RKPORT

OF THh

DIRWl'OR OF THE; HOSPITAL

TO THE

BOARD OF SCIENTIFIC DIRkCTORS

OF

THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH

f I r   JANUARY 20, 1917

Volume V   January, 1917 - October, 1917


Rufus Cole.

                   The extension of th Eorpitdl laborrtory

rpeaewhioh~norrbe~providedw~~ah~Qdmdt& nm qarfiora

uillnuoh%dlitrto tb work.   Thlorr&vlBbeeasauD&layminoalTploting

thm u-nngamntm inth nmX-~lrborrtory, but it ir mu o cpeated that

rithlnrwuy dmrttime ill t&X-~workmnba orrriad anlntkm poll

,The mmber of patients admitted to tb HOID-

pitA &ring the put quuter hfm been leaa tbra that rdmitted dUAng t&

oomwond* qgarter luti year. ThijL&ydum totheaat that tha

manbar of dlabater prtlontr admitted ham boon oelynuoh raducmd, o ??? ???

Allenher beendovotinghi8 mntilrt3nmtomcp~nkl8tudie8, a2153 only

patienta of actrm~ly sevmra typ, or ahf~~~uxuuel fe8tuxw0, km- been

needed for t& hu.dles being madm by the other mn thaw in tb, invuati-

tunetely, kmwever, both tIm State UXI City Eemlth Dsp6wtnmnt am nm$m-

puwd to nuke diagnoaer ai typo, and to provide tinan in suitable cnbn8a


No extsnslan of the work IUUI been madm ip

new dlrootim, u will qapear frun the detailed report.

Tb, only additicm uhioh hu been
eta.

to am working form.  we rraabavm intbr homgitdl fburvohntaryrrsir~


                   DrA.R.Do&orhmabeen gmmtodloavmaf

o baenoo to maocmgmay Dr Bigga to Franca to inveetigmto ths situ&ion in m-

gad to tha p11vdenae of tubamalO8is.  IkDo&or'&partu~@wwuldba~

bean* grwLtlorrtotbe Eroopitml, oxmptiorthm f&t tbrt hr ir goingbut

for rixto eight we&a, lindinthaumantimm the intererting&udiesrhiuh

ha hea~&rtakanoanbe aarriedan byDrAvwymdothermmrnbmwaitho

Tb studlao being cerriod ~1 in tb Hom-

pital cwkatbe d.i80U88du gmupdundartha direluerbaing investi-

gated, tkmgh omrkin nmultm do not m1rt.e dimotly to them dioecusta

uuitlm-ofomwillba Qsaribodu wpoaiml &udiar frmtb vmxiourlabol

rstorima.

?? ????? ??? ??? o ntfr, *p of thi8

put oftkrrork.  Wahwmmuthrmobma8unbrinmani~ianfort~

preparation of wnm cd Typa I, t-m form II md onm for Typo III.

Certdn difiiaultiom brs been o noouato md, tbshone~bmminglmae0r

ill, motbttk augplyaimerumpmduued~~notbwnulargsurru

hopedfor,butwe mhmll&ww enmghTyp0 18erumforour~eupplyend
that oftb 8evwral brpttrlrwbrra the 8exumi8 beingtriodaut. 'Th6r,

are @till 8olDb 8utter8 to be 8etil8d boforr the wnm OIII k o ocaamiWly
'and utiiisotoklypro&aad.-                 :                            '*
              ??? o ???? o?? ???* ????? to ??????? ???
                                                             ? ? ?

I


sation.. Ourpmmantmothod ir aumwhmtaxuda adnowtbtthe wnmir be-

ing prodwed in dIfferwe plaoe8 it koom~s very inportmt that a proper

iillmnity unit b8 fixed.

nr Avery hka ha thir matter under lnveeti-

&ion, oon8iQnbleworLchea already bea.~ donm, and it ir hopedtktby
                              SeN

oomlation of the proteation r&lo         and the agg1utiMticmend
                            cllltum

pmoipiktioatitrr ofrxmmberofwrr, anployingaalt~~ of difforont

and xwtsimtb apeoifioitpofthm typ~pnauumo0~ frm rhlohitir dmrivmd


rithanyofthethrae firsd types of~ooocu@.  Ithaa beemfamdu

early a8 twelve burr &or the hithal chill in the4 urine at a petlentrith
pnanwaie due to IP1006U8 iafeotion, wad W persirted Qlrine dalrrysd XW801U-
tion of aType I pxmumnie, 'Baxtinaoxam5aation8 oftbs urine ar. mada In

ad108808 tOdOte~it8~~w~ disqpem with mfe~snce to

tb dinicil aourme of tlm diaeaw, itr rwl8tiOn to pros-i8 end it8 8ir

nifi&WtXM ia iQilitrti= UI Scrrly dbgll08i8.  It 18 pmMnt in thB Uti-

?? ????? ??? thlxda of ??? ????? o rpaoimlly inthow mart 8evwly infected,
80 it8 datedion 18 a&wady of cxmml&~ble pFa0tif-l diw-tio and pmg-

&dOd 8tUdiO8 80 fU h 8ha that thi8

fab8taaaa in ~rln8 Ia t& .follw oImmotori8tiom:-

             1.  It i8 tti8t8bl., X'W818tw boil-.

             8.  ItimnotmmtbdfrParurina byutrsotionwithetbr

8.  It 18 ~ZWi~it&Pd w COllOibl i-l4

6.  It8 immmologio qmoifloity i8 mt o)ruwd by di@8;-  ;


the intndennio route might afford a lllbslu of rtudying tb pmmry tori0

a&ion of wrtdn produute of panmocoocu~, muah U f;t8 trraofaxin aad thr

rolublo eubrtama to which mfermca tir been w,  T& XWSult8 80 far bvu

b9N 8U&308tiVm, bIlttb8 8tAldy bu lrotJ'&pm@W8ti nrfiiGi@UtlytO-t

furtkmr mport at thir tim.
                   DrBlakmtuuken~~~furtherhudiba

oonwmfrrg tb xmture of tkm p-88 rrdting in m&mmoglobin fonmtia by

pnmwoowi m&i other oxidation XWrofiOn8 umoiated with tb growth of m-

lmaocsoi.  It had been found t&t if pmmDw#l weL1.mixed with lmalne wmm

endtbn &blood ~118rrrr,l~r~d,~~tbmagTobinforr~rtim Ocarzwd.

In this roustion a&utlnrtion Of paumuooci ~uuuz%d m&it ~a8 qpmrtion-

8bb uh8timrtb fallura aftho rmutiontoooc~ruu duototbb -bition

of oxldatian prows8 oi t& pnemo~owua,orwinthertim inhlbitioamra in

IQP, way uroatrted with 8&utkution. By IC 8il@@ upedi.nt, rhddng tb

mixture of buune menam, bmuterir lad red blood oollr, o o tlrt agglutiartion

im prevented or &l-d, it Imu been found tht the inhibition doe8 not Ocicur

rs8ult8 Of th8 8tudy will be reported later.

                  hte of mtibodie8 after int+wIomu8 ialootiaa

of '8eW  ?* o ptiOu8 mporb, mntionnu mad8 Oftb obrsr&ion oftb

rharrod that thir hhibiiiag parer mq~ bo pormmmd by other inaamtory       *

emdate pmdmed by the injsation of prmtmwowi. ~stUdi#8WOr,thOQ~

eonwmingthe diuppeumw ofagglUMnia8 frantha bloodfolloningtho

int=vQm8 ~ectlon of $&no 8.m into mated mdnonzul rabbit8. It


,I

8

                            w   I
~~omentratiopab mgglutinins intk bloodand,morsovsr, in suchcm~o           ,

tb agglutinkrs diwpmr fraathebloodrppm mspidlytha~they dofrcm

tb blood of Mbits whiuh IXLV@ not been inf'eoted.   -8 Of the s&U-          I
                                                                           ,

mw being rmde, samples of serum being oolleoted every few hws.  It is

found thmt in the severely hfeatod patients ths agglutinine intmduoed

intkm m 8mxmdlsappemrsrym&lly, endIt fs diffiaulttopro&m      I

My eonslde~b1e gmrri8tent aarosnt~tioa of inmum bodies in the blood.

On the otbsr had, la th early or Proderrtoly infected tmsos, the aggluti-.        ,

nin8 introduood mm,in intb olraslrtion. The alinical wuxme how8 a

a dlmot mlatioxmbip to thi8 ph6noamcm.  Theme obsemations offer an

o O??????? cb Wb it 18 80 importMt to traat ths petisats early, and rrby

inth#vmrma880880 pprohlargersuuuxts ofe4wumare~quirsd.

All th6se observations suggest that baateria

whengmrring'intho body, pm&~ substaaceswhichnemtrall~tkn imrmaity

prinaipl~s.  Theytbsrefore a80 ShWWhy it i8 80 diffidtto influsnob

lowl prooerwm by gezmral pmmslve tamMizmtlon. Tkm difficulty of r&Beat-

i~~lOdpM88 18 dUBIY)tQnlytOtbs diffitityof CUUswtbs &I-

man8 bOdie8 to pwetnt. the walled Off pcoce81, k;lt also to tlm faat that

in the fluids 0f.tho lo&l pee088 tlmre are ligcumulated sUbstarmerWhi&
neutrali tb ilnlmnity i?&itor8,  ThbSO faot8 UW poosibily Of Quit0 W&d.
~iati~~~&ZVd!L8tll88- uithth8 obrarvation8 02 Bail 0'

whioh tb -881tn th8o+ 58 based, tht&h ths interpmtrtiOn i8 BQPT

what difareiat.  ~tbrtbnmdrsilizing 8ublltant308 ar~identi~ with

ths pmoipitablo 8Ub8t8XIm8 now be- 8tudied by moba and Avery i8 not
WI'tdXl, though it.18 lXWibl8 that thOy mpY be identiU&

                 =8tilhBlki8 Ooolti~hi8 8tIldi88 COZP

wrning opidmIiology.  Sputm i8 nm being collected from all tbs person8

liVix@ in tti hrpuse8 frcm whioh &unU&a patient8 c~Q118, aad a study i8


                                                               j--s
                        \
                                m " \a                   (11:
                                                                           .
&A80 being mede of the dust of the moms omup+d by pneumonia patients

before their admission to the Hospital. Dust he been obtained from the

home mana of 18 of our pneumnia patients. Fmm the dust of 11 of these

ID-, pne- ai were obtained.  In 4 ln8tMws these pne~oowl were

or Type I, th, 8emb IU ths type infeioting ths patients;  In 2 instances,

Type n, abothe 8am utb inf'ecting orgBnip11, and inths other ~ase8

t~y~oagrdtot~und~erentlatedCraup IV. tit from5 8lmilarhaaaer

in whlah M pneumnia was parent contalzmd in 3 instance8 pmumcoool,

all of Typo IV,

A Qscriptlon of the rtudy made in one c8ao

ShOWSths phl Ofthi8WOx-k.  3'hir patient was admitted to tkm IiOSpftd

with pamxmaia&aotoprmamoocoi ofType I. mtnm~@bs obtainedfntb

three other mmibers of th Ixnumhold a& axe daughter, 5 ysarr old, mu found

toberuerrierofpneumooocoi,Type I. Tha other tuormmberr abtho bowe-

bid mre mgatim.  Dust, kmmm, obtainadfmmthe roompmmiausly~c-

cmpied by the patient in thi8 house &owed the ;~OSMW of -imP@

1.  OnIkomberlOtht~ dh.ildrru o onttoboard inmother hou8ehold. Sh8

renalned tbsn but thmo dqm.  six day8 after 8b left, o child in thi8
kmucam domqrithm, ti80 dtl0 t0 pammowooiofTypeI. Ths

cmltpm8f~th8 8putumoftbothormmber8ofthFs kwmbold~wemnsga-

the, butfmmthe dn8toftb floorof thirbou80 pkunmowiofTyp.1
                                                            

U0x-e i80~8tebd.~ ~thsdM&WOf~thsOrigkul WtimXt-left thi8 h&P
holdhdhioi'~wu bowding,` tlm third &y, rb wa8 luat~to raotYrr
                                                                           :',.

and also fmm th6 dust obtained fmm tkm hous. did not iI.mw tlm plasenca

Qfpawmo~ooiTypeI.  Latertbs ohildmts w&to BrooUynaadwhUe

Cdh8frUf1thO 8piltWn Ofd.lthbEMhN-8 abthi8 hOUlS~WOXWZbB~titn,

dust uolleatedfxwnthe roomoccupied bythe ohlld showedtbs pmsenw of


_---- .

                                `3'( !
                                                                           . ,
the mpeciflcType Ipnamcccccus.  Later studies ofthe cbildhavb shum

that the opscifio type pmumcoccu~ haa dirappeemd fran her mcuth.

Several instances which eeem to be amtaot

infection or infection fracn tbs sam sourea hvs been studied. One wamn

admittedtothe~Eospitrl bdpmviouslybeen nursing Imr child at ham6,

sick with gcmmah. Bothtb child andthermthbrwere found to bvm

sTypeIprmumcc ocuus infect ion,  A few dqa mg0 8a rotor ix-an the I+ng

Plats t&e&m uaa admitted to tbs Hospital with Tw 11 pxxmwcoccu8 in-

fect Ion.  The day &tar he bewnm sick 8 fellow actor, who occxlpied tb

aatm drarrlng rocmwith him bt tb thsatm, alro became illwithp-,

and also bsd ~11 bfectlon dua to -ccccxxs Type IS.

                  This kind of study entails a &mSt deal Cd

work, but it i8 hopedthotby obtcriaingrl~msb oi 8vidWOO~O OQLl

detemimwhethsrormtwe are Justified inoonsiderlxq pltmmonio due to
t+VB 8I#OifiOt3&88 88 OtXhCt iIkWtiOIi8.
               IkPaherbwbeen0arryingoafux%bsr'8tudie8

0Onwrn~ acido8i8 in pwuxtxinlo.  Thi8 8tudyhM ooxmlrtad in8xI .SttitiOn

withYa+ Slykm'8 o ppx&ua aftha can~dMxido oanblaingpmeraftb blood

pl-,Uld~8tUdyOftb,'~WCCIUtiO0 U fO11olr8: 68tirPatim Ofth.  
hydrOg8n in oOmentxatiopII, bitrat+ a&dity between tIm 8 .of 6.0 and 7;4,    ..:
                                                                           \  
                                          
bt@nairutioa Of MlMNAio~Md PhOlpbPf.8. m tb 'data thl8 obtained it 18
                                                                           _-    :-:f
pa8crible to oalculato t& amunt of `bee orgraio mid -,i& tlm:urhm at ,-T ,i .,_, 1. ' "-, ' .'
                                                  ;
                                                                
                                                            
e.`5.0 .Blood &Ed$'808.I'0tnrl tb f&t.tbat'OrA8 8dda.flndr 08-m d&dim ..',:?'

                  tiltI 8till 8t tb6 w kCh&t8 ti- Hos-
pital Dr Palmer ob8erved by titration ind jphaaphcrlo pcid detmz&mtiOW t&t

tbUI%. ob~e~ifbp6&ient8Of't~8 GOIltsio8 Ow~yrOid8Ub8t&IUX Otbr


             *                                      -. I
                                  b     Y                     ! ri

than phosphoric acid and not B-oxybutyrio s&d.  By ether extraction and sub-

sequent purification a crystalllno subetshce of elementary composition and

mo~ecdlar Weight oorreepsnding to the fotia (l$qj02 has been obtained. %r

Palmer is engaged in further parlficat5on snd the attempt to determine isa

etructurs3 composition, which is unusual, as the substance b&s the properties

of neither ths lorr molecular fatty acidsnor of en alcohol.

                   Othk studies in the bacteriological laboratory.

Dr Chicksring in addition to his duties as Reaiddnt Physlcisn hss oollabora-

ted with Dr %ull in ths production of a potent antityphoid horse senwn. A

hors0 hsa been imnlnlsed intensively by the intravunour injectian Of lip@

typhoid bacilli, and up to ths prssent timb four bleedlngs Znv8 been msde,

with a ylold of &out 12 liters of sennn.  This ~r~llll has en sgglutin tit-

of 14OMOO for wrtaln strains;  ths OMUSO~ rortb prpose ofirtmun&sa-

tion end tb %mvlln~~ (U.S.Army)8train.  For other strains th6 agglutinin

titrs is l-12600 to l-61200. Through th8 oourt8sy of Rr w it k&a been,po8sible
to mqu.im about 66 differant rtrainti frool hzs8n csses of typhoid fevsr of

th0 Paaifio ooast.  It hea been found that with certain of.th6se 8train8,

about'15 lnmmbem, whichare culturallyE.Typhosue, our se~8gglutinoks

only in dilutioni of l-60 to 1400 or lsoe.  Recently~~saab of.the8e strains
have beenui;idSnthb fbi%her tnrmnisationofthe horw, sndthis holr bsen

          ,_                                  .
sccompaniih by"a moderate inor8ase in the agglutiziin t,itxw of ths 8eron4 .
              "

llbtbr wi* on this point in 18 progress.  By corxxuztratingths antityphoid
serum by.ulring fhs B8n8ho8fcGibson Mmonium rulghko method, which is ths

s&hod used for thr concentration of dlphtberls satitoxln, ws have found that

8lmOet the Whole egglutinin content of tkm senun io containsd in that fraction
behaveen 32$ and 54% raturotion with (YrmDnluIp sulphets or ra;lghly in ths pwp-

doglobulin r-tim.  This would seem to be a praoticsl stud ccmvenient s&hod

,


for ocmcentrsting Pntityphoid se&.  F'rau ths Work of other invest1gutors

andmctr*, espec1allyfrcmcertainexperimntal studiee ofDrRul1 on the

nature of the mechanism of immnity to the typhoid bacillus in snimls, potent

concentrated antityphoid horse mmm wculd eeer~ to offer a very usef!U inatru-

ment for tkm study of iamlnity to the typhoid bscillue in hmaz~ individuala.
It ie hoped thet en oppotunity to make such a clinical study may b,/sible
                                 .

next eumner.

plrbetes

Dr JUen ie continuing his studies concerning

eqerlment8.l diabetes in animrla.  Certain diabetic dogs have been kept under

observation aver since Dr Allen came to the Hospitxl, 80 that obeervations

have ncubeennmde on sow oftbmomr very longperiods of time.

                   Ihring ths past -r mch attentim ha;

been given to the effecte of fat feeding in nomal and diabetic animals. The

observed affects of fit feeding are olassifiablm in four divisions.

                     1.  Wect on Acidoei&   It is WellknmJn that

the OrdinsS2'y h~r&o~ SZlime38 Shorr IlO kBtOrlUri8 Oil fEdin& Thsm f$ Xl0

distinction bstween carnivora arul h6rbivox-a in this remn%t. 21re expeti-
m&a oonfixm tbk stdmmnt of -and others, U&young pu~pfes shm

*sting lyxQuri~.  TImir wamboe8 ir the mein difficulty for sxperimsntal        :i
                                                                           ,,,'
                                                                           i]

p8, .Ad& dogs becams subject to 8cidOsie by perti& pancx%ateotaay under

three ocaditiona.                                                           $
                    A. loldorir on feedinn.   Suitible fat diet           /. ,
                                                                           : ,I.
g&v@8 ri; to aeiri0818~ in smmrely diabetic dogs po88eeeing auffioient peer  ij /
                                      iti' i
    .
of fat dip&n. ~'Bcaakdmn of'dige8tiOn lo ths principsl difficulty to be   id i
                                                                           :

avoided.  with Nccesdll mmgeuant, ths acidosis proceeds to typical diabetio  :;/I :
                                                                           ,:,
                                                                           /,:

0-.  The f&t xmtion employed has gbnsrslly been 100 to 250 gmms of suet        ;

dad1 y.  As in hmmn diabetis, protein and carbohydrate failed to stop this           I
                                                                           


aaidosis, so tbalj da& go Into oopl~ an full-d diet. Tim oerbondioxids

cawity of the blood plarp f&Us only in the moat sevem later ata@, 'Luf

in CCua eppmximotes that of bmmn patisnte.  Dose0 ofelIuiLlieesilyK&xl~

bin the blood alkalinity, but do not pemsptibly lengthen life. mS 8x-

omtion of acetons bodies lo geabxmlly mch lose tkmm in human patienta,

but the concentration in th, blood is rully oaapsabls.

& Aaidosls oza f&&at- Whsa a dog with

pohtirlly ssve11 biokks is kmpt fmofmmglyuosuriasndgraduslly~t-

tQ-dbf=!-- ofalouprotoin, highfatdlst, glyuosuriaultlEat0lp bevmlOp6

sndacQPdiflonunk attaInad inuhl&tIm Mabel devmlopa fatal croidcuim

on fQating, rrprodnalng tb oodltts md tbs sylqptaM ooourring in certain

human patients,

            c, &i&$8 without glggmrh Pamal
                                                                --

psacmabwtclp(lr omatu susosptibility to acldosls oven ukmn glyuosurio is

sntimly prevented by suitmblo dist.  Bush sninmls m saitsblo f&t dlot8

.-                    :
       3, ~Pmduuiloa"af &xAationinlVoxmib~
    ,>', : ._;        .  MS: ', Youq $pplu am aiiily

T&me is no @lolien between the pxmdiwt~on af aostona bodies and ix&d-

-tbn ks -88 mtP936.  Tb 63'6@9M~1066 OfhSiX', 80#rrr,1066 ti
-i&t, and vary prononnasd tsmiml atudr ud plunlly ionMsioas,


4.  EfYectonLipmnia, Partialpm-

CPBatectCaDy 0CC&6fOll6 ody e slight lipStiC tSZXitXICy 111 th8 8b68nce Of

glycoeuria, ad glycomuria produced by phloridsin Is knam to k OCCCSP

panled by only a slight llp6mi8, but whentbs partially dspmcreatised

aninnle ~rs allavedto dewlop SS~S~S glyeoeuria, tbbybwcum Susceptible

to txue diab&io lip&a m ht feeding.  As highutenperosntfat bar

been found in their plmmn.

                  The eaqmrimsntr indicate that auidosis Is     '

not &IS 6018ly t0 lack di mbohydrate, but thSt th8 PrplCmtiO fUnCStiC13

be eomshou oommmd, possibly indlmztly thmugh the livsr or othezwiso.

Tb rtudies further ftunirh evidence th6t diets of low protein 8nd high

fat, suoh as warn prwiou6ly mxmmxlSd for diobstior,am imp-r and

inanimlrmeysv8ninduaeafatSl cmtoam,

                Dr Fits, with I& Vur Blykm's USi6tSW8,
haa besnworking onthe applloatian to bloodeqmoimsns of'kn Slyk8*8

nstbdfortb detennlnatian ofaastaao ~ndB-oxyktyrlomi& Blood

or plsrsn is f&sod frOPDproteinwith aolloid& iron uxd the filtrate    .

treated aa dosoribod elsrrrhero.  &odfrunnoxnnLiadlvidualr slwrrr adly 2x" .i
l-8 mg. of acetone bodies mr 100 00. blood, rrhils,t&t from dirbs&S -7.        .'

Study the dationsip bet&n the t&al metaeboliaa o;f `-&a( f... -    d `:

                                      <                   

fonartionofdlamtia mdaxyWtyriam~d& Fb@&k&tkCOgS* -
orstionuzd oxygSn a&mqt~,&rrhichtkr iat and wbobgdrrte aam-
bustion are aaladlated, r Tisrot rpiramter orpabli ob holding 100 liter8
                .~


holrbwa1asliba~t6d.  Rbraxybut*o enddiacmtio8oiAdwtsmi--tionswe
lwraths newazulaccumtonmthods devisedby`?mtSlyb. It is bopedto
uwrtoinbyo~smwithnoxnml bdividualswbsttir, 66 rtpnmsnt
believed but not kxxmn, tb, fornrtion of Qcmtms bodiesm in dtrbetm
18 dlle 6ntirolytotb6lm6mcmntof~bohyd&s bumt, inpmportlon
tofrtmndpmtain, orwhtbortb dirbstiohua spsalfiat6ndsnayto
fonn thse 6ubstsxums, and gbrux&es than- nmtabolislng amnts of
carbohydrate, fat and protein much QS w&d not give rise to acetom bodies

hoped to obtain mcumte d&r onths r6latioxmhSp bkwom tkm oonesntraticm

of6cutOn6bOdi66 lath bloodand t~iruaroti~.

                AuidosLs._   ~rkbyDrPalmrisunder
w4ywhiah~suto 01arifytkm sigpiilaams oftb "8u8lttolemnc6~
09-i mkatie test for BCMOS~S bwid indw=d-ti~ by P-r
hlmmlf,wo&ngwithBsndaraon,rppd by Sollards rtJohn6HopUns. Tb
blwrbonate dOsagop6rLilo b~dyweigtht mqullrd totuattiurins tiMin

ia being caqmmd withtb6 bicmbomte ommntration oftb6 pla6mrt ti .

tims tlm dosage is StBrbd.

0.036 6ioloau.W, whioh-is about tlm - no&+l~t.

thsuriae turnaalkalins'to1itrna8.  l!@ alkali r&6ntlon test thmofolnrpc   3
                              i
psms to aastitute a tltrrtion of ths birrrbonrrto aoxhmt of tlm entim body (
                                                                           /
a6 Sndioated by aYlysis of th6 plwma;. If this statement stand6 tkM tssts' ' i

to whbh it will be m&httd, it will mable 01s to oalaulato ematly frm    j


.

thspl-m~the mount ui blarrbonate rsquim3 to oormct sny obeewved

dsgme of auid0818.  Ths dose neededwillbe l'.4Og..ofNaHO3perkilo body
weight for oath psr cant by wrbioh tbb pl~wpe CC2 falla belcm this nomnal

~u6of6operwIlt. Tlu, a penaa of 70 kilos, with a plasma CO2 of 25
                              70x36

percsat(severe &3idOSiS) would rrquirr       z6lgofblmrbcmate. In

I, fsw teats o dinbetlcs this mda of cml as! ation hpa soermdto be quit.

               &jut Msuss~ Dr cola, Wo& is being con-
tipped on tbs action ti digitslie.  In wcordmas with ear pleawe arm atwly-

lugprrtlsntewhofalln&ursllybto gmupe InwhiohtIm p rominent f8Bturs8

?? ???????? ?o?????o?* ?* ???????? ??? o letrrtlon of blood pxxmmara. At first
tlm work wu aonflnd t,o obwr tb a&ion of tlm dmg in maea b whioh
tlm r&@hPwuaoImal, the bloodp~rrurrrrPtel~~tod,~aowarrrup~#nt
Harem foundthat,uaspt lnhsutr wp&anootiymabjeatto~hnngm inrate,

noilrllin~tmtookplaoe;  tbt tbre wu a0 hflusnae on cnatplt or urine

,

Joctirtg stm$mnthia lntraveanuly with tb view, first ai as~brtainlna whether

                                             
tb arikrir~e brve amplqmd in studying digitelir aatiool am mailable, and


secondly, in Herr short a period paeffeat am be.obtained,             i 4
                                            we believls it

nmeseary to obserwm the follouing~xules in sslectlng patients for amkiag

thbse obserations;  fir&, that digitalis in no form mu ulmlnistsrad k-

foxwtb InJ~Cfilon, 6econd,thtrEt~ CrysfallirM dxophmt~ ilumd,

third, that t4 pmper douga is fuund. lhltum ~quixumnts smsn thmt tb

cmllootion of mxCflolmt~tawUl~qnlr, rrtlnrrlangtimo.

                 We&ve rwaahlyobservedintsMnghumr~oloatro-

oudiogrmatbt r+terblnding~prtloatsadmlso ritortb ingestim obr

l~~toi~~r,tbbTrr~oitlrgUIP,isPOt~y~~~diPionq

but also o~iodimotiama. Iaviuwoftbfutt4t, ezosptfbrrfrw

?????o?? ???????? o lodmeudi~is amdAmredaot to titer, this fIx&


=3x-

X
e.. .
J $

afatropineandfamdthemaimilar.  Ha was also able to skm that rtroplno

had in tb sarly rtage &tor its dmlnistmtion a very dooided stimulating

action on vagus Inhibition w shcmn by ths luqth of ths mriculo-ventricular
canduotion (P -B ) tims, snd that this mtion might Wm place indapendsntly

of ita mtioa aa 4axt rate.  This im an obsemmtion which amfixms ens prs-

viously mde by Cohn WI Ikusr in patients.  AuAhsrpointofmohlntenst

whioh 4 o strbllsbsd was t4 follouingj- Itrru thought t4tt4 fkiluro to

pmduw a aantimaaas bleak my 4~0 be0n due to t4 use of tb gluaoslde rtro-
phsnthln. Amordinglymattemptto obtainrmolr oontimcam bl~&rrosmecls
byarringtbwholodxug intb~iormbothofiluiddigi~~urdrlsoe~Qid

mctraat ab diglWis.  Tbwprepuatiosmirilodu didstmphmthin,mndin

-tly ths ssm my.  coQtavy to wht w experienae alipiorlly, digiti8lir

When gitnn intrrvmmw lyacrtoduqpi~yaadthDo~ot~u~ortr'
t~uwkmnst&p~thinwugimm~  T4rm Is ia this exgarlnunt a posslhio
rueon for alteriag our i&u xwlating to t4 diSmmmo in m&ion, and ooa-
ssqwNyinuse,bstw8~thitv+mgs.


               -h-                                     .

nurvivm inJection dould facilitate the rrark.  The attwpt W0a u&e at first

to rsoord tbs obssrvatiomi withmyoaardiographs attached to t&m arp0-d Imart

ths aninrrls being anesthtieed.  Thismethod hu beenunsuooosa~, fortIm

mlndm did not euxvive long enrrugh.  The oleotroua.rdiographAo mthod of

mgiatration whioh is now used will pexmit extended obsexvatians, la&i.ng

Dr Lundsgaard i6 OO~rotfng with Dr Cob

In studying, byohmniaalnmthodr, themirute volum of th6 kamrt mtmtin

pattints with Imart dieeass.  Two authodu axw being tried out. (a) Dstsmi-

nati- oftbs difiommo in wgen content between venous onduterisl blood.

hopD t4 dMYomnoe tbs ogqen taken by ths tirsuse fmm a lifer Of blood

my be aalculated, dd from tbs latter, and the 0-m oonsmption psr tits,

ths camber of liters of blood pausing t&m lungs psr a&nuts oan be ostiantsd.

The arterisl mygum Is dstoxmined indimatly by satumtlng vmous blood with

air.   (b) A similarmsthod ofEaldana*r buedontb6 differems between

venom snd srterial anrbon dbxide a-tents, andths aarbondioxids wcrs-

tion psr minute.  Thn soumss oferror in each mbthodm atpmwntbeing

rtudisd.

                  An outgrowth ?? ??? o boo,problsmlsastudy

oftho relntionship between&uuz voluuqmdths mctexnal chmstnmmmmsnts,

which hw yleldsd informtlon tbot o pwntly o eblee It to estimrte ths psr-

wntage of tot&l lung volumewhlohis&nctioning iaagivm indivimrntr Ths

                                                                           .'
                                                                           .i h.
ahebstnmasnraakn to.-taken 8X0 ,t4 4ight Of sternum; dorsi-ventral do* . ': ::'-i@
                                                                           ..:
                                                                                "I.

waaurmd iraa stortaam to spim at.ths bight of tIm third rib, late&.--s'-
                                                                           2.

ment at the fourth rib.' T&mss three ~flgums titiplied togstbr &vm tk:.% .:??
                                                                           _?

volupr ofarectaagular prismas bighaaths 8ternwn, andaswids uddmp . . o

as the ehest,msWtmbdatths points cbbsem.  T4 asrating volulrm oftkelungs

is mbasurod by bating the eubjsat bmstha into a bag contahihg two l.iten

of owgen until tIm gamma are oanplately mimd, for whioh parpow three OX-

pizmtions usually suffice, though more are taJmn. The ~lurre of air in the


lbngmie than cmlculatedfraath0 nitrogen contantaithe mixed @mea, It
has been found that during rmepirrtlon at resttbs lylmmlnren orwamnhuua

eerating volunv vd ?????? ??????* o xplrrtion end lnapirrtion frcm 31
                                             f

to 37per conttlargo M muchrprim, the variation being only   3Pr-

cent frcm 34.  Three tubavuloria petienta in mob of wbmm onm luq mu COODY

plotely oollapmod by artificial pmumothoru o homd Mly lmlf th nod

eemting volume, viz.'16 to 17 par omt in tlm ebovm unitr,  Cho patient tmu
fore pneuamthorsx ahmod 29 per oent (only rlittlo below noxml), after-*

mothoru 16 percent.  The umthod will be tried on pneuannir patlonta to oa-

timetethe1uq lnvo1voamnt.

A moondproblgnbor; been tbb develogarmnt ofr'

nrpidmbthodforoqqwndotenniartion inthm blood.   It qpperra o saont~        !
                                                                           i

to at tlrm Irmultmbeforeths blood lme rtoodaalong 0s mqulrmdbytheRar-

oroft method.   1t8ppearsth8tthe principle ofvwuuln o xtr8utlon utilisod        II

lntbs detmmlnation ofplaano -bon dicaida canolmo be srpplbdto oocygevn

dotermination, the knoglobb being treated with ferrocyenbde and th6 oxygen       4

ret free extrrotad by rhaklng for a f6W escoord~ in 8 Torrioellian vacuum,

efter which the ges obtained ir nmasured.. Tbs detaila ere not yet maplete.

Nmhritla   Workoa~thia rubject hrr bomtm-

pomily diminished oulng totbb dqarlwm of~DrUcLeanfordNaer Hmkuu

been& the Ho8pikl for8 sborttinvthia mlto oasnploteworkprevlamly
                                                                           -.

reportad, cud to g@ it mmdy for publiortlon. TN8 is now oqplot&

               A rtudy of certeln problmw relating to no@-
ritio is ZXJW being undertaken by Dr Pailmr, empoolally tbs Fplehtlon of ult

end wetor zw&ation end tla nettuw ai oedmm.  It io planned to rpprmeh the

problem by the dxdy of thb phyeical and chemical properties ofthe mm,
namely the molecular cxmcentrrtion(fFee~lng point) end tot&l olectrolytom
(oondtlotivity), tlm rodium ohlorldo oontent, CO2 ocrnbining parer, phoaphatem,


urer(lnaluding rate of exurrtlon) and varirtionm in blood volum. Dr Palmu%
tmining fito him sspeoiallgto undertaka thi# problem mdwiththe rerimtanco
Of Dr Vm Sl3.b mdUr Culls it is bopedtht ImportrntinformotiCmmyba

obtained.

              Other Studierr In tbs Cbsmicrl IAoxstorio~undar

Dr Van Slyb's DirectioaL  The chaic& studio@ ofDr.Fita, Dr Palmormad

Dr Edgmr Stillmur and Drhndaeprxd prwimrlymentioxmd are being carriodrm
in th ohanlcal laboratom under tb dimotion of and with ths eaointanm oi

Dr van Slyb.  In addition to tbao &udie8, o number of othr InPestlgCtiOru
am in progmu by Dr VUI Slyke and him amietanti.

             Work ir being eanoludmd on certain detail8 oi tb

beta-hydmrrktyria aaid detennlmtim.  Th~dlffolrntfWtonoapabla of irr-

fluenoing rrmltr hve'bem rtudiod, ruchutempexrtura otwhichtha =y-

butyrio aoid lm ofxiuaed to metme mncl the aonoentmtiaa of tl.m dlYf.mnt

raagmtr, vlr. muIpbu.rio maid, mmmry and diohramtam Th work is w
tioelly aonaludednaw, mdtbonmtl?od in itspnmmtfomraoble8 one to

~t*mbe oqrbutyria muidmtonlymm mccuxmtely;ta~t muohmm o i.a@yth-

heretofom. It ianeamurg ourmlytomiXt& reBg@ntm and the'urine inan

-1-r flu& boil under a rwflux oondemm rfbr6Oto80mlauter,~ni~~

'prefonmdacmtolw (a&oimaddlaaetio~id) lm dote-the --my,
o xoeptthatnodichrawto 18 mddmdto ox+&sothe oqrbutyrlomid.

              Mr Cull- km errmged o loctrlcal app~~t'u8 for m

?????? o tUdy ?? tlm hjrdroggl ion oamontzdiaa of th blood, and m &PO t0
fiad *bt &gmo ab aaldo&(acid retmntlon) wuslly oocum in dlabetiom bofO#a


-k-

Cb)
i i..,

the aautrrlity-regulating~chanicnnbrsake dmn, and actual change in the

motion of the blood occurs.

                     With Mr Cullen the work on the ate of protein

diaeetion moduots also will bs aoatinued. The pxxment point under attack is

tkm old qusstion as to wImtkmr intenmdiate products or only smino acids are

absorbed into ths blood from ths mlimmtary tract. Preliminary experiumts

have given d&a which indicate that during the early stages of digastion in-

termsdiate products um absorbed, but durlrq thb later stagbe only smino auib.

                   A& Cullen Is also s-d In a detexmirmtlon

from a nm stsndpoint of ths acid constant of mbonio usid,   Thir oonataat

is of ixrportsnoe in studise of ths neutrrlit~mgulrtlng nmchanism of th body,

and therm is at presenti disegreecnsnt conoernlng its watt magnitude.

Dr Avwry Is oompletlng his biological rtudy,

by the Fxroipitin and oanpleuent drviation tests, of the /dsntitv of ths

=6ina tqdilbumins afhmsnandaows'mllkrespeotively.  Theproteins

ham been prepared + unusual plrity by Urs Vinograd-Vlllckr, who aotumlly

obtained the albumins in arystrlm.  Ths maulto show that ths rlbumins frOm

the twomilks are entirely diff'aront, thebiologicaltost agraeiog withthe

results of the ohambal Lavw&iEptlana ~rtplssn at Dr Bolt's euggestim   'j -1
                                                                           `1 I.
and =portmd lut&ane,  The biologioal tort, Imover, @ms furthor~uld .   j
                                                                           i,$

@per
Tb study of the treatment of oanoer

by the use of X-rays has not procwded suf'fioiontly to permit any oonolurions

tobedrawn.  The pmblema which am presented for solution by this study am:-

1. Ts.ths effeot of X-reys on husmn tumors direct md, local, or i8


    is It a general ef'feot, 98 the animal experimmts would

     indiaate?

2,    If it is a generrl o ffact, is this due to, or at any mbte

    mmocinted with, I) lymphooytio maotiont

3.   If this lymphoaytio rsmotion is important, is it possible,

    by payine special attention to this factor, to m&e X-ray

     tmatxc4mtmox-e effective?

It Is mulily seen that tb whole pmblm is

quite umplex snd so f&r as ths studlss cm hmen ptients am concern&d the

solution is beset with consideddo Uficulty, for gmat aam nust bo tabn
to do no htmn to th6 patient.  Sinoe at th6 tkn) the work WSB comnenoed llttlo

or nothing wms known in regard to stinmlation of the lymphooytio reaation in

hmsn patients by X-ray treotmsnt, before the clinical studies proper oould

be started with my proape& of success it was neoeesary to try vcsrious

degrees of dosage, kinds of mys, eta. in the hops of producing the desired

reaat ion.  Thisisthe Undofwoxkt~thmab&ndone. Eeleye in the reb

arrangement ofths X-ray plant have momwhat intarfered with the work, but

In spite of this progress has been made,  The etudh on lymphoaytio z-e-
action must, of cmurse: be mde oh p&i&to suffering from cancer, and in

aabrrying out this work very oaretil and repeated blood exm8&WAons must           .1
                                                                           ? . .

be de, the olinical oourse rmet be oarefully followed ,tbe X-y treat-
mente namt be aoiumbtoly given, 6and given according t,o a well thwght-out

plan, subject, of course, to modification depending upon o-s in the

patients'  omdlt ion.

                This work is being directed by Dr Muqhy, who

is sssisted by Dr Morton in the clinioel studies, and Dr Wetherbee who sd-

.;'

;
-'

ministers ths treatment.


The progress ofthio studymastforths re(ucm

1 hmmmenti~led bs af neoessity slarr, andths f&t that already lmportamtob-

servrtions hpve beenmade is gtatiiying.  26 patients bava so far been tm&ad,

It haa been found necessary to keep theme patlente in tti hospital only for

short periods aft-, M thy oan x&urnu froquentlyas neededfortseet-

mentcrnd o xaminatian.

                   It 18 too soon to speak of clinloal results.

Four of the patients treated have died.  With perkpa two exceptions, the

otbr oases hvs eitbr remained st~tionmy or lmve shown mall but dirtlnot

iarpxwements in ths local oondltions. Tb, eliaical results then, while not

striking, are distititly o ncourmging.  In may asses it has been poesible to

aase e distinct lymphoaytio rrootlon, in others this hm been Sm,posalbls.

The experianca sof& has not been insuffioisntto saywhetlnror nottbra

ia e definite relationship between the lymphooytio xwPotion and oliniaal oourse,

though the observstione so far amAe 8uppOti this hypotheeis.