REPORT

OF THE

DTRECTOR OF THE HOSPITAL

TO THE

CORPORATION OF THE

ROCKEFEFELLER T'?STTTWTE FOR MEDICAL RESEARCH

Volume Iir    January, 1915 - October, 1916


                                     !) `C,
                                                     ' ;
                                                   _. . c
i3 7PCRT                               .

OF

THE DIRECTOR ,CF THE HOSPITAL

October 1916.
---

         Chancres In the 8tafl..   It is a source of gratification that the
l:ilober Of men desiring to join the staff of the Hospital is constantly increasing
llid that the training of the men desiring even tompcrary appointments is of high

1 CWl.  There is now a deman%n the part of cell trained men for voluntary assist-

nnts;lips.  mile it has not been the policy of the Institute to admit voluntary Plop

?.!2l-S, the trafning of certain men applying has been so good that in certab in-
struxos lt has been thocgk'i; advisable by the Board of Scientific Directors to grant

such privileges, especially in those cases where men have agreed to remain the entire

-y c `ar.  Last year such a privilege was granted to Dr Ernest Stillman, PreviouslY
Assistant nesidant Pathologist at the Presbyterian Hospital.  He has worked on the

Ep idemiologp of Pneumonia.  During tno summer of 1915 and 1916 privilege to work in
the hospital was granted to Dr J.T. Halsey, Professor of Pharmacology in Tulane uni-

versity.  He has worked on subjects related to heart-block.  mring the coming win-
ter privilege to work in the hospital has been granted to Dr Francis G. Black of Hw-
yard University and Peter Bent Brigham Hospital, Boston, to work on problems con-
ndcted with infectious diseases a.d to Dr Samuel A. Levi-of Harvard University and

the Peter Bent Brigham Hospital, Boston, to work on problems in connection with heart

dtsease.  It is believed that ti the future this training of certain men in the
special near methods employed in the hospital may be a highly efficient means for
bringing the methods into more widespread and effective use.
                   During the year the Hospital has lost the

3,: y-7 ices of one of the mosf promising of its younger men, Dr Franklin C. McLean, who


                           -29

has been appouted Professor of Internal Medicine and IIead of Union Medical, College,
                                                                           . .
the neT! medical school to be organized by the China I:edical Board in Pekin.

    Dr A.P. Dochez, who for two years has vev capably served as ,J&sident
                                                                           /
Physician of the Hospital, was at th6 June meeting of the Foard of Scientific Di-

rectors made an Asoociate Member of the Institute.  He no longer vrill live in the
hospital and he will be succeeded as Resident physician by Dr H.T. Chickering, who

far three years has acted as Assistant Resident Physician.   Other changes in the

st?.ff *::iii be found in the Eianager@s Roprt.

     c1:cqus in the EOSPital onin,-, to need for increased laboratory space, and

iroFosf;A chanztjs to accomodate patiel;te.

     At the April meeting of t:m Doard of Scientific Director6 the Director

of the Hoepital made certain suggestions and recommendations bearing on immediate

and future hospital needs,  Changes to satisfy a numbor of these need8 have al-

ready been made, either in the way proposed or by ways which, after further con-

siderat ion, have seemed more advantageous.

     At the meeting the Director pointed cut that since its organisation the

activities of the hospital had increased to such an extent that there was an i.m-

mediate need for increased laboratory space.   To meet this need slight changes

have been made on the Rest end of the sixth floor of the hospital which ~a8 origi-

nally intended as a nard floor.  Also by builddx,g a bridge over the fsolation Build-

ing the third floor of the or&S&& laboratory building has been brought into &-

mediate connection with the hospital and has permitted the use of this floor by

Lx.:bers of the hospital staff who, in order to carry on advantageously laboratory
              6                        .
work in connection with the care of patients should have their laboratories very

accessible from the vlards.

     Improvements in facilities for X-ray vork in th& hospital were much needed,

LsTecLaily for the etud;* o f the act ion of X-rays on cancer.   There is therefore


              - -


t c: f r.g installed on this floor a new X-ray department which vrill now be first-class

in 311 respects.  On this floor also are rooms in vrhich experimental work on dogs

-3;' be carried on by Dr Allen and Dr Cohn,
d.                          Nuch of the work of these physicians
racluires experiments on dogs and it is not thought advisable that these animals be

`crought into the hospital proper.  Another room for operating on dogs is alsO pro-
vided which can be USed by other member8 of the staff vho only occasionally need

such facilities.

     Additional Room for Patients.  The addition of the nork on treatment of
zancer will probably slightly increase the number of patients in the hospital. Also
,.;ith the increased development of other activities in the hospital, some thought is

jeing given to possible expension.  If, later, this should be thought adviaable by
the mmbers of thd Corporation and If resources be available, the experience of the
hospital indicate8 t&%t any future need will beet be met by providing additional

single room?,  In a very complexmixed semice such as ve have, consisting of both

sen and vromen, it ha8 been found difficult to separate patients suffering from various
diseases without overcrowding certain ward8 and leaving other wards containing few
      b
patients.  Such separation is certain cases seems very important. For instance*
it is Very important not to treat pneumonia patients in the wards Containing Patients

with heart diseasee.  It has not seemed wise to place diabetic patients, ho are not

acutely ill, and whose mental state is of considerable importance, in wards con-
taining acutely sick pneumonia patients,

    It has also been found advisable to keep patients on whom verY accurate
chemical or metabolic 6%*06 are being made in single rooms.  Moreover, the demand
on the Part Of persons of the better classes for adniesion to the hospital has grov%
and it is found that in many nay8 these are tne best patients for study, as they are
more ready to cooperate in the studies being made.   These patients also require

separate room6.


-41.

    It would seem, then, that the first extension of hospital facilities should
provide for additional single rooms.  This can probably best be done by using the

second floor) non occupied by nurses, for this purpose.   In the original phndng
rnd construction of the hospital this floor was built with this possibility in mind,
ad this floor could be used for this purpose with comparatively slight change.

     PJrsee Home,  Such a use of this floor would, of COUIXI~, necessitate
L:aking ~~wieion for the nurses elsewhere,  The nurses quarters are already over-

c roy;Asd.  IL very accurate work and complex studies, such as are made in the hoso
pit al, the number of nurses required is large, much larger than may be thought nec-
ceseary by those who have only had experience in the ordinary general hospital*
The nut888 are needed, not only in caring for the immediate needs of the patients,
but they MO eqloyed very largely in assisting in making oboervationa and ~JI as-
sisthg in the technical procedures carried out.  The provision for a Nurses' Home,
therefore, would release from the hospital buildings a number of room ddch aPPar-
ently can very soon be profitably used for hospital purposes.

Resort of Scientitio Fork

    The nork haa largely been a contmtion and exfension of that done 5.n the

preceding year.  The only new class of patients admitted has consisted of those

mf feriug from cancer.

    @te Lobar FWuraoni~   The work on this disease has gradually resolved
itself into investigating modes of specific therapy, fir&    of
                            thav making use of bob
                        of

inlmrnity reaction, and second thal/ employing drugi which have a specific action on
the infecting organisms.  In attempting to apply the known principles of WitY
progress is theoretically possible in two ways.  Fir&, it is possible that the
Patient himself may be stimalatird to himself produce the immune substmces, UPOn


-59

,:rhich natural recovery in pneumonia undoubtedly depends, faster and in larger amount

thar, he vrtuld do unaided,  While numerous experiments have been made along these

1irieS up to the present it ha6 been impo6Sible to obtain promising results. The
other meihod ha6 been to aupl& him vrith those bmne substances which are contained

i- the 6erdm of animal6 artificiaily immunized.
.I                             This latter method ha6 been the

cne %?ich has given the most promising results.  ~6 previously stated, this form

c f thcrml- :S only possible if, in every case, the type 'of Infecting organism can be

rIli l 'i:y ar.1 a:curately determined.  Thie the previoue work in the hospital ha6 made

4 p2SSili3,  lrhe resuits of serum treatment have 60 far been succe66fUl only in the

infection6 due to pneumococci of Type 1.  Here, however, further experienCe ha6 con-
fizzed our PreViOU6 conclusions, and made it quite evident that 6erum i6 of very

great value in thie type of infection,

    mile the extent of our statistical data is as yet not large, we now feel
that we have sufficient to urge that all case6 of Type 1 ih@ection be treated with

the appropriate serum.  Up to July 1,19X, 396 cases of pneumonia have been treated

in this hospital, of which 106 were treated during the year 1915-16. Of these 396

4  Ca6e6, 113 were due to Pneumococcus Type I, 104 were due to Pneumococcus Type 11,
37 were due to Pneuno~~~~~s(nuco~~~) Type 111, 74 were due to Pneumccocci of Type 1%
in 48 cases the type of pneumococcus causing the infection was not detemhed( cccu*
bg mainly before methods for datemining types had been deviwad) and 20 cases mm
diagnosed as acute lobar pneumonia in which the infecting organism was Friedlander's
bacilius, Influenza bacillus, streptococcus or staphylococcus, or combinations of

  these.   It is evident that about one third of all caee6 nere due to PneUmococcuS

  Type I.  Of these cases due to this type of pneumococcus 72 were treated with im-


   murie 60&W&  Of these 72, six died, a mortality rate of a little over 8% Of the
six that died, moreover, one died on the 16th day, after recovery from the Pneumonia
from p'UlmOnary embolimn, one died on the 54th day following the paemOnia from a


                         -6.             -`Y '

                                                               .>,"f*%
:c:i=ral 6treptococcu6 infection with empyema and multiple abscesses, three were     y,y I



-,. .-CA
,A -c-b. 1 OyiiY On the Jay of death, and only one 31as treatad for two days, the fifth


:.. s ! sixt!l.  It is evident that lfi at least tco of the fa',al cases(those first men-
tiur-ad) no Specific treatn;ent could have been of service.
    l'ha it is considered that the mortality in tha untreated ca6es duo to
TYPs 1 i:ifection, judging from the cases here before s~ruz treatment aas undertaken
and aleo frm the caees observed in other hosy:itals, is froo 25 to 33 per cent, it
is evident that the low mortality observed, 8 per cent, ic decidedly encouraging,

even quite convincing.  The importance of ttis form of treatment is evident &16n

we consider the great frequency of this form of infection.  In 1915 probably 1800
deaths in New York City were due to Acute Lobar Pneurtonia of Type 1 done.   This
is as maIIy a6 all the deaths from typhoid fever, measles, scarlet fever, *ooPing
cough and cerebra-spinal meningitis combined, and almost as many as all the deaths

occurring in the present epidemic of poliomyslitia.
    In the previous annual report it haa been stated that it Has been bPo6-
6ible to Froduce an irznane serum active agsinst Type III pneumoGocci.  Our experi-

menta were or&~ conducted with small animals, however.  Since these fR6re negative,

no attempt6 were made with horse6.  During the p&t winter, however, tha.State Board
of Re6.lth, under Dr Wadsvtorfh' s dire&ion, notwithetanding auf neg&ive re6ult8, PrO-
ceeded to imnxanilte a horse to Tppe III pneumococci and sent us some of the serum. To
Our surprise the senxn nas found to have some agglutinating power and also slight

protective power for mice,  Vhlle thfs serum is, as compared nith `f-W3 I 86-J ex- 1
tremelp meak and therefore not suited for therapeutic purpose6, neQ6x%0less its

production does have much theoretical importance,  VJS have repeated this work with
horees and have produced a eimilar serum,  This serwn has been tested by Dr Avery
on all the Type il1 strains available, and the reaulta indicate that all Type 111
pneumocci are tinologically identical.
                                              .


r;                                                   .
-. -

., .* -
    "
> ,,

      It is not yet certain; why ft should be pcssible to produce an ef-

"e"`
v.1"8 88l7.C agai,?st pfi3-~ococci o f 2ype I and only one of mch hS6 value

.y.I ::c : ;-;ce~~oco~ci of 'i';rpa II, and one of veryslight value against pneumo-


.-.
-_ -:t 0: T:`i;a I::.' P&se difierczs 86 aprarantly 'sear 63L;e relatiGr.silip to iht3

?Ga6asS:on Of CaFei.lles by organisms 0: tile varioua types, those of Type ITI

:;s-AL, -ye 1-y large capsules, those of Type II moderate sized capsules, and
                                    .*'

tiicsa 0: Type I mailer caFm,&s.  Etaiiiss are being conducted tc detemine

  * I.
   4-e 9 :,a 'v;;re of the ~zzps::latr sLbstan:e, and its relative antigenic activity, in

1

:La ho:ss that light my be shed on this inportana md perplericg r.roblem.

The second method of specific therapy, n&rely, the u8e of drugs

havir.5 specific action on tha pte~ii;ococcu6, ha6 6260 be3C investigated, 0m-

playing the drug ethylhydrocuprein, or "optochln" which r;as prepared by Pro-

fessor Edorgenroth in Oormany.  In our last report,  the results obtained in the

preliminary inve8tigatione of this drug by Dr. Moore were given. During the

past winter studies concarnlng the action of this drug on patients suffering

from pneuirionia vwre mule.  Previous experiment8 had shoned that this drug iS

3  Szctaricidal for pneunmcocoi in the test tube, even in dilution6 as g;feat as

- .
- . Z,OW,O% and Neore showed that this action wan exerted equally on all

typss of pneur!lococci.  It has also bsen shown that when thie drug is adreinis-

tered to ani- or patients the ssrum also acquires bactericidal properties.

The drug ha8 bean employed in the treatment of a considsrable num-

"or Of patien%s in Germ-y and England but the reports concerning its efficacy
1

ar3 conflicting.  I?0 standard dosage, howver, has been an@oyad, and it would

sem that dosage is very iinport~~, since in animal8 considerable aDnOUnt8 mU6t

'03 given to cure, 3ut if very littie more than these amounts be adEini8ter6d,

;oisoni,n.g ra6xlts.  1:: oSh6r nor-da, t:?e curative dose is very ClOSe to-the


      . . .CXf.Z lOSd. IL :;.a3 tlie fo:.:ii: o,lfects are zainly 83en in the effects on the

   rj1.c :.:-A esr; ~arti31 or total ':lin?.r.ess I;as occurred in a considerable nuziber

    ,j i  t:;e zreatei; cases.  mile this so far has apparently not been permanent,

   ~~Li:liziess lasting for a -7ee;[ t9 te:) days, a6 in one of our ca686, i8 a very

  ,~~iou:; drawback to the u63 of the drJg.  It has seemed that by studying the

   `>?.ctericidzi power of the blood of tke patients to vhorr, the drug was adminis-

    terod r:~c:-. coul~d be lear2e2 con:ezi!:;g propar JoeaCe, the pro-x&13 ideal cohdi-

  tio:i bdir.g Obtained Kher I *Jactej.icfd-.: cc*';er iS c';taln32 i:; the shortest tirp8

I
a.   ?i'.d -'ha:- t!LiS is rL?kt::ic8i Coc,Jt,7Yt --'-A'-olij f?uc?uation.
                                                I_ .-.              The latter is es-

   ?d:irdi;' ispO:-tR..t since it :.a6 -:eij: 6hCX $'-a: if tl;e Lacteris be e.qosed to

   a cal:zentrntior. cf ti.3 <-WC; not s:::'ficient t: kill, tL3y quickly ~ecor.ie r3-

   sistaat to t;ie dmg ar,cl very r.xch !-.:c%er conzentratio;s tre re;uired than 7ias

   rlriginaiiy the case.  3rS. IiIoore aid C'r.eaney have therefore Eade an exhaustive

   study of tine ba?tericidal Toner of the blcod of patients after the adzinistra-

   liOl1 of opto:kii in vaq-i1:g dO8.36 a&d adsfni8ter3d in WWiOU8 waya.  Without

    7-n i q- into
      '-., -. t>    the details of their study, I$ r?ay be stated that the optinum ra-

J   .?..L.C~,: a??3 obtained rrhen ar. initial large dose of the drug is given, and this

      :
      W.2 Y foflowed by repeated szall doses given every two hours, day and night.  In

  rezAating the size of the d089, the weight of the patient is of very great

   iqortazce, e.ud they have fourA that the patients should receive 0.024 gm.

  per kilo&r= of patient's wight, yer 24 hours.  They have thus made it possi-

   ble to properly tes f the act&on of the dnrg in patients and it is planned to

   do this fairly,extensively during the coming winter in caee a supply of the

   drug can 'be obtained. At prasen", :f is r;lade only in (I-erznany and ~3 are having

  great difficulty in obtaining a mfficient supply.  Last winter the nwber of

Cp.836 progarly trekked m~6 not laqe, only 25.  Th36e Vere mostly Ca836 of


.`a Xl and III in which the mortality is high,  fa the66 fern treated case6 the mor-

. ity was 16 per cent, which, :Ihile not a brilliant result, i6 not diSCOWaging.

E&dJemio~o&& -
     .I-    The study of this subject has been contimed by Dr Ernest

`ihan,
1    whose results mainly confirm those given in our last annual report.  Dr.

.Ilman has examined the saliva of 398 nonal individuals; in 172 instances pneum-

-2i MfX% PreSeZlt.  In 4 of these positive cases, PntNmCoCCi of Type I nere ob-
irrtjd, and 3 of these gave a history of close association with a case of lobar pneu-

.i3, tvro of them knom to be due to Type I organisms.  In 4 instances org-iS=S of


, i.
,I 4 11; were obtained nr,d 3 of these also gave a history of close association with

.:.: -r;ar,la patient;  in all 3 of them the patient was known to be i-fected with `Qpe

,A Gr$ws3zl6.  PIXWUOCOCCO a: Type III mere found in normal mout'ne 44 times -a i.n
,r;t. cases no close association viih prmunonia cases could be traced.  So far as could



; ~otermined those Type 111 orgmi6me differed &I no ma~(iZan~ologically or other-

`;se) from those found in disease.  This axmnalou6 fact, that `pneumocO$Ci Of the lm6t
JirUlent type my ocaur in healthy south6 without giving rise to disease, cannot be

explained. Atypical l'ype II pne~mocaccf m-we found 26 times and Type fV organiSm6

110 tim06. The ~en@a of t3.w durixq vklch a convaleecent may harbor tbr infectiog -
Qrganiem way ale0 studied, and it was found that organisms of the fnfecting trpe mSY

persisf for ~5 tang time, in one case even 85 days.  These fact6 a%1 have = imPOr--
tnnt bearing cm prob&kme connected with prevention and it i6 b&wed that later Prac-

tical Use may be anade of them,

   Jreparatioq of Antipnetiooo~w~ ~enun. The Work entake& ti the preparb
tim of Ehi~-netrrPOCQChS 662vp3 has grown to a considerable extenit 6nd nom rewire6
s. -onsiderabla part of Che time of ooze man.  Tith better fat ilit ies however, off ared

`:: 2. :leTJ an.lmaL house, &d with the imprcvements ctevjsed in the preparation of the

i -,-
4 "PI urn to be veel?tioned b6qo;T, It ie thcuat timt ,Gk,e labor and expenses involved ma?

bz &:%6ri&t.) red.ucs3.,  `;>:.r-.~~g t'n3 p7esant 6um3r D:: Ml;ora has been actively engawl


in the praparat ion 0 f sem so that we non have a considerable supply on hand. In
nliition, several of the state Boards of Eealth are preparing the serum SO that it
is believed that during the c0mir.g season a large mnber of patients &suffering from

Typo 1 infection, both in this Hospitd and el.sewher't), can t e t reat3d by this Eetho4
   The mothod of producing imune sexum by using d&ad !nstsd of living culture
ml injecting every day on alternate veakc, instead of only one day a r;oek as for-

curly done, has non been tried in horses and found to be very succes6fu1, just as
(.;.r previous experiments had shovn, it to be in emall animals, This method is now
tejng used, and by it horses can be ;nade imune in six to eight weeks imtead of in
' 4 to 6 months ae rme formerly the case,  Sp fat it has been impossible to produce
an:, mre active serum than w&s previously done, though et forts along this line are

still being peraieted in.

   It hae not yet been possible to employ the concentrated S~IUS as prepared
by the method of Gay and Chickering on any coneiderable number of cases.  It has been
tried in 9 cases of Type iX with apparent good tesulte(al1 the patients recovered),
but the number of cases fe etill too small for any conolusiona to be drawn.  It ie
                                       in

planned during the coming niirter to continue its use, bomt$ng it with optochia

,i    A mber Of other Madie concerning pneumonia and pneUmocoCCU8 laf t%tiOW
have been carried an, which however at pteeent have theoretical rather thti practicd

int crest.  Such studies are those reported by Miss Gtryker on Variations in the PnWo-

~0~~8 tiduc8d by Growth b Xqnurrre Serum.  The Batent Period on the Wowth of Bacterfa,
by Dr Chesa8y, Antiblwtio &m&p by Dr Dochea, Studies by Dr Avery on the m&h
of pneuorocooci in Biltr, ErpertaMal and ollnic8zl 8tudiee on the 8gglutiaation -8
of, 88r8 @et fhe adm%aatratioa of %mune 88~~10 8re being m&e `in the hop8 of obtaia-
%og better ;irrd%catib?s for proper dosege,

     Over eevsnty ~asee of diabetes have nom been under treatment at the has-
pita1 of the Rockefeller Institute.  The methods of t4r6atment that have been reCOm-


- I1 -

Lmdad by Dr Allea have now also received nide employment elsewhere.  The eqmrience

:`u and the general opinion of those who have had eqerience else whew is that a

"7 Jet`inite and marked improvement has been made in the method oi treating thi8 di-

: 30.  The Journal oi aAme~i~an Medicinen has this year presented to Dr Allen a gold

~31 which is given annually to "the physician V&O has made the most notable contri-

tion to medical malemae".

   DWing the p-t pear Dr Allen has devoted LI large part of his time to eqeri-

..td Qtudies on dOg8.  The patiante have been under the Immediate care of Dr Still-


.i. and Dr Fit&  During the early part at the yew Dr Stillrum gave much time to
. ..o organiaation of the diet kitchen and cliniad laboratory, and to 80 Orgmiaing ad

:dvoloping the method oi treatment tha+ it can be aarried out in a routtie manners
;I- Stillman was zuuch alded b the work by Miss CIaland who has had aharge oi the diet

1. &hen. .  She ha8 shown IL very speck aQptib$Uty to this kiad oi work and ha8 made
ihi8 departmeat a model that is being very largely Mtated throughout the COMtFp.

The rethods tiaed ti the dietetic treatment oi diabetes have boon demonstrated dutw

the past year to a very large number of phyaiclane who have come here for the pUrpo8e

of learnin&

-    Dr F&t%, in additlom to the cam apd treafolmt of patienta, has beam errgasced
in studying the kUnsy fthwtioar trr saaes Q! diabetes aud in an $aveetigation oi the

;uestion 02 o8dma ol o&t motsboliau in t&$ci diream,  The remaltr obtaIned are ada

ready iar publfoatio& Mwh the Isas been devoted by Dm, Allen, Stillmsa and Fita

to tine pr6psrstlon of a loonogruph dedlia$ fit& t&e treabmt of diabetee and giving   .


the complete 6llnioa$ ergeriewe ohta&ed hers,  This moafqraph ie assr~ completton
and it 18 hoped al.3 be a most valuable und authoritative ca&butioa to the subject.
    Dr P8h8rh8 oar&d oa a aeriek of mtudieo ooaomniag the concentration of
6UgEkX` ir, the firmme ol 13oti a,nd diabetio aaiaiala. `Chi8 etudy ie now completed.

    br Alloa ham a80 CO-Operated with Dr glbuaoio @i th8 Ruass$l Sage Foundation

in a calorimtric study of metzb6lism in fasting and non-fasting diabetic patients.


- 12 -

7he resulta have shown an increased metabolism in diabetic persona aa contrasted

;ith non-diabetics, and also that the metabolism of diabetic persona is considerably

lacreased during the fastingtreataent, thus establishing one of the hypothestie on,

:lich the treatment mas based.

    Turin- the entire vear Dr Ailen has ctJntinued his study of diabetes in the
:.:rtiaiii hpancreatized dogs and during the past half year has investigated eSPCiallY

..I FroLuction oi hipemia, acidosis and coma in dogs.  He has succeeded in imitating
ralutely all the f catures of the dieeaee as it `isasen in man,
. .                                          The nature of dia-

                 . .
.tic lipecia in man has been unknot=  It has long been observed that the blood of



I -::;..o Diabetic patients may be creamy in character and contain as high as 20 per cent

I-l t.  This condition is never found in human pathology outside of diabetes, There
. . ..vo been two theories, one that this fat is derived from the fat of the food, and
tiia other that it ie derived fr@ broken-down cells, but neither of these theories
1;~s had much evidence to support it, and there hae been no explanation as to *Y
such an enormous excess of circulating fat should be heaped pp; Dr Allen has shown
that thie conditiona may teguiarly be reproduced in diabetic doge. The necessary
conditions are that the dog have good digestive poneria severediabetes, and receive

' a fat rich diet. It hae not beenseen in Minr)neki+s and Sandmsper~s forms of' dia-
.

betes becauoe euch doge have poor digestton for fat. Dr Allen*s experiments @how that
the fat of the t+od ie'dervied frop3 t&g tood fat,  ~ist.uW~ancse, h fat ,funbtionR
stand in direct relaltibn to other diabetic pheqmeaa.  Doga with &dosis do not .

riecesl;rily have lipexf13.a;  thirr $8 like the rule with human patients; but all .doga -.

nitt lipemia have acidosis,           *
   Acidosis can regularly be produced in dlabetia dogs by fat feeding.  It also

~~:urs when fat dogs, by properly conducted eqer$ment, are rendered glycosuric.
These dogs ehovr low CO2 aapaaity of the blood and exceee of ketone bodies in the

l;FiYlf3.  1x1 proportion to weight dogs excrete less acetone bodies than man, but the
                                                                           .
concentration is similar.  V/hen the acidosis is increacad markedly, noma s~!por%a~~S.


                            - 13 -                       :g('s?
                                                                           ..q a
                                                                           ". r, f
.th the same program of symptoms as eeen in man, namely, malaise and prostration

Lth decreasing CO  in the blood, terminating in co% with very lam CO2.  It is easy
               2
. keep the CO2 up to the normal height by means of bicarbonate and other alkalies

<t the benefit is very transitory.  No dogs have been saved by the use of alkalies.
    It has been possible to produce acidoeia which clears up on fasting and aci-


   ALI .ia which progreoaes and provee fatal on fasting, just as occur in human patients.

      Heart Disease,
          .-.s _ -*----
    The studies concerning heart disease have been carried on by Dr Cohn with the

  zistaxe of Dr Jarxieson until February, rihen Dr Jamleson leit tp join the Canadian

ilj.tar)r Medical Force.
    A large part of the work of this and preceding years has conelsted in a Cltii-
~11 and experimental study of digitalie, the most itrportant dnxg we poseese in the

treatment of heart disease,  The plan has been to study each year the effect of this

frug in a epecial type of eelectsd ca8ee.  &aring the past year the patients studied

ngre mainly those suffering from auricular fibrillation and oedema.  The study of the
action of digitalis in acute infectionrr with fever(especially pneumoniq) has been
continued end extended. Be a reeuit of the clinical and eqerimental studiee the we
* of thfe drug ia Benumonia has been made nuch l~l~te iational and therefore effective.
    From the careful stcidp of the heart during pneumonia it vIas foubi that al-
roost ten per cent of the` case8 ahome& auricular fibrillation or flutter at SOme time

during the course of the diseaes,  It la in these patients especially that the use
of digitalis may be helpful. It 58 of great importance, however, that the dQ@talia

~ifeo'i8 be obt&ned at the proper time,  To obtain digitalis effect time is neceeaaV
anci moreover the amount of drug required in the individual case is more or less an

il; 1lvilual E:aL*ter,  I@t the detection of uhanges in the electrocardiograph curves
PrWiouslY described it is non possible to know when digitalis effects are being
obtained before the toxic(poisonous) ef fecte appear,





                                                                           I


- 14 -

.`rcm the careful study of 126 cases of pneumonia it has been possible to accurately

:;monstrate the beneficial effects of this drug.

    Experimental

..yFertrOphy is being

:icnl lasions of the

    Nephrit ia
       we-. .w-'

studies concerning cardiac hypsrtraphy in dogs are being conductsb

produced by Beans of muscular excercise end by producing arti-

valves,

Up to the tine Dr 3cLee.n left for China he m.s waged in a study Of the

JI h3nis~T. ol me3 excretion and urea retention.  Study of the numerical lam gOV*m%
                                               with
.
- ._ 6 fu?;tt ion :las been made in patients with nephritis and those/disturbed circulation

4 rdi: to dart failure.   In over 1000 observations these laws were found to be Valid,

In certain cases it was possible to follow the changes in function occurring during
recovery from acute nephritis and also during the period preceding uremia. A similar

study of the chloride metaboliszn was carried on.  In patients shortly before death

from uremia a eudden fall b the concentration of the aodlum chloride in tho blood

plasma wae observed.  thie fall is associated with increase of H ion concentration

of the blood and Hambmgor has shown experbentally that such an increase of H ion

concentration cauaea the sodium chloride to increase in the cells and to diminish

- in the plasma.

These observations led to experdznente which were made by Dr McLean and D~s

Vafi SlYke.to test the effect of the introduction of acids bases and salts and non-
ektrolytes into the circulation on the chloride content of the plassna,  It ie ex-

pected that these sttidiee which were well under way will be completed,ky Dr McLean
after his return to this country,
   JQv&an. Ikboratom
                 - -urr-
    During tha ysar there has been much activity b the chemical laboratory Dr
"?A Fly?:, and his assistwts *aking part in many of the studies previously mentioned,

35 Wll as carrying on icdspendent investigations,   Dr Van Slyke,with ldr Cullen


- 16 -

;;I Fr 2:cLean has continued stu.iies or, tile fate of protein digestion products. TO
nzy out these 6bdiee it bcame necessary to improve the methods for the guati-

:.tive 3eteminatione of the proteins of the plasma.  &rked Improvements in them

u ti;ode have been made by Mr Cullen.  Niss `Jiaograd has continued the study of pro-

:c ir.3 of hunan and COB's milk.  The results indicate that the albumins from the tVK)
e~~r~~~`~~ quite different, but that the caseins, 80 fat as could be determined,


; I c ident ical.

    Acia  An bportant part of the work carried on in the cha&al Mm-
.=atofp has had to do with the queetion of acidosis occurring in diabetes and other
.

c orrdit ione,  The method devised by Dr Van Slyke for determining CO2 capacity Of the
clood has proved of great value and its ekaplicity make8 it one of the most import=t,
al not the most valuable of the clinical nethods for determining the presence and

degree of scidosie.  Such a method is of very #eat importance a8 a control when

fasting ie being carried out in diabetic patients.  From the etudp of diabetic pattent@
ty Dr Stillman with theee methods It has been possiblb to group the cases intO four

c1asse8.

     1.  C~ee with little tendency to sf~w acidoeis eithet whem fasting or Qn

a diet,

   3. Case8 w$th a tendency to hts aoidosio on fastingb   These case6 UO
few but their oacurrer)cg saker i,t extremely important that patients undergoing fa8tix
bycarefully test& i':' t3m ta tiawi Theo6 66666 rpaj seem t& $8 qtite'milb Fro- '
Wentlp On the sscond'and third att@@f to tie the urine sugar-free by faathg DC

acidosis ulay oocur.

     3.  h6e6 showing acute acidorris, curable by fasting, Many severs cam3 with
matked acldasle may show this ph&mmm.  The occurence of them Ca6es is one of

the rebsw why f aetiag is so &nportant in treatment.

     J& h6es with chronic acidoeis.  These are the most diff fcult cases to treat

in the effort to clear UF tl;is condi';io4_.


   !l'ile studies on acidosis have led Dr Van Sl$ke to attempt to find a mumerical
factor for the acid excretion in the urine which would bear some relationship to the

a.;%a.l &.lkaYiine raserve of the blood.  An empirlca~ application of the Ambard for-

ula i:;dic.attrs that rmch a relationship exists.

   A13 these studies on acidosis have led to improvemente in the older methods
of blood md wina analgeis and to the development of certain methods, such as that

for the determination of B-oxybutyric acid in the urine,
   Dr Psimer has made certain observationa which indicate that during pneumonia
;onsiJerable amounta of an unknown organic acid are found.  He ie making an effort

to isolate and determine ths nature of this substance.

     Cancer:

    In his last annual report, Dr Flexner described briefly the most interesting

results abtainsd by Dr Murphy in his studies concerning the effect of X-ray treatment

of cancer in mice.

These experimental results suggested strongly that resistance to cancer grovtth

1s wry largely a matter of activity of the wphatic tissues,  The lymphatic tissues

can be. stimulated to increased activity by mild doses of X-rays snd it is probable

_ that the chief beaeficld effects from this form of treatment ~821 $8 obtained by such

method6 of applioation as mill produce this stimulation.  The effect of large there

peutic doses of X-rays in dsstroyixq cancer cslle by direct application is alight.
Ther'efore, since the X-ray treatment of cancer haa been ea~ployed mainly with this end

in view, using maaaive doses, ht is probable that in many cases aot ably was no goodd

but actual ham accomplished.  The effec,t of X-rays in stimulating the lymphatic
tissuea cm readily be det6rm5ned by estimation of the munber of lymphocyt/ea in the

c irculat ing blook.  Thus we have a ready means for determining proper dosage.

    These obeervatioas seemed so well established by the experimental studies

t..at the Beard of Scientif:c Directors fa'it justified in authorismg a clinical trial

bf the m4thdds proposed.  During the past year, therefore, a number of patients


              \
                                                                           `r`h
                                        ,: `{ :I  . .


                         - 16 -

patier,ts suf f Sri:ig frolr. cancer hzve teen admitted tc this Hospital for X ray
trca*.: ent in the m&w.er suggested.  A ?or?ioa of the expease involved in this

6 `, L'. 1.: . is bein; r:et by income from the autkerford Fund.

    ,The stuJie6 in patients so far carried out dmonstrate that in certain
ca6e6 at least, it is pceslble by proper application of X-raps-to stlmlate tile
body to inCrea6ed activity of the lyqhatlc tiseues.  It is too socn tc drau my

conclusloes as to the clinical results to be ottafnod from the form of therapy.

The mtter is SC kportar.t, however, and of so mch interest that I append the

follomiLg trief reE0z-t of Dr. IAarphy 02 the clic:cal otsexatiox so far made.

       "The cases so far 8tuditd can Se rorgh;y divided ?r.to three
      classes.  The first, the onp ve started out with and still intab
     to rtake om major Gtudy, cor.eieta 0 f post-0Perat ive breast cancer
    where the prognosis is tad, either because of infiltration of the
    large veseel8 of tile axilla or of the cliest wall.  In o&her v7ords
    these are cased in which the surgeon know he left tamer ti6SUa
    behind but nhefe there are no large macmes to be taken care of. Vie
    endeavor to have these individuale adaitted a8 soon after operation
     as they can te waved.  This group folio% very closely our experi-
     Lent OG animals.  It mill require at least two years before we can
    say mything very riefir.ite about the results, if they result favor-
     ab Jr.  A negative result might be expected earlier. Y7e have eight
     such cases, seven of which have been under observation for at least
     six months, two of them for over nine.  The latter tmo case0 mere ones
    in which prompt recurrence mas expected. They, hom3ver, are still in
    exceLlent c?ondition and as yet ehom no sign of a retuen of the dis-
       ease.  The other cases of this group are also in very good oondi-
    tion and as pot shorn no recurrence of the disease, but it is much
    too early to make any positive statement whatever about them.
      tiring the early part of the summer it seemed desirable to
    test out the limit8 of our treatment a% it is used at present.
    20 40 ???? ?? ??? *???????? ?? o ?o???? case8 with grow CanceI: Pree-
   %nt, %o that th% progress could be accurately followed.  These
    cases have consieted of two types,those of small palpable metaS-
    taBi& dFd those of massive recurrence and metastasis.  Of the for-
     mer type, we have had five cases.  I7ith one exception the eir%s
    of the nodules have remained practically stationery, two ahorning some
    definite retrogression, and only one has progreased unfavorably.
      The third group consist8 of advanced recurrence. me have
     had six caee8.  Tt70 of these, we have been unable to influence b
      any way - both are vroznm~ vrith massive growths in the neck and both
     were far advanced when VI% firat saw them. They have 8 te;;;;{epone
    dowa hill and are at present iii. a critical condition.
    ad+anced case of tlarcomt of the hip with metastasis in the lung
    ha8 undcubtaCy bean temporarily helped. One case of this group


with extensive locel recurrence in the chast wall and a large
mass in the neck has rcarkedly tiproved.  Fifteen nodules, varying
in size from a Fea to an almond, k.aw all disappeared.  The ln-
duration in the neck has also cleared considerably, until there is -
only one small nodule left, about the site of a walnut.  This is
far from a cure, as yet, but offers definite encouragment. A fifth
case is one of massive recurrence after removal of a prostatic cancer,
v;hich was beginning to interfer with urination.  This tumor mass
has softer&d and retrogressed considerably and all of the subjective
synptons have disappeared.  The sixth case is as yet too recent
to report 0~"

RUFUE COLE