gr. 1/250 (0.00025 gm.) and 
strychin, gr. 1/40 (.0010 gm.) four times a day. lodid of potassium was 
begun in doses of gr. x-xv (0.05-1 gm.), but as it was not well borne, 
it was abandoned. A Wassennann test later gave a negative result. The 
patient gradually improved and the pulse became legular, except for the 
periods at night when the nurse desciibed waves of "weakness" of the 
pulse and occasional intermissions. 
On February 20 the patient was allowed to sit up in a chair and take a few 
steps, the exercise being gradually increased. As a result the pulse rose occa- 
sionally to a little above 100. 
On February 28 the nurse described one intermission of fifteen seconds during 
which there were but three or four pulse-beats. 
On March 15 the patient suddenly felt rather weak, the face grew pale and 
the pulse, taken for a whole minute, showed about 29 beats. Immediately there- 
after the pulse became regular, 80. 
Three days later, March 18, the pulse again fell and became very slow, the 
rate ranging from 35 to 41. many of the beats coming in pairs with long pauses 
between. During the long pauses the jugulars could be seen to pulsate three or 
four times, but no auricular beats were audible. After about two hours, ten 
minutes after the patient had taken a small amount of whisky, the beats began 
to come through more often until soon the pulse became about 90, the jugular 
tracings showing a perfectly normal condition. 
On the afternoon of March 20 the pulse suddenly became slow and irregular, 
34 to 40, with pauses of three or four seconds, and frequent series of ventricular 
beats following one another in rapid succession. The jugular pulsations were 
fairly regular at about 100. Later in the evening the pulse became regular at 96. 
On the following morning at six there was suddenly a complete pause in the 
pulse of eight seconds' duration and again at Ila. m., a period of slight irregu- 
larity, intermissions of three or four seconds without a beat and then one, two or 
sometimes three beats in rapid succession. At times one of us (F. W. P.) was 
able to hear the contractions of the auricle, the rate of which was clearly 
determinable by the visible jugular pulsations at about 100. After nearly five 
hours the pulse suddenly became 93 and then 88, every auricular impulse coming 
through.  
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At 9 a. in. the following morning, March 22, the block set in again. There 
were several complete pauses of as much as 10 seconds' duration. After a few 
minutes the pulse became regular again. At 10:10 at night there was a period 
of block lasting for ten minutes with long pauses of thirteen seconds, anti at 11 
p. m. a period lasting three hours and a half. The following note was made by 
Dr. Peabody: "During this period the pulse varied from 10 to 45 and the respi- 
rations from 8 to 15. The long pauses between beats were generally of about 
ten seconds' duration, but not infrequently they were as long as seventeen or even 
twenty seconds. During the pauses the face became very pale, the respirations 
became slow or ceased for long periods, perhaps twenty seconds, and at times in 
the long pauses there was twitching of the hands, feet and muscles of the face. 
On one occasion the patient had a fairly well-marked convulsion, throwing his 
hands up over his head. Sometimes he rolled his eyes upward, the pupils became 
dilated and there was loss of consciousness for a few seconds. Between long 
intermissions he was clear and comfortable. Early in the attack he vomited 
several limes a dark liquid matter and now and again, in spite of morphin. there 
was vomiting or retching with an empty stomach. There was no nausea and the 
vomiting was violent, almost projectile. The abdomen was somewhat distended. 
After the only well-marked convulsion he said he saw yellow lights. Between the 
pauses the beats occurred singly, in pairs, in threes, or at times as many as 25 
regular beats at a rate of about 80. There were frequent beats which seemed 
like extrasystoles. The beats were usually of good size and tension, sometimes 
rather feeble. Between 1 and 2 a. m. the pulse became more regular and the 
intervals shorter. At 3:20 the pulse suddenly became 88, the patient felt better 
and fell asleep." 
On March 29 the patient was allowed to sit up in a chair. Shortly after this 
the pulse suddenly became slow, ranging from 30 to 40. and remained so for about 
fifty minutes, except for about three minutes, during which it was regular and at 
a rate of 70. The longest intervals during the attacks were twelve seconds. Ue 
was given atropin, gr. 1/60 (0.001 gm), hypodermically and ten minutes later 
the pulse became regular, 80 to the minute. Within an hour after the atropin 
was given the pulse-rate reached 100. 
The patient remained in good condition until April 11. when suddenly, at 
9:10 a. m., the pulse fell from 30 to 40, remaining slow for about twenty minutes. 
Five days later. April 16, there were several periods during which the pulse 
was slow with complete pauses of from six to eight seconds, and in the evening, 
at 10:30, the pulse again fell to from 21 to 49, with pauses of ten. fifteen and 
eighteen seconds and a nearly regular pulse between. Atropin. gr. 1/60 (0.001 
gm.), was given hypodermically at 11:22 p. m. Fourteen minutes later the pulse 
was 75, every beat coming through. At midnight, twenty-two minutes later, it was 
88 with an occasional intermission. At 3:45 a. m. the block returned with a pulse 
20 to 35, irregular, with periods of intermission amounting to from fifteen to 
seventeen seconds. The auricular rate was 96 to 100. Atropin. gr. 1/60 (0.001 
gm.), was given hypodermically at 4:18 a. m. At 4:25 the pulse was 21, at 
4:30, 74, all beats coming through. At 5:40 a. m. the block returned with 
pauses of fifteen seconds. Twice there was loss of consciousness. Often a series 
of 8 to 10 beats came through at a rate of about 80. There was vomiting. 
Strychnin, gr. 1/60 (0.001 gm.), was given at 7:01 a. m. and was followed almost 
immediately by stoppage of the block; pulse 80, regular. At 10:45 the pulse 
was 104. 
At 12:35 p. in. the block returned with pauses of eight to twelve seconds; 
the auricular rate was about 100. Atropin, gr. 1/60 (0.001 gm.), was given at 
1:13. The pulse at 1:18 was 32; at 1:23, 31; at 1:28, 27; at 1:32, 64; at 1:34, 
eleven minutes after administering the atropin, 82, regular, all impulses coming 
through. During this attack a long series of as many as 18 beats would come 
through regularly, only to be succeeded, at times, by a pause of about ten seconds. 
At 6 p. m. the pulse was 84 and the usual respiratory variations were observable &!> 
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Tracing 5.-Case 1; March 18, 1909. Right jugular, carotid and brachial. Partial dissociation 12 
in the pulse. At about 9 o'clock, however, the block returned again with pulse of 
35 to 76. 
At 2:35 the patient was seen by one of us (F. W. P.) ; he was then fairly 
comfortable; there were no long pauses between the beats and the pulse was for 
the most part fairly regular, but slow, averaging about 30 beats to the minute; 
auricular rate about 100; respiration irregular. Atropin, gr. 1/30 (0.002 gm.), 
was again given hypodermically at 5:52 a. m., but there was no great change in 
the pulse, which was 24 at 5:57; 25 at 6:15; 23 at 8:10; 43 at 9. Just after 
noon the block suddenly stopped and the pulse became regular at 92. During the 
evening there were again pauses of five or six seconds. 
From this time to the day of his discharge, on May 15, the patient remained 
perfectly well. The nurse reported an occasional momentary intermission in the 
pulse, but beyond this, nothing. 'The patient was up and about, walking without 
discomfort, the recorded pulse ranging from 70 to 98. The blood-pressure during 
the time spent in the hospital ranged from 140 to 175. 
On May 14, examination of the heart showed that the outermost point of 
dulness to the left was 11.5 cm. from the median line in the fifth space; to the 
right dulness extended about 4 cm. from the median line. There was no change 
in the character of the sounds; the pulse was regular, 22 to the quarter. 
On May 15 the patient returned to Philadelphia. Tn June there was another 
period of block, lasting off and on till the end of July when there were several 
syncopal and convulsive attacks. After this, with the exception of one brief 
attack in February, 1910, the patient remained well till the late spring, when he 
had another severe period of bradycardia with convulsions. From this he recov- 
ered, and is now (November, 1910) in apparent good health. 
On October 29 the patient consulted one of us (W. S. T.). He was in excellent 
condition; the pulse was 84; blood-pressure, maximum, 156; cardiac area and 
sounds as on last note. Tracings taken at this time show a regular pulse with a 
normal jugular tracing, the a-c time averaging 0.2 second, or slightly less. 
In May, 1910, I saw Mr. T. again, about a week after a grave attack. He was 
in bed, but appeared to be in excellent condition. The pulse was regular, of normal 
rate and there was no change in the character of the heart sounds or in the size 
of the heart. 
In a man of 53 with rather thickened arteries and a slightly enlarged 
heart with a rough systolic murmur of maximum intensity at the aortic 
area, the following manifestations occurred: 
1. Syncopal and convulsive seizures associated with bradycardia with 
intermissions in the ventiicular pulse amounting sometimes to nearly or 
quite half a minute in length, and a marked irregularity in the size and 
sequence of the beats which occurred often in gioups of thiee or more in 
rapid succession. The auricular rate was always 100 or above. The 
longer intermissions in the ventricular pulse were usually associated with 
long periods of apnea. 
2. Similar attacks, usually without convulsions, in which the auricular 
rate was slower, once as slow as 59. while the ventricular beats occurred 
in groups of from two or three to ten, always at the same rate, and 
apparently following the same impulses as the auiicular beats, but separ- 
ated by long intermissions amounting sometimes to as much as fifteen 
seconds. These groups of beats were frequently ushered in by an appar- 
SUMMARY OF CLINICAL OBSERVATIONS  
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Tracing 6.-Case 1; April 16, 1909. Right jugular and brachial. Partial vagus (?) block. Ventricular contractions in groups with long intermissions. 14 
ently spontaneous ventricular systole. Such attacks yielded in three 
instances to atropin, gr. 1/C0 (0.001 gm.), injected hypodermically. 
3. Periods during which there was a fairly regular ventricular rhythm 
of about 30 to the minute with an auricular late of 100 to 120, giving 
one the impression of a complete auriculoventricular dissociation. One of 
these attacks failed to yield to atropin, gr. 1/30 (0.002 gm.), injected 
subcutaneously. 
4. Periods during which there were intermissions of the ventricular 
pulse of shorter or longer duration, occurring at varying intervals. Dur- 
ing these periods the waves of regular auricular contractions could be 
seen in the neck. 
5. Periods in the intervals between these attacks in which the heart's 
action appeared to be regular and normal. 
While the patient was in the .Johns Hopkins Hospital numerous 
cardiographic and sphygmogi aphic tracings were taken. 
CONSIDERATION OF SPIIYGMOGRAPIHC TRACINGS 
Tracings 1, 2, 3: Normal Rhythm 
Tracing 1, Xov. 28, 1908.-This is one of a number of tracings taken 
on this date. The record is of the brachial and jugular pulses which are 
apparently normal in all respects. The a wave is rather large, and the 
a-c time averages under 0.2 second. Tracings were taken at a slower rate 
of the drum and through longer periods of time, but no irregularities or 
abnormalities were noted. 
Tracing 2, March 1.-This tracing was taken during an interval 
between attacks. The pulse was regular, 70. The jugular and radial 
tracings show no abnormalities. The a-c time, which averages 0.2 second, 
is occasionally, however, a trifle longer. 
Tracing 3, March 15.-This tracing was taken four hours after an 
attack of dissociation in which the pulse had been irregular at a rate of 
about 29. At the time the tracing was taken, the rate of the pulse was 
80 and regular. The jugular tracing is again normal, and the a-c time 
averages 0.19 second. 
Tracing 4 was taken dining an attack of block. The jugular curve 
shows that the amides are contracting at the rate of about 130 to the 
minute. The intervals between the time of onset of the auricular beats 
vary from 0.32 to 0.56 second in length. Much of this discrepancy in 
the length of the intervals between the beats is due to the fact that it is 
very often difficult to determine the exa~t point of onset of the a wave. 
Ventricular contractions, as shown by the brachial curve, come either 
singly at a regular rhythm or in pairs. The occurrence of these beats in 
Tracings Jf and 5, March IS: Partial Block  
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Tracing 7.-Case 1; April 16, 1909, 11:25 p. m. Right jugular and brachial. Partial vagus (?) block, showing an intermission of over ten seconds. Three 
minutes after the administration of atropin, gr. 1/60 (0.001 gm.). 16 
pairs does not follow with regularity. The longer intervals between 
ventricular beats are from 1.37 seconds to 1.58. The shorter intervals in 
the two instances on this tracing are, respectively, 0.81 and 0.72 second; 
that is, not far from one-half the longer intervals. Moreover, the time 
from the onset of an isolated contraction to the first of a following pair 
of contractions, or from the second of a pair to the following isolated 
contraction is from 1.37 to 1.58. 
There are thus two distinct ventricular intervals, a long interval of 
from 1.37 to 1.58 and a short interval of from 0.72 to 0.81 second, the 
shorter being about one-half the longer interval. With the longer interval 
the ventricle is contracting at a rate of about 40 to the minute. If the 
shorter interval be taken as a standard, and the longer pause considered as 
due, perhaps, to a dropped beat, the ventricular rate is about 75 or 80. 
It will, however, be noticed on studying the tracing, that this apparent 
halving of the longer intermissions is only approximate. That the con- 
dition is not one of partial block with a regular 3 to 2 or 3 to 1 rhythm is 
shown by comparison with the jugular curve. There would seem to be 
little direct relation between the auricular and ventricular rhythms. 
While the relation of the a wave of the auricular contraction to the c 
wave of the ventricular contraction is in many instances such tkat one 
might fancy that the impulse had passed through the auriculoventricular 
bundle in the normal manner or with but slightly prolonged conduction 
time, at other points the c wave and the a wave fall at the same time and 
form one combined elevation on the jugular pulse. In one only of these 
combined waves is it possible to distinguish the a and c impulses with 
certainty. Here, at x on the tracing, a small wave superimposed on the 
summit of the larger elevation appears to correspond to the c wave, 
following the onset of the larger wave by 0.1 second. This apparent 
coincidence of the auricular and ventricular waves occurs three times in 
connection with an isolated ventricular contraction, once in connection 
with the first of a pair of ventricular contractions. Tn a tracing taken 
at the same time (Tracing 5), with a somewhat more rapid drum, there 
appears to be a more definite relation between the auricular and the ven- 
tricular contractions. The tracing includes two pairs of beats with the 
beginning of a third, and in all the c wave follows the a wave after an 
interval of 0.18 to 0.28 second. In the shorter ventricular pauses there 
is one auricular beat not followed by a ventricular impulse, and in the 
longer pauses three a waves without a succeeding c wave. 
Do these tracings represent a paitial auriculoventricular dissociation, 
or is the relation of the c waves to a waves only apparent? With short 
auricular intervals a large number of the ventricular beats must fall at 
such periods that they are within a normal or but moderately prolonged 
a-c time. Whether such ventricular beats are caused by the same impulses Tracing 8.-Case 1; April 16, 1909, 11:36 p. in. Right jugular and brachial. Normal rhythm. Fourteen minutes after administration of atropin, gr. 
1/60 (0.001 gm.), during a period of partial block. The tracing was taken eleven minutes after Tracing 7. 18 
which excite the preceding auricular contractions, or whether they are 
due to an independent contractility of the ventricle, their relation to the 
auricular contractions being purely one of chance, is often difficult to 
determine. Careful study of these two tracings, however, reveals an 
interesting point. Out of fifteen ventricular contractions three occur 
almost simultaneously with the auricular impulse, so that the two waves 
are fused, in one the c wave follows but 0.1 -f- second after the a wave, 
while in the other eleven beats, the c waves follow the a waves after a 
period of time varying from 0.17 to 0.28; hut this is a period which might 
well represent in some instances a normal, in others a conduction time 
which is but slightly lengthened. 
Now if, in the four instances in which a and c waves are practically 
combined, one compares the probable time of the onset of the c wave- 
which from comparison with the brachial pulse, would seem to represent 
the beginning of the combined waves-with the preceding a waves, we 
find that the periods of time between the two amount, so far as can be 
estimated, to 0.32, 0.34 and 0.38, respectively. Might these periods 
represent prolonged conduction time? It is conceivable, but it would 
assuredly be remarkable that the conduction should vary from 0.17, a 
normal period, to 0.38, a greatly lengthened period, in a wholly irregular 
manner during these fifteen beats. The improbability that these periods 
represent prolonged conduction time is rendered more evident by another 
consideration. As a rule, in disease of the bundle of His with partial 
block, the a-c time becomes longer with successive beats and is shorter 
with the first contraction following a blocked impulse. Here, on the 
other hand, the contrary is true. The longest a-c periods occur after 
long intervals in the ventricular beats, while the a-c interval in connection 
with the four beats occurring after the short intermissions, where one 
might have expected a prolonged a-c time, amounted to 0.23, 0.18, 0.24 
and 0.19, respectively. We are, then, rather inclined to regard these beats 
with long a-c periods as spontaneous ventricular contractions. 
Might it be that these tracings represent a total dissociation of auricle 
and ventricle, an automatic ventricular rhythm? Those beats which 
appear to be spontaneous ventricular systoles may well be evidence of an 
attempt on the part of the ventricle to initiate an independent rhythm. 
The occurrence, however, of so many other beats, each one of which 
follows an auricular systole after an interval of a length not far from the 
normal, would suggest that the stimuli giving rise to some of the ven- 
tricular contractions on these tracings, passed through the auriculo- 
ventricular bundle; that the condition, then, was one of partial disso- 
ciation. 
Might one not fancy that these long intermissions are dependent on 
a lack of irritability of the ventricle, rather than on the blocking of I 5*7 
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stimuli? The first contraction of a pair, occurring either spontaneously 
or after a stimulus reaching it in the normal way. might conceivably be 
the result of a summation of stimuli which have individually failed to 
produce a response. As a result of such a summation of stimuli, spon- 
taneously, or set off as it were, by the last impulse, a vigorous contraction 
occurs. This contraction, by improving the nourishment of the heart 
muscle and removing waste products, might render the rested ventricle 
readier for a time to respond to the subsequent regular stimuli. 
Tracings 6, 7, 5, April 16, 1909: Partial Dissociation Relieved by Atropin 
In Tracing 6 the jugular tracing shows the auricular waves occur- 
ring with fair regularity at intervals which average 0.66 seconds in 
length, giving an auricular rate of 90. The tracing from the 
brachial artery shows a very different condition from that which was 
noted in the previous tracings of March 18. The waves of ventricular 
contraction occur either singly or in series of three or more contractions, 
the individual beats of the series being in most cases equally spaced. The 
pauses without ventricular contractions sometimes amount to ten second * 
(Tracing 7). After the pause the first beat is small and those succeed- 
ing become progressively larger, doubtless owing to the fact that the 
artery, empty at first, becomes fuller with each contraction. The average 
length of the intervals between the waves which occur in series on the 
brachial tracing, is 0.6 of a second, exactly the same as that of the auric- 
ular intervals. During these series of beats, then, the ventricles are 
contracting at the same rate as the auricles and the a-c intervals are 
essentially normal. In the two instances in which the a-c time is much 
longer than the normal, it is probable that the r wave from the preceding 
beat has masked the onset of the following a wave. The ventricles are. 
therefore, during these periods, responding to every impulse causing the 
auricular contractions. There is one exception to this rule. On all our 
tracings the interval between the first and second beats of a series is 
longer than that between the second and third. This is shown in Tracing 
6, in which the first intervals are 0.67 and 0.96 second, respectively, and 
the second intervals, 0.57 and 0.61 second, and on Tracing 7. in which 
the first intervals are 1 and 0.95, respectively, the second 0.58 and 0.66 
in each group. Moreover, the relation of the c waves associated with 
these contractions to the preceding a waves is not analogous to the rela- 
tion between the succeeding a and c waves. While the a-c time of the 
beats which follow-with the exceptions above mentioned-is of about 
0.2 second in each case, the a-c intervals of the first beats are 0.11 (time 
of c wave estimated from the brachial tracing) 0.51, 0.42 and 0.28, 
respectively. It is difficult to comprehend why, when a partial auriculo- 
ventricular block is beginning to give way. the a-c time of the first impulse | vz| 
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Tracing 10.-Case 1; April 18, 1909. Total block. 22 
to come through should be longer than that with the following beats. 
One would expect exactly the reverse-a short a-c time at first, becoming 
gradually longer until the beats begin to drop out again. It seems more 
reasonable to regard these first beats as automatic systoles of a ventricle 
which has become irritable during the prolonged pause. The first ven- 
tricular beat of the first series on Tracing 6 occurs synchronously with 
an auricular impulse so as to cause a combined wave on the jugular pulse. 
The position of the c wave, calculated from the time of onset of the 
brachial wave, would make the a-c time 0.11 second, too short a period 
to justify the assumption that the auricular and ventricular contractions 
resulted from the same stimulus. One is then justified in regarding this 
beat, as well as the isolated beat which precedes it (a-c time = 1.38 
second), as spontaneous ventricular systoles. 
A second interesting peculiarity of the rhythm of both auricles and 
ventricles is shown in this and other tracings taken at this period. This 
consists in the progressive prolongation of the pulse intervals during each 
series of beats. Thus, in one instance, while the interval between the 
brachial waves at the beginning of the series is 0.5 second, that between 
the beats toward the end of the series of ten pulsations is 0.8 second. 
In Tracing 7 the intervals increase during five beats from .59 to .82. The 
same slowing of the rate applies to auricles as well as to ventricles; that 
is, the auricles are apparently subjected to the same influences. Moreover, 
this slowing of the auricular rate persists for a few beats after the ven- 
tricular contractions cease. The a-c time remains more or less constant 
and does not, as might be expected, if the lesion were one of conduction, 
become progressively prolonged. The relation of the isolated ventricular 
contractions to the contractions of the auricle cannot be determined 
absolutely. In some instances they occur at such times that it is possible 
that they may depend on the impulse which caused the preceding auric- 
ular contractions, but at other times they fall so far from a preceding- 
auricular contraction that it would seem more reasonable, as has been 
said, to regard them as automatic ventricular systoles. A study of the 
tracings then, leads to the conclusion that the dissociation at this period 
was partial rather than complete. 
Further evidence of this is given by the result of the atropin test. 
After the first tracings had been taken, atropin sulphate, gr. 1/60 
(0.001-j-gm.), was given subcutaneously. Three minutes later Trac- 
ing 7 was taken. This tracing shows an intermission of over ten seconds' 
duration. Shortly after the atropin was given the beats at the wrist 
became more frequent and the pauses became shorter. A tracing taken 
fourteen minutes after the injection (Tracing 8) shows that every auric- 
ular contraction is followed by a ventricular contraction with an a-c 1 y2-4' 
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Tracing 11.-Case 2; April 21, 1909. Right jugular, apex and brachial. Relatively total block; 3:2 rhythm (?). 24 
time of 0.2 second, which is well within normal limits. The heart's 
rate is 71. 
The atropin test which was used by Dehio to distinguish between 
bradycardia of vagal origin and that dependent on changes in the heart 
muscle is generally regarded as being the best clinical test of complete 
organic heart-block. In typical cases of Adams-Stokes syndrome with 
permanently slow pulse the administration of atropin causes a rise in 
auricular rate without changing the ventricular rate. Tn case of partial 
block in which the dissociation is due in part, at least, to vagus influences, 
atropin usually accelerates the auricles and puts an end to the dissociation. 
It is noteworthy that while in this instance the dissociation was tempora- 
rily relieved, yet the rate of the heart when every impulse was coming 
through was only 70-80, somewhat slower than the previous rate of the 
auricles. This is extraordinary and, so far as we know, a unique feature 
of the case. And on the two other occasions on which the administration 
of atropin was followed by a disappearance of a partial dissociation, the 
same phenomenon-a diminution of the rate of the auricular pulse after 
atropin-was observed. 
A point which is probably of some importance was, however, pointed 
out by Professor Howell; namely, the intervals between the auricular 
beats after the disappearance of the block, while longer than the average 
intervals before, are yet shorter than the intervals occurring just before 
and at the onset of the periods of long intermission in the ventricular 
pulse. 
'The action of atropin in dissipating the dissociation suggests strongly 
that at this time, at all events, vagus influences played a part, to say 
the least, in its causation. This is supported by the behavior of the res- 
piration during the attacks. That the a-c time in this and in other trac- 
ings is so rarely prolonged beyond the normal limits justifies the query as 
to whether the defect may not be one of the irritability of the heart 
muscle rather than a disturbance of the mechanism of conduction. 
One might fancy that the course of events during these periods is as 
follows: With a heart muscle the irritability of which is diminished, 
there occur, with waves op increased vagus actiom a gradual slowing of 
the auricular rate and a diminution in the intensity of the stimuli pass- 
ing to the ventricle without delay in their periods of transmission, or a 
further diminution, under the same influences, of the irritability of 
the ventricle, sufficient to result in the cessation of ventricular contrac- 
tions. This increase in vagus action continues for a short time after 
the falling out of the ventricular contractions, as indicated by the delay 
in the several succeeding auricular beats. With the passing of this 
depressing influence and the resumption of a rapid auricular rate, the 
diseased and exhausted ventricle tails to respond to the succeeding  
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Tracing 12.-Case 2; April 21, 1909. Right jugular, apex and brachial. Relatively complete block. 26 
individual stimuli. After a varying period, owing, perhaps, to a sum- 
mation of stimuli ( ?) there occurs an apparently spontaneous ventricular 
contraction. This spontaneous contraction removes waste products and 
improves the circulation and nourishment of the heart muscle so that 
the rested ventricle is again able to respond to each stimulus as it arrives 
through the auriculoventricular bundle. But after a certain number of 
beats, with the return of a wave of vagus activity, the auricular rate is 
slowed and the ventricular contractions again fall out. 
Tracing 9. April IS: Complete Block Unaffected hg Atropin 
Jugular tracings taken during this attack of block show auricular 
waves occurring at intervals averaging 0.5 second, a rate of 120 
per minute. The ventricular rhythm, as determined by the brachial 
pulse and auscultation, showed that every ventricular beat was coining 
through to the wrist. The condition is quite different from that which 
is seen in Tracing 6. The ventricles are contracting regularly at intervals 
which average from 1.9 to 2.07 seconds, giving a rate of 31 + per minute. 
This is about the rate which is common in complete auriculoventricular 
dissociation with a permanently slow pulse. There is, however, an 
occasional beat with a shorter pulse period, as may be seen on Tracing 10, 
where the average rate is slightly more rapid. Comparison of the ven- 
tricular rhythm with that of the auricles shows that there is no apparent 
relation between them. The c waves occur at varying times after the a 
waves and, in some instances, fall synchronously with an a wave, so that 
one simple elevation is formed on the venous curve. It is, however, 
rather remarkable that out of twenty-one ventricular contractions studied 
on three good tracings, in which the interval between auricular waves 
averaged from 0.45 to 0.50 second, the a-c time was between 0.18 and 0.31 
second in fifteen instances, 0.12 in one, while in five the a-c waves were 
fused. 
Was this a complete a-c dissociation? In order to determine this 
question atropin, gr. 1/30 (0.0021 gm.), was given subcutaneously. 
No change in the ventricular rate was observed. This result tends to 
confirm the view that, at this time, the dissociation was complete and 
suggests that vagus influences played little or no part in its production. 
About five hours after the atropin was given, and ten hours after the 
establishment of the dissociation, the attack ended spontaneously and the 
pulse became 92. It is worthy of note that during this attack, which was 
characterized by a slow regular pulse, the patient's general condition was 
quite different from that observed during the attacks in which the pulse 
was irregular. The unpleasant symptoms which accompanied the long 
pulse pauses-pallor, flushing, loss of consciousness and convulsions- 
were absent. Throughout the attack the patient wr, comfortable and z 
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Tracing 13.-Case 2; April 21, 1909. Hight jugular, apex and brachial.Partial block; 3:1 rhythm with ventricular extrasystoles. 28 
undisturbed. He slept quietly, and ate his meals without any subjective 
discomfort. During the forty-eight hours preceding this attack of com- 
plete dissociation with regular pulse, he had five other attacks of irregu- 
larity with intermissions lasting from fifteen minutes to one and a half 
hours. Two of these were stopped by atropin. No atropin was given in 
the others. During the hour preceding the establishment of the slow 
regular rhythm the nurse's chart shows that the patient's pulse was very 
irregular, varying in rate from 36 to 76 with pauses of 8 to 10 seconds 
without beats. During this time he was aroused from his sleep and had 
frequent "flushes." With the establishment of a regular pulse the patient 
said that he felt a little short of breath, but was quite comfortable. The 
pulse-rate during the whole attack varied from 24 to 44 per minute. The 
urinary output was decreased. On the succeeding day there was another 
short attack lasting about eight minutes. After that, with the exception 
of occasional dropped beats, the pulse remained regular and at a normal 
rate until his discharge from the hospital four weeks later. 
SUMMARY OF THE TRACINGS AND GENERAL DISCUSSION 
The tracings from this case show the following: 
1. Regular normal rhythm with normal a-c conduction time. (Trac- 
ings 1, 2, 3, 7). 
2. A dissociation of auricular and ventricular contractions (Tracings 
4, 5), which, at first glance, appears to be complete, the auricles con- 
tracting regularly at the rate of over 130, the ventricles at a rate of about 
50, somewhat irregularly owing to the occasional occurrence of beats in 
pairs with shorter intervals. Although no constant relation could be 
determined between the auricular and ventricular rates, yet it was found 
that a large proportion (11 to 15) of the ventricular beats followed the 
preceding auricular contractions within a period corresponding closely 
to the normal a-c time. We are, therefore, inclined to regard the con- 
dition as one of partial dissociation. 
3. Partial dissociation of auricular and ventricular contractions 
(Tracings 6 and 7), both auricles and ventricles beating at a normal rate 
and in a normal sequence, with the exception of frequent long intermis- 
sions in the ventricular pulse. After these intermissions the first ven- 
tricular beat was apparently a spontaneous contraction bearing no definite 
relation to the preceding auricular systole. Then followed ventricular 
contractions occurring usually in groups of about six to ten in number, 
essentially regular in rate and bearing a normal relation to the action of 
the auricles. Slight slowing in the rate of both auricular and ventricular 
beats was noticed during the last several contractions before the periods of 
block, and in the first several auricular contractions after the onset of 
ventricular intermissions.  
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Tracing 14.-Case 2; April 22, 1909. Right jugular, apex and brachial. Relatively complete block 30 
This form of dissociation yielded, on three occasions, to the adminis- 
tration subcutaneously of atropin, gr. 1/60 (0.001 gm.). The auricular 
rate after atropin was, however, slower than it was before, but more rapid 
than the rate of the several slow beats at the time of onset of the periods 
of ventricular intermission. 
4. Apparently complete amiculoventricular dissociation with a regu- 
lar ventricular rhythm of 30 to 35 (Tracings 9, 10). This condition 
was not relieved by atropin, gr. 1/30 (0.0021 -|- gm.), injected subcu- 
taneously. 
It is unfortunate that we have not a good tracing taken during one 
of the attacks (see second paragraph under "Clinical Notes on Specific 
Attacks") with very long intermissions associated with convulsions and 
wholly irregular ventricular pulse. One tracing which we have studied 
(taken by Dr. Stengel) during the attack on January 2 suggests a com- 
plete dissociation. It is also very unfortunate that no graphic records 
of the respiration were made. 
How are we to account for these various manifestations? One of the 
striking features of this case is the lack of essential lengthening of the 
a-c conduction time, even during periods of marked dissociation. The 
lengthening at several points where it appears is but slight and without 
regularity. This is unusual and raises the question as to whether a 
depressed excitability of the heart muscle may not play a part in the 
production of the symptoms. It would seem possible to account for most 
of the manifestations of the case on a hypothesis which supposes changes 
in or adjacent to the auriculoventricular bundle sufficient to cause (a) 
perhaps irritation of the bundle, (b) paitial and at times, complete block 
but insufficient totally to destroy the bundle, (c) changes in the heart 
muscle which manifest themselves in a diminished irritability, (d) 
periods of increased vagus action occurring at times more or less regularly 
in waves. 
At times there were periods of apparent complete block with rapid 
auricular action, irregular ventricular pulsations and long intermissions. 
At other times there were periods of total dissociation with a regular ven- 
tricular rhythm of about 30, and an auricular rate averaging about 120 
to 130. Again, there were periods of paitial dissociation with the occa- 
sional dropping of ventricular beats, the cause of which might have been 
diminished excitability of the ventricle or a diminution in the intensity 
of the impulse due to disease of the bundle or, perhaps, to vagus influence 
alone, or combined with this. Finally there were periods of partial block 
in which vagus influences must have played a part. In the absence of 
essential lengthening of conduction time at the periods in which the 
auricular rate became slower and the ventricular contractions fell out 
(Tracings 6 and 7), one would be tempted to suggest as an explanation  
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Tracing 15.-Case 2; April 22, 1909. Right jugular, apex and brachial. Relatively complete block. 32 
that, under the influence of increased vagus action, the impulse passing 
through the diseased auriculoventricular bundle was insufficient to call 
forth a response from a ventricle of perhaps diminished excitability, 
either because of a diminution of the strength of the stimulus itself, or 
through some depressing influence on ventricular irritability. 
That stimulation of the vagus by pressure, in the presence of disease 
of the bundle of His, may result in the falling out of ventricular beats 
with slowing of the auricular rate, but without notable prolongation of the 
a-c time was demonstrated experimentally by one of us (F. W. P.) in 
Case 2. 
Of great interest is the apparent recovery of the patient after periods 
of dissociation so grave, at times apparently complete, and of such long 
duration, especially in the absence of any evidence of syphilis. 
What may have been the nature of the disease of the bundle? It is 
difficult to answer the question with certainty. The physical signs- 
hypertrophied heart-rough aortic systolic murmur-point to a sclerosis 
at the aortic ring. One might suspect coronary changes arising perhaps 
at the root of the aorta with myomalacia followed by sclerosis, or a more 
gradual sclerosis due to similar changes in the neighborhood of and par- 
tially involving the auriculoventricular bundle. 
One might, indeed, fancy that the disturbances depended on sclerotic 
changes in the artery of the bundle. 
There are several cases in the literature of auriculoventricular dissocia- 
tion with normal or nearly normal a-c time. In Hay's case,2 during the 
periods of block, there was often appreciable prolongation of the a-c time 
which, however, was normal in the intervals. Nevertheless, there were 
times at which a sudden halving of the rhythm occurred without apparent 
lengthening of the intervening a-c periods. Wenckebach3 reports a similar 
case and regards both instances as examples of intermission due to dimin- 
ished irritability of the ventricles. 
Gossage4 reports a like instance with ventricular intermissions and. 
indeed, a tendency at times, to the establishment of an independent ven- 
tricular rhythm without prolongation of the a-c time. 
One of us (W. S. T.) has recentlv observed a case in which physical 
effort was immediately followed by halving of the ventricular rhythm with 
a slight acceleration of the auricular rate, without prolongation of the 
a-c time. Vagus pressure in this case caused a single complete inter- 
mission of both auricle and ventricle (sino-auricular block?) followed by 
2. Hay: Bradycardia and Arhythmia Produced by Depression of Certain of 
the Functions of the Heart, Lancet, London, 1906, i, 139. 
3. Wenckebach: Beitriige zur Kenntniss der menschlichen Herzstiitigkeit. 
Arch. f. Anat. u. Physiol., 1906, Physiol. Abth., p. 328. 
4. Gossage: Independent Ventricular Rhythm; Heart-Block and the Stokes- 
Adams Syndrome, Without Affection of Conductivity, Heart, 1910, i, 238.  
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Tracing 16.-Case 2; April 22, 190!). Right jugular, apex and brachial. Relatively total block. Occasional response of ventricles to impulses passing 
through the auriculoventricular bundle. 34 
a slowing of both auricular and ventricular rhythm without prolongation 
of the a-c time. During the period of pressure, after the first complete 
intermission there were occasional blocked auricular extrasystoles. The 
case was one of arteriosclerosis and chronic myocarditis. 
In all these cases the most reasonable hypothesis for the explanation 
of the ventricular intermissions would appear to be that of a diminished 
irritability of the ventricles, and in all there were obvious cardiac defects. 
The autopsy of but one of these cases has been reported. In this case, 
that of Hay, there was definite involvement of the bundle of His, which 
was partly destroyed in a patch of fibrous myocarditis. 
CASE 2 
Adams-Stokes' syndrome; chronic myocarditis ; hypertrophy and dilatation of 
the heart; partial and complete auriculoventricular dissociation with prolonged 
a-c intervals amounting, sometimes, to over 0.5 second; audible sound and visi- 
ble and palpable impulse at cardiac apex with auricular systole; acceleration of 
cardiac rate wiith alternating pulse following atropin; development of 2 to 1 
and 3 to 1 rhythm, following pressure on vagus, without essential change in 
auricular rate; improvement. 
H. J. (Gen. No. 68,051), colored, aged about 83, entered the hospital 
April 6, 1909, complaining of shortness of breath. There was nothing of 
importance in his family history. In 1906 he was operated on at the Johns 
Hopkins Hospital for trigeminal neuralgia. He had always been a heavy drinker 
of whisky and gin and a constant smoker; had had gonorrhea and syphilis. 
Present Illness.-This was of about three years' duration. Since this time he 
had had occasional attacks of dizziness and fainting. During two of these, which 
occurred while he was walking along the street, he fell to the ground. He did 
not know how long he was unconscious. During November, 1908, the patient first 
noticed shortness of breath on slight exertion. At the same time his feet and legs 
became painful and swollen. In the last two weeks the dyspnea had become worse. 
He now had considerable pain in the right side of the chest, radiating toward the 
xiphoid process. The patient said that when he walked he became breathless and 
that if he did not stop he would fall. It was impossible to get a very satisfactory 
history. 
Physical Examination (F. W. P.).-This showed a well-nourished old man. 
Thorax: Well formed; expansion, equal on the two sides. Lungs: Percussion 
note resonant over both fronts and axilla; marked diminution over the bases 
behind, where the fremitus was weak and breath sounds were barely audible. 
Forced inspiration was accompanied by numerous medium and fine moist rales. 
Heart: Point of maximum impulse visible and palpable in the seventh space, 
11 cm. to the left of the mid-sternum; impulse, heaving, unaccompanied by a thrill. 
Dulness extended 4.5 cm. to the right in the fourth space and above to the third 
rib. On auscultation the heart's action was irregular with a definite pause between 
each three beats. There was a systolic murmur of considerable intensity at the 
apex, transmitted to the mid-axilla. At the base of the heart the first sound was 
barely audible; pulmonic second was loud and sharp. Aortic second was less 
distinct and followed at times by a very short diastolic blow. Pulse: Seventeen 
to the quarter, irregular in force and rhythm, large, at times slightly collapsing 
Vessel wall moderately thickened. 
Treatment and Course of Disease.-The patient was put to bed; a diet, limited 
in quantity, and infusion of digitalis, 2 drams (8 c.c.), every four hours, were 
ordered. After several days the pulse was slower, between 50 and 60, falling on 
April 13 to between 40 and 50 to the minute. On April 20 it was noted that the  
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Tracing 17.-Case 2; April 24, 1909. Right jugular, apex and brachial. Partial block. Automatic ventricular rhythm modified by the occasional 
response of the ventricles to impulses passing through the aurieuloventricular bundle. 36 
pulsations of the veins of the neck were more frequent than those in the radial 
artery, but it was impossible to make out any definite relation between the two. 
The digitalis was omitted and atropin, gr. 1/120 (0.0005 gm.), to be injected 
subcutaneously twice daily was ordered. This was continued until April 25. The 
pulse ranged between 40 and 50, sometimes regular at a rate of about 40, some- 
times showing distinct irregularities of rhythm. The jugular pulsations were 
obviously more frequent than those at the wrist. 
On April 26 one of us (VV, S. T.) noted that there were three impulses visible at 
the apex; one very distinct pulsation followed by two similar, but smaller ones. 
The impulse was visible in second, third and fourth spaces. There was no dulness 
over the manubrium. Point of maximum impulse was 9.5 cm. from the mid- 
sternal line. Dulness extended 10.5 cm. to the left at this point and 3 cm. to the 
right in the fourth interspace. The first sound was very faint, followed by a 
slight systolic murmur. The second sound at the apex was distinct; there was 
marked protodiastolic gallop. This was not audible over the right ventricle. The 
heart's action was regular, 72 to the minute. 
On May 3, W. S. T. observed that "the pulse is beating at the rate of 76, some- 
times quite regular. At other times there are intermissions at irregular intervals, 
but, if one feels at the apex carefully, a small impulse is always felt during inter- 
missions and there is a visible pulsation in the neck. When one listens at the 
apex this is easily heard as a slight, soft sound. This sound is also heard, but 
rather more faintly, in the tricuspid area; it is undoubtedly an auricular sound. 
It is of entirely different character from the first sound and is not associated with 
a second sound. There is at times a slight, early diastolic gallop at the apex." 
On May 29 the pulse was 80 and for the most part regular. Pressure over the 
vagus nerve in the neck, however, caused an almost immediate halving of the ven- 
tricular rate. On auscultation during the long pauses produced by pressure on the 
vagus, there was heard either a single sound or two dull sounds with a very short 
interval. The systolic murmur at the apex was louder at the slower rate than 
at the normal rate. At times the pulse assumed a bigeminal rhythm of its own 
accord. The second beat was then weaker than the first. 
On June 1, shortly after 7 p. m., the patient complained of shortness of 
breath. Respirations were quick and shallow, 44 to the minute; the patient seemed 
in considerable distress. The pulse at the onset of the attack was 88 to the min- 
ute, but within a few minutes fell to 72. Continued pressure over the vagus on 
the right side of the neck resulted in a diminution of the respiratory rate to 28. 
The patient seemed very much relieved. 'The pulse-rate also diminished to a very 
perceptible extent. 
June 16: It is now two weeks since the pulse has been as low as 50. The 
hourly pulse-chart shows that it has been usually regular, between 75 and 90. 
Slight pressure on the vagus is always followed by the establishment of partial 
block, generally a 2 to 1 rhythm, although one tracing shows two auricular systoles 
blocked by this means. The urine at no time showed more than a faint trace of 
albumin and an occasional granular cast. 
The blood-pressure was at times as high as 180, but gradually dropped to about 
140. The temperature was normal practically all the time. 
The pulse-rate, from 70-90 during the first few days after admission, dropped 
to about 45 at which it continued for about a week. During the next four weeks 
the rate varied considerably. On the hourly pulse-chart, the rate, while often 
between 40 and 50. is shown at other times to have jumped to somewhere between 
60 and 80. At either rate the rhythm was usually regular. Toward the end of the 
patient's stay the pulse-rate became more steadily high, at about 80 to 90. The 
condition improved so much that the patient was discharged on June 21. 1909. 
The treatment, beyond that already mentioned, consisted of strychnin, gr. 1/30 
(0.002 gm.), three times a day and, during the periods of especial irregularity 
of the pulse, iodid of potassium. 
June 3, 1910: Several attempts were made to follow the course of events dur- 
ing the winter months, but without result. At last, however, we succeeded in Tracing 18.-Case 2; April 24, 1909. Right jugular, apex and brachial. Partial block. Automatic ventricular rhythm mod 
ified by the occasional response of the ventricles to impulses passing through the auriculoventricular bundle. 
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finding the patient June 2, 1910. The attacks of dizziness and momentary loss of 
consciousness had been more frequent, the patient having fallen in the street 
many times. His general condition, however, was much as when last seen. He 
was rather short of breath and there was edema of the legs; the pulse was slow 
and at times quite regular at about 40, at other times showing occasional inter- 
polated beats which were not followed by a compensatory pause. On morning of 
June 3 the cardiac impulse was visible and palpable in the fifth interspace, 11.5 
cm. to the left of the median line, and occasional small impulses might be seen and 
felt at the apex between the regular ventricular contractions. The first sound at 
the apex was strong, fading out into a slight systolic murmur; the second clear 
at the apex and base. At times, at the apex, an extra sound was heard between 
ventricular beats. This sound was soft, just audible and obviously associated with 
auricular systole. 
A man, aged 83, had dyspnea on exertion for three years, with several 
attacks of dizziness and faintness. Physical examination showed hyper- 
trophy and dilatation of the heart with relative mitral insufficiency and 
probable aortic insufficiency. Following treatment with infusion of digi- 
talis, but persisting for more than a month after its discontinuance, 
periods of bradycardia occurred, during which the pulse was sometimes 
regular at about 40, at other times irregular. The pulsation of the auri- 
cles, as observed in the neck, was evidently more frequent than that of 
the ventricles. Auricular pulsations were manifest by a slight audible 
sound and sometimes by a palpable and visible impulse at the apex. 
Slowing, usually halving, of the pulse-rate followed pressure on the vagus 
nerve. The pulse, during a period of somewhat over two months in the 
hospital, gradually returned to a rate of 80-90. A year later the patient 
showed a pulse, nearly regular, at a rate of about 40, with occasional 
interpolated beats. During the year there had been numerous attacks of 
faintness and momentary losses of consciousness. 
SUMMARY OF THE CLINICAL MANIFESTATIONS 
ANALYSIS OF CARDIOGRAPHIC AND SPHYGMOGRAPHIC TRACINGS 
Tracings 11, 12 and 13: Relatively Total Bloclc With 3 to 1 
and 3 to 2 Rhythm 
Tracing 11, April 21, 1909.-The pulse is 44 to 48. The maximum 
blood-p'ressure is 190; minimum, 90. The venous pulsations in the 
neck appeared at the time to be more rapid than the arterial. Tracings 
of the brachial artery show that the ventricular contractions are 
nearly regular, at intervals averaging about 1.25 seconds, a rate of 48 
per minute. The auricles are contracting more rapidly than the 
ventricles, at a rate of about 70, and there is no apparent simple 
ratio between their respective rates. Examination of the jugular pulse 
reveals the dissociation more clearly. The c waves appear to bear 
no constant relation to the a waves. They occur at different periods dur- 
ing the auricular intervals and at times synchronously with the a waves.  
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Tracing 19.-Case 2; April 24, 1909. Right jugular, apex and brachial. Normal rhythm with prolonged a-c time. This tracing was taken 
twenty-nine minutes after the administration of atropin, gr. 1/30 (0.0021 gm.), following the taking of Tracings 17 and 18. 40 
Under these circumstances, one combined wave appears on the jugular 
curve; this wave is frequently of unusual size, doubtless because the 
auricle, unable to open the atrioventricular valves during the ventricular 
systole, must, therefore, exeit a stiong back pressure into the veins. 
Fuither evidence of the am iculoventiicular dissociation is shown by the 
tracings of the apex impulse. Here, the waves due to auricular contrac- 
tion, which were easily visible and palpable, are shown clearly. The varia- 
tions in their relations to the anacrotic wave of the cardiogram are clearly 
evident. This tracing then, might appear to reveal a condition of com- 
plete amiculoventricular dissociation. But another interpretation might 
be put on it. 
One might fancy that, to begin with, the first a-c wave depended bn 
an extremely prolonged conduction time which had resulted in the coin- 
cidence of a c wave corresponding to a preceding a wave, with a succeed- 
ing a wave which is blocked. The next a-c time is 0.325 in length; the 
next 0.73 -f-. Then follows a blocked a wave. This is again repeated, 
an a-c period of 0.29 being followed by one of 0.67 which, in turn, is 
followed by a blocked a wave, and then again by a shorter a-c interval. 
It might be asserted that it is quite unjustifiable to assume the possibility 
of an a-c period as long as 0.6 to 0.7, but, in a case in which the a-c time 
amounts sometimes unquestionably to over 0.5, such a fancy can hardly 
be regarded as wholly unreasonable. If this explanation be accepted, we 
have then, not a total block but a 3 to 2 rhythm. The strongest argu- 
ment against this explanation would seem to be that the a-c time at the 
beginning of the second, fourth and sixth beats occurring on this tracing 
is 0.325, 0.29 and 0.17, respectively. But at no other period on the many 
tracings that we took of this case is there any certain a-c period as short 
as 0.17. In another tracing (Tracing 12) with a slower drum, the rate 
of the radial pulse is about 44 and regular. It seems impossible to deter- 
mine any definite relation between the jugular and the ladial pulse. The 
rate of the jugular pulsation is about 76. 
There is apparently a complete dissociation of auricular and ven- 
tricular rhythms. The rate of the ventricle is, however, more rapid than 
the usual automatic ihythm. One might ask whether this were, perhaps, 
one of those instances described by Erlanger and Blackman5 of "rela- 
tively complete block," where an automatic ventricular rhythm has arisen 
in a heart in which the auriculoventricular bundle is still capable of 
transmitting some stimuli. These stimuli are, however, usually of sub- 
minimal strength and incapable, ordinarily, of interfering with the estab- 
lished ventricular rhythm. It is not uninteresting, however, that the 
second, fifth and eighth ventricular beats following the preceding auric- 
5. Erlanger and Blackman: Further Studies in the Physiology of Heart- 
Block in Mammals, etc., Heart, 1910, i, 214. 1 
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Tracing 20.-Case 2; April 25, 1909. Right jugular, apex and brachial. Normal a-v rhythm. Prolonged a-c time. 42 
ular contractions by respectively 0.30, 0.31, 0.385 second are preceded 
by intermissions slightly shorter than the average. May it not be that 
in these instances the normal impulses reaching the ventricle at a time 
when it was nearly ready to contract from its inherent rhythmicity, have 
slightly hastened the contraction? 
Another tracing (Tiacing 13) taken on the same day does not appar- 
ently show a complete block. There is a bigeminal ventricular rhythm 
The c elevation corresponding to the first of each pair of ventricular 
beats follows an a wave after a fairly constant period, varying from 0.30 
to 0.38, a conduction time similar to that observed in this case at other 
periods during a normal auriculoventricular rhythm. The second of each 
pair of contractions is, however, associated with a combined a 4- c wave 
on the jugular pulse. By comparing the a wave with the brachial tracing, 
however, it is found that the a-brachial period suggests usually a normal, 
or but slightly increased conduction time. May these second ventricular 
contractions depend on the same stimuli as those causing the preceding 
auricular beats? The short a-c period in association with a contraction 
immediately following another with a lengthened conduction time, espe- 
cially in a case in which at all other times the a-c period is markedly 
lengthened, would be difficult to explain, unless one assume that the 
impulse causing this contraction is ectopic, arising at a point farther 
down in the bundle than usual; but the auricular impulse follows the 
preceding after the usual period. Moreover, it is interesting to note that 
the second of each pair of ventricular contractions follows the first after 
an intermission which is almost constantly of about 0.6 second, a period 
more constant than that separating it from the preceding a wave. It 
would then seem probable that the second beat of each pair is a spon- 
taneous ventricular systole to which the preceding ventricular beat bears 
some causal relation. The third auricular contraction associated with 
each group of beats is obviously blocked. There is one exception to this 
rhythm. The third auricular impulse in connection with the sixth pair 
of beats is followed after 0.49 second by a c wave and a radial pulse. 
The tracing would, then, appear to represent a partial dissociation in 
which there is a fundamental 3 to 1 rhythm which becomes a 3 to 2 
rhythm because of regularly interpolated ventricular extra-systoles which 
cause a bigeminal pulse. 
Tracings U+, 15 and 16, April 22, 1910: Relatively Total Block, with 
Evidence of the Occasional Passage of Stimuli Through the 
Bundle of His 
In Tracing 14 the radial rate is about 50; auricular 78-79. The 
ventricular intervals are fairly regular, varying from 1.18 to 1.25 in 
length. The auricular intervals vary from 0.73 to 0.90. On studying the 
tracing one sees a combined a + c wave in the jugular; an a-c interval 1 
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fracing 21.-Case 2; April 29. 1909. Right jugular, apex and brachial. Normal a-v rhythm. Prolonged conduction time; 2:1 rhythm. 44 
of 4.2; a blocked wave. This is followed by a similar sequence twice, 
the lengthened a-c time averaging from 0.39 to 0.42. The combined 
a -f- c wave shows in two instances a double summit corresponding respec- 
tively to a and c waves. The a-c time is 0.10 in each case. In the third 
combined wave the onset of the c wave is not evident on the jugular 
pulse. The onset of the systolic elevation of the cardiogram corresponds 
exactly with the beginning of these three combined waves on the jugular 
curve and falls 0.10 second before the small notch indicative of the c 
wave where it is present. This is not much longer than the ordinary 
transmission time, apex to jugular. The character of these waves sug- 
gests, then, that the auricle and ventricle must have contracted almost 
simultaneously. 
A second tracing (Tracing 15) with a slower drum, shows 11 ven- 
tricular beats to 16 auricular beats. On studying the tracing it is rather 
difficult on first glance to avoid the conclusion that it represents a com- 
plete dissociation. The comparative regularity of the auricular and ven- 
tricular rhythms and the great variations in the a-c periods would seem 
to be difficult to explain by another hypothesis. The rate of the pulse- 
between 49 and 50-is, however, rather more rapid than is common in 
essential ventricular rhythm. 
On a third tracing (Tracing 16) showing 11 ventricular and 16 
auricular beats, there appears to be in the main no definite relation 
between auricular and ventricular contractions. The intervals between 
the ventricular beats vary from 1.13 to 1.30 with the exception of one 
beat, which follows the preceding after an interval of 0.88. The intervals 
between the auricular beats are fairly regular, from 0.75 to 0.94. The 
regularity of the ventricular rhythm is here again suggestive of a total 
dissociation. It should, however, be noted that the ventricular rate on 
this tracing is not so regular as on the two preceding records, and it is 
significant that with the two ventricular contractions following the 
shortest intermissions (0.88 and 1.13) the a-c time is 0.32 and 0.37 
second, respectively. Now, on tracings from this case at periods in which 
there is a regular auriculoventricular rhythm, for instance on Tracing 20, 
the a-c interval is often of about this length. It would, therefore, appear 
not improbable that these two beats have been hastened by the regular 
stimulus which has passed through the bundle. Tn other words we are 
probably in the presence of one of those instances of so-called relatively 
complete block in which, without total destruction of the a-c bundle, the 
ventricles have yet initiated an independent rhythm. The enfeebled 
stimuli coming through the injured bundle reach the ventricle as a rule 
either at a refractory period, or with a strength insufficient to call forth 
a response from a heart muscle, the irritability of which is diminished. 
But here and there, as with the second beat on Tracing 16, an impulse 
may come through the bundle strength sufficient to call forth a ventricu- I -7^ 
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Tracing 22.-Case 2; April 29, 1909. Right jugular, apex and brachial. Normal a-v rhythm with prolonged a-c time. Occasional 2:1 rhythm. 46 
lar response resulting in an occasional beat after a shorter interval. At 
other times an impulse reaching the ventricle at a moment when it is 
nearly ready to respond to the stimulus which one may regard as 
accumulating in itself, is sufficient to call forth a slightly precocious con- 
traction. If, now, we turn back to Tracings 14 and 15 it is interesting 
to note that, in the shortest intervals between ventricular beats, the 
terminal c wave follows the preceding a wave after a period which is not far 
from that common in this case at times when stimuli are certainly passing 
through the bundle. This is seen on Tracing 14 in the intervals before 
the second, fourth and sixth c waves, and on Tracing 15 before the eighth 
c wave. We are, then, inclined to believe that although an independent, 
automatic ventricular rhythm at a rate of 40 to 50 has been initiated, 
yet the conduction through the auriculoventricular bundle is not wholly 
interrupted. The normal stimuli play a part at least in the excitation of 
some of the ventricular contractions.6 
Tracings 17, 18, 19, April 21/, 1909: Partial Bloch' Believed by Atropin 
1. Before Atropin (Tracings 17, 18) : The jugular tracing taken 
before the administration of atropin shows fairly regular contractions, the 
intervals averaging about 0.9 second, a rate of about 66 per minute. The 
analysis of the ventricular rhythm is less simple. The ventricular rate is 
much slower than that of the auricle, about 40 to the minute, and at first 
sight there might appear to be no relation between the two rhythms. It 
will, however, be noticed that the ventricular rhythm is not regular, the 
intervals varying between 0.9 and 1.47 in length. At two places on two 
tracings there are two short beats in succession and in each case the inter- 
6. Another possible explanation of Tracings 14 and 15 occurred to ns when 
we first studied these records, an explanation similar to that advanced by 
Griffith and Cohn (Quart. Jour. Med., 1910, iii, 136) to explain almost identical 
phenomena. 
On Tracing 14 one might fancy that, after a transmission time of 0.42, the 
next impulse passed through the bundle so slowly that the ventricular response 
occurred after the succeeding auricular beat, which, as well as the following 
auricular contraction, is blocked. The cycle then begins over again. On Tracing 
15, according to this hypothesis, we see an a-c time of 0.31, then of 0.69. then a 
blocked a wave. This is followed by an a-c time of 0.24. then one of 0.59, then 
an exceedingly long period of 1.03 and then a blocked a wave. Then comes an a-c 
time of 0.48 followed by one of .98 and a blocked a. The next cycle begins with a 
transmission time of 0.35, then one of 1,74 and then a blocked a and so on. In 
other words, the condition might be regarded as a 3 to 2 and occasionally a 4 
to 3 rhythm. 
In Tracing 16, except for the close sequence of the first two beats, a similar 
course of events may be made out. But such an explanation of these events we 
are inclined to discard for several reasons. 
1. It is difficult to explain the comparative regularity of the ventricular action 
in a rhythm which changes from time to time from 3 to 2 to 4 to 3. 
2. Just such a sequence of events as this might be expected to occur from 
the natural ratio one to another of the beats of two independent regular rhythms. 
3. The possibility of an a-c period of over one second is not yet proved. Tracing 23.-Case 2; May 17, 1909. Right jugular, apex and brachial. Normal a-v rhythm. Prolonged conduction time 48 
val is about 0.9 second, which is nearly the same as the auricular interval. 
The a-c periods in connection with the two heats following a short inter- 
val are each a trifle over 0.50 second.7 The ventricular beats after the 
long pauses bear a less definite relation to the auricular beats and often 
occur on the jugular curve at nearly the same time as the auricular beats 
or at about 0.1 second later, so that one broad-topped double wave is 
formed. It is improbable that these latter beats depend on the stimulus 
causing the preceding auricular systole, for in this case the a-c time 
would amount to over 1 second. There aie, however, six other ventricular 
beats in which the a-c period varies from 0.45 to 0.49. One of these 
initiates Tracing 18. The other five are preceded by intermissions of 1.25, 
1.29, 1.25, 1.28 and 1.24 seconds, respectively. The intermissions preced- 
ing those ventricular contractions which, on the venous curve, occur 
synchronously with or shortly after the a waves, are of 1.47, 1.42, 1.44, 
1.45 and 1.45; that is, appreciably longer in every instance than the 
intermissions preceding a-c periods of 0.45 and 0.49. Xow an a-c con- 
duction time as long as 0.45 to 0.49 second is shown in this case on 
Tracings 21, 22, 23. We are then inclined to regard these tracings as 
indicating a partial block in which the ventricle is attempting to initiate 
an intrinsic rhythm of 41 or 42 to the minute (intermissions averaging 
1.446). With every third or fourth auricular systole the stimulus pass- 
ing through the bundle after a prolonged conduction time, reaches the 
ventricle at a period when it is nearly ready to contract automatically. 
The result of this is a slightly precocious impulse such as is seen in the 
second and fourth beats on Tracing 7, and the third, fifth and seventh 
beats on Tracing 8. In addition to this, on two occasions, the succeeding 
normal impulse passing through the bundle, in each instance more slowly 
than the preceding, is yet sufficient to excite a ventricular contraction. 
That the condition was not one of total block is shown by the result 
of the atropin test. 
2. After Atropin: Atropin, gr. 1/30 (0.002 gm.), was given subcu- 
taneously and Tracing 19 taken twenty-nine minutes after its adminis- 
tration. Here the ventricular rhythm is regular at a rate of 75. The 
auricular rate is the same; each auricular beat is followed after a trans- 
mission time of from 0.26 to 0.39 second, by a ventricular wave. As a 
result of the atropin, therefore, the ventricular rate has risen from 40 to 
75; the a-c time has diminished materially in length: the auricular rate 
has risen from 66 to 75. 
Tracing 20. April 5,1909: Normal Rhythm. Prolonged Conduction Time 
Tracings taken on this day show that the auricles and ventricles are 
contracting regularly and in normal sequence. The only abnormal point 
in the curves is that the a-c time is prolonged (0.28 to 0.34 second). 
7. The position of the c wave in the second is estimated from the time of 
onset of the brachial pulse. Tracing 24.-Case 2; May 17, 1909. Right jugular, apex and brachial. Tracing taken fourteen minutes after administration of atropin, gr. 1/30 
(0.0021 gm.), given immediately after the recording of Tracing 23. Alternating pulse. Rapid cardiac action, a-c time slightly shorter than in 
Tracing 23. 50 
Tracings 21 and 22, April 29, 1909: Remarkably Prolonged Conduction 
Time; Occasional Halving of the Rate 
The auricles are contracting regularly at about 90 per minute. The 
ventricular pauses fall into two sets, one of which is approximately twice 
as long as the other. The long pauses are from 1.20 to 1.42 seconds long. 
The short are from 0.62 to 0.76 in length. During the period of 
rapid ventricular action every auricular systole is followed by ventricular 
systole with an a-c time which is from 0.48 to 0.56 second in length. 
During the period of slow ventricular rate there is a 2 to 1 rhythm. 
Every other auricular systole is blocked and the a-c time varies from 
0.37 to 0.45 second. The shortening of the a-c time is probably due to the 
greater opportunity for the conduction fibers to regain their functional 
power during long pauses. During the shorter pauses the conduction 
time is so long that the a wave of the venous pulse follows immediately 
after the preceding c wave; it has an unusual height as the auricle is 
contracting at a time when the ventricle is also in systole. The condition 
present on this day was then a normal auriculoventrieular rhythm with a 
long conduction time, changing at frequent intervals to a partial block 
with a 2 to 1 rhythm. The length of the a-c periods in these tracings is 
remarkable, the longest we believe that has been reported with the excep- 
tion of the case of Griffith and Cohn.6 
Of interest on this tracing are the distinct waves on the jugular curve, 
which we have marked h. These elevations occurring after the sharp 
auricular contraction which is combined with the v-wave, represent, 
probably, a centrifugal impulse associated with the closure of the mitral 
curtains incident to the sudden filling of the ventricles. They correspond 
fairly well to the position of the h (Gibson "b") wave on the normal 
jugular curve. The same condition is beautifully shown on Tracings 23 
and 24, where the protodiastolic elevation of the cardiogiam, which bears 
the same relation to this wave that it does in the normal tracing, is to 
be made out. 
Tracings 23, 21/. May 17, 1909: Normal Rhythm, Prolonged Conduction 
Time, Acceleration of the Rate with- Development of Pulsus Alter- 
nans Following Atropin, gr. 1/30 (0.0021 -j- gm.) 
The first tracing (23) shows auricles and ventricles beating regularly 
in normal sequence at a rate of 90. The a-c period is from 0.45 to 0.5 
second. Atropin, gr. 1/30 (0.0021 -|- gm.), was given subcutaneonsly. 
Five minutes later the pulse was regular at 104. Twenty-three minutes 
after administration, another tracing was taken (24). The rate had then 
risen to 120. The pulse was regular. The conduction time averaged 
0.41 second. There is a distinct pulsus alternans evident in the brachial 
tracing, one interval being slightly shorter than the preceding, the large 
beat following the short interval. The action of the atropin, therefore.  
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Tracing 25.-Case 2; May 19, 1910. Right jugular, apex and brachial.Effect of pressure on vagus, 2:1 rhythm. 52 
lias been to increase the rate of the auricles and ventricles, to shorten the 
a-c time slightly, and to produce pulsus alternans, so commonly present 
with an enfeebled myocardium. 
Tracings 25 and 26., May 19 and June 5, 1909: Heart-Block Induced by 
Pressure on the Vagus 
In Tracing 25 the rhythm is regular; the rate 71. The a-c periods 
vary in length from 0.32 to 0.36 second. As a result of light pressure 
on the vagus nerve in the neck, there was an immediate slowing of the 
radial pulse-rate due, as the jugular pulse shows, to the establishment of 
a partial block with 2 to 1 rhythm. The long ventricular intervals are 
about double the short ones. The beats after the long pauses are con- 
siderably larger than those following the shorter periods. The a-( time 
after the long pauses is slightly shoiter than with the beats after the 
short pause. There is little, if any, effect on the auricular rate, although 
the average length of the auricular periods during pressure is 0.84, with- 
out pressure, 0.80 -|-. The dropping of alternate beats began almost 
immediately after pressure was applied to the neck, and continued more 
or less regularly until the pressure was removed. The change in rhythm 
was accompanied by no subjective symptoms. 
A similar tracing taken on June 5 (Tracing 20) shows at one point 
the blocking of two successive a waves by vagus pressure. The a-c time 
after this long pause was 0.31 second as compared with 0.4 second before 
it. The auricular rate is slightly, but distinctly slower during vagus 
pressure, the intervals between beats averaging 0.765, as against 0.71 
These results are of real interest when considered in connection with 
certain of the events in Case 1. Here, it may be remembered, there were 
long pauses in the ventricular pulse, alternating with periods during 
which every auricular contraction was followed after a nearly normal 
interval by a ventricular beat. On several occasions the administration 
of atropin hypodermically resulted in the resumption, after about fifteen 
minutes, of normal auriculoventricular rhythm without essential change 
in the length of the a-c interval. In endeavoring to explain this phenom- 
enon we advanced the hypothesis that, owing to alternating waves of 
vagus action, the strength of the impulses passing to auricle and ventricle 
was at times so far diminished as to fail to produce a response in a 
ventricle, the irritability of which was, perhaps, reduced, or that, through 
the same influence, the irritability of the ventricle was further affected. 
It is not uninteresting that an analogous condition should have been 
produced experimentally in this case, in which, in addition to disease of 
the auriculoventricular bundle, myocardial disease was clearly present as 
indicated by the hypertrophy and dilatation and the diminished contrac- 
tility (alternating rhythm). i .^7 | '73 
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Tracing 26.-Case 2; June 5, 1909. Right jugular, apex and brachial. Effect of pressure on vagus, 2:1 and 3:1 rhythm. 54 
Tracing 27, June 3, 1910: Complete Auriculoventricular Dissociation 
Numerous tracings were taken on this date, but it was never possible 
to obtain a record of other than a regular pulse, the occasional interpo- 
lated beats disappearing as soon as the patient lay down. Tracing 27 
shows auricular intervals varying from 0.78 to 0.99, averaging 90 a 
rate of about 66. The ventricular intervals vary from 1.55 to 1.61, aver- 
aging 1.585, a ventricular pulse of 38. On referring to the key it may be 
seen that there is no constant relation between auricular and ventricular 
contractions; there is apparently a complete dissociation. 
SUMMARY OF TRACINGS AND DISCUSSION OF THE CASE 
Tn summary the tracings from this patient show: 
1. Regular auriculoventricular rhythm with much prolonged a-c time 
(Tracings 20, 23). 
2. Partial and relatively complete auriculoventricular dissociation 
with prolonged a-c time (Tracings 21 to 24). 
3. Partial auriculoventricular dissociation relieved by atropin. gr. 
1/30 (0.0021 gm.), given subcutaneously (Tracings 17, 18, 19). 
4. Prolonged conduction time with occasional blocking of alternate 
ventricular beats (Tracings 21. 22). 
5. Rapid cardiac action with alternating pulse following atropin, gr. 
1/30 (0.0021 gm.), given subcutaneously (Tracings 23, 24). 
6. The production of a 2 to 1 and a 3 to 1 rhythm as a result of the 
blocking of alternate and once of two successive auricular impulses by 
pressure on the vagus (Tracings 25 and 26), with little effect on auricular 
rate or on conduction (a-c) time. 
7. Apparently complete amiculoventricular dissociation (Tracing 27). 
This would seem to be a typical instance of disease of ihe auriculoven- 
tricular bundle with diminished conductivity in an hypertrophied and 
dilated heart. There was great prolongation of the a-c time with the 
characteristic falling out at times of alternate beats, at times of every 
third ventricular beat. At other times there were evident attempts on 
the part of the ventricle to initiate an independent rhythm. At no time, 
however, was the pulse-rate so slow as is common in complete auriculo- 
ventricular dissociation. These tracings appear to us to represent an 
independent auricular rhythm which has been set up in a heart in which 
the bundle of His is not wholly incapable of performing its functions. 
On a number of tracings those ventricular beats which follow the pre- 
ceding auricular contractions after a period corresponding to the usual 
a-c transmission time in this case, are slightly precocious. This suggests 
to us that the impulses causing these beats have in reality passed through 
the auriculoventricular bundle (Tracings 22, 24, 25, 26, 27, 28). J 
.8S 
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Tracing 27.-Case 2; June 3, 1909.» Right jugular, apex and brachial. Total (relatively total?) block. 56 
An-apparently spontaneous ventricular rhythm at a rate as rapid as 
45 to 50 is a notable feature of this case. It would be interesting to know 
whether the last tracing represents a total or a relatively total block- 
whether the destruction of the bundle is complete. Further observation 
of the patient should give us the information. We had hoped to persuade 
the patient to allow us to pursue the study of his case by means of the 
electrocardiograph before the publication of these observations, but we 
have not as yet succeeded. 
The production by vagus pressure of a partial block (Tracings 25, 26) 
with slight slowing of the auricular rate and no apparent lengthening of 
the a-c time suggests the possibility that the action may have consisted 
either in the diminution of the volume of the stimulus generated and 
conducted to the ventricle, or in the irritability of the ventricle itself. 
That the contractility of the ventricle was diminished at the outset is 
testified to by the alternating pulse with rapid auricular action after 
atropin (Tracing 24). After vagus pressure, however, there was no 
evidence of alternation. 
The effect of vagus pressure in this case in producing a slight slowing 
of the auricle with occasional ventricular intermissions without apparent 
change in the a-c time is not without its analogies with the events which, 
in Case 1, we were inclined to ascribe to waves of vagus influence. Tn 
that case, it may be remarked in Tracings 6 and 7 that, following a slight 
slowing of the auricular rate without prolongation of the a-c time, there 
were frequently recurring intermissions in the ventricular contractions 
lasting often for long periods of time. The hypothesis which was advanced 
in explanation of this phenomenon was similar to that which would seem 
to explain the effect of vagus pressure in this case, namely, that by 
increased vagus action the amount of the stimulus conducted from auricle 
to ventricle was diminished to such an extent that it was unable to call 
forth a response from a ventricle, the irritability of which was, possibly, 
in itself diminished, or that the same vagus influence served to depress 
the ventricular irritability. 
The lesion in this heart is probably a fibrous myocarditis seriously 
involving the His bundle without totally destroying it. The clinical 
phenomena are remarkably similar to those in the case reported by 
Griffith and Cohn.8 In this instance there was also an exceedingly pro- 
longed a-c interval, amounting once to 0.6 second. The tracings show 
intermissions, owing to the dropping of occasional beats, or a 2 to 1 
rhythm due to the dropping regularly of alternate beats from failure of 
conduction. On another tracing, the dropping of every third beat causes 
an alternation of short and long pauses, a 3 to 2 rhythm. Occasional 
8. Remarks on the Study of a Case Showing a Greatly Lengthened a-c Interval 
with Attacks of Partial and Complete Heart-Block, with an Investigation of the 
Underlying Pathological Conditions, Quart. Jour. Med., 1910, vii, 126. 57 
ventricular extrasystoles were noted, and finally, the establishment of a 
nearly regular ventricular rhythm of about 43, which the authors 
regarded as a 3 to 2 rhythm; this might, however, and we are inclined to 
believe, should be interpreted as we have interpreted Tracings 21 to 26 
in Case 2; that is, as an automatic ventricular rhythm in which an occa- 
sional beat is hastened by an impulse which has passed through the a-c 
bundle. At other times there were periods of apparently total block with 
a rate of 26 per minute and once there was a characteristic alternating 
pulse. The lesion in this case proved to be an aneurysm of the right 
posterior sinus of Valsalva which had depressed the aortic cusp to such 
an extent that the septum membranosum was included in the aneurysmal 
pouch, severely compressing the main stem of the auriculoventricular 
bundle and cutting off the left branch. 
Case 1.-A man of 53 with rather thickened arteries and a slightly 
enlarged heart, with evidences of sclerosis at the aortic ring (rough sys- 
tolic murmur), showed: 
1. Syncopal and convulsive seizures, associated with bradycardia and 
marked irregularity in the size and sequence of the beats. These occurred 
often in groups of three or more in rapid succession, followed by inter- 
missions amounting sometimes to nearly or quite half a minute in length. 
The auricular rate, which could often be counted clearly in the neck, was 
usually 100 or above. Long intermissions in the ventricular pulse were 
usually associated with long periods of apnea. No wholly satisfactory 
tracings were taken during paroxysms of this sort. Those which we have 
suggest a complete dissociation. 
2. Similar attacks, usually without convulsions, in which the ventricu- 
lar beats occurred in groups of from two or three to ten, always at the 
same rate, and apparently following the same impulses as the auricular 
beats. These groups of beats were separated sometimes by intermissions 
amounting to as much as fifteen seconds. The auricular pulsations could 
usually be counted in the neck and were sometimes as slow as 59. Sphyg- 
mographic tracings showed that these groups of beats consisted of a pri- 
mary ventricular contraction, apparently automatic, which was succeeded 
shortly by a series of beats which followed the preceding auricular con- 
tractions after an a-c conduction time of approximately normal duration. 
During these groups of beats the auricular rate became progressively 
slower without lengthening of the conduction time, until finally the 
ventricular impulses stopped. The retardation of the auricular impulses 
continued during the next several auricular contractions, after which it 
became more rapid. 
Such attacks yielded on three occasions to the administration subcu- 
taneously of atropin, gr. 1/60 (0.001 gm.). The auricular rate after 
GENERAL SUMMARY 58 
atropin was slower than it was before, but more rapid than the rate of the 
several slow beats at the time of onset of the periods of ventricular 
intermission. 
3. Periods during which there was a fairly regular ventricular rhythm 
of about 30 to the minute with a rather rapid auricular rate (100 to 120). 
The tracings show here an apparently complete auriculoventricular dis- 
sociation. One of these attacks failed to yield to atropin, gr. 1/30 
(0.0021 gm.) given subcutaneously. 
4. Periods during which intermissions in the ventricular pulse 
occurred at varying intervals and lasted for varying periods of time, fol- 
lowed usually by an apparently spontaneous ventricular contraction 
which was succeeded by one or more beats after a normal a-c conduction 
time. This condition, as shown in Tracings 4 and 5 would appear to be 
closely analogous to the condition described in paragraph 2. Indeed, it 
probably represents a lesser grade of the same condition. 
5. Periods between these attacks in which the heart's action was regu- 
lar, and the sphygmographic tracings revealed no abnormalities, the a-c 
interval remaining always normal. 
Although there have been seven or eight grave attacks of Adams- 
Stokes' syndrome in a year and a half, the patient is to-day in good 
condition. 
The remarkable features of this case appear to be the recurrence of 
long intermissions in the radial pulse, and the appearance at times of a 
total dissociation, with little or no evidence of a prolongation of the a-c 
conduction time, between attacks or during attacks in periods of partial 
block. 
We have been inclined to regard the case as one of chronic sclerosis 
at the root of the aorta with partial involvement of the auriculoventricular 
bundle and a diminished irritability of the ventricle, many of the phe- 
nomena in the case being probably dependent on diminished ventricular 
irritability together with increased vagus influences. The cause of these 
waves of vagus action would appear to be wholly obscure. 
Case 2.-A man, aged 83, had had for three or four years 
dyspnea on exertion and attacks of giddiness and faintness in which the 
had fallen to the street. Following treatment with infusion of digitalis, 
but persisting for more than a month after its discontinuance, there 
occurred periods of bradycardia, during which the pulse was sometimes 
nearly regular at about 40 and at other times irregular. The pulsations 
of the auricles observed in the neck were more frequent than those of the 
ventricles. The auricular pulsations further manifested themselves by a 
slight audible sound and sometimes by a palpable and even visible impulse 
at the apex. The cardiosphygmographic tracings showed a regular auric- 
uloventricular rhythm with much prolonged a-c time, amounting some- 
times to almost 0.6 of a second. At times, there is characteristic dropping 59 
out of ventricular beats associated with progressive prolongation of the 
a-c period and failure of conduction. At other periods, there is an 
attempt to set up a spontaneous ventricular rhythm at the rate of about 
40, a rhythm, however, which is not quite regular because of an occasional 
precocious ventricular contraction, due, apparently, to the passage of a 
stimulus through the auriculoventricular bundle. The administration of 
atropin, gr. 1/30 (0.0021 gm.), resulted in the complete disappearance of 
irregularity and the development of a regular auriculoventricular rhythm 
with prolonged a-c conduction time. 
Pressure on the vagus resulted in the dropping out sometimes of 
alternate and, occasionally, of two successive ventricular beats. There 
was slight slowing of the auricular rate with no apparent modification 
of the a-c conduction time. 
On one occasion, the administration of atropin, gr. 1/30 (0.0021 gm.), 
was followed by rapid action of the heart with alternating pulse. 
A year after the termination of our studies, the patient was seen again 
with an apparently complete auriculoventricular dissociation, the ventric- 
ular rate, however, being about 40. 
This case we regard as a typical instance of disease of the bundle of 
His in a hypertrophied and dilated heart. The special points of interest 
are the extreme prolongation of the a-c conduction time, which at times 
was certainly as long as 0.56 second, and the evident efforts on the part 
of the ventricles to set up an automatic rhythm at a time when conduction 
was not completely blocked. 
The many analogies between this case and that of Griffith and Cohn 
are also worthy of note. 
406 Cathedral Street-13 Kirkland Avenue. ON HEMOLYTIC JAUNDICE 
\X I L L 1 A M S. T HAYE R. M. D. 
Professor of Clinical Medicine, Johns Hopkins University 
BALTIMORE 
Reprinted from the Illinois Medical Journal 
February, 1911 ON HEMOLYTIC JAUNDICE* 
William S. Thayer, M.D. 
Professor of Clinical Medicine, Johns Hopkins University 
BALTIMORE 
From early days the conception of two varieties of jaundice has 
prevailed, one form depending on a disturbance of hepatic functions and 
the other on changes in the blood. 
Castaigne quotes Bianchi (1710) as saying: "Sunt duo primarii icteri 
genera; primae classis icterus a vitio hepaiis, altering speciei icteri a causa 
solutione sanguinis" Beil (1793) describes polycholic jaundice due to 
an abnormal bile production by a direct transformation of the blood. The 
studies of Naunyn, Stadelman, Minkowski, Stern, Chauffard, Girode, 
Banti and others have led to the general acceptation of the conception 
that the so-called hematogenous jaundice in contra-distinction to the 
hepatogenous is hematogenous only in its remote origin, in so far as it 
is primarily the result of increased blood destruction. The immediate 
cause of jaundice is still generally regarded as of hepatic origin.- In 
support of this idea it has been pointed out that those jaundices which 
result from increased blood destruction are at the same time associated 
with an excessive bile formation as shown by the usually large amount 
of bile in the feces. These so-called pleiochromic jaundices have 
generally been regarded as dependent on increased blood destruction, 
excessive bile formation, inspissation of the bile, intrahepatic stasis 
followed by entrance of bile into the general circulation. One might 
fancy, as suggested by Minkowski, that the jaundice in some of these 
cases was due to a perversion of the functions of the liver cell, through 
which that substance which is normally secreted into the bile ducts, 
namely bile, takes the place of or accompanies those bodies which the 
liver ordinarily pours into the blood and lymph, i. e., sugar and urea- 
the process occurring without definite obstruction. However this may 
be, the idea of a hematogenous jaundice in this sense would appear to he 
generally accepted. And examples, such as the'jaundice seen after large 
internal hemorrhages, that associated with pernicious anemia and that 
which occurs after acute deglobulizing poisons, are too familiar to 
mention. 
It was early noticed that in certain non-obstructive jaundices no bile 
pigment appeared in the urine which, however, contained other pigments 
giving it a high color. This observation led to the long disproven 
hypothesis that such conditions might be examples not of a true bilirubin 
jaundice, but of the entrance into the blood of some other chromogenic 
product of the diseased hepatic cell. The frequency with which urobilin 
* An address delivered before the Chicago Medical Society, Nov. 10, 1910. 2 
is found in the urine in this so-called acholuric icterus tended to fortify 
in the minds of some observers (Gerhardt, Hayem and Tissier) the con- 
ception of an ortho- and a meta-pigmentary jaundice. The coloring 
matter in these instances of meta-pigmentary jaundice which was shown 
to be urobilin, was, by many, regarded as the product of a perverted 
hepatic metabolism. 
Whatever the frequency of urobilin in the urine in these cases of 
acholuric icterus, Gilbert appears to have shown that all jaundices are 
due to the presence of true bile pigments in the serum. Gilbert, and his 
associates and students have devised a delicate colorimetric test by which 
they believe that they can demonstrate the presence of bile in the serum 
of all healthy human beings in very small but yet recognizable quan- 
tities. The average proportion they estimate at about 1/30,000. Under 
pathological circumstances the amount may rise to such an extent that it 
may equal or exceed the proportion of coloring matter in normal bile. 
While the idea of ortho- and meta-pigmentary jaundice must be 
abandoned, yet non-obstructive jaundice may well be divided into cho- 
luric and acholuric varieties according to the presence of or absence of 
bile pigment in the urine. The reason for the presence of bile in one 
case, and its absence in another and the significance of urobilin are 
matters of present controversy on which one can only touch at this point. 
Tn general the acholuric jaundices are not very intense and it may be 
true that the absence of bile in the urine is dependent merely on the 
quantity of bilirubin in the circulation. Tt is unquestionable that in 
some cases of hematogenous non-obstructive icterus, bile pigment does 
appear in small quantities from time to time in the urine. As to the 
significance of urobilin, it has been suggested that it is the result of an 
excessive secretion of bile into the intestines. The increased quantity of 
stercobilin is in part reabsorbed and, not wholly arrested by the liver, is 
eliminated by the kidneys as urobilin. The amount in the circulation is. 
in most instances, too small for recognition unless it be present in the 
form of a chromogen (Chalier). Tt is absent in obstructive jaundice, 
probably because of the absence of bile in the intestine. 
Aside from frankly obstructive jaundice the conditions under which 
icterus is observed are exceedingly numerous, so much so as to lead to 
manv and confusing classifications. Tn the main these conditions are 
associated with severe intoxications or infections-and the jaundice is 
probably often the result of infective cholangitis or of degenerative 
changes in the hepatic lobule which result in the entrance of bile into the 
circulation. Tn other instances such as pernicious anemia or paroxysmal 
hemoglobinuria, a primary hemolysis plays certainly an important part. 
Of recent years attention has been especially directed to an interesting 
group of cases in which a primary hemolysis is assuredly the initial event 
in the development of the icterus. 
Gilbert and his pupils have described as chronic simple jaundice a 
condition seen often in groups of members of certain families in which 
the affected individuals show a slight jaundice of the skin and perhaps of 
the conjunctiva, and a cholemia considerably more marked than in the 3 
normal individual. The urine contains no bile but is usually rather 
concentrated and gives a positive test for urobilin. In these cases which 
occur often in individuals suffering from superacidity, bradycardia, hypo- 
thermia, and frequently with general neurasthenic symptoms, there is 
a constant excess of bilirubin in the serum above the normal, that is, 
usually a proportion of about 1/17,000. The condition, in other words, 
would appear to be an exaggeration of the physiological cholemia. 
Tn addition to these cases of chronic simple jaundice Gilbert has, 
however, described others in which there is a distinct splenomegaly. Now 
these instances of chronic congenital jaundice with splenomegaly, several 
examples of which have been described by English authors (Murchison, 
Wilson), are not unlike the chronic, splenomegalic, non-obstructive jaun- 
dice described by Hayem in 1888, a malady which he believes to be of 
infectious origin. 
Beginning with the observation of Minkowski (1900) a series of 
studies have drawn attention to these cases of congenital jaundice with 
splenomegaly. Minkowski (1900) describes a remarkable syndrome of 
congenital jaundice associated with urobilinuria, splenomegaly and sider- 
osis of the kidney. The occurrence of these symptoms could be traced 
through three generations, affecting at least eight members of the family. 
None of the individuals observed showed any changes in the blood, while 
the general health was not impaired. 
Bettmann in the same year described a similar case in which the 
jaundice displayed marked variations in intensity, deepening after exer- 
cise, food, drink, and excitement, especially anger, and also after exposure 
to cold. An experimental hemoglobinuria could be produced in this case 
by the application of cold. 
Pick (1903) and von Krannhals (1904) reported like cases, the latter 
having observed a family of which nine members in three generations 
showed a chronic, congenital splenomegalic jaundice. Tn all these cases 
the stools were colored, the urine dark, free from albumin, blood and 
hemoglobin. Tt showed constantly the presence of urobilin, but never 
bile. The number of red corpuscles was below normal-2,300,000 and 
3,500,000 respectively in the men, and on one occasion as low as 1,000.000 
in one of the women. The hemoglobin varied from 55-65 per cent. The 
red blood corpuscles were irregular in contour and varied in size from 
6 to 10 microns. There were no nucleated rods, but well-marked poly- 
chromatophilia. 
Minkowski was fortunate in obtaining a necropsy on one of his 
patients. No especial changes were found in the liver, and the bile 
passages were quite clear. A small pigment stone was found in the gall- 
bladder. The spleen was enlarged and, microscopically, there were simple 
hvperplasia and hyperemia. The kidneys showed a brownish discoloration 
produced by a granular pigment deposit in the epithelial cells of the con- 
voluted tubules. Not only did this pigmentation give an intense reaction 
for iron, but there was a large amount of material united with proteids, 
which gave the reaction only after boiling with ammonium sulphid. 
From but one kidney about 0.95 gram of pure iron was obtained. 4 
Similar pigmentation did not occur in any other organ. Minkowski 
regarded the condition as dependent on an anomaly of the blood pigment 
transformation, perhaps consequent on a primary change in the spleen. 
These cases seem to bear a striking resemblance one to another and 
suggest a common cause. The absence of evidence of hepatic disease and 
the existence of extensive siderosis, especially of the kidney, in some 
respects analogous in that seen in Addisonian anemia, on which Hunter 
especially has insisted, pointed to an increased blood destruction as a 
primary cause of the disease-an hypothesis adopted by most of these 
authorities. 
In 1907 Chauffard made an interesting contribution to the study of 
this syndrome by the discovery in a similar case, of a marked fragility* of 
the red blood corpuscles on exposure to hypotonic solutions of sodium 
chlorid according to the method of Vaquez and Ribierre. This observa- 
tion he was able to confirm in two patients presenting a similar syndrome 
in the wards of his colleague Widal. Thus, while with the normal red 
blood corpuscles hemolysis begins at 0.44 and is complete at 0.32 per cent., 
in these three cases the beginning and end of hemolysis were respectively 
0.62 ami 0.30, 0.66 ami 0.34 ami 0.52 ami 0.18 pfer cent. The average 
size of the red blood corpuscles was somewhat diminished. Widal and 
Philibert, on further study, were unable to demonstrate the presence of 
any hemolytic properties in the serum of their own patients, either with 
regard to their own corpuscles, or those of other individuals. This 
fragility of the red blood corpuscles, so marked toward hypotonic salt 
solutions, was also evident in respect to other hemolytic substances. The 
diminished resistance of the red blood corpuscles has been a constant 
feature in the considerable number of cases of this malady which have 
since then been reported. 
A few months later Chauffard described another interesting hemato- 
logical feature which he had observed in all cases of this disease which 
had come under his observation, namely: the presence^, on vital staining, 
of a peculiar basophilic granulation of the red blood corpuscles. 
Chauffard's first studies were made by staining freshly-made and fixed 
smears of blood with Pappenheim's (pyronin and methyl-green) solution. 
Many of the red blood corpuscles which are of a slightly grayish color and 
barely visible, having lost their refractiveness with their hemoglobin, show 
a fine granulation of a bright red color. These dots, generally arranged 
about the periphery, are sometimes scattered throughout the cells in the 
form of a definite granulation. The granular corpuscles are generally 
somewhat larger than their neighbors; they may be demonstrated well by 
the method of vital staining of Widal, Abrami and Brule. 
Four to six drops of blood are allowed to fall into a test-tube con- 
taining 10 drops of a basic coloring matter which is quite isotonic and 
contains in addition oxalate of potassium to prevent the coagulation of 
the blood. 
Oxalate of potassium. 2%, 2 c.c. 
Unnas' polychrome methylene blue, 10 drops 
△+0.60 5 
The fresh corpuscles are allowed to remain for ten to twenty minutes 
in contact with the solution, after which the mixture is centrifugalized, 
the supernatant fluid is removed, and the corpuscles drawn up with a 
pipette and placed on slides on which they are spread as an ordinary drop 
of blood; the covers are then dried and fixed by heat. Such preparations 
may be indefinitely preserved. 
The distribution of the granules is irregular. Sometimes scattered, 
they are usually collected in groups of two and three. Sometimes they 
are arranged in the form of a wreath or crown at the periphery of the 
corpuscle; they are generally distributed in such a manner as to suggest 
filaments wound around within the cell and showing frequent varicosities; 
they are unequal in size and of irregular form. Xot infrequently this 
granular net-work is gathered together toward the periphery or near the 
center of the cell in such a manner as to suggest grossly a nucleus. 
Sabrazes has called these corpuscles "granulo-reticulo-filamentous." 
The apparent "reticulum" is very adherent to the red blood corpuscle. 
Tf a dried and stained specimen be washed with pure water, the red blood 
corpuscles lose their blue color, while the granular filamentous appearance 
remains. Indeed, in some cases the reticulum may be found outside the 
corpuscle, lying between other well preserved elements. Widal, Abrami 
and Brule have thought that the polychromatophilia which is present to 
a certain extent in these cases bears a close relation to the- presence of 
granular corpuscles, but this does not appear to be an absolute rule. 
T have gone into this question of granular corpuscles rather fully as 
it is interesting to see how closely these observers agree in their account 
with the careful studies of Vaughan in 1903, for many of those present 
have doubtless recognized before this, the granulation which, though first 
described by Pappenheim,1 was studied with especial thoroughness 
by Victor C. Vaughan, Jr., in the Journal of Medical Research for 1903. 
Vaughan found these granular elements in somewhat under 1 per cent, 
of all corpuscles in normal individuals, and in the new-born where they 
were most frequent, the highest percentage with but one exception (7) 
was 4. Tn pernicious anemia with active regeneration they were found 
in great numbers-once as high as 18 per cent. Tn congenital icterus 
with splenomegaly the percentage is usually over 10, and figures as high 
as 40 have been reported. Chalier, however, in his excellent monograph, 
is inclined to regard these figures as excessive, asserting that he himself 
has never seen a percentage above 20. This granulation, it is needless 
to say, is quite distinct from the basophilic granulation of Grawitz and 
others. The granules are different in shape and arrangement, and are 
not to be stained in the fixed specimen. They are, of course, entirely 
distinct from the remarkable Schuffner's granules which appear with 
Bomanowski's stain in certain parasitiferous corpuscles in tertian 
and estivo-aufumnal malaria. Tt is probable that this phenomenon is 
simply an indication of active blood regeneration but there are apparently 
1. This whole subject is excellently discussed by Ferrata, who. in common with every 
continental author, ignores Vaughan's excellent work (Fol. haematolog. Leipz., 1910, ix, 
1 Th., 253). 6 
few conditions in which the frequency of these granular corpuscles com- 
pares with that in congenital jaundice-a fact which seems to give them 
a real diagnostic value. 
These observations have been confirmed by a considerable number of 
observers, and the picture of this disease, which Chauffard has called 
hemolytic jaundice, is sufficiently definite to be regarded as a distinct 
clinical entity. 
The patient often belongs to a family other members of which have 
suffered from the same condition. Early in life, sometimes immediately 
after birth, but in other cases later, perhaps not until puberty, a jaundice 
appears. This jaundice is usually of a moderate degree, varying from a 
pale lemon hue to a well-marked golden yellow. It is remarkably 
variable, increasing often under physical effort or emotional excitement. 
Tn one of my cases the mother asserts that it is always worse after violent 
exercise, dancing, or bad colds. The stools are of normal color or 
pleiochromic, especially under those conditions associated with increase 
in jaundice. The urine is of rather high color, often of a brownish, 
almost mahogany hue but free from bile. Urobilin is usually demon- 
strable. The blood shows an anemia of moderate degree, usually between 
3,000,000 and 4,000,000 red corpuscles, although in one case a blood 
count of under two million is reported. There is usually considerable 
anisocytosis, but little or no poikilocytosis. The average size of the 
corpuscle is often rather below the normal, a point on which Chauffard 
has particularly insisted. This was not noticed in our two cases. The 
color index is somewhat reduced. Polychromatophilia is usually well 
marked. Tn the vital staining the granulation described first by Pappen- 
heim. Vaughan, Sabrazes. Chauffard and others is present in a large 
number of corpuscles. The percentage of granular elements is usually 
above 10 and may be as high as 20, or even more. The serum is of a 
clear, yellowish color, and the test for bilirubin is positive. Urobilin is 
generally undemonstrable. The leukocytes are usually of normal number 
or slightly increased. The differential count shows nothing remarkable 
beyond evidences of increased marrow activity manifested by a high 
percentage of eosinophils and the occasional presence of myelocytes and 
nucleated red cells, normoblasts. The serum shows a rather high degree 
of hypertonicity. Starkiewicz regarded this condition as a mechanism of 
defense on the part of the organism to protect the fragile red corpuscles. 
Troisier, however, believes it to be the result of exosmosis of the corpus- 
cular salts as a result of the fragility of the red cells. 
The remarkable feature of this interesting condition is that subjective 
symptoms are usually absent despite the constant anemia. The patients 
are generally unconscious of any disability. They appear to adapt them- 
selves so well to their condition that it is only occasionally that a com- 
plaint is elicited. There is a complete absence of all the ordinary 
phenomena of biliary intoxication; there is no bradycardia, no pruritus: 
no tendency to hemorrhage; no xanthelasma. The patients are, indeed, 
as Chauffard has gracefully said, "a peine des malades"-"plutot des 
icteriques que des malades," barely patients, rather icterics than patients. 7 
Thus, in one of my two cases, the patient, jaundiced since birth, was a 
perfectly healthy looking girl who, despite the fact that the blood count 
on the first two occasions when 1 saw her, was 3,680,000 and 3,200,000 
respectively, considered herself 'well and took part in all the ordinary 
sports of her companions. 
There is one exception to this rule. Many of these individuals suffer 
from attacks of abdominal pain suggestive of biliary colic. These pains 
localized in the epigastrium and in the region of the gall-bladder, are 
often accompanied by fever and by an aggravation of the jaundice. In a 
number of instances they have been so severe as to lead to operation. 
They were present in both of the cases which I have observed and in the 
first led to a cholecystostomy which revealed nothing abnormal. In many 
cases it is probable that the attacks are due to the presence of small pig- 
ment stones in the gall-bladder, such as have been found in five of the 
six cases of congenital jaundice that have come to necropsy-every 
instance in which the gall-bladder was examined. 
Acquired Hemolytic Jaundice.-This remarkable syndrome-chronic 
acholuric, pleiochromic jaundice without the usual symptoms of biliary 
intoxication, associated with anemia, enlarged spleen, and siderosis of the 
viscera is not, however, always of congenital origin. Soon after Chauf- 
fard's first observation, Widal and Abrami, Chauffard and Troisier, Le 
Gendre and Brule, von Stejskal, Oettinger, Parkes-Weber and others 
reported a series of interesting observations in which a similar train of 
symptoms came on without apparent cause in adult life. The onset of 
the jaundice in these instances followed various different accidents-an 
ischio-rectal abscess (Widal and Abrami), hemorrhage following a 
miscarriage (Widal and Abrami), severe nervous shock (Chauffard 
and Troisier), acute gastro-enteritis (LeGendre and Brule). In other 
instances, such as the two cases of von Stejskal, that of Oettinger, and 
that of Parkes-Weber, the process seems to have appeared without strik- 
ing initial symptoms. Again, in a considerable group of cases a jaundice 
of a transient character presenting similar hematological phenomena-an 
anemia with signs of regenerative activity of the bone marrow, granular 
corpuscles on vital staining and a marked fragility of the red cells, has 
been observed in the course of a variety of conditions, cancer of the 
stomach (Chalier) ; cirrhosis of the liver (Chalier and LePlay) ; malaria 
(Saquepee. Chalier); repeated hemorrhages in cancer of the bladder; 
(Widal and Joltrain) ; streptococcus infection (Saquepee) ; uncinariasis 
(Darre) ; syphilis (Gaucher and Giroux) ; pulmonary tuberculosis (Lan- 
douzy) ; jaundice of the new-born (Sabrazes and Leuret; Cathala and 
Daunay), 
This acquired hemolytic jaundice, as it has been called by Widal and 
Abrami, who described the first cases, does not constitute a definite 
disease picture to the same extent as does congenital splenomegalic 
jaundice, but rather an interesting syndrome. Acquired hemolytic jaun- 
dice may be divided, as suggested by Brule, into the apparently primary 
and secondary cases. The former arise either without obvious cause or 
during the course of some acute transient malady, after which they persist 8 
with seeming independence. Secondary hemolytic jaundice is observed in 
a transient manner associated with acute infections or poisons, or as a 
terminal phenomenon in the course of some chronic disease. 
One essential difference exists between most of the cases of acquired 
hemolytic jaundice and the congenital malady,'namely: the existence in 
the former of an anemia sufficiently grave to occupy a prominent position 
in the clinical picture. The anemia may, indeed, be intense and is 
associated with the usual subjective symptoms. There are often striking 
variations in the intensity of the jaundice and grade of anemia. Sudden 
paroxysms of fever associated with painful swelling of the spleen and 
extremely rapid fall in the number of red corpuscles have been described. 
A patient of Widal and Ab rami's showed on May 19, 2.600,000 red 
blood corpuscles; ten days later, while in apparently good condition, there 
appeared severe headache, dyspnea, marked exacerbation of the jaundice, 
and in a day or two the blood count showed but 850,000 red elements. Tn 
one of von Stejskal's cases the blood count rose in eighty days from 
640,000 to 4,000,000. 
The blood picture is often very similar to that in pernicious anemia: 
marked oligocythemia: a high color index; anisocytosis; poikilocytosis; 
often an increase in the average corpuscular diameter. There are almost 
always marked evidences of marrow activity in the shape of nucleated red 
blood corpuscles, among which megaloblasts are often found. Contrary to 
what one sees in pernicious anemia, the leukocytes are usually somewhat 
increased in number, and, occasionally, there is a well-marked leuko- 
cytosis which, on differential count, shows a considerable proportion of 
myelocytes and a large percentage of eosinophils. Granular corpuscles 
are present on vital staining, as in the congenital form of the disease: 
sometimes, however, these are not so numerous. 
There are two striking points of difference in the hematological picture 
between acquired and congenital hemolytic jaundice. The corpuscular 
fragility, so evident in the former condition, is often very slight in the 
acquired disease when the test is made with unwashed corpuscles. 
Widal and Abrami showed early that in acquired hemolytic jaundice 
the corpuscular fragility may, indeed, be almost inappreciable if the test 
he made with the whole blood. With deplasmatized corpuscles, however, 
the resistance is distinctly, sometimes very markedly, diminished. These 
authors showed that this increased fragility of the deplasmatized red 
corpuscles is common to both congenital and acquired varieties of the 
disease with the essential difference that while in congenital hemolytic 
jaundice the fragility is usually demonstrable with the whole-blood, in 
the acquired condition the resistance of the whole blood may be normal, 
while that of the deplasmatized corpuscles may show a very marked reduc- 
tion. The deplasmatized red blood corpuscles of acquired hemolytic 
jaundice show also a distinct diminution in resistance toward other 
hemolytic substances, such as anti-human sera of all sorts and leech 
extract. Tn normal blood the resistance of the deplasmatized corpuscles 
does not differ essentiallv from that of the whole blood. 9 
While it is difficult to avoid the conclusion that this increased corpus- 
cular fragility has a definite association with the hemolysis which occurs 
in these cases, yet it should be remembered that no direct parallelism can 
be drawn between the degree of fragility and the extent of the anemia. 
The conditions existing in congenital and acquired hemolytic jaundice 
form an interesting paradox, as has been pointed out by Brule, on the one 
hand a marked corpuscular fragility associated with a moderate anemia, 
on the other, a moderate fragility and an intense anemia. "It is impos- 
sible to draw a direct conclusion as to the fragility of the red blood cor- 
puscles in the organism from their fragility in vitro" 
This diminution in the resistance of the deplasmatized corpuscles may 
be restored if they be brought into contact again with their plasma. 
Although there is a slight difference between the resistance of the cor- 
puscles according to the manner in which they are separated from their 
plasma (Iscovesco, Salignat), yet these differences are so slight that they 
need not be considered; in fact the quantity of serum necessary to restore 
the resistance of separated corpuscles is so large that, practically, it is 
unnecessary to wash the corpuscles deplasmatized in an oxalate solution. 
The antihemolytic power of the serum is not restricted to that of the 
patient himself. It is present in other and heterologous sera. Heating 
to 56° C. for a considerable period of time does not remove the power. 
There would then appear to be no evidence of the existence of a specific 
anti-hemolytic substance. Widal, Abrami and Brule believe that the anti- 
hemolytic power is dependent on some special physical property or prop- 
erties of the serum. 
The blood of some individuals with acquired hemolytic jaundice 
possesses one characteristic which, for the moment, appears to be rather 
special, and is not observed in the congenital forms, namely: an auto- 
agglutinative power of the serum. The test is a relatively simple one; it 
is thus described by Brule: 
One lets fall into a watch glass 10 drops of the patient's serum and then a 
drop of red blood corpuscles isolated by centrifugation; the mixture is shaken 
up and then allowed to rest. Soon the corpuscles are seen to gather at the bottom, 
sometimes appearing to form little masses. But if there be no auto-agglutination, 
we need but to shake the glass slightly to restore the mixture to its previous 
homogeneity and to disperse the corpuscles in the serum. If the auto-agglutina- 
tion be positive, one sees after a period varying according to the intensity of the 
phenomenon from one to twenty minutes, a collection of the corpuscles into little 
granules easily perceptible by the naked eye, which give the emulsion an aspect 
comparable to brick dust; violent and prolonged shaking cannot dissociate these 
corpuscles. Little by little the agglutination increases, the corpuscles gather at 
the bottom of the watch glass where they form an homogeneous pellicle, the super- 
natant serum becomes limpid, and shaking no longer dissociates the hematic pel- 
licle. If at the beginning of the phenomenon one examine a drop of the serum 
microscopically it may be seen that the corpuscles, instead of disposing them- 
selves in rouleaux as normally, gather in little islands, between which there float 
a few isolated corpuscles. 
This phenomenon has been found in a number of instances of acquired 
hemolytic jaundice. In others, such as the cases-of Widal and Joltrain, 
and that of Parkes-Weber, auto-agglutination has been absent. The 10 
phenomenon is interesting and may be of considerable diagnostic value. 
It is not present in congenital hemolytic jaundice, although the patient 
of Benech and Sabrazes whose jaundice is believed by the authors to have 
been acquired from a wet-nurse, might be regarded as belonging to this 
class. It has, however, been observed in one instance of hepatogenous 
jaundice by Brule. It should be said that it has not as yet been studied 
sufficiently to justify far-reaching conclusions as to its diagnostic value 
or significance. 
Attacks of pain in the region of the gall-bladder associated with fever 
and exacerbation of the jaundice are very common. Indeed, the first 
three reported cases (Widal and Abrami; Chauffard and Troisier) were 
all operated on for suspected gall-stones. In one of these cases a little 
bile sand was found; in the other instances the gall-bladder was quite 
clear. 
Acquired hemolytic jaundice presents itself in a variety of forms. 
The most important are: 
1. Those cases simulating cholelithiasis. 
2. Those simulating pernicious anemia with jaundice. 
3. Those simulating a chronic infectious cholangitis. Chronic infec- 
tious, splenomegalic jaundice (Ilayem). 
4. It has also been observed in some of those conditions in which the 
most striking symptoms, anemia and splenomegaly, leave one in doubt 
as to whether the case should be classed clinically as Banti's disease or a 
cirrhosis of Hanot's type. Becent studies by Chauffard and Troisier, as 
well as by Armand-Delille and Feuille suggest strongly the possible 
relationship between some so-called splenic anemias and hemolytic jaun- 
dice. Attention has also been called to this point by Parkes-Weber. 
In other instances the condition may manifest itself under the symp- 
toms of an icterus gravis (Boque and Chalier). 
The syndrome is, however, sufficiently definite and easily to be recog- 
nized if carefully studied, by the absence of bile in the urine, its presence 
in the blood serum, the urobilinuria, the presence of a large percentage 
of granular corpuscles on vital staining, by the fragility of the red cor- 
puscles, especially manifest with the deplasmatized elements, and by the 
commonly present auto-agglutinative power of the serum. 
It is important to remember that in Addisonian anemia and in chole- 
lithiasis the corpuscular resistance is at least normal: indeed, as a rule it 
appears to be increased. Tn one of my cases of pernicious anemia hemo- 
lysis began at only 0.325, and was complete at 0.275 per cent., a greatly 
increased resistance. Tn obstructive jaundice Vaquez and Bibierre have 
also shown that the resistance of the red corpuscles is as a rule distinctly 
increased, an observation which we have been able to confirm. 
Pathological Anatomy.-Several individuals presenting the syndrome 
of hemolytic jaundice have come to necropsy (Vaquez. Giroux and 
Aubertin; Oettinger; Gandy and Brule, Widal and Joltrain, Boque and 
Chalier; Micheli; Moller; Wilson; Tileston and Griffin). The cases of 
Vaquez, Giroux and Aubertin, Gandy and Brule; Wilson, and Tileston 11 
and Griffin were apparently of congenital origin-the others, probably 
acquired. Tn all cases, however, the essential features appear to have 
been general evidences of an hemolytic process as manifested by a 
siderosis of liver, spleen and kidneys. The autopsy in the case of Vaquez 
and Giroux is of especial interest as it occurred in a congenital case in 
which death followed splenectomy so that complications with other ter- 
minal processes were ruled out. The lesions which have been confirmed 
in the later cases were as follows: 
A marked congestion of the spleen especially confined to the pulp, 
the engorgement of which was in rather striking contrast to the relative 
emptiness of the sinuses. There were few macrophages in the splenic 
pulp, more in the sinuses. The endothelial cells were stuffed with iron- 
containing pigment. The liver showed no evidence of biliary obstruction, 
no angiocholitis. Many of the liver cells, especially in the centro- 
lobular zones, were, however, stuffed with large granules of ocher pig- 
ment. There was moderate siderosis of the cells of the convoluted tubules 
of the kidney, and marked hyperplasia of the marrow. 
These observations have been confirmed in all cases which have come 
to necropsy, affording thus, abundant evidence of the hemolytic character 
of the process. The siderosis of the kidney which is usually present has, 
however, been very moderate in some instances, and was apparently absent 
in Gandy and Brule's case of congenital hemolytic jaundice, where death 
occurred in the course of a pneumonia as well as in Micheli's instance of 
the acquired form of the disease. Tn no instance was there evidence of 
biliary obstruction. 
Pathogenesis.-The pathogenesis of this remarkable syndrome is by 
no means clear. The evidence of a chronic hemolytic process is not 
so very different, indeed, from that which one sees in various-other 
conditions, such especially, as Addisonian or bothriocephalus anemia, 
conditions in which chronic jaundice is not uncommon. The clinical 
picture in some of the acquired forms of the disease with crises of 
aggravation of the malady may almost resemble paroxysmal hemoglo- 
binuria. Here, as Donath and Landsteiner have shown, there is in the 
serum a true auto-hemolysin. But in paroxysmal hemoglobinuria there 
is no evidence of a diminished resistance of the red blood corpuscles.2 
Tn Addisonian anemia, as has already been said, the resistance of the 
red blood corpuscles is usually increased. 
On the other hand there is no evidence of a specific hemolysin in these 
instances of jaundice associated with corpuscular fragility, so that one 
has been tempted to separate an hemolysinic jaundice, such as the jaun- 
dice with pernicious anemia or that seen with paroxysmal hemoglobinuria, 
from the jaundice associated with corpuscular fragility, to which the 
name hemolytic has come to be applied - a deplorable complication of 
terms. 
2. It is true that Meyer and Emmerich believe that they have been able to demon- 
strate a diminished resistance of the red corpuscles in paroxysmal hemoglobinuria against 
changes of temperature, dilute acids and saponin. Meyer and Emmerich: Ueber paroxys- 
male Hemoglobinurie, Deutsch. Arch. f. klin. Med., Leipsig, 1909, xcvi. 12 
This is, however, not to say that the primary causal element in some 
of the instances of so-called acquired hemolytic jaundice may not be the 
presence of toxic hemolytic substances in the organism. Indeed, there is 
some reason to believe that this may be the case. Troisier, for instance, 
in his recent thesis, advances various arguments in support of the hypoth- 
esis that the fragility of the red corpuscles in these cases of hemolytic 
jaundice is dependent on the fact that they have already become sensitized 
by union with an hemolytic amboceptor. 
However this may be, we are in the presence of a remarkable clinical 
syndrome-acholuric, pleiochromic jaundice, anemia, corpuscular fra- 
gility, granulation of the red corpuscles on vital staining, post-mortem 
evidences of blood destruction in the form of siderosis of the liver, spleen 
and kidneys, absence of evidence of the presence of hemolytic substances 
in the serum. 
Several questions naturally suggest themselves. 
1. Where does the hemolysis take place? 
2. Where does the bilirubin circulating in the blood find its origin? 
3. What is the primary cause of this condition? 
1. As to the manner and seat of hemolysis there have been varying 
opinions. Some (Minkowski, Chauffard, Vaquez) fancy that, gathered 
in the pulp of the spleen which, as has been seen, is always markedly 
engorged, the abnormally fragile corpuscles are there destroyed. Others 
(Widal and his pupils) are inclined to believe that the destruction occurs 
in the general circulation, the debris accumulating as it always does in 
the spleen, and accounting thus for the symptoms and manifestations on 
the part of that organ. One observation, as pointed out by Castaigne, is 
strongly in favor of the circulatory origin of the hemolysis, namely: the 
siderosis of the kidneys, which is often demonstrable. Otherwise no 
important evidence can be adduced in support of one or the other of these 
views which, in the end, are essentially the same, excepting in so far as 
they bear on the second question. 
2. The cause of the jaundice: Most observers have believed the jaun- 
dice to be immediately hepatic in origin due to the over-production of 
bile by a liver over-stocked, so to speak, with products of blood 
destruction. The old idea that this was, in a sense, after all, an obstruc- 
tive jaundice owing to the inspissation of the bile and the engorgement 
of the intrahepatic bile passages, or to a diffuse intrahepatic cholangitis, 
must, however, be abandoned as a result of the clinical and pathological 
observations of some of these cases. If the hepatic origin of the jaundice 
be accepted, we must fall back on the assumption of Minkowski, that 
the overworked hepatic cell gives off a part of the excess of bile which it 
produces into the capillaries, as well as into the bile passages. 
Widal and his pupils, however, advance another hypothesis, which 
is in many ways inviting. Pointing out the rapidity with which jaundice 
follows experimental blood destruction in animals, they call attention to 
the lack of evidence of any inspissation of the bile, referring especially 
to one of their patients on whom a cholecystostomy was performed for 13 
suspected stone. The gall-bladder and ducts were empty, and the bile 
which was discharged from the fistula in large quantities was of normal 
character and strikingly fluid. On the other hand, they observe that 
Langhans and Quincke have demonstrated bilirubin in the seat of old 
hemorrhagic foci, that Sabrazes and Muratet have observed the presence 
of urobilin in cerebrospinal fluid after cerebral hemorrhage, and that 
Froin has shown that hemoglobin may be changed into biliary pigment 
in hemorrhagic exudates in the meninges and in the pleura, observations 
which have been confirmed by Guillain and Troisier, Widal and Joltrain 
and others. The urobilin which various observers have demonstrated in 
the serum is believed to be due to a direct transformation from hemo- 
globin through bilirubin such as has been shown to occur in hemorrhagic 
exudates. Troisier (These, 1910). They point to the fact that in cases 
presenting the syndrome of which we have been speaking, despite the 
long continued jaundice, there is no evidence of the ordinary symptoms 
of biliary retention, symptoms which they believe to be due to the action 
of biliary salts, namely: pruritus, bradycardia and emaciation. Bile 
acids have never been found in blood or urine. Nor do the red corpuscles 
show the increased size and heightened resistance to hypotonic salt solu- 
tions which .Rist and Ribadeau-Dumas believe to indicate an acquired 
tolerance for intoxication by taurocholate of sodium. Everything, they 
think, points to the existence of a purely pigmentary cholemia which, 
theoretically, might easily arise in the blood itself. This is a conceivable 
and seductive hypothesis. The objections based on the absence of hemo- 
globin in the circulation, which have been raised against this idea, are 
answered by Widal by the assumption of a destruction of the corpuscles 
so gradual that the quantity of hemoglobin is too small to be recognizable. 
It cannot be said, however, that the symptoms of ordinary biliary intoxi- 
cation are never present, rare though they be, for itching has been 
observed in one or two instances. On the other hand the argument that 
the absence of these symptoms is evidence of the purely pigmentary 
character of the jaundice is based on a false assumption, for King and 
Stewart have shown that it is, in fact, on the bile pigment that brady- 
cardia depends. 
It is, at the moment, impossible to form a definite opinion on this 
question. While all recognize the hemolysis as the remote cause of the 
jaundice, the majority of observers still cling to a point of view similar 
to that of Vaquez and Aubertin, which has been well summarized by 
Chalier. According to this the condition represents "a lesion of the 
blood of unknown cause terminating in destruction of the red blood 
corpuscles, in secondary splenic hyperplasia with the formation of an 
excess of iron-containing pigment and an over-production of bile by the 
liver as a result of the superabundance of pigment to transform and, 
consecutively, jaundice." In their own words (Vaquez and Aubertin) : 
. . ,if the primary cause of hemolytic jaundice is in an alteration 
of the blood, its immediate cause is without doubt an increased func- 
tional activity of the liver cell; there may exist, indeed, a biliary over- 
activity of the liver just as there exists a glycogenic overactivity of the 14 
liver, and hemolytic icterus would then be an icterus through hepatic 
overactivity (Vetere par hyper-hepatie')." Their idea as to the manner 
in which the bile pigment enters the blood is doubtless similar to that 
expressed by Leuret. "With the blood pigment modified by the spleen 
the hepatic cell proceeds to produce an excess of bilirubin to a degree 
such that in certain cases it overflows and secretes bile at both poles: 
whence hepatogenous icterus"-essentially the idea of Minkowski. The 
question must be regarded as still open, and there is much that would 
attract one to the hematogenous hypothesis of Widal, the arguments in 
favor of this point of view being set forth strongly in the thesis of 
T roisier. 
3. As to the third question, the primary cause of the corpuscular 
fragility, a positive answer cannot be given. In congenital hemolytic 
jaundice it has generally been assumed that the fragility of the red 
blood corpuscles is an inherited defect. The red cell, it might be 
fancied, has here failed to acquire those powers of resistance which are 
ordinarily gained in the first days of extra-uterine life, retaining per- 
manently its original fragility. Tn the acquired forms of the disease 
the question is, however, by no means so simple. Widal, Abrami and 
Brule, by intraperitoneal injections of toluylendiamin, have produced 
in animals a jaundice with clinical and pathological phenomena similar 
to those observed in hemolytic jaundice in the human being. According 
to the dose, the process is more acute and severe, or slower and more 
gradual and persisting for a long period after the last injection of the 
poison. No hemolytic properties could be found in the serum. On the 
other hand the red blood cells showed a markedly diminished resistance to 
hypotonic saline solutions as well as a granulation on vital staining, while 
evidences of increased marrow activity were striking. The urine in 
some of these cases, however, contained bile pigment. Obstructive jaun- 
dice in animals results neither in anemia, granular corpuscles, nor 
increased fragility. Indeed, the resistance of the red blood corpuscles is 
always normal or increased. Here, then, is a similar phenomenon pro- 
duced primarily by a soluble toxic substance, and while in many instances 
in the human being no such cause is apparent, in other cases, such as 
those occurring in malaria, syphilis and uncinariasis, the primary action 
of some circulating toxic substance would appear to be certain. It may 
be. as suggested by Widal, that the marrow, constantly called on, ends 
by producing corpuscles less resistant than the normal. But under such 
circumstances wo must fancy that some poisons have acted primarily on 
blood or marrow. What these may be we know not. The fever associ- 
ated with paroxysmal aggravations in some cases of acquired hemolytic 
jaundice is suggestive of an infection. 
It is possible, then, that the corpuscular fragility as well as the granu- 
lar corpuscles - the main stigmata of the syndrome - may sometimes 
be secondary to the action of some circulating toxic substance or sub- 
stances. 
Treatment.-Various essays have been made in the treatment of both 
congenital and acquired hemolytic jaundice. Widal and his pupils have 15 
shown clearly that the persistent administration of iron is the one method 
from which good results may be obtained. Tn the severe acquired forms 
rest in bed and the other adjuvants suitable for the treatment of any 
grave anemia should be adopted. Tn congenital hemolytic jaundice 
recovery is unknown, but a temporary improvement in the anemia may 
be obtained by persistent treatment with iron. In acquired hemolytic 
jaundice long continued treatment may result in apparent, perhaps 
indeed, in complete recovery (Widal, Abrami and Brule). This is a 
very important fact when one reflects on the futility of treatment with 
iron in Addisonian anemia, a malady which may so closely resemble 
this syndrome. 
The studies, then, of the last several years have brought out a fairly 
definite clinical syndrome, that of acholuric jaundice associated with 
splenomegaly and fragility of the red blood corpuscles. In its purest 
form this group of symptoms is manifested in a sharply defined disease 
picture, congenital, often familial splenomegalic jaundice. It is prob- 
able that many of Gilbert's cases of chronic simple jaundice with spleno- 
megaly as well as of TTayem's infectious splenomegalic jaundice are 
examples of the disease. 
A similar condition is, however, not infrequently met with in adult 
life. Tn these so-called acquired cases the symptoms are usually con- 
siderably more acute and severe than in the congenital malady. The 
syndrome has, moreover, been found in a variety of other instances of 
non-obstructive jaundice associated with various infections or poisons. 
What the essential primary element in these cases may be, is not at 
present clear. Most important for the moment is the recognition of 
those apparently idiopathic examples of acquired hemolytic jaundice 
simulating pernicious anemia, cholelithiasis, the so-called splenic anemias 
or indeed, icterus gravis; most important because of the fact that the 
recognition and persistent treatment of some of these cases with iron may 
bring a great improvement, and perhaps a permanent recovery. 
The recognition of this syndrome has opened again, and in an 
interesting manner, the question 'as to the possibility of a purely hema- 
togenous jaundice. 
The methods of studying the corpuscular resistance necessary for the 
diagnosis of such cases are, of course, too delicate for use by the busy 
practitioner, but they may be carried out easily in any well-equipped 
laboratory. One may hope that a reinvestigation of some of the many 
instances of non-obstructive jaundice by means of these methods of study 
may help to shed further light on an interesting field of medicine.3 
3. For full reference to the literature, see the article by Thayer and Morris on 
"Two Cases of Congenital Hemolvtic Jaundice with Splenomegaly," soon to appear in 
the Johns Hopkins Hospital Bulletin. On the Presence of a Venous Hum in the 
Epigastrium in Cirrhosis of the Liver. 
BY 
WILLIAM SYDNEY THAYER, M.D., 
PROFESSOR OF CLINICAL MEDICINE IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE. 
FROM THE 
AMERICAN JOURNAL OF THE MEDICAL SCIENCES 
March, 19 r i Extracted from the American Journal of the Medical Sciences, March, 1911 
ON THE PRESENCE OF A VENOUS HUM IN THE EPIGASTRIUM 
IN CIRRHOSIS OF THE LIVER. 
By William Sydney Thayer, M.D., 
PROFESSOR OF CLINICAL MEDICINE IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE. 
X., a physician, aged forty-nine years, had been for years a country 
practitioner, and had led a regular and exceedingly active life. He 
had lived fairly well and had taken, probably, three or four drinks 
of whiskey a day throughout his life. Two years previously he had 
had an attack of hematemesis, which followed a rather heavy supper. 
Since that time he had been well until eleven days before consulting 
me, when, one morning, while driving, he became unaccountably 
"nervous," coughed and vomited about an ounce of dark blood. 
Returning home, he went to bed. The vomiting continued, con- 
taining as much as a pint and a half of blood. This was followed 
by repeated tarry stools. He complained also of abdominal pain 
in the right side of rather an indefinite character. After this attack 
he placed himself on a very limited diet, but, with remarkable 
energy, he kept at work attending to a large general practice. 
In the consulting room, on November 3, 1905, he was extremely 
blanched. The pulse was about 100. regular, rather soft. The 
apex impulse of the heart was in the fourth space within the 
mammillary line; a blowing systolic murmur was heard all over the 
cardiac area. The abdomen was full. The border of the liver was 
palpable one or two fingers' breadth below the costal margin in the 
mammillary line, and about half-way between the xyphoid cartilage 
and the umbilicus in the median line; it was smooth and hard. The 
spleen was readily palpable, descending two or three fingers' breadth 
below the costal margin on inspiration. There was no ascites. 
The hemoglobin, by the Tallqvist scale, was between 20 and 30 
per cent. 
The patient was advised to enter the hospital, which he did on the 
following day (November 4, 1905). On entry, he was very pale. 
Dr. Cole noted that the veins in the epigastrium and along the costal 
margin were a little distended and that the abdomen was decidedly 
full, showing a few large veins in the groins and flanks; none about 
the umbilicus. There was slight dulness in the right flank. The 2 
THAYER: CIRRHOSIS OF THE LIVER 
edge of the liver was well felt, smooth and rounded, and the splenic 
border was 3 cm. below the costal margin in the right parasternal 
line, reaching forward to within 2 cm. of the median line. 
The patient was put to bed and given two Blaud's pills (gr. v) 
three times a day. Improvement was steady. 
November 9. Hemoglobin, 33 per cent. (Dare). 
November 16. Red corpuscles, 3,400,000; colorless corpuscles, 
4000; hemoglobin, 48 per cent. 
November 20. Hemoglobin, 56 per cent. The soft systolic mur- 
mur over the heart had completely disappeared. The abdomen 
was symmetrical; the hepatic border was palpable fully two fingers' 
breadth below the tip of the xyphoid cartilage. About opposite the 
sixth costal cartilage, over the lower sternum, just at the base of the 
xyphoid, there was heard a loud continuous venous hum with slight 
inspiratory accentuation. It was lost immediately as one passed up- 
ward. It was transmitted a little downward, disappearing, however, 
before the tip of the ensiform cartilage. It was heard about cm. to 
the right, and, faintly, about 6 cm. to the left. A few rather large 
veins were visible at this point, but nothing was felt. "It seems 
evidently superficial, is en irely absent in the precordial region, left 
or right. It must be produced by some abnormality of the internal 
mammary veins." The spleen was still palpable two fingers' 
breadth below the cosatl margin. 
November 27. Hemoglobin, 75 per cent. The urine throughout 
showed a very faint trace of sugar, only once estimable (0.4 per 
cent.) by the polarimeter. On entrance, there was fever, reaching 
102° to 103° at night, with morning remissions. After the first 
forty-eight hours it was below 101°, and during the last week it never 
reached 100°. 
The patient left the hospital on November 27, and returned to 
his work on Christmas Day. 
In January, again, he vomited about a tablespoonful of blood, 
and noticed several tarry stools. There was fever in the afternoons 
(99° to 103°), anorexia, and dyspnoea on exertion. 
He consulted me on January 19, 1906; in the morning he had 
vomited a tablespoonful of blood. At this time he was still pale, 
although the general nourishment was good. The heart sounds 
were clear, excepting a slight reduplication of the first sound at 
both apex and tricuspid areas. At the base, the second aortic was 
accentuated. The abdomen was full. The liver was easily felt, 
7.5 cm. below the tip of the ensiform cartilage. It did not feel quite 
so hard as on the previous examination. A loud venous hum was 
audible in the xyphoid notch. The spleen descended 8 cm. below 
the costal margin, 
o 
On April 27, 1906 I saw the patient again. Since December he 
had had three periods during which the stools were tarry. Four or 
five weeks before he had had a sharp attack of pain in the lower THAYER: CIRRHOSIS OF THE LIVER 
3 
abdomen, followed by the vomiting of about a gill of blood. He 
was anemic, dyspnoeic, and said he was unable to walk because of 
dyspnoea and a sense of pain in the precordium. There had been 
increasing oedema of the legs. He was still very pale. The cardiac 
apex impulse was palpable in the fifth space, 11 cm. from the mid- 
sternal line. There was a presystolic gallop and a very slight 
systolic murmur which was heard about to the anterior axillary line, 
where it was lost. The murmur was loud and rather scratchy in 
the pulmonic area, feebler in the aortic, though louder here and 
over the manubrium than at the apex. There were fine rales at 
both bases. 
The abdomen was a little full; the spleen readily palpable, 7.5 cm. 
from the costal margin. The liver was easily felt It did not seem 
quite so hard, extending only 6.8 cm. below the tip of the ensiform 
cartilage, 12 cm. above the mid-umbilicus. In the epigastrium, 
just over the xyphoid cartilage, and a little toward the left there was 
felt a distinct, fine thrill. The same loud venous hum was audible. 
The patient gave up his practice temporarily and took a long 
vacation. On his return he gave up the heavier part of his work, and 
in the course of a few months recovered his usual health. For four 
years he was in remarkably good condition and led an active life. 
At the author's request the patient called upon him again on 
October 7, 1910. He was then in excellent general condition. 
There had been occasional dark colored stools. No more 
hematemesis. For two and a half years he had had a slight um- 
bilical hernia. He had moved from the country to the city, and 
given up his practice, but had been active in several responsible 
positions. There had been in the last several months considerable 
frequency of micturition and some thirst. He looked remarkably 
well but somewhat thinner than he used to be; of good color. 
Hemoglobin (Tallqvist), 85 to 90 per cent. The face was ruddy, 
the venules on the cheeks and nose dilated. The pulse was slow 
and regular; the pressure, by estimate, 130 to 140. Nothing remark- 
able was to be detected in the heart or lungs. The abdomen was 
rather full; everywhere tympanitic. The liver was to be felt just 
at the costal margin in the mammillary line; the border was 7.3 cm. 
from the tip of the xyphoid, 11 cm. from the mid-umbilicus. The 
spleen was just to be felt a trifle below the costal margin, descending 
markedly with inspiration. No thrill was felt at the episternal 
notch. There was no dilatation of the cutaneous veins excepting the 
corona hepatica. There was a distinct umbilical hernia, most 
marked just above the umbilicus. Just over the xyphoid, not heard 
below its tip or to the right, but distinctly audible for a distance of 
about 3 cm. to the left, there was heard the echoing, venous hum before 
described. It was loudest immediately over and to the left of the 
xyphoid; was a continuous echoing sound exactly like the bruit de 
diable in the neck. There was a very distinct inspiratory accentua- 4 
THAYER: CIRRHOSIS OF THE LIVER 
tion. With complete expiration, when the breath was held, the 
murmur was diminished, and it almost disappeared when the breath 
was held with complete inspiration. There were no definite changes 
in connection with the cardiac rhythm. 
No murmurs were heard in the region of the umbilicus; no mur- 
murs over the spleen or in Traube's space. "Such a murmur must 
be due to the entrance of blood from a smaller into a larger cavity; 
its situation suggests the point of entrance of Braune's parumbilical 
xyphoid vein into the roots of the internal mammary." 
On Sunday, October 16, 1910, the patient was seized with a sud- 
den attack of nausea similar, his family tell me, to several attacks 
which he had had during the preceding year, but which he had not 
mentioned to the author. During the night the vomiting continued, 
and the patient became drowsy. 
On the morning of the 17th he became wholly unconscious. The 
patient was seen at this time in consultation with' Dr. Chambers. 
He was lying on his back, breathing quietly. The pulse was regular 
about 80. There was no suggestion of the air-hunger of a diabetic 
coma. The pupils were equal and of medium size, responding to 
light. The conjunctival reflexes were not wholly obliterated. 
The abdomen was full, bulging somewhat in the flanks. There 
was well marked dulness in both flanks and everywhere in the 
dependent parts of the abdomen. This dulness was clearly movable 
with change of position. The liver dulness was diminished. The 
border was not palpable, and in the median line the liver could be 
felt just below the tip of the xyphoid cartilage. The dulness in the 
mammillary line did not reach the costal margin. The spleen was 
of about the same size as at the last note. The venous hum in the 
epigastrium had entirely disappeared. 
The urine, examined by Dr. Chambers the day before, was free 
from albumin and sugar, and showed no reaction for bile. 
The coma deepened as the day wore on, the respiration and pu^se 
becoming more accelerated. In the evening several violent con- 
vulsions occurred, and the patient died at about 10 o'clock at night. 
A necropsy was not permitted. 
In summary, then, in a man, aged forty-nine years, with evidences 
of hepatic cirrhosis-habits, hematemesis, melena, large, firm liver, 
splenomegaly, and a slight glycosuria-there was detected a continu- 
ous thrill and a long, loud bruit de diable in the epigastrium. The 
thrill was felt just in the xyphoid region and a little toward the left, 
above the lower margin of the liver. The murmur, a characteristic 
venous hum with inspiratory accentuation, was audible in a limited 
area immediately about the xyphoid cartilage. It was not audible 
nbout the umbilicus. There were no cutaneous varicosities. Five 
years after the detection of the murmur the patient, who, a week 
before, had be n in good condition, was seized with nausea, vomit- THAYER: CIRRHOSIS OF THE LIVER 
5 
ing, drowsiness, and finally coma, and died in convulsions about 
thirty-six hours after the onset of his illness. During the last day of 
his life there was well marked ascites and the epigastric murmur 
had entirely disappeared for the first time since its detection. 
The condition was obviously a portal cirrhosis of the liver in 
which ascites was absent during the greater part of the course, 
owing, undoubtedly, to the existence of a free anastomotic circula- 
tion. The manner of death was such as is characteristic of hepatic 
insufficiency. 
The remarkable feature of the case, that which throughout was of 
especial interest to the author, was the presence of the thrill and 
venous hum in the epigastrium. What was the cause of this phe- 
nomenon? There are various possibilities. It might have been a 
murmur arising in the vena cava inferior and heard loudest in the 
epigastrium near the point of entrance of the vena cava into the 
right auricle. Gambarati advances a like hypothesis to account for 
a murmur which was in some respects similar to that heard in our 
case. 
Piazza Martini (1894) has described a slight soft murmur heard 
over the hepatic area, especially in the right axilla, which he believes 
to be due to constrictions in the vena cava as it passes behind the 
liver, owing to changes in the position or deformity of the latter organ 
or to pressure from without (tumors, etc.). Pressure or traction on 
the superior cava from an old pleurisy or pericarditis would seem 
to be out of the question from the history of the patient and the 
physical examination. One might, indeed, fancy that, in the course 
of the cava through the sulcus in the posterior surface of a deformed, 
cirrhotic liver, constrictions might arise sufficient to result in fluid 
veins capable of producing an audible murmur. 
Several considerations, however, would appear to militate against 
this hypothesis: (a) The limited area in which the murmur was heard. 
A murmur of such intensity arising in the inferior cava behind the 
liver should be audible over a considerably larger area, as it was, 
indeed, in Gambarati's case. (6) It is hardly conceivable that a 
murmur arising in the inferior cava should cause a distinct epigastric 
thrill, (c) The murmur was audible with greater intensity on the 
left side of the epigastrium, and the thrill was detected only on the 
left, that is, at a point not over the superior cava. 
Might the murmur have arisen in dilated coronary veins or in 
oesophageal hemorrhoids which, in view of the hematemesis, were 
in all probability present? The situation in which it was heard 
might, indeed, support the former hypothesis. That a palpable 
thrill could be transmitted from veins so deeply placed seems, how- 
ever, scarcely probable. 
The murmur could hardly have arisen in a large umbilical or par- 
umbilical vein, because of its absence in the neighborhood of the 
umbilicus or between it and the tip of the xyphoid. 6 
THAYER: CIRRHOSIS OF THE LIVER 
The thrill would suggest that the a eins in which the vibrations 
arose must have been in or in close apposition to the abdominal wall. 
It seemed to us from the outset probable that these a essels were 
varicosities dependent on anastomoses between dilated venules in 
the suspensory ligament and radicles of the internal mammary veins. 
The immediate cause of such a murmur would appear to be the 
passage of blood under considerable pressure from a smaller into a 
larger vessel, or, indeed, the passage of blood through a single vessel 
with varicose dilatations. 
On turning to the literature one finds a considerable number of 
contributions on the subject of venous murmurs in the epigastrium. 
P^got, in 1833, described an instance of cirrhosis of the liver with 
great dilatation of what he regarded as a persisting umbilical vein, 
attended by remarkable varicosities about the umbilicus and in the 
epigastrium. Over these veins one could hear a slight murmur- 
"par 1'auscultation, on entendait un l£ger bruissement qui n'etait 
sensible qu'k 1'ombilic." 
Bamberger, in 1851, reported a similar case with enormous 
pyramidal varicosities betAveen he umbilicus and ensiform cartilage. 
With the hand over these veins, a slight thrill Avas to be felt, and, with 
the stethoscope, a continuous rustling sound could be heard. 
Since this time many observers have referred to the thrill and 
murmur which may at times be heard over the varicosities occa- 
sionally seen about the umbilicus and in the epigastrium in cirrhosis. 
Charcot, indeed, says: " A murmur which one hears by auscultation, 
a thrill which the hand detects, are perceived over these veins. They 
are," he says, "on general principles, signs of a favorable import." 
Catti describes a case of cirrhosis with cutaneous varices in the 
epigastrium, especially of the left vena epigastrica tegumentosa. 
Over this vein a few centimeters to the left of the navel, an intense 
thrill and loud murmur Avere audible-a characteristic venous hum. 
Below, over the abdomen, there could be heard a musical ringing 
sound like that of an /Eolian harp. By compressing the vein 
about 1 cm. below the point Avhere the thrill Avas most marked, the 
whole phenomenon stopped abruptly, to begin again on removing 
compression. Pressure above had no effect. At autopsy, the sub- 
peritoneal veins Avere found to be large and the ligamentum teres Avas 
voluminous. Such a murmur was clearly due to blood passing 
under rather a high pressure from smaller anastomotic vessels into 
the dilated vena epigastrica tegumentosa. 
There has been more or less discussion as to the exact nature of 
the disturbances of circulation causing these extensive varicosities. 
Rokitansky's original contention that the condition was asso- 
ciated with the dilatation of an incompletely obliterated umbilical 
vein Avas disputed by Sappey, Avho showed that some, and con- 
tended that all, of these instances were dependent on dilatation of THAYER: CIRRHOSIS OF THE LIVER 
7 
small parumbilical veins running in the broad ligament. While this 
is doubtless true in many, perhaps in the majority of instances of 
extensive caput medusas, the observations of Bamberger, Hoffman, 
Baumgarten, Picchini, and others show that in some instances at 
least the large vein in the ligamentum teres is truly a persistent 
umbilical vein which has been distended as a result of the abnor- 
mally high pressure in the portal system. 
There are, however, other instances in which a loud venous hum 
has been audible in the epigastrium in cases of hepatic cirrhosis 
without the presence of notably large cutaneous veins. Sappey, in 
1859, describes a case which was demonstrated to him by Trousseau. 
The patient was a man of about fifty, with cirrhosis of the liver. 
4'On applying the ear or the stethoscope to the abdomen of this 
patient, one perceived a very distinct bruit, consisting in a sort of 
continuous murmur." At necropsy, there was found "a voluminous 
vein extending from the sinus of the portal vein toward the umbilicus, 
where it ramified and anastomosed with the epigastric veins, which 
seemed to be its prolongation Underneath the vein, in the free 
border of the suspensory ligament, was to be seen the cord of the 
umbilical vein." Sappey concludes that this large vein was the 
result of the dilatation of one of the venules which accompany the 
umbilical vein, and not of the vein itself. 
Picchini, in a case of cirrhosis in a boy of sixteen, noted a well- 
marked thrill on palpation in the epigastrium. This was present 
in a fairly extensive zone, extending from 1 cm. under the apex of 
the xyphoid to the umbilicus, with its maximum intensity along the 
median line, diminishing toward the sides so as not to be felt beyond 
either parasternal line. It ceased immediately below the umbilicus. 
It was continuous, slightly diminished by pressure. On ausculta- 
tion, there was an intense murmur unmodified by respiration or by 
heart sounds, best audible when the stethoscope was lightly applied, 
and loudest a little above the umbilicus. The spleen was large; 
the liver was rather small. There was ascites. After tapping, the 
murmur became less intense and was limited to the median line. 
At necropsy, the external anastomoses about the umbilicus were 
slight. On the internal surface, along the median line, a large single 
trunk was found, "which, from the umbilicus, along the fold which 
unites this with the triangular ligament of the liver, had an upward 
direction, reached the inferior surface of the liver at the incisure 
which separates the right from the left lobe, and then folding itself 
under this, continued toward the hilum of the liver." On further 
dissection, it was shown that this vein left the anterior surface of the 
portal vein 3 mm. before its bifurcation at the hilum. Here it was 
more than one-half as large as the portal. After a course of 2 or 3 
mm., it received three trunks of from 2 to 3 mm. in diameter, one 
after the other, one from the branch of the portal vein destined 
to the right lobe, the other two from the branch directed to the left 8 
THAYER: CIRRHOSIS OF THE LIVER 
lobe. By these additions, the vessel acquired a volume as large as 
that of the portal vein. In its course along the concave surface of 
the liver it received no new branches and none between the liver 
and the umbilicus. There were varicose dilatations about the 
umbilicus. Picchini considers this a true although somewhat 
anomalous umbilical vein, firstly because he could find no trace 
of the obliterated vein, and secondly, because of the absence of anas- 
tomoses in its course between the liver and the umbilicus. 
Audry mentions the case of an individual, aged fifty years, with 
exophthalmic goitre, jaundice, and a liver descending to the iliac 
crest. Above the xyphoid process and along the linea alba there 
was an intense, continuous souffle, with systolic accentuation, analo- 
gous to the murmurs of the chlorotic. Below the umbilicus, a 
systolic murmur only was heard. No necropsy was reported. 
Herbert Davies is quoted by Verstraeten as having described an 
analogous case. He found a continuous snoring murmur, varying 
in intensity with inspiration, and occupying the epigastric region to 
the right of the median line, a little above the umbilicus. This 
abnormal murmur existed in an individual suffering from hepatic 
cirrhosis. Davies regarded it as dependent on a collateral current 
which was established between the portal and epigastric veins. 
F. Taylor describes the case of a boy who showed the first 
evidences of cirrhosis of the liver at six, dying at twenty. 
He had been ascitic and had had various attacks of hematemesis, 
but the ascites had disappeared. Death resulted from a general 
infection. During the year before death an epigastric venous hum 
was noted. Particulars as to the anastomoses in the epigastrium 
are not given. 
Von Jacksch (1893), in a case of cirrhosis with large liver and 
spleen, observed a remarkable thrill, which was palpable when the 
hand was laid on the abdominal wall between the umbilicus and ensi- 
form cartilage. On auscultation in this area one could hear a hum- 
ming murmur, which might best be compared to the rumbling of a 
threshing machine. No mention is made of dilated cutaneous veins. 
At necropsy which revealed a high grade of cirrhosis, " the vena coro- 
naria ventriculi, which opened here 1 cm. above the vena lienalis, 
into the trunk of the vena portae, was greatly distended, markedly 
tortuous, and beset with many varicose dilatations which, in part, 
were so large as to admit the extremity of the thumb and to form 
true blood cysts." The vena umbilicalis was wide open from the 
left main branch of the portal vein for a space of 7.6 cm., at which 
point it connected with a thin-walled, varicose Sappey's vein coming 
from the umbilicus and of an average diameter of 8 mm. From 
this point to the navel the umbilical vein was pervious only for a 
hair sound. "From this observation," says von Jacksch, "there can 
apparently be no doubt that the murmurs which were heard in the 
case arose in the vena coronaria ventriculi." THAYER: CIRRHOSIS OF THE LIVER 
9 
Scheele, in a man of forty-six, with jaundice, ascites, and a 
large, tender, and uneven liver, detected in the region of the umbili- 
cus a very well marked continuous thrill. There was no dilatation 
of the cutaneous veins. In the dorsal decubitus there was a distinct 
bruit de diable, accentuated on inspiration and diminished on expi- 
ration and by pressure on the crural veins. It disappeared in the 
erect posture, was audible only in the umbilical region, and was not 
transmitted toward the heart. There was no apparent abnormality 
in the heart or large veins. 
Gambarati, as above mentioned, has described an interesting 
case which in some respects resembles that described by the author. 
The patient was a man, aged forty-nine years, with a retracted right 
chest from an old pleurisy, and an apparent hepatic cirrhosis. The 
liver was small, the superficial abdominal veins were dilated, espe- 
cially in the epigastrium passing up toward the chest. The spleen 
was enlarged. There was ascites. Over the sternum and all over 
the hepatic area there was a continuous murmur similar in character 
to the ordinary venous hum in the neck. It was composed of two 
phases, varying in duration and intensity. The author compared it 
to the murmur or roaring of a strong wind blowing through a small 
orifice, and the variations in the intensity of the murmur reminded 
one of the irregular gusts and lulls of such a wind. Sometimes the 
murmur appeared more intense with cardiac diastole. It was very 
superficial and its point of greatest intensity was distinctly at the 
base of the xyphoid, but it was not heard below or over the xyphoid 
itself. On very deep, long breaths it seemed louder-clearly a 
humming-top murmur. It was not altered by lying on one side or 
another, but was a little louder in the erect posture, and when, after 
standing, the patient suddenly lay down and assumed the knee-elbow 
posture, it sometimes diminished or even disappeared for a time. On 
tying a tight bandage about the chest a few centimeters above 
the base of the xyphoid, the murmur became weaker, but if the 
bandage was applied below the costal arch, it became much feebler 
and sometimes even disappeared. Gambarati believes that the 
murmur was due to "a contriction of the inferior cava in its passage 
through the hepatic sulcus, dependent on atropic changes in the 
liver." 
Rolleston says: "In rare instances, a venous hum may be heard 
over the epigastrium, which is increased on inspiration. It has 
been explained as the result of compensatory dilatation of the venous 
communications between the portal and general systemic veins. 
The thin-walled and dilated veins may readily be kinked as the 
result of adhesions, or temporarily distorted by the descent of the 
diaphragm, or even by the pressure of a wooden stethoscope. 
'Tn a man, aged forty-three years, who was under my care at St. 
George's Hospital, there was a continuous bruit de diable in the neck. 
At autopsy, the liver was markedly cirrhotic and the round ligament 10 
THAYER: CIRRHOSIS OF THE LIVER 
contained a thin-walled vein as large as the little finger." This is 
stated to have been a parumbilical vein. 
Catti describes the case of a man, aged fifty-one years, with 
atrophic cirrhosis and a palpable spleen. The cutaneous abdominal 
veins were moderately dilated. In the xyphi-sternal notch a very 
loud venous hum was audible, which was transmitted with dimin- 
ished intensity as far as the mid-sternum; it was increased on inspira- 
tion. There was no thrill. After paracentesis of the abdomen the 
murmur was much less intense. 
It should, however, be remembered that epigastric venous mur- 
murs are heard under other conditions. Roeser, in 1862, comments 
on the occasional presence of a continuous murmur in the epigastrium 
in advanced cases of splenic enlargement, apart from the not infre- 
quent souffle in the splenic artery. Moreover, he says: "There are 
cases where the portal vein is accessible; it is here a continuous 
murmur." 
Piazza-Martini (1898), in three cases of chronic splenic tumor, 
has heard a venous hum in Traube's space below the apex of the 
heart from the sixth space to within 1 cm. of the costal margin, and 
between the left parasternal and anterior axillary lines. In the 
right lateral decubitus the area in which the sound was heard was 
lower down and farther out. When lying on the left side it was 
heard higher up and nearer the parasternal line. He is inclined to 
think that it arises in the coronary vein of the stomach. 
Von Jacksch describes an instance of cirrhosis in which a 
venous hum was audible in the left side of the epigastrium in 
the angle between the large liver and the spleen. At necropsy the 
splenic vein was found to be so far dilated as to admit the tip of the 
little finger. All the radicles of the portal vein were dilated, as well 
as the veins in the lesser omentum and those in the ligamentum teres. 
"From the anatomical observations there can be no doubt that the 
murmurs arose in the splenic vein." It must be said that the char- 
acter of the murmur appears to have been not so distinctly that of 
a venous hum as in some of the other reported cases. 
Catti asserts that in his experience a venous hum is audible over 
the spleen in nearly every fifth case of chronic tumor; this was best 
heard, as a rule, over the anterior part. 
Other observers have called attention to the occasional presence 
of a venous hum in the epigastrium just above and to the right of 
the umbilicus-a hum which is believed to arise in the vena cava 
inferior. 
Cejka, in 1850, says: "With yielding abdominal walls, one needs 
only to seek the ascending vena cava with the stethoscope according 
to the dictates of anatomical topography, to perceive a humming 
murmur (N onnengerausch') to the right of the median line, and to 
follow it downward in the course of the vein to the point of its 
division." THAYER: CIRRHOSIS OF THE LIVER 
11 
Hammernik, in 1853, describes at length the venous hums over 
the crurals and inferior cava. These murmurs are usually found 
only in young and anemic individuals, and may be followed upward 
from the crurals to the inferior cava. "This venous hum (Nonnen- 
gerdusch') is continuous, shows no period of accentuation, and is not 
altered by the respiratory movements." 
Friedreich, in 1881, says: "I have myself heard these not infre- 
quently by pressing slowly and continuously on the right, near the 
linea alba, at about the level of the navel, with a stethoscope with a 
wide funnel, until the vein in the depths is fully compressed; this is 
easy to accomplish with the patient on his back and the legs drawn 
up, especially in those individuals with lax abdominal walls. On 
suddenly letting up the pressure, there is a loud, rapidly diminishing 
venous hum. Sometimes, if pressure is properly adjusted, there 
is a continuous singing or humming murmur." In one case such a 
murmur disappeared on pressure on one or another crural vein. 
Audry asserts that the presence of a venous hum in the epigas- 
trium, a little above and to the right of the umbilicus, is by no 
means rare. It is similar in character to a diastolic venous souffle, 
and it is, he thinks, due to the emptying of the veins with diastolic 
filling of the ventricle. He has not been able to confirm Friedreich's 
observation of the disappearance of the murmur by pressure on 
the crural vein. The timbre and the continuous character of the 
sound, as well as its localization over the vena cava inferior, justify 
placing this phenomenon among the venous murmurs. Audry com- 
ments on the fact that in the several notes on epigastric venous hum 
in cirrhosis, no mention is made as to the differential diagnosis 
between it and these murmurs, which he believes due to vibrations 
arising in the vena cava inferior. He was able to detect these hums 
in ten out of forty cases. Most of the patients were anemic or 
suffering from conditions associated often with low blood pressure 
and vasodilatation, i. e., neurasthenia, typhoid fever, pelvic peri- 
tonitis. The murmur which was sometimes audible on pressure, 
would appear to be similar to that described by Friedreich. 
Verstraeten asserts that venous hums in the epigastrium are not 
very rare. He has been able to make out such murmurs in six out 
of 100 cases. They arise, he thinks, at the point where the vena 
cava enters the liver. 
Yet another form of venous hum has been described in the region 
of the liver. Piazza-Martini (1894) notes a continuous venous hum, 
which is audible sometimes in the right axilla over the liver This 
he regards as entirely different from the epigastric murmur. It is, 
he believes, due to pressure on the vena cava by a displacement or 
rotation of the liver or by extrinsic compression or tumors within 
the vessel. Verstraeten also is familiar with this murmur, which he 
likens to a distant waterfall. It is accentuated with full inspiration 
and is audible, especially in marked anemias. 12 
THAYER: CIRRHOSIS OF THE LIVER 
The writer has, in a limited number of cases, sought for the mur- 
mur described by Friedreich and others as arising in the vena cava 
inferior. By following Friedreich's technique, it is indeed possible 
to produce in some cases a slight venous hum. In one very anemic 
man it was fairly loud. This is, however, quite distinct from the 
loud murmur and palpable thrill heard in our patient and in the 
several other cases of hepatic cirrhosis above described, on light 
application of the stethoscope. 
With the soft murmur in the right axilla described by Verstraeten 
and Piazza-Martini, I am unfamiliar. It is, however, not to be 
confounded with the epigastric venous hum of cirrhosis. 
To return to our own case. The phenomena here observed were 
somewhat different from most of those reported in the literature. 
In Andry's first case-a man, aged fifty years, with exophthalmic 
goitre, jaundice, and a liver descending to the iliac crest-there was 
a continuous souffle, very intense, with systolic accentuation, analo- 
gous, according to the author, to the souffle of the chlorotic. This 
was heard above from the xyphoid, along the linea alba. Below the 
umbilicus there was a systolic murmur alone. In this instance 
the murmur was apparently loud and heard well up to the xyphoid 
notch, over a liver which may have been cirrhotic. Such a murmur 
may have been due to varicosities in the abdominal wall or sus- 
pensory ligament. 
In most of the other cases the position of the murmur was such 
that it may well have depended on large umbilical or parumbilical 
veins. 
The cases of Gambarati and Catti and one of the cases of von 
Jacksch are most similar to that which forms the subject of this 
communication. In all of these instances the point of maximum 
intensity of the murmur was at the base of the xyphoid process. In 
von Jacksch's patient, to be sure, the thrill was felt at a point some- 
what lower than in our case. In the other two instances, however, 
the point of greatest intensity of the murmur was at the base of the 
xyphoid. 
In Gambarati's patient the distribution of the murmur was 
remarkably wide, extending over the entire hepatic area and to the 
episternal notch. This wide distribution of this murmur might 
be regarded as supporting his hypothesis that it depended upon 
fluid veins arising in the inferior cava. Against such an hypo- 
thesis, however, would seem to be the complete absence of the 
murmur in the back. This he accounts for by the statement that 
there was hydrothorax on the right side. It should be observed, 
however, that he also asserts that the right chest was retracted from 
an old chronic pleurisy, a condition which it is difficult to harmonize 
with the presence of a hydrothorax. 
Of all the cases in the literature that of Catti is the one which is THAYER! CIRRHOSIS OF THE LIVER 
13 
most analogous to ours, and the hypothesis which he advances to 
explain the phenomenon agrees entirely with our own conclusions, 
formed before we were familiar with his communication. 
In our patient the limited area of transmission, the extremely 
superficial character of the murmur, and especially the presence of a 
thrill, seemed to us, as has been said, to suggest that the murmur 
arose as a result of anastomoses in the abdominal wall between veins 
derived from the suspensory ligament of the liver and radicles of the 
internal mammary vessels. Catti, in his excellent article, refers to 
the admirable studies of Braune, who, indeed, has described a 
venous link which connects the large parumbilical vein (Sappey- 
Luschka) with the left vena epigastrica superior profunda in the 
neighborhood of the xyphoid. In Braune's own words: "This 
venous link extends above the fascia transversalis umbilicalis of 
Richet, from the larger parumbilical vein near the obliterated umbilical 
vein, passes between the folds of the suspensory ligament of the 
liver for a certain distance upward behind the sheath of the rectus, 
breaks through this close by the middle line and, behind the muscle 
substance of the rectus, in the anterior side of the posterior fold of 
its sheath, near the xyphoid process, it enters into the left vena 
epigastrica superior profunda. It is a double, well recognizable and 
easily injected vessel, which, therefore, leads from the sinus venae 
portae upward to the mammaria interna." Braune further points 
out that by the transverse xyphoid vein this vein must carry the blood 
from the portal to the internal mammary of both sides. He regards 
this vein as a regular structure. 
Catti is inclined to consider the murmur in his case, which is so 
similar to ours, as dependent upon vibrations arising from the 
passage of blood from Braune's veins into the left deep epigastric 
vein, the root of the internal mammary. Such an hypothesis would 
seem to be directly applicable to our case, more so, indeed, than to 
any other instance in literature. 
To what may we ascribe the disappearance of the murmur during 
the last hours of life? This is, of course, a question which, in the 
absence of a necropsy, cannot be answered. The coincidence of the 
onset of ascites with the disappearance of the murmur might suggest 
the possibility of thrombosis. The fact, however, that a loud venous 
hum, sometimes accompanied by a thrill, may be detected in the 
epigastrium in cirrhosis of the liver, is worthy of emphasis. It is 
not inconceivable that this phenomenon might, on occasions, prove 
a point of diagnostic value. It would be well that its occasional 
occurrence might generally be recognized. 
In conclusion, it may be said: (1) A venous hum accompanied 
sometimes by a well-marked thrill may be detected in the epigas- 
trium in some instances of hepatic cirrhosis. 
2. The thrill and murmur may be appreciable: (a) directly over 
the extensive cutaneous varicosities, or (6) in instances where there 
is little or no external evidence of venous engorgement. 14 
THAYER: CIRRHOSIS OF THE LIVER 
3. In most of the cases where an epigastric venous hum has been 
heard in cirrhosis, in the absence of cutaneous varicosities, the sound 
has been audible best about the umbilicus and along the median 
line in the epigastrium-in other words, along the course of the 
round ligament. 
4. In a few of these instances it has been found that the incom- 
pletely closed umbilical vein has become greatly dilated as a result 
of increased portal pressure. In others, a large dilated vein has 
been found in the round ligament running alongside of the obliter- 
ated umbilical vessel-doubtless a dilatation of a small parumbilical 
vein. 
5. These murmurs should be distinguished from the slight venous 
hum sometimes heard in the anemic just above and to the right of 
the umbilicus, over the inferior vena cava-murmurs which may be 
brought out by pressure in thin individuals. These murmurs are 
said to disappear in some cases with pressure on one or another 
femoral vein (Friedreich). 
6. A venous hum has been described in Traube's space and in the 
left side of the epigastrium in the angle between the large liver and 
spleen in cirrhosis (von Jacksch, 1899) and in splenic enlargement 
(Piazza-Martini, 1898), which may arise in a varicose splenic vein. 
7. A well-marked thrill and an intense venous hum may be heard 
in hepatic cirrhosis over a limited area in the epigastric notch, in 
the immediate neighborhood of the xyphoid cartilage, at a point 
so far above the lower border of the enlarged liver that it cannot 
depend upon currents in a varicose umbilical or parumbilical vein. 
Such murmurs may, in some instances, arise in varicose coronary 
veins (von Jacksch), while in others, as those observed by Catti and 
the author, the seat of origin is probably in anastomoses between 
the roots of the internal mammary and the inferior deep epigastric 
vessels, very possibly to the entrance into these latter veins of an 
enlarged parumbilical-xyphoid vein of Braune. 
Bibliography. 
Audry, J. Note sur les souffles veineux continues de la region sus-ombilical. Lyon m£d., 
1892, Ixx, 359, 391. 
Bamberger, H. Granulierte Leber. Wien. med. Woch., 1851, i, 5, 37, 53, 134, 168, 244, 
259; Handb. der spec. Path. u. Therap., red. v. R. Virchow, Erlangen, 1855, vi, 572. 
Baumgarten, P. Ueber das offenbleiben fotaler Gefasse. Centralbl. f. d. med. Wiss., 1877, 
xv, 722, 741. 
Braune. Das Venensystem des Menschlichen Korpers, 8°, Leipzig, 1884 (Veit), 63. 
Catti. Ueber Venengerausche bei der insterstitiellen Hepatitis. Ztschr. f. klin. Med., 
Berlin, 1907, Ixi, 269. 
Cejka. Beobachtungen uber das Nonnengerausch. Prager Vrtljhrschr., 1850, vii, Jhrg., ii 
(xxvi), Erganzungsbl., s. 3; Weitere Beobachtungen uber das Nonnengerausch, Prager 
Vrtljhrschr., 1850, vii, Jhrg., iii (xxvii), Erganzungsbl., 13, 14, 15, s. 1. 
Charcot. Lecons sur les maladies du foie et des reins, 8°, Paris, 1877, 240. 
Davies, H. Quoted by Verstraeten. (Original article not found.) 
Friedreich. Beitrage zur physikalischen Untersuchung der Blutgefasse, Deut. Arch. f. 
klin. Med. 1881, xxix, 256. THAYER: CIRRHOSIS OF THE LIVER 
15 
Gambarati, V. Sopra un caso di soffio venoso udibile sull' aia epatica in individuo affetto 
da cirrosi epatica volgare. Riforma med., Roma, 1903, xix, 153-156. 
Haminernik. Ueber einige Verhaltnisse der Venen, der Vorhofe und Kammern des 
Herzens, und fiber den Einfluss der Contractionskraft des Herzens und der Respirations- 
bewegungen auf den Circulationsapparat., Prager Vrtljhrschr., 1853, 10 Jahrg., iii (xxxix), 32. 
Hoffman. Vereins-Berichte. medizinische Gesellschaft in Basel. Correspondenzbl. f. d. 
Schweitzer Aerzte, 1872, ii, 65. 
von Jacksch. Ueber ein intraabdom inales Venengerausch in Verlaufe der chronischen. 
interstitiellen Leberentztindung. Prager med. Woch., 1895, xx, 13-14; Kasuistische 
Beitrage zur Kenntniss der im Verlaufe der chronischen interstitiellen Leberentztindung 
voikommenden Gefassgerausche. Prager med. Woch., 1899, xxiv, 535, 560, 585. 
Pdgot. Tumeur variqueuse, avec anomalie du syst^me veineux et persistence de la veine 
ombilicale, d^vellopment des veines sous-cutan^es abdominales. Bull. d. Soc. anat., Paris, 
1833, viii, 49. 
Piazza-Martini, V. Del rumore di soffio venoso udibile sull' area epatica. Riforma 
med., Napoli, 1894, x, pt. 4, 663, 673, 687; Su di un rumore di soffio venoso udibile sullo 
spazio di Tarube. Lav d. cong. di med. int., Roma, 1898, ix (1899), 198-200. 
Picchini, L. Contributo allo studio del soffio e fremito epigastrico nella cirrosi epatica. 
Segno, Firenze, 1890-91, i, 326-364. 
Roeser. Note sur les bruits anormaux des vaisseaux abdominaux. Bull, de l'Acad. de 
m^d., Paris, 1862, xxviii, 18. 
Rolleston, H. D. Diseases of the Liver, etc., 8°, Philadelphia, New York, London, 
(Saunders), 238. 
Sappey. M^moire sur un point d'anatomie pathologique r^latif A 1'histoire de la cirrhose. 
M^m. de l'Acad. de m^d., Paris, 4°. 1859, 269. 
Scheele, L. Ueber einige seltenere Nonnengerausche und ihren diagnostichen Werth. 
Internal. Beitr. z. inn. Med., Berlin, 1902. ii. 41-58. 
Taylor, F. Cases of Cirrhosis of the Liver in Children, etc.. Guy's Hosp. Rep., London, 
1895, lii, 45. 
Verstraeten, C. Contribution A 1'dtude des souffles veineux dits bruits de diable chez 
1'homme. Ann. Soc. de m^d. de Gand, 1894, Ixxiii, 387. CLINICAL NOTES. 
(1) INTERMITTENT FEVER IN INFLUENZA SIMULATING 
MALARIAL FEVER. 
(2) GRAVE MALARIAL FEVER WITH FEW PARASITES IN 
THE PERIPHERAL CIRCULATION. DANGERS OF THE 
INTRAVENOUS INJECTION OF QUININE. 
By William Sydney Thayer, M. I)., 
Associate Physician, The Johns Hopkins Hospital, Baltimore. [From The Johns Hopkins Hospital Bulletin, Vol. XXII, No. 241, 
April, 1911.] 
CLINICAL NOTES.* 
(1) INTERMITTENT FEVER IN INFLUENZA SIMULATING 
MALARIAL FEVER. 
(2) GRAVE MALARIAL FEVER WITH FEW PARASITES IN 
THE PERIPHERAL CIRCULATION. DANGERS OF THE 
INTRAVENOUS INJECTION OF QUININE. 
By William Sydney Thayer, M. D., 
Associate Physician, The Johns Hopkins Hospital, Baltimore. 
Every one who has observed much malarial fever is familiar 
with the fact that well-marked paroxysms may occur with 
the presence of very few parasites in the peripheral circulation, 
(a) This is not uncommon in mild tertian infections, (b) 
Furthermore, it is observed at the onset of mild and even of 
more or less serious aestivo-autumnal fever, especially during 
the period of the paroxysm. The cause of this is evident 
enough when we remember that the sporulation of the para- 
sites which immediately precedes and accompanies the par- 
oxysm in both tertian and aestivo-autumnal fever, occurs, espe- 
cially in capillaries of certain of the internal organs, particu- 
larly in the spleen and bone marrow. In most mild cases of 
aestivo-autumnal fever, it is rather difficult to find sporulating 
parasites in the peripheral circulation, (c) The same con- 
dition, i. e., well-marked fever with few or no parasites de- 
monstrable in the peripheral circulation, is seen in both tertian 
and aestivo-autumnal infections, but, especially in the latter, 
where quinine has been given in insufficient doses early in the 
attack. 
In most patients, careful examination of blood reveals para- 
sites within the twenty hours succeeding the paroxysm, 
and, even in the absence of parasites, the diagnosis is usually 
sufficiently clear through the history of the case and the physi- 
[101] 
♦ Remarks made before the Johns Hopkins Hospital Medical 
Society on Oct. 17, 1909. 1101] ( 
cal appearances, in connection with the condition of the blood 
which shows usually (1) leucopenia, (2) pigment-bearing leu- 
cocytes, (3) a relative increase in the large mononuclear leu- 
cocytes. 
Nevertheless, it is well known that there are occasional cases 
in which, without splenic puncture, a diagnosis can be reached 
only by the therapeutic test. These cases are not common and, 
in a community where a study of blood is a part of the routine 
examination, as it is here, where one usually waits for the 
demonstration of parasites before the administration of qui- 
nine, it is easy to lay too much stress on the negative results 
of such examinations and to forget that grave and even per- 
nicious malaria may occur in an individual with so few para- 
sites in the peripheral circulation as to deceive even the skilled 
observer on repeated examinations. 
On the other hand, however, 'tis very important to remember 
that certain other infections may give rise to paroxysms which, 
intrinsically, and in the character of their periodicity, may 
closely simulate malaria. 
The paroxysms of streptococcus, pneumococcus and gono- 
coccus septicaemia are usually distinguishable by the irregu- 
larity, often the great frequency of the paroxysms, and the 
short duration of the individual access. The paroxysms oc- 
curring in tuberculosis may often suggest malaria, but are 
usually readily distinguishable. In the experience of the 
writer, influenza is the malady which gives rise to those forms 
of intermittent fever which most closely simulate malarial 
paroxysms. Of the four cases of which we shall speak this 
evening, two are examples of influenza simulating malaria; 
two are instances of grave malarial fever with a remarkable 
paucity of parasites in the peripheral circulation. 
Case I.-Influenza-Tertian Paroxysms Simulating Malaria. The 
first chart, which has already been published in my " Lectures on 
the Malarial Fevers," * is that of a woman, E. D., aged 29, who 
was a patient on Ward " G " of the Johns Hopkins Hospital. The 
chart, as you will see, shows a febrile paroxysm beginning be- 
tween 2 and 4 p. m., on the 28th of January and lasting 12 hours. 
[102] 
* Thayer, W. S.: Lectures on the Malarial Fevers, New York, 
D. Appleton & Co., 1897. 
(2) [1021 
Chart I.-Influenza. 
(3) [103| 
[103] 
Chart II.- Influenza. 
Chart III.-Malarial Feve ^Istivo-Autumnal Tertian. 
Chart IV.-Malaria.--|stivo-Autumnal Tertian. [102] 
] This was succeeded on the 30th by a similar paroxysm beginning 
about two hours later and lasting about the same length of time. 
The patient came from a malarious district and we naturally sus- 
pected a tertian infection. On the first of February, however, 
there was no rise of temperature and on the 2d and 3rd, sharp 
elevations occurred, one between 12 and 2 in the morning and the 
other between 8 and 10 on the following morning. These latter 
paroxysms, of course, would be sufficient, on examination of the 
chart alone, to render the diagnosis of malaria improbable. 
Now, this patient complained of coryza and cough with a green- 
ish purulent expectoration, and showed the signs of a general 
bronchitis. Examination of the blood revealed no malarial or- 
ganisms, and a leucocytosis of 17,000. Influenza bacilli were cul- 
tivated from the sputa and the patient recovered without relapse, 
and without the administration of quinine. 
Case II.-Influenza-Remittent and Intermittent Fever Simulat- 
ing Malaria. The second chart is that of a patient whom I saw in 
February, 1907, with Dr. Friedenwald. As you will see, there is a 
period of four days of irregular fever, followed by three quotidian 
paroxysms, each beginning between 8 and 10 in the morning and 
closely simulating paroxysms of a regularly intermittent malaria. 
One might well have fancied that the case represented one of in- 
fection with mutiple groups of parasites which, under rest in bed, 
had gradually given way until the effects of two strong groups be- 
came clearly evident. 
The patient, however, was a boy of about 17 who had been ill 
for about three or four days before the beginning of the chart, 
complaining of coryza and cough with purulent expectoration and 
the general symptoms of influenza which was prevalent at the 
time. From the onset, he had been treated with quinine, gr. iii. 
(0.2 gm.) every four hours. Well-marked chills continued for 
nearly a week after the onset of treatment. The blood showed no 
malarial parasites. 
I saw the patient first on the 14th of February, at which time he 
showed a general bronchitis. Quinine was omitted and aspirin, gr. 
v. (0.325 gm.) every four hours ordered. Cultures from the sputa 
showed B. influenzce. 
The point of special interest in this case would appear to be the 
sharpness of the paroxysms which were associated with definite 
| chills, and the regularity of their onset in the morning hours, as is 
common in malaria. 
Case III.-Intermittent Fever of the Type of Aestival Tertian. 
No Parasites Demonstrable in the Peripheral Circulation. Imme- 
diate Disappearance of Fever under Quinine. The third chart that 
I would show you presents a rather different appearance. As you 
[104] 
6 will see, there is continued fever on the 19th and 20th of October, 
the temperature reaching a sub-normal point on the 21st. This is 
followed by sharp paroxysms on the 22d, 24th, and 26th, the 
paroxysms beginning in the early morning hours and lasting 
nearly 24 hours. The chart is typical of aestivo-autumnal tertian 
fever. 
The patient was a medical student of 28. He had been in a 
malarious district and, two days before admission, had begun to 
complain of general malaise and on the day preceding admission, 
of fever. On the day of admission, the 19th of October, he had 
taken three doses of quinine, how much is not known. On en- 
trance, the temperature was 102.4° F. at 5 P. M., the pulse 80, 
respiration 24. There was nothing striking on physical examina- 
tion of the patient beyond a palpable spleen which extended 3 cm. 
below the costal margin. The examination of the blood was nega- 
tive; no parasites and no pigment were seen and the leucocytes 
were 6400 per cmm. 
Oct. 20. The temperature remained elevated. In the afternoon, 
there was a chill and the temperature rose to 105.8° F.; leucocytes, 
4640. 
Oct. 21. The temperature fell gradually to 98° F. at noon. 
Oct. 22. There was a sharp rise in temperature with a chill at 
about 6 p. m., the temperature reaching 106.7° F. This was fol- 
lowed by a rapid fall, and, on Oct. 23, the temperature was normal. 
On Oct. 24, the temperature rose slightly in the early morning 
hours, a sharp paroxysm beginning at 8, with a chill at noon, 
during which the temperature rose to 105° F. During all these 
days, the blood was carefully and repeatedly examined in both 
fresh and stained specimens. Neither parasites nor pigment was 
to be found and the leucocytes diminished to between 3,000 and 
4000 per cmm. 
At 8 p. m., on the 24th, quinine sulphate gr. x (0.65 gm.) every 
four hours was ordered. 
On the 25th, the temperature was normal. 
Early in the morning of the 26th, there was a slight paroxysm, 
much less intense than the preceding but lasting a full 24 hours. 
After this, the temperature remained permanently normal. 
Quinine was continued for a long period of time and there was no 
relapse. Repeated examinations of blood showed no parasites 
whatever and no pigment. 
Now, the history of this case, the time of the year at which it 
occurred, the character of the febrile curve, the palpable spleen, 
toe leucopenia and the apparently specific action of quinine, leave 
no serious doubt in one's mind that this was a case of malaria, 
probably aestivo-autumnal. 
This is the first case in the history of the hospital in which we 
L104] 
7 LI 041 
have been obliged to resort to the therapeutic test for the proof 
of the existence of a malarial infection. 
Splenic puncture would probably have assisted us materially in 
the diagnosis. This was not performed because of the danger, 
minimal though it be. I have, myself, aspirated many spleens with- 
out the slightest trouble, and, in any case of emergency, I should 
have no hesitation in so doing again. Some years ago, however, 
I witnessed a fatal result of splenic puncture. The patient was a 
foreigner, unable to understand English. He failed to comprehend 
the procedure and jumped on the introduction of the hypodermic 
needle. This resulted in a small tear of the splenic capsule with 
fatal haemorrhage into the peritoneal cavity. Although I feel con- 
vinced that with proper precaution, the danger is almost nil-and 
this has been the experience among more careful Italian observers, 
one of whom Prof. Bastianelli, is with us this evening, yet I can- 
not feel that splenic puncture is justified excepting in cases of 
real necessity. 
It is interesting that Ruge * makes the surprising statement that 
" the mortality from splenic puncture, which has been observed up 
to the present time, amounts to 1% per cent." 
It is highly probable that the early administration of quinine 
was in this case responsible firstly, for the development of the 
regular paroxysms; secondly, for the disappearance of parasites in 
the peripheral circulation. 
Case IV.-Grave ^stivo-Autumnal Tertian Fever. Remarkable 
Paucity of Parasites in the Peripheral Circulation. Convulsions 
and Death Following the Subcutaneous Injection of Quinine.-In 
addition to these three cases, I would speak of another patient 
whose history is remarkable from various standpoints. The 
chart, as you will see, shows that which on first appearance appears 
to be a wholly irregular remittent fever. There are, however, cer- 
tain very sharp remissions while many of the smaller oscillations 
are dependent upon the administration of baths. A careful study 
of the chart shows that every other day (on the 14th, 16th, 18th 
and 20th of October) there was a sharp rise of temperature some- 
where between 6 and 10 a. m. This is followed by a remission 
during the afternoon and night and a second rise on the follow- 
ing day with a fall occurring in the afternoon or evening. In 
other words, the chart suggests the pseudo-crisis and subsequent 
elevation first described in sestivo-autumnal tertian fever by 
th" Italian observers. Such a chart might well suggest an aestivo- 
autumnal tertian. 
This patient was a sailor on a bay boat, a Spaniard, aged 29, 
* Einfiihrung in das Studium der Malariakrankheiten, 2 aufl. 8°, 
Jena, 1906, Fischer, 221. 
8 who was said to have had malaria 13 years before. One week be- 
fore entry, he began to complain of abdominal pain and diarrhoea. 
Four days before entry, there was headache, anorexia and nausea. 
On Oct. 12, 1909, he was admitted at about 2 p. m. with a tem- 
perature of 105.8° F.; pulse, 104; respiration, 24. His appearance 
was typhoidal; the spleen was large, soft and palpable; there were 
several suggestive rose spots. The blood showed no parasites. 
The count was: 
[104] 
R. B. C 5,280,000 
W. B. C 5,600 
Haemoglobin 90% 
The coagulation time was three minutes, thirty seconds. 
Urine: Normal color; sp. gr., 1.015, slight trace of albumen. 
In other respects, not remarkable. 
On Oct. 13, 1909, I saw the patient on a morning visit. The 
temperature had fallen from nearly 106° to 99.4° F. He had a 
characteristically typhoidal appearance. The temperature was re- 
garded as suggestive of malaria, but fresh and stained specimens 
of blood were negative. The Widal test was negative; the Diazo 
reaction was positive. 
The chart illustrates the course of events. Daily blood examina- 
tions revealed no parasites. There was a leucopenia of 3,800 to 
5,200. Five days later, a slight jaundiced tint was noted. The 
blood pressure, which at the outset ranged from 97-114, was on 
the 19th, 84 mm. Hg. 
I next saw the patient on Oct. 20, 1909, just a week after my 
first visit. At that time, the temperature was about 105° F. There 
was a great change in the general picture. The facies was very 
dull and typhoidal. There was a very distinct anaemia and a slight 
greenish-yellow jaundice. The respirations were from 28 to 30. 
The liver was readily palpable. The appearance was wholly char- 
acteristic of malaria. A fresh specimen of blood was taken im- 
mediately and a considerable number of aestivo-autumnal para- 
sites were found. These were for the most part bodies containing 
a few fine pigment granules, often arranged as a central mass, 
sometimes in a block (pre-segmenting bodies). The patient was 
obviously an ill man. It was suggested that he be given vigorous 
treatment, i. e., quinine bi-muriate gr. xv (1 gm.) in 10 cc. normal 
salt solution intravenously, to be repeated, if necessary, in four 
hours, and afterwards, quinine sulphate gr. v (0.325 gm.) every 
four hours by mouth. 
The solution was not made by the apothecary until several 
hours after the visit and then, by a misunderstanding, of double 
strength, so that at 12 o'clock on the 20th, the patient was 
given quinine bi-muriate gr. xv (1 gm.) in 5 cc. of normal salt 
solution. Immediately after its introduction, there was a momen- 
tary convulsion accompanied by a slight twitching of the eyelids 
[105] 
9 [105] 
and lower lip, followed at once by general spasmodic contractions 
of the trunk and extremities. The eyes were rolled up and the 
head was somewhat retracted and turned to the right. Recovery 
was almost instantaneous and the patient soon seemed better than 
he was before. Thereafter, he was given quinine sulphate gr. x 
(0.6 gm.) by the mouth, every four hours. 
Oct. 21. At 1 a. m. the patient was given a second intravenous 
injection of quinine bi-muriate gr. xv (1 gm.) without unpleasant 
results. In the morning, the temperature had fallen to 100° F., 
the pulse was from 90 to 100, and the patient seemed better. At 
4 p. m., however, the temperature was rising again and a third 
intravenous injection of quinine bi-muriate gr. xv (1. gm.) was 
administered. Immediately upon its introduction the patient be- 
gan to show convulsive twitching of the eyelids and lips; this was 
followed by a general convulsion. There was marked cyonosis: 
the pulse oisappeared; the patient failed to respond to stimulants 
or artificial respiration. 
Re-examination of the stained specimen of blood made on the 
19th, showed, after long search, two characteristic aestivo-autumnal 
rings, which had been overlooked on a previous examination. 
The necropsy made by Dr. Thomas twenty-eight hours after 
death, showed a severe but not intense malarial infection. The 
brain showed nothing remarkable-little pigment in the ves- 
sels. The spleen was large and soft, and microscopically showed 
much pigment-for the most part in leucocytes. Smears showed 
numerous segmenting parasites. The liver weighed 2700 grammes 
and was of a slate color; the cut surface was opaque. There was 
marked parenchymatous degeneration and the capillaries con- 
tained much pigment. The bone marrow showed numerous para- 
sites in smears. 
Both kidneys showed marked cystic degeneration,-the right 
measuring 16 x 10 x 7 cm. The entire surface was studded with 
cysts, the diameter of which ranged from a millimetre or less to 
2%cm. The contents varied in color-clear-brownish-opales- 
cent, and in some instances apparently contained changed blood. 
The pelves were greatly dilated. On section, the tissue which re- 
mained showed few changes in gross, but microscopically, there 
was a definite increase in fibrous tissue and some congestion of the 
vasa recta; in the portion of the kidney showing cystic change, 
there was considerable cloudy swelling with marked increase in 
fibrous tissue. The cysts were lined with cuboidal epithelium. 
This case is exceedingly interesting as an example of grave in- 
fection with few parasites in the peripheral circulation through- 
out a week of study and observation. 
The occasional absence of parasites in the peripheral circula- 
tion, especially in grave cerebral cases, has been emphasized by 
10 many observers, notably by Bastianelli. I have never seen, 
however, a case of such severity with so long an absence of 
parasites.* 
The correct diagnosis was suggested here by the character of 
the fever, the general appearance of the patient and the leuco- 
penia, and, even in the absence of parasites, I should have 
ordered quinine when I saw him on the 20th. 
The most interesting point in connection with the case is the 
question as to the cause of death. From the result of the 
necropsy and from my observation of the patient, I should feel 
sure that it was not due directly to his malarial infection; on 
the other hand, I should feel reasonably sure from the history 
of the case that it was directly due to the intravenous injection 
of the quinine. 
The literature upon quinine poisoning is very large and there 
are many instances of apparent death from large doses. The 
amount administered to this patient was, however, by no means 
remarkable, although considerably larger than that which is 
customary in this hospital. Several points are, however, 
worthy of note. 
The first of these is the concentration of the dose. The 
speaker has always been in the habit of giving quinine in- 
travenously according to the method of Bacelli in a solution 
consisting of 
[105] 
gm. 
Quin, dihychlor 1. 
Aquae 10. 
Sod. chloridi 0.065 
one-half of this being given in one median basilic vein and one- 
half in the other. In this instance, a dose of double the concen- 
tration was given at once. The patient had received 6 grammes 
of quinine in 24 hours, 7 in 28 hours, 3 grammes having been 
administered intravenously. The direct sequence of the symp- 
toms in connection with the first and third injections of quinine 
was such as to leave little doubt as to the relation of the dose to 
the manifestations. While the dose was certainly strikingly 
* Although I did not examine these daily specimens, seeing the 
patient but twice, yet I am sure of the care with which the case 
was followed by a most capable ward physician. 
11 [105] 
concentrated, yet one must probably assume also that the indi- 
vidual was hyper-susceptible to the drug. 
The specimen of quinine was from the same sample which 
had been used in other cases, and, so far as could be made out, 
showed no impurity. 
A point of interest in connection with the case which may 
have an important bearing upon the fatal outcome, is the fact 
that the patient had cystic disease of his kidneys. Prof. Abel 
was much impressed by this fact, feeling that it suggested 
strongly that an unusual retention of the drug might have con- 
tributed toward rendering the patient more susceptible to the 
last dose. It must be said that the excretory powers of the kid- 
neys seemed to be good and that anatomically there was still 
considerable cortical substance. However this may be, the 
observation seems to be worth recording. I have for years been 
in the habit of advising the intravenous injection of quinine in 
urgent cases. Such an experience as this would certainly sug- 
gest caution in administering a solution of a concentration 
greater than 10 per cent. More than this, it points, it seems to 
me, to the advisability of conservatism in the administration of 
quinine intravenously in other than urgent cases of pernicious 
malaria. 
In conclusion, let me emphasize one point, an old lesson, 
after all, which these two latter cases illustrate, i. e., that while 
careful and repeated examinations of blood in a vast majority 
of cases answer the question as to the presence or absence of 
malarial infection, really grave malaria may exist for consider- 
able periods of time without demonstrable parasites or pigment 
in the peripheral circulation. In case of doubt, do not delay too 
long before applying the therapeutic test. 
12 ON DISSEMINATED CASEATING TUBERCULOSIS 
OF THE LIVER. 
By William Sydney Thayer, M. D., 
Associate Physician, The Johns Hopkins Hospital, Baltimore. [From The Johns Hopkins Hospital Bulletin, Vol. XXII, No. 242, 
May, 1911.] 
ON DISSEMINATED CASEATING TUBERCULOSIS 
OF THE LIVER. 
By William Sydney Thayer, M. D., 
Associate Physician, The Johns Hopkins Hospital, Baltimore. 
Focal tuberculosis of the liver is a condition rarely giving 
rise to recognizable clinical phenomena. Those instances 
which are detected during life are, for the ipost part, large, 
solitary, conglomerate tubercles or tubercular abscesses. Dis- 
seminated caseating tuberculosis, while not uncommon, espe- 
cially in children with intestinal and mesenteric lesions, is 
not often recognized intra vitam. 
Rolleston1 says: " There are very seldom any definite 
symptoms pointing to the liver." 
Brown2 says: " Complications of the liver have more path- 
ological than clinical importance." 
Hale-White3 describes the condition purely from an ana- 
tomical standpoint and says: " This form of tubercular dis- 
ease does not give rise to any clinical symptoms, as there is no 
damage to a sufficient number of ducts to cause jaundice." 
Ebstein4 says: "But also in these very rare cases (large 
conglomerate tubercles), tuberculosis of the liver has a purely 
anatomical interest." 
The recent observation by the writer of an instance of tuber- 
culosis of the liver where, during life, the hepatic changes 
stood in the foreground of the clinical picture would seem to 
justify a brief note. 
[146] 
1 Diseases of the Liver, etc., Phila., N. Y., London, 8°, 1905, 342. 
2 Osler's Modern Medicine, Vol. Ill, p. 320. 
3 Allbutt's and Rolleston's .System of Medicine, Vol. IV, Pt. I, 
p. 199. 
4 Ebstein-Schwalbe, Handbuch der praktischen Medizin, 2 Aufl., 
Stuttg., 1905, Bd. II, ^34. 
(1) fl 46] 
M. B. (Med. No. 22216), a colored woman of 49, was admitted 
to the hospital on February 11, 1908, complaining of pain in the 
right lumbar region and in the back. Her family history was un- 
important, excepting that her husband had died of tuberculosis 
26 years ago. She had had measles in childhood; had been 
married 28 years: had had two children, one of whom died 
of tuberculosis. In July, 1902, a hystero-myomectomy was per- 
formed for sub-mucous myoma of the uterus, tubo-ovarian abscess 
and follicular salpingitis. 
About five years ago, she had begun to suffer from rather ill- 
described pain in the left side which had continued. She had 
had a slight cough with occasional blood-streaked expectoration 
and increasing dyspnoea on exertion; night sweats for two years, 
constipation. About two months ago, there was slight jaundice 
of the conjunctive, lasting about a week. 
On physical examination the thorax was clear, except for a few 
scattered sibilant rales. The abdomen was full and on deep 
bimanual palpation there was an indefinite sense of fluctuation 
in the right flank, although the percussion note was tympanitic, 
even in the flanks. The border of the liver was not palpable. 
Blood count: 
R. B. C 4,136,000 
W. B. C 6,120 
Hb 49% 
Differential count: 
Small mononuclears 7% 
Large mononuclears 3 
Transitionals 0.5 
Polymorphonuclear neutrophiles 87 
Polymorphonuclear eosinophiles 0.5 
Unclassified 1 
• Stool: semi-fluid, light yellowish-brown. On standing, the 
upper third was fluid, the lower two-thirds, a brown and granular 
material. No parasites or eggs in the sediment; few cholesterin 
crystals. 
The urine was increased in quantity and contained a trace of 
albumin and a good deal of pus and, considering the resistance 
in the right flank, it was thought well to catheterize the ureters. 
The patient, however, refused. An X-ray plate of the right side 
was taken which was broken in developing. By this time, the 
suspicion that the resistance in the right side might depend upon 
a renal mass having passed away, no further X-ray examination 
was made. 
The temperature during the patient's stay in the hospital was 
irregular, ranging from normal or a point slightly sub-normal, 
(2) often to 103° F., sometimes to a point above this. It was gen- 
erally of an hectic character. 
The urine continued increased in quantity, the specific gravity 
ranging from 1.002 to 1.010. Albumin was sometimes absent 
but often present in a slight trace, and occasional hyaline and 
granular casts were found in the sediment. 
The blood pressure ranged from 120 to 158 mm. Hg. while the 
patient was in bed and resting. 
[146] 
March 22. Blood count: 
R. B. C 3,636,000 
W. B. C 6,420 
Hb 70% 
March 29. Blood count: 
R. B. C 3,776,000 
W. B. C 6,840 
Hb 63% 
On April 1, the author noted that the abdomen was held so 
rigidly that palpation was difficult. There was, however, a dis- 
tinct resistance at the right costal margin and the sense of an 
indefinite mass. 
The patient was discharged at her own request, on April 4, 
1908, with a diagnosis of chronic nephritis and possibly tuber- 
culous peritonitis. The fever still continued. 
She returned to the hospital on August 10, 1908 (Med. No. 
22989). On this occasion, she had complained for about a month 
of swelling of the legs, feet, and abdomen, of tenderness in the 
right upper abdominal quadrant, and of fever and night sweats. 
There had been a slight cough, but little expectoration; there 
was constipation. There was slight puffiness of the eyelids, 
and moderate oedema of the ankles and legs. Slight enlarge- 
ment of posterior cervical, axillary, epitrochlear and inguinal 
glands. The lungs showed a few crackling rales at both bases. 
The abdomen was full, measuring 88 cm. in the umbilical line. 
It was tender on palpation and had rather a doughy feel; evident 
movable dulness. 
On August 29, Dr. Futcher observed that the liver was distinctly 
felt 10 cm. below the costal margin in the mamillary line and 8.5 
cm. below the xyphoid; 3 cm. above the umbilicus in the median 
line. There was no special abdominal tenderness and no masses 
were to be felt. There appeared to be slight impairment on per- 
cussion at the right apex with harsh breath sounds and a few 
medium moist rhles at the end of inspiration. The temperature 
was irregularly continuous and remittent. 
The urine was of rather low specific gravity and showed a 
trace of albumen and hyaline and granular casts. The diagnosis 
[147] 
(3) [147] 
on this occasion was again "Chronic nephritis; tuberculous peri- 
tonitis (?); enteroptosis." 
The patient returned again on March 12, 1909 (Med. No. 
23828). According to her statement, she had remained in fairly 
good conditidn until about four or five weeks before admission 
when she began to complain of diarrhoea, weakness and loss of 
appetite. There had been a little blood and mucus in the stools 
and later, some loss of control over the sphincter. There had 
been no abdominal pain; no cough; no shortness of breath. Two 
months before she had been troubled for a time by sweating at 
night. On entrance the temperature was normal but soon rose, 
remaining irregular and remittent while she was in the hospital, 
ranging from 99° to 102° F. On physical examination, she was 
moderately well nourished, but had obviously lost considerable 
weight. There was slight dulness at both bases with numerous 
moist crackling rales. The heart was in no way remarkable. 
The abdomen dome shaped, much distended. The edge of the 
liver was seen to descend with inspiration, and the edge firm and 
irregular, was easily felt to the right of the median line. The 
surface of the liver felt rough though no large masses were to be 
felt. The flatness extended from the 5th rib to a point 11 cm. 
below the costal margin in the right mammillary line and 12 cm. 
below the tip of the xyphoid process. Dulness on the left side 
shifted with position. 
Blood count: 
R. B. C 3,444,000 
W. B. C 4,600 
Hb ' 63% 
The stools, repeatedly examined, were semi-solid and fluid, 
showing a certain amount of mucus, evidences of occult blood 
and occasionally a few red corpuscles. Microscopically, there was 
no excessive amount of fat; no amoebae were found on careful 
examination. 
The blood pressure was rather low-95 to 120 mm. Hg. 
The leucocytes were normal in number, even sub-normal, 4500, 
on the day before death. 
An Ewald test meal showed 100 cc. of thin watery fluid which 
separated into two layers, the upper consisting of a turbid, dirty 
yellow liquid and the lower of finely-divided food elements. It 
was acid; total acidity, 18; free hydrochloric acid, absent; lactic 
acid, absent; test for occult blood, negative. Microscopically, fat 
droplets were present in considerable numbers; starch granules, 
epithelial cells and vegetable fibres. 
The Wassermann reaction was negative. 
The urine apparently rather reduced in quantity, showed a 
(4) specific gravity of 1.011, a heavy ring of albumen, and numerous [ 
hyaline, finely and coarsely granular casts. 
On the 18th of March, the writer noted that both apices showed 
a slight tubular modification of the respiratory murmur, and fine 
crackling rales were detected, especially above the left clavicle, 
as well as a peculiar superficial crackle, which sounded almost I 
pleural in character over the whole left chest. There was little 
modification on percussion of the bases behind. Numerous fine 
rales were to be heard at the apices and occasional crackles 
throughout both backs. Abdomen, large and full. Flanks bulged. 
The umbilicus protruded. Diastasis of recti. Respiratory move- 
ments free. Edge of liver sharp, firm and smooth, but not quite so 
sharp in the right flank as elsewhere. Upper limit of liver flatness, 
6th space in mammillary line. Lower border, 10 cm. below the 
costal margin in the mammillary line, 9 cm. below xyphoid; 
notch, well felt. No fluctuation detected. 
March 21. The patient had been growing progressively weaker 
and for three days, the posterior parts of both lungs had been 
filled with fine, moist rales although there had been no dulness. 
The heart has been markedly irregular at times. There appeared 
to be no fluid in the abdominal cavity. 
The patient became gradually weaker, the amemia, more 
marked. 
Blood count: 
R. B. C 3,000,000 
Hb 50% 
Numerous fine rales appeared throughout the chest. At 8.30 
p. m., she died. 
In summary, then, the history is that of a colored woman 
of 49, who, a little over a year before her death, came to the 
hospital suffering from remittent and intermittent fever and 
vague abdominal manifestations-tenderness, resistance. Six' 
months later, she returned with a history of diarrhoea of four 
or five weeks' duration; weakness and general debility. There 
was irregular fever with morning remissions or intermissions. 
The liver, which was somewhat prolapsed, was much enlarged 
and firm and there was a well-marked anaemia of a secondary 
type. There was, at times, occult blood in the stools which 
showed considerable mucus. No excess of fat or fatty acids. 
The diagnosis of tuberculous peritonitis, made on her pre- 
vious entry, seemed reasonable when one considered the race 
of the patient, the fever, and the general abdominal symptoms, 
the diarrhoea suggesting a tuberculous enteritis, but the 
.147] 
148] 
(5) (148) 
hepatic enlargement seemed difficult to account for on the 
basis of tuberculosis, although the possibility of a fatty cir- 
rhotic liver was considered. 
Considering the age of the patient, the degree of anaemia, 
the progressive enlargement of the liver, its firmness and 
slight irregularity, one could not but think of the possibility 
of a neoplasm of uncertain origin. The well known occur- 
rence of fever in association with hepatic neoplasms would not 
have been against this diagnosis, although no suggestion as to 
the primary seat of such a growth could be found beyond 
the possible significance of blood and mucus in the stools. 
Another possibility which suggested itself was that the case 
might be one of amoebic abscess of the liver. The slight fever, 
the diarrhoea, the jaundice present at one time, although 
amoebae had not been found in the stools, and the progressive 
hepatic enlargement formed a clinical picture not unlike that 
which is occasionally seen in such cases. 
The necropsy was performed on March 22 by Dr. Winternitz 
(No. 3188). 
(Abstract.) Anatomical diagnosis: Tuberculosis of the mesen- 
teric and retroperitoneal lymph glands with involvement of the 
receptaculum chyli; chronic adhesive peritonitis; chyliform as- 
cites; tuberculosis of the spine with abscess formation; general- 
ized tuberculosis; extensive tuberculosis of the liver with cavity 
formation; tuberculosis of the spleen and liver; tuberculous 
broncho-pneumonia, caseous and gelatinous; fatty degeneration 
of the liver; chronic fibrous pleurisy; chronic diffuse nephritis; 
arteriosclerosis; chronic fibrous myocarditis; thrombosis of 
ovarian vein. 
The peritoneal cavity contained a considerable amount of chyli- 
form fluid which was extremely milky in appearance. The omen- 
tum was definitely plastered to the parietal peritoneum but was 
not evenly adherent, so that encapsulated areas appeared in which 
the above-described fluid was found. The intestinal peritoneum 
was not adherent either to the omentum or to the parietal 
peritoneum of the anterior surface, so that when the omentum 
was severed from its attachment, the abdominal contents were 
easily exposed and the intestines were found to lie almost entirely 
in the lower half of the abdominal cavity. A large mass was found 
in the upper portion of the abdominal cavity filling the entire epi- 
gastrium and the upper half of the umbilical region as well as 
the hypogastric region on the right side. This mass which 
proved to be the liver, was covered over its entire surface by 
(6) Disseminated Caseating Tuberculosis oe the Liver, with Cavity Formation, in an Adult. adhesions which were formed by fibrous cedematous union be- 
tween the peritoneal surface of the organ and the parietal peri- 
toneum. The liver was closely bound to the diaphragm above on 
both right and left sides. The stomach was bound down by dense 
adhesions. The mesenteric lymph glands were extremely large 
and yellowish-grey. On section, they were rather firm and 
mottled, the greater part of their structure being composed of a 
rather friable yellowish substance which had a faint green tinge, 
while throughout one could see other areas which were slightly 
more translucent and depressed. 
There was nothing remarkable in the heart. 
The lungs showed a disseminated tuberculosis with larger areas 
of broncho-pneumonia here and there. 
The spleen measured 10 x 6% x 4% cm. The capsule was 
everywhere adherent to the diaphragm and surrounding viscera. 
On section, the Malpighian corpuscles were indistinct, and 
smaller opaque yellow tubercles were to be made out. 
The stomach, duodenum and pancreas showed nothing of im- 
portance. 
The liver was considerably enlarged, measuring 30 x 28 x 10 cm. 
It was flabby, and the surface was covered with nodules varying 
from 0.5 to 1 cm. in diameter, which were yellowish-grey. On 
section, the liver was everywhere studded with these nodules, 
some of which were firm and yellow and caseous; many were, 
however, cavities showing greenish bile deposits in their centres. 
Many of these caseous masses were surrounded by thin, trans- 
lucent, reddish-gray capsules. The remainder of the liver was 
pale. Lobulation was indistinct. The tissue about the hepatic 
vein was reddened and the peri-portal veins were everywhere 
very visible. Small tubercles were also scattered throughout the 
liver tissue, many surrounded by transparent gelatinous zones. 
Kidneys: The right measured 11 x 6% x 3% cm. The capsule 
stripped off with slight difficulty, leaving a rather smooth, pale 
surface. On section, the kidney was everywhere studded with 
yellow nodules which, in some spots, were as large as 1 cm. in 
diameter. Most of these were small, measuring 2 mm. The 
cortex of the kidney was swollen, averaging 7 mm. The striations 
for the most part were regular and the parenchyma was ex- 
tremely pale, showing here and there yellow irregular areas more 
opaque than the surrounding. The glomeruli were prominent 
and transparent, pale pink in appearance. The left kidney re- 
sembled the right in every respect. 
The thoracic duct, which was dissected out carefully, was found 
to be in communication with a mass of glands which lay in the 
region of the receptaculum chyli. 
Nothing remarkable in the bladder. 
The glands lying over the spine on the right side from the 
[1481 
[1491 
7 [149] 
eighth dorsal to the first and second lumbar, were soft and a puri- 
form fluid escaped from them. There was tuberculous caries of 
all the vertebrae from the sixth thoracic to the first lumbar. 
There was no essential curvature of the spine. 
Examination of the ascitic fluid showed that, after standing for 
several hours, it had become more milky in appearance. Specific 
gravity 1.018. Microscopically, there were large numbers of de- 
generated peritoneal epithelial cells. In addition, a few small 
round cells and some fat globules were seen. No tubercle bacilli 
were found. 
The liver, microscopically, showed many large areas of case- 
ation, some involving bile ducts the remains of which could be 
seen in the necrotic ulcerated centre. The remaining liver tissue 
showed an extensive fatty degeneration. Around some of the 
larger tubercles, there was a zone of tuberculous granulation 
tissue which was rather fibrous showing here and there well- 
formed tubercles. This doubtless represented the translucent 
grayish zone which was observed about the large tubercles in 
gross. There was no definite cirrhosis throughout the remaining 
portion of the liver, but one found here and there small patches 
of cellular tissue which were possibly healing tubercles. In these 
one found no areas of degeneration but a mass of rather well- 
preserved spindle cells and round cells. Among these numerous 
blood vessels might be seen. Some of these were evidently the 
tips of well-formed tubercles. Others of the larger tubercles 
showed a dense mass of fibrous tissue surrounding a caseous 
centre. The fibrous tissue, however, was not well preserved and 
had apparently undergone hyaline degeneration. Tubercles, how- 
ever, in these areas, were definitely circumscribed and were 
apparently old processes that are walled off. In other areas, 
masses of miliary and conglomerate tubercles were to be seen 
which seemed to proliferate irrespectively of any general position. 
These did not involve the bile ducts and were not in close rela- 
tion to any particular portion of the vascular system. 
The kidneys showed here and there dense bands of fibrous tissue 
extending in from the capsule. Here the renal tissue had under- 
gone definite atrophy, the tubules being very much smaller than 
in the surrounding tissue. Glomeruli might be found in this mass 
as dense hyaline staining masses. In fact, the glomeruli seemed 
to show most marked changes. One found in many places, where 
the uriniferous tubules were apparently not markedly degen- 
erated, that the glomeruli were large, filling up, as a rule, the 
entire capsule. In some places, there was a slight exudate 
between the glomerular capsule and the tuft, but this was not 
often found. There were not very many intermediate stages be- 
tween glomeruli which appeared normal and those in which there 
was a dense fibrosis. Where these were to be seen, the thickening 
8 seemed to start in the glomerular capsule which proliferated at I 
the expense of the glomerular tuft. The uriniferous tubules 
throughout stained diffusely red. Their lumina were dilated 
and contained serous-like material and many casts. Many of the 
epithelial cells of the tubules showed large vacuoles which filled 
the entire cells, and smaller vacuoles might be seen near the 
basement membrane, but not as large as those which have been 
described. In some places the entire tubules showed this 
vacuolar degeneration. 
To summarize then, we have before us the history of a 
colored woman, 49 years of age, with a record of rather in- 
definite abdominal pain of a year's duration and almost con- 
tinuous remittent or intermittent fever of a moderate degree, 
with sweating at night and progressive emaciation. Examina- 
tion of the thorax showed little beyond the appearance toward 
the end, of rather diffuse fine rales throughout the lungs. 
During the last eight months of the patient's life there was a 
steady enlargement of the liver which finally extended to a 
point 10 cm. below the costal margin in the right mammillary 
line. It was somewhat tender and very firm, and, on one 
occasion, slight irregularities of surface were noted. The 
border which was distinct, seemed a little blunter in the right 
mammillary line. There was considerable anaemia of a 
secondary type, but without leucocytosis, a persistent albumin- 
uria and cylindruria without polyuria but with a rather low 
specific gravity, and, in the end, diarrhoea with mucus and 
occult blood in the stools. 
The progressively enlarging liver, the age of the patient, 
the anaemia, the fever which after all, is common in hepatic 
neoplasms, all led us to lean toward this as a possible diag- 
nosis, despite the fact that beyond the diarrhoea with occult 
blood in the stools no suggestion as to the seat of a primary 
lesion was to be made out. 
The indefinite abdominal pain, tenderness and fever, to- 
gether with the diarrhoea occurring in a colored woman were 
strongly suggestive of peritoneal tuberculosis, despite the ab- 
sence of definite pulmonary signs, but the progressively and 
apparently great enlargement of the liver did not appear to 
us to depend upon tuberculosis alone. It was thought that a 
rolled-up omentum might be adherent to the liver, thus in- 
1149J 
9 [149] 
creasing its apparent size, but the sharp border of the liver was 
against this. 
A steadily enlarging liver, with persistent, slight fever, even 
in the absence of leucocytosis, is by no means unusual in 
amoebic abscess which occurred to us as a possibility. 
Syphilis was ruled out by the absence of a Wassermann re- 
action and by the fact that anti-luetic treatment had been 
without result. 
The case was, indeed, presented to the class with the main 
possibilities as to diagnosis set forth in the order named: 
hepatic neoplasm; amoebic abscess of the liver; peritoneal and 
intestinal tuberculosis with a rolled-up omentum adherent to 
the liver in such a manner as to exaggerate its apparent size. 
The anatomical appearances, well illustrated in the plate, 
are rather remarkable in their extent. A disseminated 
caseating tuberculosis of this degree in the liver of an adult is 
most unusual. But the feature of the case which is of special 
importance is that such disseminated caseous tuberculosis of 
the liver should have given rise to a tumor sufficient to con- 
stitute the central figure in the clinical picture. 
It is also important to note that for a week at least during 
the course of this case there was jaundice-a rare manifesta- 
tion in hepatic tuberculosis. 
In conclusion then, it may be emphasized that disseminated 
caseating tuberculosis of the liver in an adult may be asso- 
ciated clinically on the one hand with appreciable jaundice 
and on the other with hepatic enlargement sufficient to form 
the most striking feature of the clinical picture. 
10