June, 1915,

 

To the Beard of Hclentific Directors of the
Rockefeller Institute for Medical Research,

Gentlemen:

The Director of the Hospital hag the honor to submit the following report

of the work Carried on during the last quarter year,

with com: ietior of a number of the studies which are nov ready for publication,
Aeu39 Lobar Puowionia, The type of pneumococcus concerned has bow been

Je-:3rmined in 237 cases of Phoumonia admitted to this Hospital, Tn addition,

Jv Dishardson has determine? the type of pneumococcus concerned in 195 cases of

-Honia adnitted to the Pennsylvania Hospital. te have thus quite satisfactory

Sos3rvations dn 432 cases, The results are shown in the following tables:

Casas ix the Hospital of the Rockefeller Institute,

“tiological Agent No. of Percentage Mortality in Cases not
Cases Indidence treated with Serum
*roMocogCUS type J 78 33% 254
n n Ty 75 324% 29%
fn © rrr 22 9% 45%
" "ow 48 204% 12. 5%
Vrer Bacterda .
Influenza Bacilius 8
Streptococcus 3
Strenteceecus
mMicesus 1
Staphylococeus 2
Pasiitus Priedlender2
Scrertecoceus,
“vararlesseons ang ,
Iniluens:, Bacillus 2
l¢ 6%
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Cases in the Pennsylvania Hospital.

Etiological Agent No. of Percentage Mortality in Cases not
Cases Incidence treated with Serum,
Preumococcus type Y 60 31% 30%
7 " TY 39 20% 25%
n " IIY 13 6% 50%
8 "ow ~23. 43% 12g

The Zigures indicating percentage of incidence in the two series are not exactly
comparable since Dr. Richardson has not included in his list the cases due to or-
ganisne other thas pneumococcus. The results indicate, however, the correctness
of the conclusions previously drawn from a emall number of cases,

At the last meeting of the Board Dr. Janeway,drew attention to certain
races of pneumococci isolated at Baltimore, which, while agglutinating in undi-
luted sezum of type II, nevertheless did not agglutinate when then diluted serum
was added to them, and when protection tests were made with them the results were
not clear cut and unequivocal. or. Bloomfield kindly sent us these five races
end these have been shoroughly studied by Dre Averys They were all found to be
of low virulence and, a3 has before been noted of the type strains of low virulence,
the svotection afforded by the sera of different types was irregular and inconstant,

in cortain instances eyen normal horse serum was able to protect against them.

Naeem mt Ng Snag te cae

4ll these strains were rendered highly virulent by frequent p passage through hice.
Tots} on testing protection against these virulent strains, . it was found that type ITZ :
serum protected against all of then in a typical manner, while type I serum and

ormal Horse Serwa had no protective power whatever. The agglutinability of these

Strains, however, has in this manner not been increasedy It seems evident there~

fore that these are true typs If strains, but which have relatively slight agglu-
tinability. Tris is qucta analogous with what is known of B. typhosus, certain

Strains of yvhisn ara tligibly agzlusinatle. I< is not thought that these exper=

iments effer eny evidence thet the atypical strains are changed into fixed types.
 

PN

uO. .

The Cccurrencs of sueh

strains, moreover, need not necessarily eause any confusion

du the mathed of diagnosis of type employed by uss

Esrum Treatuent of Cases due to Pneumococe 4 of type Y. Forty-eight cases

236 46 Dneumososed of type I have now been treated with immune serum of these,

tour ified, contrasting with the mortality of 25 = 30 per cent. in the untreated

cases c2 this tye. Of the four fetal “aes, however, one died suddenly during

convalescence fron pulmonary embolism; two of the cases were only treated when

“18y Vere almostMiy ®xtremis", a few hours before death. This leaves only one

case that can be considered to have been treated with any hope of success,
tuds

and
a8 treated only on the fifth and sixth days, the patient dying on the sixth.
jaye

Epidexiology. Dre Dochez and Dr. Avery have completed their study

oO: carriers. he types of pneumococci occurring in the mouths of 113 normal ine

dividuals have been studied, Paosumococe: of the fixed types were found 11 times,

and these were always present in the mouths of persons in close contact with pneu~

nonia patients, the type found jn ead¢h case being that present in the case of pneve

=tnia with whieh the  porsonstudied was in contact. In 55 other persons Pneumococes

weve 2iso pressnt, but these were all of the atypical group, Group IV. The per=

Bistence of fixed types in the mouths of pneumonia patients and of carriers has also

veen studied, the final results agresing roughly with those previously reported.

Anablastic dmmynity. Dr. Doches and pr. Avery have completed the study

of anablastic immunity, and the results are ready for publication,

Extraction of Immune Bodies from Serum Preci itates. Dr. Chickering has
neem OM Serum Precipitates,

continued the study commenced by Dr. Gay and Dr. Chickering and has so developed

the method as to obtain constant results, The best method of extraction has been

found te consist in dilute sodinn carbonate at 42° C. One patient suffering fron

e% intection with a type IT pneunococeus has been treated with such an extract given

suvcutaneously in irexcently repeated doses. In this case the clinical results

Were excellent, and the tests of the pationtts blood sseried to indicate that this

 

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vreatment caused a greater increase in immune bodies than had previously been ob-

served. The work of Dr. Buil also suggests that this may possibly be the method

A: ere ie
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of

snoice as by this method the immune bodies may reach the blood more slowly. tf
Tis method will ve tried further in cases of type IT infection. In the study of it

71353 Olracts a nuuter of observations of theoretical interest have been made.

 

1

a3 Tecan by Or, Caickering dealing witb thaso points is ready for publication. |

Jve Chistsring has een granted leave of absence for six months. He goes to work

a

‘ith Dr. Gay and W222 cooperate with hin in treating a series of patients with

typnoid favor by an analogous method. He will return in November to continue his

vork here on pneumonia.

Pr RT Re rent:
Fite vie alee? acon

Effast of Combined Injection of Optochin and Immune Serum. Dr, Moore

igharnmtl

“a8 worked in the Hospital during the past six veeks and has extended his studies

wipe.

of optochin, commenced with Dr. Flexmer, in an endeavor to learn whether the ef-

MOR EEO

fectiveness, of irmure serum may be increased by the addition of this druge The

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results have boexn quite clear cut and show that the maximum dose against which im

‘¥

eres

ane serum will protect is definitely increased when the animals are treated at the

fame time with .5 gm of optochin given simultaneously, or better, when 0.5 gm. is ;
riven the first day. 0.45 gm. the second day, and 0.4 gn. the third day. These |
#0368, Lovever, are railatively very much greater than the doses that can be safely {
ministered tc man, Experiments are now in progress with larger animals of other . .

cpsciss to see whether it is possible that a relatively smaller dose may be effective

-2 larger animalse

Methods of producing Active and Passive Immunity, Studies carried

cut in large series of aninals show that the development of immune bodies in the

Serum of immunized animals is inhibited if very large doses of dead culture or

antigen prepared in various Ways are employed. Eighteen rabbits go treated failed
to shov any durnne bodiss in the blood whatever. They all showed some active in-
uunity, hovever, 4 certain iustances of considerable grade. These experinents |

ring further procf shat there are certain features in active immunity besides the

 
presences of igzune suostancos in the body fluids. We have called the former type

s

Os immunity somatic immunity in contrast with humoral immunity.

All the studies indicate, however, that pure humoral immnity may be effective
af 23 infection ve not oxtrene, and if the concentration of the immmne bodies in
wc Dleed be of sufficient degree. The attempts to increase the effectiveness of
whe ivuoral factors vy other methods of immunization have shown that this may be
dows ur Ireguently repeated small doses of dead cultures or probably better by give
ing frequently rersated dmall doses of live culture, combined with immune serum,
From thea studies on rabbits and goats it seems that a very definite advance has
been made in the practical method of immunizations ;

Hoart Disoase Dr. Cohn and Dr. Jaméeson

Tho records from cases of pneumonia have been collected and are being studied;
first, to see, in properly standardized curves, such as these, what changes occur
in the electrocardiogram as the result of the disease; second, to see whether
digitalis causes changes in the curves from these patients similar to those seen in
“ne curves from patients suffering from heart disease. The studies indicate that
Cems 2 than jer le oscur as the result of pneumonia, and these changes serve as a
svi fov devte:udliing the degree and nature of cardiac involvement due to pneumoniae
In regard to the second point, it has been found that digitalis does induce in
pusvnonia patients changes similar to those seen in patients with non-febrile heart
disease, as indicated by electrocardiographie curves.

The problem of the reliability of the electrocardiogram as an indicator of
cardiac hypertrophy is being studied. Comparisons are being made with the X-ray
Shadows, and also with the weight of heart muscles Dr. Jamiesen is trying to
Produce aypertrophy in dogs by work (on a treadmill). Dr Cohn is making a similar
effort in dogs in whieh artificial valve lesions have been produced.

the study of patients with chronic heart disease is being contimed along the
idnes previovusir indicated,

Studiss corcerui:.; rhesonena of contraction and conduction are planned. To

 

 
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vender these studies possible it has been recessery to install a second galvanometer,
so that simultaneous records from two points on the surface of the heart or on other
contracting organ may be madée This second galvanometer was andered last autumn
‘ut, owing to delays incident to the war, has just been installed. The installation
92 this galvanometer is 0: importance in the work, not only because these special
stulios are rendered possible, but also because the new instrument is of much great—
-v ageurasy than the old one, and 80 much more exact studies are rendered possible.
> 3 rew instrument vas mainly constructed in this country according to design
corpished by Dre We Be Williams, and the tests have shown that the instrument en-
Sisvcly fulfills the expectations.

Diabetes. Dr. Allen is contiming experiments showing the effect of
voising and lowering metabolism (food, temperature, exertion, thyroid, etc.) upon
oxperinental diabetes, observations thus far supporting the idea that increased
metabolism increases, and diminished mesabolism diminishes the strain upon the

internal pancreatic function. The coming of Dr. Palmer has made possible a series

seers ie Mee
a

of experiments to test the hypothesis of combined sugar. This series of experiments
jeais with feeding and injection of sugar in normal and diabetic animals, with tests
of the blood for sugar, estimation of hemoglobin content, and estimation of various
physical properties, (viscosity, surface tension, freezing point, conductivity)

and parallel observations concerning the urine, lymph and tissues.

Dr. Stillman is carrying on the treatment of patients on the lines pre=
viously laid down. The number of patients at any one time averages from ten to
*4fteen. Ha ia studying particularly the question of acidosis and blood-sugare
In regard to acidosis, the analyses made are for the three acetone podies and ammon~
ja in the uriga, and © Og tension in the alveolar air, in parallel with the blood
studies of Drs. Van Siyke ané Cullen. The C 02 determinations in the alveolar air,
and blood seem to offer the most satisfactory index of acidosis. Patients with
slight acidosis or nowe may, during the initial fast, show the same slight acidosis

as a fasting normal person. Cases with severe acidosis, however, invariably show

 

 
om Ton
a deoreass in acidosis during the fasting. All tests confirm the clearing up of
acidosis under the treatment. Sugar is determined in the whole blood and in the
sineua, with some idea of observing the permeability of the corpuscles, but chiei-
ly to learn whether the treatment reduces the sugar conteht to normale This has
rroved to ts so in some very severe cases, but in some older patients it may per=
haps not de necossaryrto attempt this, and the question whether it is possible in
uvery case cannct be answered at present.
€tudies carried on in the Chemical Laboratéry.

Much of the work reported in April is still being contimed, but some of
tne problems have boon brought to a sufficiently definite conclusion to prepare
ior putlication:

Studies of the Abderhalden Reaction by Dr. Van Slyke and Miss Vinograd
Sufficient data have been collected with our quantitative method on the pro=

 

+aase content of normal and pregnant sera to justify considering the problem as
closed, and tha Abderhalden reaction for pregnancy as worthless.

Miss Vinograd, with material furnished by Drs Isaac Levin, has had similar
results in atteupting to apply the Abdernalden reaction to cancer diagnosis. As
only one preparation of eancer tissue was used in the tests made, however, the
usslessness of the reaction for cancer diagnosis cannot be affirmed with the same
degree of finality that appears justified in reporting the results of the pregnafc
teste

Diabetdc Acidosis. Dr. Van Slyke, with Dre» Cullen and Stillman, is
making an extended study and has obtained sufficient data for publication on the
first points of attack{ Data have been obtained covering, in some cases, months,
with almost daily analyses of the urine and determinations of the alveolar carbon
dioxide, with, for comparisor, determinations of the actual reserve alkalinity of
the plasma by our new v.ethods, viz. the determination of its carbon dioxide capa=-
city, and of its c:ility to maintain a neutral hydrogen ion concentration after

2odstion of seid. ® 2386 tacts show the actual condition of the blood, and are

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co iglicate that they readily show even the slightest physiological variations in
reserve alkalinity. The alveolar carbon dioxide determinations run fairly parallel
-ith the blood vesults, and we have not yet observed a pathological change that was
-o4 chomm simultaneously by both. After the direct blood tests, it appears that
“6 elveotar carbon dioxide tension is the most sensitive indication of a state of

aciiests. Urine analyses of any kind are much less reliable, although a gross

change in the direction of acidosis is usually accompanied by an increase in the

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aunorza cutpute ™:3 acetone bodies, on the other hand, may give no warning, even
cui the verge of comma.

One point in which the blood and alveolar air tests promise to be of aid
in the Allen Treatment of diabetes is in controlling the condition of fasting pa-
tients. Some develop no acidosis, or very little; but in other cases acidosis
doses develop rapidly, becoming marked after a single day's fast . A control by
quisk and sensitive methods for detecting the presence and degree of acidosis seems
‘roortant, for as yet there is no way of telling which cases will develop acidosis
an the treatment, and which will not., The sensitiveness of the methods developed
“23 uncovered a physiological problem as an offshoot of the acidosis work. It has
seg saldeved by some authors that during digestion acid products were ppured into
she blood, and that these were responsible for the increased general metabolism and
233% production noted after a meals By others it has been pelieved that, on the
contrary, the alkalinity of the biood increases, because of the secretion of gastric
hydrochloric acid. Experiments on men which wé have already performed to test this
point have already shown that an appreciable increase in blood alkalinity usually
follows a meal. ‘The work will be contimed on both animals and men, the effect of
digestion of carbohydrates, fats, and proteins being studied, and also the offect of
stimulation of gastric secretion in the absence of digestible foods, so that the re~
lative effects of H Cl. excretion and of absorbed digestive products of various
nature of the bleod alkalinity can be débermined. |

Tha work of 1438 Vinograd with Dr. Osborne of New Haven on the amino

 

 
acid soxosttion ef 2ocd protoins is now boing propared for publication. The
basic constituonts of rico protoin, whcat gliadin, and milk albumin have been
dotormminod By entirely differont methods in the two laboratories, so that errors
by vach could be eliminated. Consequently these determinations are probably the
most thoroughly controlled that have evem been thada in amino acid determinations
cf proteins. Tne results have a direct bearing on the interpretation of the im
portant work of Mondel and Osborne in their "Growth Studies", in which lactalbue
min and gliadin hevo beon used as ropresentative proteins.

Nephritis. Dr. Mc Lean's studies with tho sensitive functional tests
¢Z cvoa and salt excrotion, are boing continued, with a gredually accmmlating
moss of data which promises to be of definite value in the diagnosis and prognosis
22 dicferent types of nephritis.

One case of post-pneumonia nephritis wos perticularly interesting as

so nophritis was accampanied by an exceptional type of acidosis. Plasma tests

saoed a degree of acidosis which, at its height, was nearly equal to that seen
ix, diabetics threatened with cam, but the ommonia excretion, instead of being

iucroased, was abnormally lov, boing less than one per cent of the total nitrogen,
Daring convalescence the return of blood alkalinity to normal has accompanied the

restoration of kidney fumction, and the ammonia, excretion has risen gradually to

normal, Henderson and Palmer, of Harvard, have reported nephritics in whan a

‘

low ammonia excretion accompanied an acid urine, but could not demonstrate exist-

ence of actual acidosis, as has been done vy the plasm, tests in this case.

 

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