REPORT OF THE DIRECTOR OF THE HOSPITAL

 

October 21, 1921

 
REPORT OF THE DIRECTOR OF THE HOSPITAL

October 21, 1921.

In the past year the Hospital has had the advantage of
having the most mature and experienced staff in its history. While
during the early years of the hospital the staff consisted chiefly
of young untrained men, the oversight and direction of whose work
was almost entirely in the hands of the Director, during the past
year there have been included in the staff several cen of mature
years whose training and experience have fitted them to carry on
independent research and to direct the work cf others. As a result
the work in the Hospital has gradually becoue more cr less separated
into that of several divisions, more or less analogous to the divi-
sions of the Laboratories of the Institute. Te Director of the,
Hospital now shares the responsibilities of tne work with several
associates, each of whom is responsible for the work carried on in

his department. It is wall recognized that there are greater diffi-

culties in the development of this kind of organization in the Hospi- —

tal than in the laboratories, but it is hoged that with close
cooperation between the different divisiong there will occur no loss
- put & great gain In efficiency.

During the years since its organisation the Hospital has
served as a training place not mly for its own men, those who now
constitute ite staff, but it has also served to train men to occupy
acadenic positions im internal nedicine in the universities, Espec~
fJally during the past year, on account of the reorganization of the
departwents of medicine in several medical schools, this demand for

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men trained here hag yesulted in the departure of a number of the

 

 

 
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most valued members of the ataff. Doctor Blake, who has been 6n-
gaged in important studies concerning measles,wes called to Yale
University to becone Professor of Intemal Medicine in the medical
school which has been undergoing reorganization. Doctcr Stadie,
who has been a werbar cf the Hospital staff for three and a half
years, also left to go to the sane inetitution as Assistant Profes-
sor of Medicine, and Doctor Peters likewise was called to the save
place and accepted a siniler position. While Doctor Peters occu~
pied only a voluntary position in this Hospital, being sent here by
Vanderbilt University, of the faculty of which he was a cenber,
nevertheless, on account of his ability and industry, he had becors
an inportant member of the staff and his departure ueant 4 vory dis-

tinct loss.

: Doctor Blake aleo took with him Doctor Trask, who had been

cooperating with hin and assisting him in the study of measles. Doce
tor Trask had been on the Hospital staff for two and a half years
and had developed into a most capable worker, Doctor Austin, who
hae been resident physician in the Hospital, has been appointed Pro-
fessor of Research Medicine at the University of Pennsylvania, and |
Doctor Glenn Cullen has been appointed Associate Professor cf Research
Medicine in the sane institution. The appointments of these two men
becom effective on Jamary 1, 1922, and they will remain at work in
our Hospital until that date.

These changes make serious inroads upon the effective
staff of the Hospital but several new appointuwents have already been
nade and it is hoped that the new organization will soon becouse welded

into an effective force.

 

 

 
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wer

Doctor Christen Lundsgaard of Copenhagen has been given
an appointment on the staff of the Hospital, and it is expected
that he will arrive about November first to take up his new duties.
For the present he will live in the Hospital and will act as Resi-
dent Physician. He previcusly worked in this Hospital, in 1917,
carr, ing on studies of isch j.portance in the field of abnormali-
ties of respiration. He had had a long experience in internal
redicine in the Rikshospital at Copenhagen and has been the first
assistant in the University Clinic of Professor Faber. Doctor Hugh
Morgan, of the Johns Hopkins University, has been appointed an assist-
ant resident piysician,Mr. James Neill has been appointed assistant
in the chemical laboratory, and Dr, 4. B. Hastings has been apzointed
an assistant, to carry on work along the lines of that now being done
by Doctor Cullen. Other appointments will be made as suitable men
are found to fill the vacancies in the staff.

With the arrival of Doctor Tnndsgaard it is plamed to ex-

tend the studies of nephritis and to prosecute this work along now

and more comprehensive lines.

te Respiratory Diseases.

Te study of acute respiratory disease has been cont inusd
but along somewhat different lines. The treatment of cases of Type I
pneumonia with specific icimne serur. has been continued with results
agreeing with those previously reported. This is only an incidental
part of the study, however, since it is believed that the efficacy of
this serum has now been yell demonstrated and ite further euployrent,
as well as its mamfacture, should be left to others. The efforts

to produce serum effective against the other types of pneumonia have

 
 

not proved successful or promising and it is believed tnat the
successful treatment of these other forms will have to be attained
by sowe other and new uethod of approach. Consequently during the
past year attention has been given to the study of certain funda-~
mental properties of the bacteria concerned in the etiology of pneu-
monia and to a more detailed investigation of the functional
abnorcalities occurring in patients suffering from this disease.

Doctor Avery and Doctor Cullen have contimmed their studies
on the ferments present in the bodies cf pneucococcus, which were
described at sone length in the previous report. These investiga-
tions have shown that by reans of sterile solutions and yxtracts of
pneumococci, it is possible to correlate many af the functional ac-
tivities of the living cell with the enzymotic processes of the intra-
cellular substances removed from the growing organisi.

Further study has demonstrated stili other activities of
these pneumococcal substances, These specific intracellular agents
exhibit other properties in the presence of different substrates.

For instance, when allowed to act on blood, active solutions of pneu-
wococei are strongly hemolytic, causing complete dissolution of the
red blood cells, and wider proper conditions may effect important
changes in the blood pigcent, transforming the hemoglobin into met-
hemoglobin, These substances partake of the nature of endcheotox-.
ins and nay prove to be concemed jin certain blood changes clinically
associated with pneurococcus infection in man.

During the past year it has been found that in addition to
the enzyotic and henotoxic properties above referred to, in the
presence of bacterial substrates consisting of heat-killed pmeumo-

cocci these active enzyne-containing solutions cause couplete and

 

 

 

 
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Prompt lysis-.of the dead bacteria. This bacteriolytic enzyme
manifests extraordinary specificity, exerting its dissolving action
only on pneumococci and not on hemolytic streptococci or staphylo-
cocci. On green-producing streptozocci, which may bo nore closely
related to pneumococci than either of the other two oganisms, the
bacteriolytic enzyne of pneucococcus exerts a lytic action which,
however, is never so active or so complets as in the case of the
homologous organism itself. Investigation of the bacteriolytic
property of the intracellular substance of pmeumococcus has show
that this enzyme, Fike those concerned in protein, fat and carbohy-
drate cleavage, manifests its optimal activity over a hydrogen ion
concentration similar to the: sone optimal for the biological activi-
ties of the growing organism itself,

In connection with tho investigation of these intracollular

enzymes, a study is being wade of autolysis or pneumococci, It has

been found, when washed pneumococci from actively growing cultures

are suspended in solutions of various salts, that the extent and ra-
Pidity of self discolution of the organisms is dependent upon the
hydrogen ion concentration of the mixture. Autolysis is most rapid
and complete over the zone of pH 6,5 - 7.5; within which range lic.

the optima of the protease, lipase and invertase of pneumococcus. — In

fact within this zone, all types of enzymes of pneunococci thus far

described can act simultaneously. This fact recalle the observation
of Dernby that autolysis of animal tissue proceeds furthest at a re-
action vhere the various enzymes can function sicultaneously.

In the course of this study, observations have been made
on the effect of autolysis on the heat precipitability of pneumococ-

cus protein, It has been found, that under the influence of heat,

 

 

 
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precipitation of the autolysate occurs at a definite reaction, and
moreover, that the point at which pracipitation with pneumococci,
Type III, occurs, is different from the point at which precipitation
of pneumecceci of Types I and IT occurs, Te reaction point of pre-
cipitation is also different from the zone of acid agglutination of
these groups as determined by Gillespie,

' Doctor Avery and Doctor Thijotta have besn undertaking
studies on bacterial mtrition, which have dealt anecifically with
certain accessory substances concerned with the growth of homophilic
bacilli. Particular attention has boun givun thus far to the mitri-
tional xpquiremants of Bacillus influenzae, since this organism bolongs
to a group of bacteria which heretofore have not boen grown except on
usdia containing blood or blood derivatives. The reason for the po-
culiar sensitivensss of thuse bacilli to the presence or absence of
oven mimte traces of blood in cmalturo media has been the subject of
mich discussion and investigation, Closer analysis of the growth
requirevents of these organisms, however, has shown that this so-callisd
hemephilic property has buen based on a lack of knowledge ef their
actual matritionel necds,

To substances in blood, upon which growth of Bacillus in-
fluenzas doponds, have boon tracod by experimental custhods and found
to be dependent upon two separable and distinct factors, both of
which are requisite for growth and each of which is separately inac-
tive. Study of the growth stimlating action of these substances |
and their chemical and yhysical properties has brought out certain
facts as to their biological significance in the cultivaticn of
Bacillus inflvenzae in particular, and their relation to bacterial

matrition in general. Both of these substances differ in character

 

 

 
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one from the other in ways suggestive of their separate functions.
Ons of these, the so-calied V factor, is a vitamine-like substance
which can be extracted fro. red blocd corpuscles, from yeast and
vegetable celis; it is relatively heat labile, readily absorbed

from solution by charcoal, and similar in its growth promoting

action to the known vitanines. The second substance, the so-called
X factor, in blood is heat stabile, present in greatest concentration
in red blood cells, absorbed from solution by charcoal, and effective
in such small amounts as to suggost its catalytic nature.

It kas been found further that these growth accessory sub-
stences which occur in blood are also present in plant as well as in
animal tissue. These observations on the growth cf the so-called
heuophilic bacilli on blood-fres media have demonstrated that sub-
stances of bacteria} and vegetable origin (potato) can function in
the sase canner as the growth inducing factors of blood.

From the results of this investigation it heema not un-
reasonable to assuse that mutritional deficiency in the cultivation
of other bacteria may be overcome by the addition to culture media
of the appropriate growth accessory substance,

Doctor E.G, Stillman has completed and published his study
on the biolofical classification of hemophilic bacilli. This work
has made possible the recognition of distinct varieties of organisms
closely related biologically, yet differing quite sharply from one an-

other in their biochemical reactions. Within this group of hemophil-
ic bacilli, Bacillus influenzae is recognized as the type organist.
With the limits of this group more clearly defined pacteriologically,
Deetor Stillman has undertaken a study of the occurrence and distribu-

tion of Bacillus influenzae in the noses and throats of nermal

 

 
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individuals and of patients suffering from acute respiratory dis-
ease. While it is rocopnized a this bacillus may be of doubtful
Significance in the etiology of clinical influenza, its importance

as a secondary crganism in respiratory infections in general is lit-
tle questioned, A study therefore os the incidence of Bacillus in-
fluenzae, especially in asscciatian with acute lobar pneumonia has
been made. It has been found that this organism occurs in the throats
of about 30 per cent of norcal persons. In 30 casus of lobar pneu-
onia, on the other hand, Bacillus influenzae was recovered from the
throats of 80 per cent of the patients. The marked increase in the
incidence of this organism in association with disease due to FnewLi0-
coccus infection suggests that possibly Bacillus influenzae Kay be one
of the contributing factcrs which allows the non-invasive pneuLococcus

to penetrate the lower respiratory tract.
Doctor Blake and Doctor Trask.

During the past year a most interest ing and important inves-
tigation concerning the transmissibility of measles to monkeys has been
carried on by Doctors Blake and Trask. Owing to the departure of
these men to take up their work in Yale University, mention of which

‘has been rade elsewhere, a study of measles will be discontinued in

“this Hospital for the present. Doctors Blake and Trask intend to
contirmme their studies at Yale University. The following is a some-
what extensive report of the results of their work as far as completed,

Although Anderson and Goldberger had reported the successful

transmission of measles to monkeys, and Hektoen had reported the arti-

ficial transuission of weasles from man to man by subcutaneous injec-

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tions of blood, others had failed to make such successful transmission

 
 

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exporiments and the latest experiments under the direction of Sellards
had been entirely negative. ‘Therefore, at the tine of undertaking
this work by Blake and Trask, the question of the transmissibility of
measles to anizals was unsettled. In taking up this problem and in
devising vethods of attack, Doctor Blake was influenced by the exper~
ience gained in his studies concerning the production of pnsumonia in
animals. He decided that it would be advisable to use comparatively i
large amounts of vaterial thought to contain the virus, and second, |
that it would be advisable to inoculate this vatorial in what it was
thought to be the natural path of infection. Clinical observation
has indicated beyond reasonable doubt that the virus of measles is
abundantly present in the secretions of the respiratory tract during - {
the preeruptive and early eruptive stages of the disease and that the |
respiratory mucous membrane is the natural path of entry of the virus.
The pethod used in the preliminary experiments, therefore, consisted al
in the inoculation of the mcous membranes of the respiratory tract of
monkeys with unfiltered nasopharyngeal secretions of patients in the

early stages of measles. The secretions were collected by irrigation

 

of the nasopharynx with 20 to 40 cc. of sterile 0.85 per cent salt s0-
lution. The monkeys were inoculated with 5 to 10 ec. of these naso-
fharyngeal washings by intratracheal injection in order to facilitate
retention by the animal of as mich of the material as possible. When
as uuch as 5 to 10 cc. was injected a eauall axount was comsonly regur-~
gitated and spread itself over the mucous membranes of the buccal and
nasal cavities.
By injecting in this way the unfiltered nasogharyngeal

washings from cases of neasles in the preeruptive and early eruptive

stages of the disease a relat ively constant group of symptoms was

 
 

 

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induced in the monkeys which closely resemble those of measles ia
map. Of seven monkeys inoculated intratracheally with unfiltered
nasopharyngeal washings from seven cases of:measles, five developed
the symptoms. The same group of symptoms was induced in one mon+
key by inoculation of thy mucous pembrane of the nose and mouth

with unfiltered nasopharyngeal washings from a case of weasles, In

these experiments a variety of organisms, largely saprophytic inhab-~

itants of the nasopharynx and mouth, were present in the material

inoculated. There is sufficient evidence, however, that these organ-

isms were in no wey responsible for the reaction, since the same

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group of symptoms was induced in two monkeys by the fntratracheal
injection of nasoyharyngeal washings from three cases of measles

after the washings had been freed from ordinary organisuas of the

mouth flora by filtration through Berkefeld N filters.

Te characteristic group of symptoms which follows the in-
oculation of monkeys with the nasopharyngeal washings from patients -
with measles has been successfully carried through six passages by
intratracheal injection of saline emulsions of the skin and buccal
mucous membranes of monkeys killed from 2 to 6 days after the onset
of the redaction. From the fourth passage monkey the reaction was
also successfully induced in three monkeys by means of citrated vhole
‘plood injected intravenously. This experiment showed the blood to
be capable of inciting the reaction from at least the 7th to 13th
days after intratracheal inoculation of the donor monkey, but incapa-
ble of inducing it from the 2nd tp 4th days. Cultures of the blood

" showed no growth. |
The group of symptoms induced has been constant and definite

in character. After an incubation period of 6 to 10 days the aninal

 

 
“

 

becomes listless and drowsy, the conjunctivae become injected, and
small, discrete, hyperemic macules appear on the labial mucous men-
brase. These spots increase in number and uay sventually coalesce

in the course of 2 to 4 days to forma diffuse, red, gramular rash.

 

This rash is usually limited to the labial mucous membrane but may
axtend to the inside of the cheeks. Tne individual maculss may or
may not show the minute bluish white center characteristic of Koplik
spots. From one to several days after onset an eruption of small,
discrete, red mamlopapules appears on thy skin, usually coming ont ie
first on the face. ‘The rash progressively increases in the mmber :
and size of the individual lasions and may in the course of 2 to 3
days extend to the skin of the neck, shoulders, upper arms, chest,
abdomen, and thighs. It is caostant in character but varies con-
siderably in extent in different animals. By the time the exanthem
ig fully developed, the rash on the mucous membranes has begun to
fade and soon disappears. The exanthem in turn progressively fades,
sometimes with a branny desquamation, sometimes without. Tere may
be moderate pigmentation. By the 6th to the 10th day after onset
all symptoms have disappeared and the animal again appears well.
Coincident with this group of symptoms there is a constant and defi-
nite reduction in the total leucocyte count, frequently constituting
a true leucopenia. Other symptoms of irregular occurrence are fho-
tophobia, diarrhea, and fever. Symptoms of rhinitis and bronchitis
have not been noted. |

Microscopic examination of sections made from the skin of
the animala during the period of eruption have shown that the lesions
present resemble exactly those seen in the lesions of the skin in

human patients. Numerous attempts were made to obtain cultures of

 

 

 
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a virus from the lesions and blood, but it has so far been inpo*~
sible to abtain cultures of any organism which seems to bear any
specific relationship to the disease. | The results of these exper.
iments, therefare, have indicated that the disease, apparently
identical with measles in man, cay be successfully transmitted from
man to monkey and from monkey to monkey.

In order to bring still further evidence that the disease
produced in monkeys can be truly termed experimental measles, Doc-
tors Blake and Trask have studied the immnity present in the monkeys
following the disease produced by experitrental inoculation.

Since eri apparently pernanent immunity against reinfection
characteristically follows one attack of measles, the sane phenomenon
should hold true with respect to the experimental disease if the two
conditions are to be regarded ag similar. Furthermore, an acquired
immunity, if present, should theoretically be efficient against a vir-
us of heterologous source as well as against that of howologous origin,
since there is little clinical evidence to show that one attack of
measles fails to confer an imminity that is effective against all sub-
sequent exposures. Authentic reports of repeated attacks of measles
in the sa.e individual are so few as to be negligible in this connec-
tion. In order to test the validity of the foregoing assumptions a
series of reinoculation expericents in nonkeys which had recovered
from a previous attack of experizental measles wes carried out.

The result of the experiments shows that one attack of ex-
perinental measles confers an apparently complete inmmnity against
reinfection with measles for at least a considerable period. In all
probability this immnity is permanent. Moreover, monkeys which

have recovered from oxperi.ental measles are limune to reinfection

 

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1

 

 
with the virus of measles irrespective of vhether the virus is of
homologous or heterologous origin. In this respect experimental
reasles in tne monkey corresponds with ieasles as observed in human
beings, and the result is the sane whether the virus is inoculated
on the respiratory mucous meubrane or is injected intravenously.
However, the exact nature of the 4izainity produced in mon
keys or the immnity developing in nan following a natural infection,
is still obscure, The way, however, has now been opened to a fur-
ther study of this probdlou. as well as to the extremely important prac-
tical question regarding wsthods for producing artificial immnity in
man, Preliminary expericents by Doctors Blake and Trask indicate
that the production of artificial immunity may be quite possible
though the studies have not yet reached a stage which will justify
drawing definite conclusions. The successful outcors of such an at-
tempt wotld undoubtedly be of vury great value, for although under
ordinary conditions weasles itsolf is not a serious disease, yet the
couplications following weasles present one of the greatest hazards
of childhood. The dangers of this disease are enormously increased
when it occurs among groups of individuals living in urhygienic or
crowded surroundings, as in asylums, or as occurred among the soldiers
during the war, Knowledge of a method of prophylactic inoculation
at the beginning of the late war would undoubtedly have saved many =.

thousands of soldiers fro. death.

Doctor Van Slyke

We have contimed the work begun last fall with Doctors
Austin, Cullen, McLean and Peters, in collaboration with the labora~

tory of L. J, Henderson, to ascertain the normal gas and electrolyte

 
“reg

composition of thse dliood cells and plasma, and the changos in thom
resulting from changing GO. and 0. tensions. ‘The object of the
work has been twofold, (1) to elucidate the blood changes that form
a part of the respiratory process, and (2) to obtain accurate nortal
blood pictures more complete than those hitherto available, which
may be used as a basis for couparison with the blood pictures in
patnological conditions, such as pneumonia and neyhritis.

It was found necessary to pay attention to technique before
results of the degree of accuracy required for soxe of the phases of
the problex. could be obtained. For forner purposes, such, for ex-
ample, as studies of acidosis, co. determinations on the blood were
sufficiently accurate if the error did not axtceed + 1 volume per cent,
For the present work it has been necessary to refihe the technique
so that the error was reduced to + 6.2 volume per cent. Similar re-
finements proved necessary in the current technique for rapid satura-
tion of blood with atmostheres containing controlled tensions of C0,
end oxygen. The necessities for, first, umisual accuracy, and second,
raplaity in order to complete operations before extra~vascular changes
alter the blood; have. required the deve lopuent of new technique for
this entire field of work. The deve lopuent of the necessary methods
for this problem has consumed an unexpected augunt of time. Before
the close of the past year, however, results of a high degree of cons
stancy were being obtained, and we hope to assemble thé desired data
before Doctor Cullen and Doctor Austin leave in January.

Doctor Stadie has improved the details of his oxygen cham
ber, so that the control is simplified and waste of oxygen eliminatéd.
During the pmeumonia season a mumber of severely ill patients were

treated in it. ‘The results confirmed those of preliminary experiiuernt.
 

a point that it can be used quite without cooperation from patients,

. Tes

during the preeading year. Cyanosis disappeared when tre oxygen
content of the air was raised to 40-50 per cent. In cases where
oxygen saturation was low the oxygen conttent of the blood was

caused to «pproach or regain a normal level. Respiretion became
Slower and devper, and tachycardia was markedly diminisned., In
short, the symrtoms which might be attributed to oxygen want wer;
diminished, and the comfort and clinical conditions of the patient
appear to have been unffermly improved. The course of the infection
does not appear to have been altered, however. The temperature was
not brought down. And if, while the temperatures was still high, the
patients were removed from the oxygen chamber, they quickly relapsed
into about the condition in which they would apparently have been
had oxygen not been administered. In order to improve by oxygen ad-
ministration @ patient's chance of recovery, therefore, it seems
necessary to maintain him contimously in the oxygen-enriched air

until he becomes convalescent. When this is done, it does appear

I

that the oxygen treatment improves the chance of recovery in patients
who are unable in ordinary air to kegp their blood normally oxygenated,
The favorable effect seems to result, not from influencing the course
ef the infection, tut by protect ing the patient from the added in jury
of oxygen want, and from the exhaustion that results from the specd-
ing up of the respiratory and eiroulatory apparatus in the effort to

compensate for incomplete oxygenation. Such protection apparently

 

aids a certain propertion of patients, vho would otherwise die, to
survive unti} the natural factors of resistance overcom the infec-
tien. t

Doctor Binger has developed the hmg volume method te such

 
 

4

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and can be employed without inconvenience even to those who are ill,
As mentioned in the March report, this has been accomplished by
having the patient breathe from a spirometer a mixture of oxygen
and hydrogen, the hydrogen being accurately measured, the oxygen
merely approximately measured in amounts to afford the patient a
sufficient supply for the 3 to 5 minute period of the experiment.

At the end of the latter, the ratio of nitrogen to hydrogen in the
gases is determined, and from it the nitrogen volume and hence the
air voluge contained in the lungs at the start is calculated. The
method has yielded results of interest with heart patients, although
the data are as yet not sufficiently complete to generalize. Doctor
Binger will this year probably apply the method also to a study of
the lung changes in pneumonia, particularly during resolution. The
latter problem was the one for which the lung volume work begun with
Dector lundsgaard was first planned. —

Miss Hiller has contimed her work on the unidentified
basic amino acid of gelatin. It has proved possible to recrystallize
it only as the phosthotungstate. The free base has been prepared
from the yhosghotungstate, and has proved to be an amorthous solid.
One half of the nitrogen is in the form of amino groups. When the
substance is heated in vacuo at 100° to dry it, it slowly decomposes.
Because of the difficult properties of the substance, which presuma- .

bly have prevented its former detection, the problem of determining

. the structure is not easy, and will probably require a'considerable

amount of time.
Miss Hiller at the same time has brought near completion
her systematic study of the protein precipitants applicable to analy-

ses of blood and of protein digestion products. The nature and

 

 

 

 
; Tse

purpose of this study were indicated in the report of last March.

Doctor Edgar Stillman has carried the work on nephritis
through the year, and has collected an amount of data m correlat-
ed functiaal and clinical observations. It is hoped that infor-
mation thus accumlated may ultimately afford us additional aid in
differentiating the types of nephritics and the corresponding types
of treatment that are justified. The work is necessarily long, in-
volving as it does systematic following-up and re-observation of
patients until sufficient data have been accumiated either to con-
firm or to alter the present methods of classification and treatment

of the disease,

Doctor Swift

 

 

Clinical studies: During the past year clinical studies
of patients with acute rheumatic fever have been contimed. Tmir-
teen such patients have been studied. Special attention has been
paid to the effect of the administration of salicylates on the course
of the disease, having in mind the question of the specificity of
this drug.

t In collaboration with Doctor Cohn definite evidence is
being collected of the presence of myocarditis and impairment of the
impulse conduction during the course of the disease. Electrocardio-
grams are still being made daily in the acute stage of the disease
and at longer intervals in the subacute and chronic stages. With
the assistance of Doctor Cullen, a study is being completed of the
reaction of the joint exudates. These have been found to range _
from pH 7.2 to pH 7.4, showing that there is no appreciable acid pro-

duction in the involved joints.

 

 

 

 
2 TES

Bacteriological studies: Joint exudates and blood of
patients have been cultured aerobically and anaerobically, cultures
having been made during the year. In no instance did the cultures
show growth. Hheumatic nodules found subcutaneously and in the
tendon sheaths of patients with acute rheumatic fever have been ex-
cised and cultured by the Noguchi anaerobic method; thus far no
growth has been observed in these cultures, nor have organisms been
observed in sections of the nodules stained with eosin and methylene
blue and by the Giemsa method. The supply of such lesions has been
limited, owing to their infrequent occurrence in the patients stud-
ted. During the coming year it is hoped that a greater abundance
of material will permit us to exploit more elaborately this method
of attack, for these nodules, which are considered characteristic
of the disease, seem to offer the most hopeful method of approach
to the etiologic agent.

Transmission exper iments: The attempt to transmit the
' disease to animals has been cont immed. Last year rabbits and
guinea pigs were inoculated with joint exudates and blood of patients.
We were unable to reproduce the clinical picture of polyagthritis,
although several of the animals developed @ twonarthritis. A histo-
logical study of the hearts of these animals is being completed.
Certain of the hearts have shown myocardial lesions, the interpreta-~
tion of which is still unsettled.

Fourteen monkeys have been injected with blood and joint
exudate... The results of this work have been confused by a concur-~
rent parasitic infection of the monkeys which manifests itself clin-
ically by fever, leucocytosis, eosinophilia, joint swellings, sub-

cutaneous nodules and blisters on the palms and seles; from these

 

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latter lesions have been recovered the ova and the adult female of
@ worm which has been identified by Dr. Stiles of the United States
Public Health Service as a member of the super-family trichinelloi-
dea. Dr. Stiles rvports that he can find no record of a similar
infuction in monkeys,

It is probable that this disease has beon present ii the
monkey house for at least three years. In order to continue trans-
mission experiments it seemed necessary to learn more of this dis-
ease which simiated in several rospscts rheumatic fover. During
the last three months such a study has been undertaken,

The fully developed female worm, which measures from 1.3 -
1.5 cms in length, and about 0.5 mm. in thickness, appears just be-
neath tho skin of the palms and soles, giving rise to a papule. The
worms recovered at this time are motile and contain many ova. The
evidence indicates that the worm burrows beneath the skin, forming a
serpiginous blister, and the eggs are deposited. The blister rup-
turas and the ova are scattered outside tha body. Forty to 120 ova
have been found in a single blister, These ova are brownish in col-
or, lemon shaped, 70-90**long, and 25-40 # wide, with opercular plugs.
At the time of rupture of the blister the female worm seems to be
part tally disintegrated. No male worms have been recovered from the
skin lesions. The subcutaneous nodules have been examined histolog-
ically, some of them showing the presence of a coiled worm. A few,
however, have shown no parasite. A few of the monkeys have bean
autopsied recently to determine the visceral lesions. Eneysted adult
worms were found beneath the micosa of thd colon and in the omentum
close to the transverse colon; these worms were slightly thicker in

the body than the worms found in the skin lesions. Most of them on

 

 

 

 

 
 

aoe
removal from the cysts were actively motilé; a few seemed dead,
Some of the cysts contained only a brownish substance and no worm.
These worms are probably of the male sex. Specimens of these have
been sent to Dr. Stiles whose reply has not yet been received.

Salicylate investigation: The non-hemolytic streptococ-
cus is still believed by many to be the etiological agent of acute
rheumatic fever, and salicylic acid has been considered a specific
remedy. If these views are correct, it would seem that some pro-
tection could be afforded against artificially produced streptococ~
cus arthritis by the administration of the drug. We have just
completed such a study in rabbits. Fifty-two rabbits were used,
one-half receiving salicylates by mouth in dosage comparable to that
used in the treatment of acute rheumatic fever in man, the other half
acting as contrel, All the rabbits were injected with strains of
non-hemolytia streptococci recovered from cases of rheumatic fever,
Polyarthritis developed in both the rabbits receiving salicylates
and in the control rabbits. No difference in the frequency of oc-
currence or in the muamber or severity of the joints involved could
be found in the two series.

Dootor swift has contimed his investigation to determine
whether or not the imme bodies formed by injection of non-hemolytic
streptococe’ into rabbits could be enhanced by a aimiltenecus admin-
istration of salicylates. His results have corroborated his previ-

ous ones, to wit, that no increase in antibody production followed

the administration of salicylates.

 

 

 
Doctor Cohn

In the early part of the past year, the old laboratoriss
on the third floor of the administration building and on the sixth
floor of the Hospital were abandoned and the new onés on the eighth
floor of the Hospital building opened. The Hospital building has

been re-wired and new wires have deen run to the roof of the admin-~

 

datration building to connect Doctor Carrel's laboratory with the
galvanometer room, as well as to the animal house. Tese changes
have proved to be eminently satisfactory in a technical sense and
have afforded the opportunity for considerable increase in the range
and volume of our activities.

The problem of the behavior of the heart 4n acute rheu- ”
matic fever has been studied in association with Doctor Swift. It |
has long been known that the endocardium and the pericardium of this
organ are frequently involved in rheumatism, and criteria for appre-
ciating disease of these structures are available. Tha disorders
of these structures have long been regarded as constituting heart
disease, Bat at least of equal importance with them is the reac-
tion of the muscle, which after represente the bulk of the heart.
This has until recent times been relatively speaking a silent area.
‘Since the introduction of graghic, and more especially of electric
methods, it has becoma possible to study in certain important details
the events which take place here. We have taken advantage of this
technique, It was imown before that the bundle of His, a thin a
cular strand which connects the ventricles to the auricles, is in-
volved in the rheumatic process and when involved causes defects in
impulse conduction. ‘The orderly, coordinated, beating of the cavi-

ties of the heart is thus seriously compromised; there are gross

 

 

 

 
 

<

disturbances. We found ia addition to the gross changes that

alterations of a more subtle nature were in point of fact taking
place from day to day, the degree increasing or decreasing, These
gave us an insight into the daily progress of the disease in so
far as it affects this structure and served as a valuable guide
in studying the state of the disease, In a similar way, altera-
tion in the great mess of the ventricular mscle has been investi-
gated. This can be followed by studying the details of the
ventricular portion (Q R S-complex) of the electrocardiograyhic
curve. In the same person, such curves usually have a remarkably
constant form. Changes of a striking nature were, however, actu~
ally found in the curves of at least one patient. While the exact
significance of the observations requires further investigation, it
is probable that advance in knowledge of the disease process can be
nade by this method. And not only knowledge of the disease pro-
cess, but also perhaps a guide to treatment may be found. So long
as alterations like these go on, no matter what the other signs show,
the course of the infection cannot be regarded as having cose to an
end. The ordinary rhythmic irregularities in the mechanism of the
heart beat wore also found. Although these are of interest, they
were not unusual, except that by good fortune we were able to photo-
graph a transition from the mechanism of eur icular fibrillation to
one of normal mechanisn. |

Recently, in Garmany, Frey, acting on 4 suggestion of
Wenckebach, re-introduced the use of a cinchona derivative (quini-
din sulphate) in the treatment of cardiac affections, notably fib-
rillation of the auricles, an affection in which the pulse is com-

pletely irregular, with the view to restoring the normal cardiac

 

 
 

mechanism. In aceurelisling this he, as well as others, was

successful in more than nalt the cases treated. Doctor Lovy
has given the drug to 12 patients in the Hospital of the Inzti-
tute and like the other observes har succeeded in restoring tie
normal rhythm in 3 cases. The mumber of patients it has bees
possible to treat is insufficient to serve as the basis of + sta-
tistical account of the drug's action, tut he has Levn able to
make very detailed studies both of the methods of giving the drug,
and of the nature of the mechanisms which the drug induces and
through which the heart passes on the way back to its normal state,
Concurrently we studied the action of quinidin in dogs.
It seemed important to us to do this for two reasons, first, in
erder to study exactly the behavior of a drug which has so. profound
an effect in altering the mechanism of the human heart; and second,
because quinine has been regarded as having a depressant action,
that is to say, an action which reduces the contractile function of
the heart muscie. If this were a prominent feature of its activity,
its usefulness as a cardiac remedy might easily be lessened. The
most striking alteration we found was, contrary to our expectation, .
an increase in the power of contraction of the ventricles, It is
on this account that for clini¢al purpose we attach significance to
our experiments, for if the drug is not a depressant, a residual
hesitation to use. it may ve removed. We have safeguarded: our cane
clusions by making a@ varicty of tests, to exc}ude the possibility of
error due to the natyre of the experiments, such as anesthesia and
the necessary operative precedures. We wish, however, to be guard-
ed in drawing inferences from our work bearing on the use of quin-

idin for cliniesal administration because of the importance and

 
seriousness of the conditions in which the drug is employed.

The other actions of the drug in dogs, which we found,
yield no information of a striking nature except that a fall in
blood pressure takes place, at first great and transient ~ later
moderate but permanent during the duration of the experiment.

This effect it was necessary to study in detail, because it is

itself important and because it may be involved in bringing on the
increase in contraction which has been described. In patients,
however, a similar fall in pressure wes never seen; the drug has no
danger from this point of view. Of its relation to the increase in
contraction, we can report that a mumber of control experiments in
which the blood pressure was made to fall by other means, failed to
duplicate the result obtained with quinidin. Its contractile action
then, is exerted apart from its action on blood pressure, and the lat-
ter is an effect which, as has just been mentioned, we have not sem
in man,

Doctor Levy studied in animals, in a preliminary way, the
action of a new strofhanthin compound, prepared by Doctors Jacobs
and Heidelberger, This drug appeared to be less toxic though ther-
apeutically as effective as the mother substance. In view of the
importance of the strorhanthin group of drugs in the treatment of
patients, it seems desirable to possess them in pure form and to
study the action of variant forms with the view to finding ones serv-
ing the specific needs of clinical physiology.

Doctor Lavy is studying alterations of the size of the
heart in pneumonia. This study is important because of the doubt
which still surrounds the occurrence of collapse in the course of

this disease, and the relation of cardiac dilatation and failure to

 

 

 
 

its mset. But it is important in addition to this because
apart from collapse, changes in the pulmonary circulation are be-~
lieved to take place in this disease and to be attended by changes
in the size of the heart. If, as experiments in our laboratory
show, digitalis acts on the heart during pneumonia, and if, as our
experiments also show, this drug increases the contractile power
of the heart, additional interest attaches to this study. For
should a change in the size of the heart appear to be usual, we
have a means at hand, through ability to increase contraction, to
bring about relief of this candition.
The method employed has been to make X-ray photographs

with great care - all photographs being made as nearly as possible .
with an identical technique. We are then assured of having plates
so nearly comparable that their measurements can be compared day by
day. The plates are placed two meters from che target of the X-ray
tube; the target is elevated to the level of the substermal angle,
. the median line of the front and of the back of the chest are in
the same line with the target; the exposure is made during normal
inspiration.

. Doctor Levy has found that if these conditions are ade.
quately met, the X-rays of normal persons do not differ by more
than 1.0 cm. in the transverse dimension of the heart's shadow nor
by more than 10.0 sq. cm. when the whole area of the shadow is meas-
ured. A more accurate method than hitherto available has been de.
vised for outlining the cardiac silhouette. When these results are
compared with the situation in ten cases of lobar pneummia, it is
found in nine that there is a distinct increase in both measurements,

in the transverse diameter as mech as 19 per cent, and in the area

r
.

1.

 

 

ms
 

Sag

as much as 37 per cent. A similar increase is rare in broncho-

pneumonia, that is to say, an increase was found in two of six
cases. The size of the heart decreases with the fall in the tem
perature and the pulse rate, but usually it lags behind these and
dogs not return to the base line until some time, perhaps a matter
of weeks, afterwards. Occasionally, during early convalescence,
the size falls below that finally attained.

The observations, although still insufficient in number,
indicate that the management of convalescence has a bearing on car-
diac size - sitting up in bed, especially perhaps if permitted too
early, is attended by a return of increase in size, There isa
single observation in which it appears that giving digitalis pre-
vented the anticipated delay in the return to normal size. ‘These
illustrations point out the practical bearing of this study.

Doctor Binger has worked on a method for measuring the
quantity of air in the lungs of patients suffering from shortness of
breath, and has now perfected it. The nethod determines not only
the so-called vital capacity or that volune of air which can be ex=
pelled from the lungs after naximm inspiration, but also the resid-
ual air which remains in the lungs and camnct be expelled even on
forcad expiration. Residual air is measured by allowing the subject
to breathe to and from a spirometer containing a mixture of oxygen
and hydrogen. By a chemical analysis of the spirometer contents
before and after the patient has breathed, the degrees of dilution of
the oxygen and hydrogen mixture with the ling air is estimated and
thus the volume of the lung air is calculated. By @ similar tech-
nique the volume of air resaining in the lungs at the end of a usual.

expiratory movement may be determined. This method has the advantage

 

 

 

 
‘
-7Y

TRY
of demanding a minimm of cooperation on the part of the subject

and Snerefore is applicable to patients with severe cardio-
respiratory embarrassment ~ the very type in which a study of

lung volumes is needed. Previous methods have not proved satis-
factory in this type of case. It has been applied tc a series of
individuals suffering from heart failure with the view to under-
standing further the mechanism of their circulatory and respiratory
incapacity. A series of observations has been sade on normal indi-
viduals for control purposes, The measurements obtained have been
correlated with certain physiological standards as a further control.
It is planned to carry this work further with particular attention
to the volume of air content in the lungs in the expiratory phase of
normal breathing, and to study its value in relation to the so-called
tidal air, which is the amount inhaled and exhaled with each breath.
By these relative values it is believed that a more or less quanti-
tative expression for dysmea (shortness of breath) will be obtained.
The method for measuring lung volumes in its present form, we be-
lieve, is applicable to the study of pneumonia, in which an investi-
gation of the sir content of the lung during stages of consolidation
and resolution would be very instructive. So far as we know, pre~
vious wa thods of studying lung volumes have not been practicable for
such investigation.

The study of respiration in heart failure has pointed to
the intimate relation between circulatory failure in the lung and
decreased lung capacity. It has emphasized again a fact long ob-
served at the Rockefeller Hospital that patients suffering from
heart failure have a tendency to elevation of temperature. An ex-

planation of this phenonenon has presented itself in a more or less

 

 

 
 

hypothetical form as being due to impaired heat excretion due to
the fact that the blood is stagnating in the internal organs and
not adequately brought to the surface of the body. This inter-
pretation of the findings has suggested a field for investigation.
Apparatus has been designed and is under construction for measuring
by an electrical thermo couple the temperature of the circulating
blood in man as well as the temperature of the body surface, and
more accarate determinations of rectal and mouth temperatures than

are possible with the ordinary clinical thermometer.

RUFUS COLE