REPORT

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LTRiCTOR OF Tin HOSFLITAL

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CORPORATION OF

THE ROCKEFELLER INSTITUTE FOR MEDICAL RtSkARCH

OCTOBER, 1917
REPORT OF THE WORK IN are
——_—_—_————e i

THE ROSPITAL

Rufus Cole

Changes in the Staff.

The entrance of our country into the war has led to the
departure of a mumber of the members of the Hospital Staff, to undertake
duties in comnection with the Army. Those who have been called directly
to this service are Doctors Chesney, Fits, Morton, Larson and Morison.

Dr. Chesney joined the Hospital Unit of Washington University and is now

with this unit in France. Previously he had accepted an appointment as
Assistant Professor of Medicine in this University, his service to begin

this autum, and he has therefore permanently severed his connection with
this Institute. Doctors Fitz ani Morton joined the Harvard Base Hospital
Unit No.5, and are aleonow in active service in France. Dr. Larson joined
the Medical Officer's Reserve Corre and was ordered to Fort Benjamin Harrison.
Dr. Morison also joined the Medical Officer's Reserve Corps and was de-
tailed by the Surgeon General to join the staff of the Hospital for Cardiac .
Diseases of the British Medical. Service in London,

_ In addition:to. these’ men, who have entered active military -
service, Dr. Palmer has left to: assist “Dr..Longcope in the teaching of: =.
medical students at the College of Physicians and Surgeons... Dr. Paimer -:--
has- received an appointment’ as Assistant Professor of Medicine at Cornell |
Medical School, but will not take up his work there until ‘after the clese ..
of the war.

Doring the past year, in addition to the regular staff, = -
four voluntary workers have been engaged. in the study of problems relating

to the diseases under investigation. These men are Dr. Ernest Stillman,
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Doctors Blake, Levine and Iundsgaard. Dr. Stillman has received an appoint-
ment on the regular staff of tha Hospital for next year. Dr. Blake has
been appointed Assistant Professor of Medicine at the University of Minn-
esota, and has already commenced his work there. Dr. Levine has entered
the Medical Officers' Reserve Corps and has been detailed to the Hospital
for Cardiac Diseases of ths British Me@ical Service in London. Dr. Lunds-
gaard will shortly return to Denmark to again take up his studies in the
University in Copenhagen.

It may be sean from the above that very serious inroads have
deen made into the working staff of this Hospital. ‘This, howavar, was to be
expected, and it is a source of satisfaction that the Hospital has been able
to furnish so many men ready for active service.

Moreover, during the year, and especially during the present
summer, a nomber of the man have been engaged in activities which ars not
directly related to the scientific investigations of the Hospital, bat which
are of aid to the Nation or to the Stata. Dr. Dochez was given leave of
absence during the months of January, February and March to accompany

Dr. Biggs to France to investigate the conditions in that country regarding

tuberculosis. ‘Dr. Chickering has spent several weeks at the Naval Hospital

OR Fa Dib as 1 Be

| at “Portemouth, Ya., assisting ‘ia the “investigation of ‘the outbreak of ‘epic.

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denice meningitis ocourring there, “Since the “Opening © of ‘the War Denonstra~ “3

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22 Son Lfemtens Da thie irom of oma. Serarowe Mare cone Dawes (ha Wa am

COE bos AR tee 7 Daca Sat ay BE BRK GS ace ATR EG WTR AA Le ates results.

tion Hospital, Dr. Cullen has been mgaged there on chemical work, ‘in con- |.

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nection with the Oarrel-Dakin method of treatment. Daring the sumer, s

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wets fk, OT aie poy.

‘Dr. “Avery, Dr. Doches ‘and’ Dr. St4liman have given mach time ‘to the instruc-

tion of ary ‘medical officers concerning pneumonia, ‘and in teaching them

the actual methods to be employed in diagnosis and treatment of this diseme,.
The Surgeon General has also requested Dr. Cohn to instruct a number of of-
ficers of the Medical Reserve Corps in the technique of examination of ‘the
cardio-vascular system. In compliance with this request, a mumber of of-
ficers detailed here for this purpose are now being given a course of in-
struction by Dr. Cohn, Dr. Van Slyke has spent the months of July and
August at the Laboratoty of the Hooper Foundation at San Francisco. He has
gone there at the invitation of the Director to demonstrate to the menbers
_ of the staff of that institution new chemical methods which have been devel-
oped in this hoepital under Dr. Van Slyke's direction, Through the kindness
of the State Board of Health, Dr. Stillman had the opportunity last winter
of investigating several small epidemics of pneumonia occurring throughout
the State. This study gave us much information concerning the mode of spreal
of thie disease.

Scientific Report.

Acate Lobar Pneumonia.

During the past winter, 133 cages of lobar pneumonia were
treated in this hospital, making a total of 529 cases that have been stud-
ied here. Of these, 438 have been shown to be due to Pneumococcus, and the
type of infecting organism has been determined. 1651 of these cases were due
to Pneumococcus Type I, 133 were due to Pnewumococcus Type II, 59 were due to
Pneumococcns Type III and 95 were due to Pneumococcus Type IV. 106 cases of |
Type I infection have been troated with serum, with 8 deaths, 34 cases were
treated during the past winter and only 2 died; and one of these fatal cases
proved to be complicated by-extensive and advanced tuberculosis. The results
of serum treatment’ in this’ type of case, therefore, have continued to be ex-
cellent. Similar results have been obtained olsenhers. Major Nichols has
lately reported the treatment: of 45 cases among the troops on the Texas =
border with only 5% mortality. . .

This work relating to pneumonia has been carried on in three

directions during the past year. First, attempts have been made to render
* | !

the general routine treatment of patients with Type I infection more prac-
tical and convenient. Second, further studies have been made concerning 7
the epidemiology of tha disease, in the hope of devising measures for lower-
ing its veryhigh incidence. Third, studies concerning the mode of action of
the etiologic agent have been contimued.

Tne need for determining the etiologic agent in every case of
pneumonia before serum treatment is undertaken prevents to some extent the
general exployment of this method. Where the laboratory arrangements for
making such determinations can be property organised, however, the difficul-
ties are really not great; the method is neither complex nor aifficult. It
“has been thought however, that an accurate standardization and description
of the method would aid in its general empleyment, and this has been made by
Dr. Blake. ("Methods for the Determination of Pneumococcus Types", Jour.
Exp. Med., 1917, xxvi, 67).

Dochez and Avery have demonstrated that changes frequently
occur in the blood and urine of patients with pneumonia, so that if samples
of these be mixed with specific immne serum precipitation occurs, This fact
may be made use of in the diagnosis of the type of infection. (Dochez and |

Avery; "The Elaboration of Specific Gotubie ‘Substances: by Pnewmoceccus orig
Growth™, Jour. xp. Med., Octoder, 1917, ) al ‘that 1s necessary is to mix -

small anounte of the rine and equal quantities of the various ‘Mmrane sera.
A reaction ‘occurring in one 2 of > these ‘mixtures indicates thet the infection

. is due ‘to. the sane ‘type of Paramoedocus as as ame exphoyed in producing a .
serum Lia which the ‘reaction occurs. In certain cases the ; Aagnosis of aa
type & may be made vy this method without « any trouble ont ‘almost at once, De

applicability of the method for + Alagnostic: porposes, however , “4s limited oy

the fact that the reaction occurs in only about one third of the cases, in

those more severely infected, and especially late in the disease. Notwith-_

standing this drawback, however, the mthod is of considerable practical

value.
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Efforts have also been made to determina more accurately the
best : method of administration of serum, the proper dosage and fraquency of
treatments. Studies on animals and observations made in patients during the
past winter have shown that, after infection has lasted for some time, sub-
stances are found in the patient's blood which neutralise the immnity prin-
ciples in the horse serm. (Cole, "The Neutralization of Antipneumococcus
Immune Bodies by Infected Exudates and Sera", Jour. Exp. Med., October,1917).
This fact strikingly emphasizes what has previously dean insisted upon;
namely, that the treatment should be comuenced early and large doses of
serum should be employed.

Simplification and improvement in the matter of production of
the serum and improvement of mthods of standardization have baen needed, and
these problems have been studied during the past winter. The old method of
immunising horses consisted in the weekly injection of cultures &f increasing
eisb, first of dead, then of living bacteria, To produce high grades of im-
munity, it has been thought necessary to use a large doses. Studies made
during the past year have shown that the immunization of horses can be much
more rapidly accomplished by making injections of small doses overy aay on
alternate weeks. “Tt has deen shown that large doses of culture, sach as me

‘those .fomerly axployed, may ‘tnbivit, rather ‘than ‘stimulate ‘the production

“ ” ita
of ‘immmane ‘substances ‘(Cole and Yoors, “Te Production of Ant ipnemococous

: “oder ts : cee ly ES TSS
Serun", Jour, Exp. Mea., October, 1917),

uo “RBetorts ‘have also ‘been. made to improve ‘the ‘methods of stand-
‘ardisation, : and owpectally to ‘tax a practical, ‘standard to Which ‘all sera used
for therapeutic ‘purposes should. conform, During the past winter the various
antipneumococcic sera producea by manufacturers in this country wore tested,

and most of them were found to have ‘ttle or no content in antibodies for
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Type I pmeumococci. We have therefora worked out a mthod of standardization
which we believe is as satisfactory as it can be made with our present know-
ledge, and we have recommended that the Hygienic Laboratory of the Public
Health Service requira that all antipneumococcus sara sold for therapeutic
purposes meet tha requirements that we have laid dowm, Major McCoy, Directo:
of this Laboratory, has vory willingly cSoperated with us in this matter, and
it ie believed that allthe serum employed by the Armay, at least, will be of
satisfactory potency. The production of serum of Type I in fairly large
amounts is now under way at the farm in Princeton, and the production of
this serum at the Institute has been discontimed,

The studies concerning the epidemiology of pnsumonia have ;
proved of great interest and have yielded results which, it is hoped, afford
a basis for instituting rational preventive measures. Up to the time these
studies were undertaken, it was believed that infection in pneumonia is av-
togenous; that is, persons having pneumonia are infected with the organi sme
they habitually carry in their mouths, the reason for such infection being a
lowered general or focal resistance on the part of the patient. The observa-
tions made hers have brought striking evidence against this assumption, at.
least as far as pneumonia due to Type I and Type II pneumococci is concerned.
They strongly suggest, that pneumonia, at east of these two types, does not.
differ in this, respect from other infectious diseases, and that infection in
thie disease also neually, occurs, from without,,,, The evidence in favor of this
point of, view, has, been derived, from a, study of the, types,of, pneumococol.,pres-
_ent,in the mouths of, normal. healthy Andividuals who -have not been, in contact
with cases of pneuminia, ahd those present in the mouths of persons living —
in close contact with such patients. The varieties of pneumocece!. found in”
the mouths of pneumonia patients during convalescence have also been studied,
and also the types of pneumococci found in the dust of rooms occupied by
pneumonia patients, as well as those in the duet of rooms not inhabited
by such persons.

Without going into the details of the study, it may be
stated that pneumococe! of Types I and IT are practically never found in
the mouths of healthy persons not in contact with pneumonia patients, al-
though these two types of organisms cause over 60% of the cases of pnev-
monia, On the other hand, a considerable percentage of persons living in
close contact with pneumonia patients, especially membsrs of the family or
friends who have cared for these patients, are found to carry organisms
of these types, the type of organism found in the carrier being always that
causing the disease of the patient. Neither the patients nor these healthy
carriers, however, carry pneumococe! of these types permanently. Usually
these types of pneumococci disappear in three to four weeks, and either no
pneumococci are then found, or if present, they are of thse type commonly
found in healthy mouths, Type IV. Finally, pneumococci of Types I and II
are not commonly found in dust, but they may be present in the dust of rooms
occupied by pneumonia patients, convalescents, or healthy carriers,

All this evidence strongly indicates that infection in pneu-~
monia is not aot ogencus, ‘bat that the organtsms are received by the patient

a abtror at
either directiy, by ‘contact ‘with “qnother : case or a ‘convalescent or a ‘nealthy

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‘carrier, or i inaifectiy ‘through: ‘the “dust ‘from the enviroment of such a

ees MORES OOS AT Bhat : 48 creer tae

carrier, It becomes “Seident, ‘then, that pasmmonia, 80 ‘fat as these two

int Taye Barty om Jvay side grog ia fom

‘types. are ‘concerned, does ‘not “aitter sudenatanty “in ‘dts ‘mode’ ‘of spread

thee dty a4 Hera ee 8 fan PEGE ot mew igs

. other’ infect fous ‘diseases, euch “as dipitherta or ‘meningitis. The avorage

susceptibility ‘to Cnsumonia m may ‘be less than ‘to ¢ these ‘other “dnfectious dis~-.

eases, and the ‘number of healthy carriers may therefore be greater, bat this

is not certain.
In any case, in order to reduce the very great prevalence -
of pnewmonia, measures similar to those employed to prevent the spread of |
other infectious diseases should be instituted. This will be especially
important in the case of troops,for pneumonia ordinarily occurs with great
inteneity among raw recruite, and it is to be feared that, unless preven-
tive measure can be instituted, the history of this disease in our om
National Army will be the same as that in other armies and in other wars.

Another possible method for preventing the occurrence of
pneumonia is by the employment of prophylactic vaccination. This does not
seen practical in civilian populations, but among troops, where the disease
is likely to be widespread, this method shonld be considered. Considarable
work has already been done in investigating whether or not this procedure
would be likely to be successful and if so, in devising the best methois for
carrying it out. A number of problems are still unsettled, but some of these
are under investigation by Dr. Chickering at the present time, and it is
planned to continue this investigation during the autumn,

Since it is very important that the present knowledge concern=
ing serum treatment and prevention of peumonia should be readily available,
this has been collected in a pamphlet Walch it is hoped wilh be ready for
distribution before, Anis meeting of the Board. aia thts pamphlet As five

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a dotatied and practioal description of, me thoas enployed, .

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. anong, the expertnentel ‘and theoretical studios comerning

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paenonta that have been carried on uring the ast year, aside fron those ‘
ade t e

already mentioned, have been those of Dr. Doches and Dr. avery concerning _
the nature of the precipitable substance arising during the growth of . a
pneumococci, both within and catside the: body. The possible role of this

substance in the intoxication of the dieease bas been investigated. Dr, -

Blake has also made further studies concerning so-called Wantidlastic®
so 0 es
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immronity, and Dr. Palmer has studied the question of the increased acidity
of the urine in pnsumnia. These studies are of much theoretical interest,
but ara not at present applicable to the practical problean relating to this
disease,

Heart Diseasa.

The work during the year has included a continuation of that
previously carried on, having in view the improvement of the methods of
treating heart disease, especially the methods of using digitalis.

In addition to tnois work, ths following specific problems
have been studied:

1. Esatimation of blood pressure in patients with fibrillat-
ing auricles. In such persons the pulses beats are not only vary irregular
in time, but are aleo of vary unequal force. In ordinary measurements of
blood pressure, the method employed consists in estimation of the force of
the pulse beats. Since in fibrillation no two of these beats may de equal,
it is evident that the ordinary methods are not applicable. To overcome this
difficulty, the attempt has deen made to estimate the pressure by determining
the number of beats at each of several levels of pressure, and obtaining an
average. This is very unsatisfactory and is believed to give an inaccurate
idea of the "effective" blood pressure, which ‘does not depend entirely upon’
the force of the beats. “It seane probable that the “effective® biced pres-

_ deen that a ecertad } tee we eS « te
sure can dest be determine tat the point of “outflow *Pfom the arterial Srenere Q

voir. system dn o the. soptiigzies, “a at “which “point “pressure: Variations gestae?
a miniarom. “pp. Cohn ana “Dr. ‘Dundagaard have investigated the variations in
pulee pressure “an the larger arteries. ‘and “in ‘the dorsalis. pedis arteries in
dogs, both when the heart is ‘peating ‘normally | and when the auricles are mde
to fibrillate: It was found ‘that ‘the pulse pressure, which is very. small in

the dorsalis pedis “artery; “not over 5 ma. of ‘mercury, is not. increased when
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the auricles are made to fibrillate. To estimate the blood pressure in
man at a corresponding level of the arterial tree, use has been made of
the Girtner tonometer, which was formerly used in estimating blood pres
sure, but which has bean given up for other methods which are more con-
venient. Studies on a large number of patients and norm) persons have
now been made in this hospital, and it has beendemonatrated that it is
possible to make accurate readings with this instrument, and that by this
method consistent and accurate determination of the "effective" blood
pressure can be made in patients with auricular fibrillation.

II. Dr. Levine hae carried on a series of experimental
studies to determine whether the occurrence of digitalis effects on the
heart is dependent upon a certain concentration of the drug in the blood
passing through the heart, or whether this occurrence depends upon the
actual amount of the drug which has been absorbed by the heart muscle,
even though the drug ia administered vary slowly. This point is of con-
siderable importance in connection with the problem of digitalis dosage. -.
In these studies cats have been used, and in the same cat the results fol-
lowing various methods of administration have been observed. It has not-.'

: been possible to obtain a: complete solution of the problem, but the stud-~
‘iLes indicate’ that both the total. amount: of. tha-drug aduiniatered and: itsal

* concentra tion are ‘of importance in determining the results obtaineds It

 

>} #eems:-thaty a certain.small total amount: is ‘necessary: to-produce: Sffedtey
4 dut. that: ‘thie: amount:'sannot’ be: taken up: until. the concentration (of fngttal
7 4n the blead ‘reaches: ar Optinnun ‘levalsnccrasd,: 2% La toa noon to any hone
Tha citet- ITT. + Dre Morieon ‘made ‘the very: interesting observation. ‘s
that electrocardiograms taken vdefore and after phlebotomy showed certain«
differences. It was thought that these differences might be dependent

upon blood volume, and he has made a series of experimental studies in
a io
animals and has made mmerous observations in patients to determine the oo

exact effacts, if any, which changes in blood volume cause in the electro-
cardiograph., It has actually basen found possitie to produce changes in the
electrocardiograms of animale, and also of pat ients, by producing changes
in blood wolume by the administration of very large amounts of water or by
sweating and freezing. Observations on the blood, made at the same time,
by Dr. Palmer, showed that actual changes in volume took place. These stud-
les are of value in explaining the form of the electro-cardiograph, con-
cerning which there are several theories,

IV. Early in the yar Dr, Lundegaard undertook certain stud-
ies having for their purpose the development of a method for determining the
rate of blood flow, or the minute volume of the heart output. Before coming
here, Dr. Lundsgaard had conducted important investigations on this problem
and had found that, while accurate results could be obtained by the method
devised by Krogh and Lindhard, this method was not suited to clinical in-
vestigation. It seemed possible that information could be obtained concern-
ing the rate of blood flow by comparing the difference between the oxygen
content of the arterial and the venous blood. If the metaboliam is constant,
the amount of oxygen removed from the blood is inversely proportional to
the rate of flow of the blood through the capillaries, Before any practical
use of this principle could ve made, however, it has been necessary to ob-
tain much new physiological data,. for the matter is much more complex than
the simple statement above might indicate. So far as this method of es-
timating rate of ‘blood flow is itself concerned, it is too soon te say how
great its clinical value may be. The studies on patients so far made ine
dicate that, as a means of estimating the changes in the rate of blood flow

\n the same individual (as during compensation and during decompensation),
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the method gives very interesting and instructive results. Whether absolute
standards can ba obtained which hold good for different individuals, is not
yet certain, At any rate, however, the method promises to have considerable
value for clinical study. Moreover, out of this work has developed another
line of investigation with very practical results.

Vv. In the course of the preceding investigation it was found
important to have methods for the ready determination of the functional lung
volume in any individual. Dr. Lundsgaard and Dr. Van Slyke have therefore
carried on an investigation to determine whether or not in normal persons
there is a constant relationship between the lung volume and the chest volume.
The lung volume is determined by measurement of pulmonary gs exchange, and
the chest volume is determined by simple actual measurements of the chest
wall. From the study of a large mumber of normal persons it has been pos-
sible to show that there is such a constant relationship. From the chest
volume, therefore, it is possible to calculate what the normal lung volume
should be. A series of patients with tuberculosis were then studied through
the kindness and with the assistance of Dr. Garvin of the State Sanitarium
for Tuberculosis at Raybrook, In these patients the actual lung volume, as
determined by physiological methods, was compared with the lung volbme as.
calculated from the chest. measurements, and very interesting results were
obtained, .It seemsa..that .by, this method the portion of lung tissue failing

to functionate.can be, at least roughly, determined, 2... 00: eae ue

 Diebetes ws oO Da a et tae Bt hes
During the year Dr. Allen has contimed and extended his

atudies concerning the disturbance of the metabolia of fat in diabetes,

which were mentioned in the last anmal report. These studies confirm the

view that in the diabetic organism fats and lipoids are less readily taken
13
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“up by the cells from the blood, than they are in the normal individual. In
diabetes there is a primary and specific impairment in the metaboliam of
fat, as there is of carbohydrates. These studies furnish further evidence
that diets of low protein ani high fat, such as wore praviously recommended
for diabetics, ars improper, and it has been ehown in animale that similar
diets may even induce a fatal outcoms.

During the year much study has beor. ziven to the anatomical
changes in the pancreas occurring in diabetes. The large amount of material
obtained from dogs in which diabetes has been experimentally produced, as
wall as a considerable amount of human pathological material which Dr. Allen
has collected from this and other hospitals, has rendered this study pos-
sible. Ever since the demonstration of pathological changes in the pancreas,
especially in the islands of Langerhans, in certain cases of diabetes, thare .
has bsen much confusion concerning the relation of these changes to the dis-
eas3. Certain pathologists have even denied that the pancreatic changes
wera of any significance. One reason for this confusion and doubt has been
that in certain cases little or no alteration has been present, and that in
general there has seamed little relationship between the extent of the al-
teration and the severity of the disease. It has ‘now been shown that in '
experimental diabetes tr animals, specific changes in the cells of the
islands of Langerhans do. occur. © These changes consist of vacuo lization |
and degensration, and the intensity is parallel to the clinical course of |
the disease, Studies’ “of “the ‘pancresees of human, patients dying. of diabetes
have shown that an expectedly high proportion’ ot these show ‘gimilar
changes. These changes are ‘not striking, mst be ‘searched for, ‘and wera
undoubtedly fornarly overlooked... One reason for this is that the tissues ,
Were usually not fixed sufficiently fresh, By means of these changes it

has frequently baen possible to decide from the examination of the pancreas

alone that the patient had suffered from diabetes, These changes, however,

 
aN tee ,
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are not recognizadls in tha milder cases. This statament requirsas a defini-
tion of ths terms mild and severe. Dr. Allen thinks that whether a case is
mild or severe can only be detsrwined by tha reaction to proper treatment.
Certain cases, especially in the young, of apparently graat severity may
improve very much under proper treatment and acquire even high carbohydrate
tolerance, Such cases are really mild, altnough wita high fat feading such
patiente might have died vary qickly in coma. In euch a case the finding
of little or no change in the pancreas would not ba an argumant against the
role of the pancreatic changes in this disease. Dr. Allen thinks that, if
the pathological changes are interpreted in the light of the new knowledge
concerning the clinical course of and functional changes in this disease,
& parallelism bacomes apparent.

Dr. Fits has completed a study concerning the urea index in
diabetic coma. Cases not in coma, but bordering on it, gave no evidence of
kidney change except possibly hyperfunction. The fatal cases, however, were

accompanied by signs of marked renal insufficiency,

' Chemical Laboratory:

The studies concerning acidosis which have been carried on
by Dr. Yan Slyke and the men working with him, and which have bean referred
to in previous reports, have furnished basis for an extensive report, oc- .
cupying 165 pages of the Journal of Biological Chemistry, under the follow.
ing ‘titles: e SRE De ea ee fe ads eet erbe hats

‘The Bicarbonate Concentration of the’ Blood Plaama, “ite” ”
Significance, and its Determination as a Measure of
Acidosis. * Dr. Van Slyke and Dr. Cullen.

A Method for the Determination of Carbon Dioxide and ~
Carbonates in Solution. Dr. Van Slyke.

The Electrometric Titration of Plasma as a Measure of its
Alkaline Reserve. Dr. Cullen.
Tne Relationship Batwaen Alkalina Resarva and Acid Excration,
Dr. Fits and Dr. Van Slyke.

Alveolar Carbon Dioxide and Plasma Bicarbonate in Norzal Men
During Digastive Rest and Activity.
Dr. Van Slyke, Dr. Edgar Stillman and Dr. Cullen.

The Blood, Urina and Alveolar Air in Diabetic Acidosis.
Dr. Edgar Stillman, Dr. Van Slyke, Dr. Cullen and Dr. Fitz.

These studies bring evidence in favor of the visw that acidosis means a de-
pletion of the alimline res3arve of tae body. This alkaline reserve consists
of the blood bicarbonate, in that it reprosents the base available for the
neutralization of more acids. The method devised by Van Slyka for the esti-
mation of the ability of tae plasma to combins with carbon dioxide under
definite tension, from which the bicarbonate content can be calculated,
therefore offers the best method for estimating the degree of acidosis pres-
ent. This method is extremely simple and has already come into wida use and
will in the futura probably prova to be one of the standard clinical labora-
tory methods.

Dr. Van Slyks has also developed a new, simple and accurate
method for the rapid determination of oxygen in the blood, which has been
amployed by Dr. Iundsgaard in tha studies concerning rate of blood flow
previously mentioned. Inaddition, Dr. Van Slyke and Dr. Fits havo devised
new methods for the quantitative determination of hiydroxybutyric and alae
cotic acids fn the blood and urine, and the method has been oaploysd by,

ay

Dr. Fits in a “large number of dotoratnations in diabetic patients. Much

2
information has been obtained Gonos rning the formation and neutralization

val

of the acetone bodies under various conditions,

| Dr. Palmer has devised a new and improved method for the
quantitative estimation of hemoglobin. In this method the hemoglobin is
changed to carbon monoxide hemoglobin by passing a stream of illuminating
gas through the diluted blood, and this is compared in a calorimeter with

& standard carbon monoxide hemoglobin solution which may be kept in a stable
16 7? wees | ~ ’
mos TM
sat wl

condition, The mathod has been thoroughly tested by comparison with
crystallizad pure hemoglobin, and it has been shown that the error of the
result ie usually not greater than one percent. The msthod should prove

of great value in accurate quantitative work.

Cancer:
The study of casea of canoer receiving X-ray tredtment
bas been continued by Dr. Murphy and Dr. Morton. With the departure of
Dr. Morton, howaver, it becomes necessary to restrict the extent of this
work, As stated in our last report, the entire question of the relation
of lymphocytes to cancer growth and the effects of X-rays upon such growths
4s an exceedingly difficult and complex one, and much time will be required
for its complete solution. The present difficulties in obtaining proper
assistants will necessarily cause a delay in tha further progress of this
work, The following is a brief report from Dr. Murphy concerning the clin-
ical results so far obtained:
"Since the last report two patients have died of cancer,
and another will probably die within the next few days. All three
of these had extensive lung matastasis at the time of admission.
The first two wore apparently favorably influenced in the
:; beginning by the treatment and showed very good reactions on the part
of the lymphocytes, . These reactions, however, were. of short duration,
_quickly subsiding to a point below normal. The reactions became less
| pronounced, however, until after a few treatments no response could be
elicited. |
The third case is one which we have had under observation
for one and a half years. He had a large sarcoma of the hip with ex-
tensive metastasis to the lungs. Under treatment his general condition

improved remarkably, and there was also an activa retrogression of the
bn

 

ne OR

tumor. The lung metastasis remained practically stationary for ovar a year.
Since that tims ths tumor of the hip haa increased and thare has baen exten-
sion of growto in tha lungs. About ona month ago his resistancsa seamed to
give way completely and there has been rapid extension of the growth,

Another casa which gave good r3action on the part of the
lymphocytes, and one which was well suatained for over a year, has show a
less elastic raaction and a greater tendency to drop below normal line. Sha
has latsly developed a rasurrence in the neck,

With these exceptions, the other cases taken soon after opera-
tion, but with a bad prognosis, have contimed in a satisfactory condition...
The group of advancsa cases which we havs had under obssrvation have bean of
interest. One woman with vary extensivsa recurrence in ths wound and metas-
tasis to the necz has shown no rssponse on ths part of the lymphocytes what-
ever, and the progress of the disease has been unaffected. Another with a
maseive recurrence after removal of a prostatic cancer rasponded remarkably
#311 with a retrogression of the tunor. He, however, died of intercurrent

dissase. One of the more recent cases came in with a metastasis in the neck

tha size of a pecan. Under treatment of X-ray on the distal portions of the

body, this has ratrogressed until now only a small indurated arsa can be
made out.

It is impossible, as yet, to maks any definite statement as
to the absolute relationship of the lymphocyte to cancer resistance in man.
Much mors extensivs observation will be necessary. We have, however, sem
increasing evidence of the indirect action of X-ray. It is now necessary
to improve our method, if possible, to a point where we can get a more sus-
tained reaction and one which will carry the patient ovar the mors critical
periods. We feel encouraged along this line and think it can be dona, but

it will be a slow, long drawn out task."