?

RIORT OF TIQ, HOSPITAL


               HOSPITAL          -i k

    With the growth of the hospital in age and diversity of

an.tivities has cme a correqponding growth of the staff in tra.in-

ing and experten%.  Whereas during; the first years of the hospi-

tal's ex!.stcnce msr; of the rmmbers of the staf?' consisted of men

of teletiw',y ;m13. exparlenco and training 2-1 scl3ntlfiz work,

now the hcsprtal sttif irc,ludes sevqral mn of w3de reptation and

s&u&if+ c p-biT it? and rapable of carrying on and dfrscting scien-

tific work.  F'hir; has resulted In a greater or Lesse? sqparat ion

of the wurk cf the hospital into several divisions, each under +&e

direction of me ttzan, with a corre$pondi.ng division of responsi-

bi'ity.

     From the nature of the material whit% is studied it is

obvious that this division of act Lvities can never be 80 complete

in the hospJ.tal as that whi& is possible in a purely laboratory

0rgEUdZa^,i0,?.  fIwe-,rer, by maintaining as clbee cooperation as

possible batwsen the various divisions At is hoped that n6 loss ia .
effeotivmsr;s has resulted or will result from this change in orgaL

isation, hG tnr;tead, that a great incream in ind.ivid.ual accolDr   .

plishu4exlt will follow. '.


    -   As a result of this modif ication in the plan of work 5%

has becone ticreasinzly difficul2 to present a report on the prog-
ress of the 5nvesG$gatian of the varj.oue diseases xihich are being
studied which till adewtely describe the act.ivities of the hospi-

tal.  Consequnntly the hospital report tiow consists more of a

report of the tidlvidual workers rather than, as, forrrsrly, of a


                        !'.131,
report of the work b the hospital as a whok             ,


     The pat iant s admittad for ettady have cons isted of

persons suffering from varloua forms of acute raspirato?y die-

"\

881~8, acute rhematlc fever, measles, nepbt',tia, or heazt dis-


ease.

!Ro s:udy of rsepiratory diseeRe has been dtiacted

along rcmAat /-~ffarent Inner than those in tiich the hospital
her be-l1 mgkge~i j.n the past.   It Is believed that the effec-

tivenens of cerum treatment in cases of pneumnia due to `Jlype I

~mmoooccus has now been well demonstrated end the technique

uf treatment has been sufficiently well developed that it my

be effect3osl.y empIoyed ia other hospitals.   The mnufactuse

of the 80rua also haa been undorta&n by others no that it hae

net wansd advisable to employ the xwourc81 of the hospital
to any great extent in f'urther study along &is line.   The

study of the question of sffeotive treatment of pn&nonia, how-

ever, has not been discontimmd crime there are umq' oas& of

Other type for which at present the28 is no effect;ivG treatmat

ka?wn.  Cur experience so far hae not indicated that it till be

poesfbi~ to make w modiiicatton in the method of serum treat-!   e :+
                                                               .`".. r _ .,
me& Mbic$ is smployed in Type I cases to rpake it applicable to
                                                                 ..;
these other form.  Attempt0 are, therefore, being made through
                                                                *     i .
more Rwz'&zrmtsS rt;uAi~s to obZain new lines of approach to the

problwn gf specif'ic ^,resrtlrent in these other caees.   In the mean-

time, jt I?aa been thmght adv$sable to 8Tudy more fully the fum
tional 3bnmizal.itios pressq'; irr pat+mts euffering from pneumfaia


                     `j w
with the possibility that improvements in treatment may bS

devised, w-en in the absence of any farm of spscitla treatnrtnt

which acts directly upcn the bacteria or their product 8.   Thb

progress uade albng these lines is Cescribed under the work of

Dr B!nger and Dr Stadie.   The follodng report by Dr Avery
includes a deacrlptian af work accomplished and in progress re-

lating to the bacteriology of respiratory infeotions.

DtS!T

        S-dies on Enzyrres of ~coccus,
     In conjunct ion wdth Dr Cullan the study of the biochesn-
                                  -w-
istry of the intracellular substances of pneumococcus has been
continued; dur!ng the past rir months, however, this study has
bsen unavoidably interrupted because of demanda made on Dr
Oullenle tlm by the work of his ok depertumt form tiich his

rervlcee could be spared only at odd times.   In t3ie November
issue of the Zournal of Experimsnfsl lkdicine there appearsd three
ptqare bp Dr Avery and Dr Cullen covering the studier on the .en-.
wnwe of ~mmoco~cus thus far completed.  These deal with tie .'
psotbolytio, lipolyticr and Carbohydrate-splitting' enoymas and &I&
01eaC the Piset t&at, by mean8 of sterile solutions'and slrtraotr of
pmmococa5, it ie possible to correlate many of the functional
activities of the living cell with the enzynotic processes of the
intracellular subatancee removed from the growing organism.
    tither study has demonstrated still other enqmot~c

activities of these pneumococcal substances.  These spclf,ic `in-
tracellular agent6 manifest their activity on various substrates.


Fcr !.netance, in the presence of blood, active solutions of pneu-

uQcoccl az strongly hemlytic and under proper conditions are

capable of tran:farEing hemoglobin into rrethemglcbin.   Cowledge

of the na+urc of these endotemotoxins myr prove significant in the

interpretation of certain blood changes clinically associated with

~eumococcel Infection In mm.  Again in the presence at bacter-

ial suhst?-atqs r:onsist lng of heat-killed pneumcocci, these act ivu

enzyme-containbq solutions cause complete and prompt lysis of the

cell bodies; this bactariolytic enzyme is specific in that its die-

solving action is exerted only on pnmmocooci and not on hemvtic

8treptacoaci or etRphplococci.  On green-producing streptococci,

rhicb nny be more closely related to pnmmcoccus than either of

the other organisms, the bacterdolytic enzym of pneumcoccus ex-

erts a lytic action, which, however, is never so active or so com-

plete as in the case of the hamologms organism itself.

     In connection with the investigation of these intracellu-

lar enzymes, a study is being mde'of autolyeis of pneumococci.

It has been found, x&en washed bacterial cells from actively grow&
                        

ing cultures ar9 suspended in @ospba& solutions,  that the ' ht e&

                            ^

and',rapidLty of self~dissolution of the organisms is depend&t
                                                       

upon the hydrogen ion~condentration of the mixture. iutol3;d.i is
.                                          ,_. , `.,..
most rapid. and*cox@ete~~ove'r tho&e pH 6.5 to 7.5; wit&"this
         

range lie the optirm of the protease, lipase, `and invertase of

pneumococcus.  In fact within this zone all types of enz,ymes of

pneumO~o~~~s thus far described can act simul%.ne~u~ly.   'Ihis fact

recalls the observation of Dernby that autolysis of animl tissue


.

                                                             :  ;w

proceeds further;% at a P.y&og@n Son corzcentrat ion tier8 the variow

enzymes can functLo3 8lwolt8necruaYy.

     fn the C-sss ti this study it was observed that if the

bacrtarial suspms!om were autoclaved folloting autolytis, precipi-

tatinn oocurred at a def in:te reaction.  FYthsrmore, this acid

bone of best pe3p?tatio3 was faund to be different for differlslt

fqpes 03 pneumclcocci a&. l!.kewlse different from the point of acid
egglutine.t%cn of the various types ea determIned by Gillespie.
nose obsemetimr eugges+,ed the pwslbility that this reaction

might in

point of

gatod by

peciLi9.r

some way be connects~ w3th differem% in the lsoelactric

the oell protafn,  911s ~enomrmm 1s now belong investi-

the cata&oresis me~kI.

  S:xd!es Qile Sol-LbilSty of I%?umococ~s
     .I_ .-     -- .a.--,          --- -.*
AB fa? ae is ~TIOWI for bacteria, solu?~ility in bile ie

to pncumococcue alone.  Eowever, this p~opsrty is pos-

sessed alao by certain

that micsocrganltm so
. (   
psculiFLr ity in comllon )
   _ ,I-: .'. _..'.?,

sp!roc&aetee and trypanosomes.   The fact
             I

widely romote biologically shonld have this
      :

led earlier Investigators to attempt the UE~
  , 2,: _      "..              . .

ia pnemococcal i.nfec:%ozm of dhemothera~utio agent3 of rsputed -t
                                                                       :
Value AI! t>e treetmcnt of dieeaaes due to organisms of the other `P
                                                             ,.
groups.  Kith %he hope that a fuller Imow~let!ge of the mechanist

of the bile yeaztion might lead to a better unrierat&ding of the
                                                         . .

action and effect of ohemical ard FhyPicxl egents on tho bacterial

cell, stxdy of the bile solubility of pntiupococc~~~ has been undsr-

taken by Dr Avery.

Heating pneumococcus to a temperatuxc &ove the `&ermsl.


.

                             `*' Yf3+L
                                                                . `.
daatbpoint (52'C.), oc dtpcting the cells to 80 acidity equsva-.
lent to cr greeter tkarl the acid de&h-point ($ 5.) renders them

lnsolub33 !.n hilt.  T p the orgmi sms are exposed to the action of

carbolic acid or saturat.ed 177itb Clram's iodin solution and then

vuaabed free of these reagents, they are no long- soluble.   The

effect an bile soluhillty of varying the concentration of salt and
of varying the hydrogen ion crmcentrat icm of the fluid in *iJ1 the

organisms are suspended Is being studied.  `J!he meximm solubility
of the bacterial cell at any given concentration of salt frop Ed/2 to
M/320 ie at pH 6.. vhile a, the acid side of thic point, bile
eolpbility decreesee ae the salt concentration increaeee, and at

reactions more alkaline than pla 6., the greater the salt conwr~tra-

tlon the greater ie the eolubility of the cell.  The explanation of

these rt%ctiona is being sought at present. .

     Bacteria adsorb ant ibody and after specific adsorption,

exhibit certain ~enomma Indicative of eurface, if not of intra-

cbllular c?lemge.  Specifically sensitized pneumococci are viable;

agglutir&ed EUA reac'.ered Bagocytable; are they still bile solublti

or ie it possible that the cell membrane has becow so altered as

to be resistant to th8 acti- of bile?  Pneumococci wwe sensitiac,d

in specific atltipmumoccrc~a senrtl, the agglut+nated organism8 thorn

ougUy washed in repeated changes of salt solutions, the chzmps of

bacteria brokan up, aN the cells resuspsnded and tested fir bile

solubiUty.  As control, pneumococci of the same type nare expowd

to heterologous izmxine serum and treated in the manner desc$?$bed.
%`he~ SpCiiiCalfy 8ensitizN bacteria wre bile'iqqoluble, v&~j.le


thc,sc similarly trea+.ed with non-specific serum were corqletely

dissoived Ir bS.iq?.

      As a 1~;: r-mtsr of patients with lobar pnewmnia give

a history of some preceding infection of the respiratory tract, a

study of the bacterial flora of the :qqer res@Rtory tract in

health and in common colds has been etarted by Dr Ernest Stilti/
                                                    -.-

Special attention has been paid to the bacterial flora of the nocc

&ore but few organisms, mostly various kinds of staaylococci, ara

found.  The work on the biological classification of Bacillus in-

fluenzae has been confirued and a study made of the distribution

of these biological types.   The incidence of Bacillus influenzas

in about 100 nom1 throats &his winter was 23 per cent.   Of 11

case8 of corysa and laryngitis studied, Bacillus influenzae was

recovered Sn 5 cases.  From 29 cases of lobar pneumonia Bacillus

lnfluenoae was recovered in 25 cases, or 87 per cent.   From 2

cases of lobar pneumonia and from one case of laryngitis, meningo-

cocci Wre recovered from throat cultures.   In 2 of these cases,

the cultures were zl.most pure.

      Studies con- prowth accessory substances in

,. ,

:'- bacterial nutrition.

. :

     These -studies are` being csrrisd an in canjunction with
Dr Thj&ta o? &rictiania, 'Director of the`Iaboratorie*s of the

Norwegian Army, who joined the hospitz staff last November. Be--

csnse of pretiuus observations cm the occurrence and growth of a

mucoid strain of B, paraty$hosus, Dr Ilhjotta became interested 13

the growth of mucoid bacilli in general and the transformation of


                                                                    I   Tl%

x3-nx.c~id Olga& sz7 ir?to the m~a5.G xWetv.  He %gsn his w;rk here

wl.th an ett.em;t to ~rx- d'flrrerzt r:ic7-oorganisrns, B. pnzatmotuz ancl

pnf3llIrQ~OCCi ` i? br9t.h coqt,Einirlg the 1111xzus prodlx:d b,v a variaty of

rmlcoid bacilli.  ?h~iing ?.tis :vc.r4 he r,ot;od tlxit B=.ci?Ius ti:fi.::en7ae

grew when !.noculr.teC. into blood-fr?e 3ro+& sonclai?inn, t'le rmxsid ux?+,cr-

ial of Baci'!!~s E'ric:dXIndGr.   Considerable ouantit.i=s of the m~coid

uubstance were soll;?cteC fr3m growth of a mucus-prpduring strain 3f

Bacillus FriedJArlde: and Tepared by quspending it i? salt solution
uad heating it one hour at 60oC,  This sterila substance, &en added

to broth in var*g anwunts ms found to support life of Ba~il?~us in-

-n&e wIthrrut the ddition of blood OT blood derivatives.   Subse-

puently Dr Thjotta found a similar growth-promoting action in extracts

of xmxoid Iraterial obtained by boiling suspensions of Bacillus Fried-

l&War and even of non-mtxcdid argfmisma stu% as Bacillus proteus.   It

is evident then that Bac'Illua inltftrenzae can grow profusely in hemoglo-

b%n-free

ourtracts

tmdla consisting only of plain broth enriched by earetlsions or

of lancoid bacilli or bacterium proteus,

fir+.hevmo?e, it w&s faund that these emulsions and extracts

CM be boiled for ten mi11&e3 and filtered through %rkefeld candles

withaut losfag their growkh-inducing property.  1% was thought not

oobiksfy that the grew?&stimulating effect of these bacterial extracts
d@S be he to eubF;tamzea of the mme nature ~3 the so-ca.lledvit&
                                

miner.  To test this asstnuptio.n, similar extracts were prepared by fi

ThJotta end Dr Avery frcm zeart cel?.$ t*ich zxre known to be rich 3x1
growth access;ry s~3stinc~0,   Tness e;;tract3, even in -rG.riate armmfh

were found capable of grosoting growth.  Extraction of the growth


                               ..I -ib

a.ccesso:g mbstances f:om another source, namely, green vegetables,

7ia8 tried; FY.vx30ts: cf fresh tomatoes, green peas and string beans

wer3 fmnd remrkcrb'ly active in stimulating growth,    These active

yeas? OI- vzge';able cxtxcts when added to broth greatly accelerate

grow& or' or~~~~ms suti irs 3acillus influenzae and pmumococci, so

that ~ittin Ti.l.3 ham3 abundant grov:th is evident.   In the case of.

pneumococcI, a sxc!ing too uzinute to initiate growth in plain broth

alone till amply SliPIce to induce ebmdmt grmth in the same medium

if a mall aPovnt of extract containing these growth accassory Sub-

S~~CCS is d-ka .   Xn the case of Bacillus influenzas, luxuriant

growth ~CFTS in plain brath containing yeast extract &en seeded from

blood wdib, Ahi-ie under identi.sal conditiaao, 110 growth takes place

in the same broth to which these extracts have not been added.   The

addftion of these growth accessory substances in concentration as

smell as 1:lOOO suffices to stimlate growth under these conditions,

However, for reasons to be dismssed later, subsequent cultivation

fails %n trot'2 mti4m containing only yeast or vegetable extracts.

     `Ahile %he- nature of these growth acceksory substances is not

hOWn, they a-e &X3 -7 a~~&ly analogous to the so-called vitnminns,   It

has been iourii. t&t they resist boiling for at least ten minutes, that

they are dest?oyed -l>y nut -lclm-Lrlg, that they are extractable From fresh

vegetables an2 fiorc growing bacter'&l and yeast cells, tkat they are

mter Sohi~~o', t3ie.t they pass a Berkefeld filter, and that extract6 of

these e&xk~?c.ea cmtatn tit little nitrogerl,- about 0,116 per cent.

Rxatever t3: e i:- m.t.u*e, it appa:s ?ha: IAess growth accessory sub-

stance5 2.W.3 iLirO;.tAllt feCt0Tu irl `bacteria3 i1?1.t2jtio,n,




    In the application of this prinhpie to bacterial nutrition,

particular attention has been thus far given to the nutritional re-

qUirexEXlt6 Of 'Bacillus iIlflUeaZa8, since this organism belongs to a

pamliar group of bacteria nihich have been heretofore considered obli-

gate hem@Alos.  Closer analysis of the growth requirements of these

organisms,however, has shorn that the so-called hemwhilic property

ham been based on a lack of knowledge of the actual nutritional needs.

It wa.s soon discovered that v&areas Bacillus i3f3x~1za.e would grow

lumriantly v&en transplanted from blood medium to plain broth cantain-

ing yeast extract, cultivation could not be contimed in yeast broth

alone more than on3 or two transfers.  'his suggested that possibly

soam other m'i~s!-zncr~ wzs carrier2 over from the original blood culture

in an amunt sufficient to supplement the yeast broth and that growth

failed in mcceeding cultures became this substance was eithe5 ex-

hawted by growth oc lost by dilution on subsequent transfers.   FOE

prposss of discussion this substance may be referred to as the X fac-
tor and the vitamine-like substance in the extracts, aS the V factor.
Neithe- of tie63 tm frzctors br itself can sustain growth of ~cilluS

influeiieae,  Evidently both are essential to growth ana both are sup-

plied iz blood used ia the cultivation of Bacillus influensae.   As

prer icusly poir ted auf , Lhe v factor is destroyed by autoclavinq. If,
therefore, blood medirlm is antoblawd, it should no longer be able to

support grcnti ol BzciLIli:; icfiuenaha.  knis is nctu,Aly Zhs tica.

If, however, the X facto? has not been asatrcyed. by heating, then this

same msdixn should be reactivated. bz the additicn of fresh yeact Ex-

tract.   This also ?s the caceL  l'he growth accessory substmse (+,h2


                                                                 . `.  ,
v factor) &ich is destroyed by autoclaving blood, can be supplied

from another source, sur31 as yeast; and this substance is capable of

reactivating a medium in v&~ich, as a result of heating, the X factor

alone remins.  Moreover, just as the V factor can be supplied by

the addition of extracts of living cells, so the X factor is found to

be contained in hemoglobin-free serum and ascitic fluid.   serum broth

containing yea& oxtyact furnishes all the nutritive requirements for

growth of Bacillus influonzae, containing as it does the requisite X

and V factors.  Sea-oh is being xade for the X substance in material

other than body tissue,  That it is not hemoglobin itself, however,

that contains this essontial substance,  is shown bg the fact that pure

crystalline hemoglobin &en added to broth fails to support growth of

Bacillus Infl-cenzae unless yeast or its equivalent in the V substanca

is also present,  This fact indicates that hemoglobin contains some

of the X factor, but is in itself not capable of sxtpForti.ng gr0wt.h.

JkthCT, sinzd ~;ui;st~u;czt, other than hemoglobin have .oeen found to

furnish *Ais X substance in greater abundance, it is evident that homo-

globA as sue\ is nJt requisite to growth and that Bacillus inf~usnzac

is r-c-. ;L stri.ztb he~oglobino~il.ic organism.  Th!.S fact, hOW3Ver, is

of 1~6 i?qc~tenc~ than tie ~inciple in I*,acterial mltrition $&ch is

irrvc ;,`Fcc? in its &xmnstr& ion.  Fu.rt%er slxdies are plannod to deter-

mine th[t ki$~~+.axe of i& :qrixiple in the culltivatf,ou of other

species of ba&sris.   f,-lmSlar analyses of tlze rmtritfonal require-
                                             1
trents of organisms new cC!.-tivatad with dti"ficuRty may Ty?.e!.l a ikller

uM.zxA~xkd".ng of th*j oTti- con?dit-io:~s for growth.   fi Kn malogy

with anir.4 nxtr5.tion, it ssems not unr?-asonable to suppose that


growth deficiency in the cultivation of bacteria may be overcome by
the addition to culture media of the appropriate growth accessory

5ubstances.

3

I)r Blake

    In association with Dr Trask the following studies have heel;

made concerning KZ as le s :
     1. Infetiivity of the blood in experixzntal msasles.
    A 8er lee of experiments dealing with the infectivity of the
blood in exp&umtal measles in monkeys has been carried out.   It

has been shown that the disease uay be readily carried through a serie

of animal passages by intravenous inoculation of whole blood from in-     ;.

:'

fected monkeys withdrawn during the prodromal and early eruptive

;i.

stages.  tie infection has thus been carried thruugh twelve wssages,

By this mathod of passage it has been found, however, that the virus
gradually becomes attenuated until it is eventually no longer capable

of causing a general infection.   It has furthermore been shown that

the vimrr is present in ,Fe plasma but not in the btiod cwp~scles i ,
                                       _,                                     - :...
.that it ;is$rasent .~ln as. eimll amount8 aa 0.1 to 1 ,cc. of blood, and
                        . . .   a_..
that it is capable of lndoc4ng a general infection by aubcuttmeour, in-
oculation, provided it is so inoculated before it &as been attenuated

by animal passage.        ,. *.                   .'

    2. Resistance of the pinrs to glycerol.
     It has been shown that the VMAS remains viable and retains

it8 infectivity for at least 2 months uben preserved in 60 per oent

glyoerol in the icebox.  Under these conditions it appars to becom
soxkhat attenuated, though the data on this point are not as yet


                               *L-k
                                              jF

sufficiently complete to ma3ss a def inita statement.

     3, Effect of intracutaneous injection of virus attenuated (?)

by aniroal passage or glycerolization.

     It has been faurd that monkeys inoculated intracutaneously

with 0.1 to 0.5 cc. of fresh or glycarolated plasma containing an at-

tenuated virus, exhibit a local react ion but no evidence of a general

infect ion.   The local reaction consista of a def inlte cutaneous edema

of 12 to 48 hours duration v&ich may or rzay not be followed in 2 or 3

dqs by a local exantham in the neighborhood of the aIte of inject ian.

A considerable number of monkeys have been thus injected to study the

clmracter of the lect?I reaction.  These mnkeys are being kept for

subsequent immnity studios which it is plamed to begin soon.

     4, Acquired immunity following experimantal measles.

      Six monkeys which had previously recovered from a.n attack

of eqertintal masles have been reinoculated, in me instance with
measles virus of homol&us eeurce,  in five instances with v5.n~ of

heterologuua mmrce.  None bp the six showed any evidenue of infect ion

v&i18 the control normal animals inoculated at the sazm tin with

qaivalent amnlnts of the MUM m.terial CEUW dorm with ex~rimsntal

maasles.

      5, Confinned attempts to cultivate the virus have not yet

yielded positive results.

      6. Attempted fnoculation of rabbits with the vinrs of

tIy3asles, by intravenous, subcutaneous end ixtratest icu%r routes have

not been definitely successful, thou@ yielding some suggestive results

eich warrant further study.


br Swift                                                         1 .

      With the assistance of Dr Boots and Dr Miller the' following

studies concerning acute rheumst ic fever have been nmde or are in

progress:

      Ten patients tie were considered to have rhetic fever at

`the time of admission have been studied in the past six months; subse-

qul?ntly twe of them have proven to have other f orm8 of arthritis: one,

a gonorrhea1 arthritis, the other a destructive arthritis.   Of the

eight patients in vjhom the diagnosis of rfiewmtic fever has been made,

only two have had a siqple polyarthrit is wdthout complication; the

others have had distinct cardiac involvement.  From pathological

studies of tha hearts of patients dying from this disease it is becom-

ing more and more evident that a specific form of acute interstitial

myocarditis is present in most fatal cases. ._ While in former times the

chief em&asis was placed upon the occurrence of endocarditis in rheu-

mat ic fever, today we are r&king an effort to determine the presence

of myocarditis during the course of the disease.   In collaboration

with Dr C&Q our patients are being studied with this point in view.

Daily electrocardiograms am rmde of each pa.tient during the acute

stages of the disease, and at longer intervals at later stages; at the

same time caref'ul bedside studies are made to determine the relation

of abnormalities in the electrocardiograms with signs of cardiac com-

plicat ions.  While these studies are still only in the preliminary

stage, it is evident that in many patients there are distinct symptoms

and signs of mocardial involvement and at the S~RD tim evidence in

electrocardiograms that the rtgrocardiurn is acting in an abnorxral


                                                                t

namer.  Prolongation of the conduction tizn3 is one of the chief ab-

normalities noted; two of our patients have had transitory attacks of

auriCular fibrillation.

     ?he action of the salicylates in rh8usatiC fever is not yet

definitely determined:  whether they act merely as antipyretics and

analgesics, or &ether they have a definite specific action upon the

arthritis, ar8 still moot points.  Careful daily charts are being

kept showing the development of each individual feature of inflaxm-

tion in each Joint and the disappearance of each of these signs and

smtoms after the patlent is fully under the influence of salicy-

lates.  No reaords of this type are available in the literature, and

it is hoped from a study of patients in this manner to be able finally

to throw so038 light upon this subject.   Another clinical study con-

tknred from last year is the toxic action of salicylates upon the kid-


neys.  Hanzlik and his coworkers in CleVelandhave reported that most
of their patients Eihortly aSter recei&ng toxic doses of the salicy-

lates have edema and other evidence of disturbed renal f'unction.  &r

studies in the past two years have failed to confirm these findings:

Ch4.y &en patients are severely intaicatedhave they shown the symp-

toms that the above msntioned workers claim to have noted in most of

their patients.

     Blood and Joint fluid cultures in all of our patients this

year have failed to reveal the presence of streptococci or other bac-

teria.  At present w8 are concentrating our attentionupon Cultures

of the joint exudate with Noguchits anaerobic methods. No definite

results have been attained; grossly, sorm of the inoculated tubes have


                                                               . * i

appeared different than controls, but microscopic examinations have

failed to reveal any definite bodies.

      Our efforts to reproduce the disease in ADjls have been

continued by the Injection of rabbits, guinea pigs and rponkeys with

blood and Wtes from patients.  Four rabbits and two guinea pigs

have ishwm a rran-arthritis; a11 but one of these animals had been in-

oculated with material from other animals of the same species that

had received the blood of rheuuat ic fever patients.   It has, however)

been impossible to induce arthritis in wbsequently inoculated ani-

mals.  so far, therefore, the clinical picture of polyarthritis

rheumatica has not been reproduced experimentally.   EIistologiCal

studies are being w;jde of the hearts of all of the inoculated animals;

mny of these ahow focal wocardial lesions the nature of which still

await8 elucidation.

     Dr Boots has carried Cut, an extensive study upon the anti-

bacterial properties of sodium salicylate in vitro and in viva, and

has dompared these properties against streptococci of the non-hemo-

lytic and green forming varieties with similar act ion against pneurro-

cocci and hemolytic streptococci.  He has shown that sodium salicy-

late in concentratbns floe to ten timss greater than it can exist

in the body has practiaally no bactericidal action; not until a con-

centration of one per Cent is retied is there ag demonstrable

inhibitory effect of the drag 5.n fltid media.   A theoretic dissoci-

ation curve of salicylfc acid has been plotted, from *ioh it is

evident that salicylate in a medium of the reaction of the body mst

all be combined with base in the form of a salt; only at a pIi of 5.


.E'

Y `; !q

or less is there any free salicylic acid; at a p1I of 4., less than

ten per cent of the salicyl exists as free salicylic acid.   It is

obvious that this degree of acidity does not exist in the blood or

inflauxnatory exudatea of patients with rhmtic fever.   It has been

determined directly that the joint eacudatee of our patients is at a

reaction of about pH 7.4; in one patient with Sta&ylococcus axreus

arthritis the oxudate had a reaction of #I 6.9.   This evidence defi-

nitely controverts the long held opinion that the action of the sali-

cyl in the arthritis of rboumatic fever was brought about by the acid

reaction of the joint exudate in this disease; in this supposed acid

exudate salicylic acid was supposed to be set free.   It has been

shown that salicylic acid at a reaction of pH 3.1 and 3.7 has little

if any more bactericidal action than HCl of a similar hydrogen ion

concontrat ion.  Sta&ylococci are more resistant to the salicylates

than are the green streptococci; green streptococci, hemolytic strep-

tococci and pneumococci are all about equally susceptible to the bac-

toricidalaction of the drug in vitro.

     The blood of patients who have been given salicylates to

the point of intoxQation and that of rabbits receiving comparable

doses has been tested for bectericidal properties:  This blood was no

-8 antibacterial than the blood ,of the same Mividual or animal

before receiPing salicylates, nor than that of norm1 controls,   It

seems evident from these studies that if! we accept the green atrepto-

coccus as the etiologic agent in rheumatic fever - an opinion not at

all proven - the beneficial effects of sodium salicyfate mwt be exer-

ted in some other wag than against the bacteria.


Dr Van Slvke

      Dr Cullen has been engaged in perfecting a simple colori-

metric method for determination of hydrogen ion concentration in the

blood plasm.  Certain slight errors attend the use of indicators in

such a solution as plasma.   `lhe proteins affect the behavior of the

indicator, and to a slight extent, the salts also.   Furthermore the
                                                 .

ph undergoes an actual increase when the temperature of the plasma
is changed from 38' to room temperature.  Our purpose has been to de-

vise a calorimetric technique &ich would yield constant results, and

then to compare these results with those obtained by the standard elec-

trometric method,   If the difference ia sufficiently constant, it can

be used as a correct ion, so that results obtained at room temperature

by the simple color imetric method may be made to Indicate the actual

pH of the blood plasma.   A considerable m.amber of human plasmas have

been subjected to pH determination by the two methods, and it now

appears probable that the problem may be successfully solved,   The

calorimetric tevhnique was first developed to a point tiere duplicate

readings could be checked within 0.02 pH.  The freshly drawn blood is

centrifuged under a layer of solid paraffin to prevent loss of carbon

dioxide,. and a sample is diluted with carbon-dioxide-free &ysiological
      j.      . .:-
saline `solution.  The l&ter is contained under paraffin oil In a ,ybe,
                   1.          ; _.                  /
and has the indicator, phenol red, already in it before the plasma is

added.  The reading is made in a comparator.   Thus far the results

have averaged 0.18 pH higher than the electrometric, and correction

does not seem to vary by more than 0.02 or 0.03 pH from this value.

If similar results continue to be obtained, they will demonstrate that,


with the calorimetric te&nique developed by Dr Cullen, reducing

the pH obtained by 0.18 gives the actual blood plasma pH with an

accuracy hardly less than that of the electrometric determination

itself.

     Such a method will be of value in the study of disturb-

ences In the acid-base balance involving alterations, not only of

I

alkaline reserve, but of the pX also.   These conditions do not wu-

ally occur in acidoser of the metabolic diseases, but they do occur

                                           .
constantly in anesthesia, as stated in our last report, and probably

in other condition8 in v&l& the sensitiveness of the respiratory

control is affected.

/                   The above mentioned work on blood changes in anesthesia


i              ha8 been cant lnued, with CeafiInBt ifm of our former resulta, Viz,

that etherization causes a lowering of both alkaline reserve end fl

in the blood, the respiratory center suffering an apparently progres-

sive deadening from the start of anesthesia to the deepest stage.

With the improvements in technique on vlhich we are at present en-

gaged, including the calorimetric fl determination, we hope shortly

to learn more about the progress of the changes, their persistance,
+d facto& affecting their severity and the rate of recovery.'
   We ale6 expedt t d `use this technique tb stuw u&e ."Cbf&
plately than heret#oM the acid-base balmke `of the blood & pneu-
mania; Newburgh, Meana and Porter raported evidence that in

experimental pneumonia the reaplratory center becomes less responsive

to carbon dioxide stimulus.  If this is the case, a decrease in the

pH of the blood is to be expected,similar to aat found in anesthesia


     Dr Cullen, Dr Austin, and Dr Peters are continuing the

work begun by tiera with Dr McLean, in a collaboration between this

laboratory end that of Prof. L. J. Henderson of Harvard, with the

' r
I

purpose of ascertaining the quad itative relationships of the

changes that occur during respiration in the carbon dioxide end

oxygen, the chloride end bicarbonate, of the cella and plaaza.

The preliminary results were of sufficient interest to indicate

that the problem ia worth developing, for the light it may throw on

the phyeiology of respirat Ion, and the aaditione that it may bring

to our rmens for studying reepiratory and airculatory dieease. We

are at present improving certain points in the technique which were

found to need standardization before results of the dosired accur-

acy could be relied tqon.

     Dr Peter8 Is engaged in the preparation of crystalline

hemoglobin for study of its acid dissociation constant and of its

alkali-binding power and buffer effect.  Hemoglobin appears to be

the most important substance in the blood in maintaining itB con-

stancy of reaction during the physiological changes of respiration,

and an accurate knowledge of the above factors will assist in form-

ulating clearly the manner in v4xlch hemoglobin stabiliizes reaction.

  `5
, `/

     Dr Binuer, for work tith heart patients, has so improved

the Lundsgaard-Van Slyke tecihnique for dbterminat ion of lung volume

that it c&n be de,pended upon to give accurate results with subjecto

v&O cannot increase the depth of their respirations, or otherwise

collaborate.  In the original method a known volume of pure oxygen

from a bag was mixed with the air in the subject )s lungs by several


deep breaths, and the lung volume was calculated from the extent to

VU&I the nitrogen gas of the lung air was diluted by the known vol-

urn8 of oxygen.  When applied to patients &IO could not breaths deep-

ly, and therefore require 2 or 3 minutes, instead of 30 seconds, for

completa mixture of the gases,  the above method becomes inaccurate

because of the considerable volume of oxygen absorbed.   This diffl-

culty has been overcome by having the subject breathe a mixture of

oxygen and hydrogen, and baaing the calculation, not on the nitrogen
content of the final gas mixture, but on the N2:H2 ratio.   SinCl3

hydrogen is absorbed but eli$Aly, accurate results may be obtained

by this method even Hhen the breathing ia continued for several min-

utes.

     !he object of this work is to analyze the lung volume than-

ges ia heart patients.  Peabody has already shown that the vital

capacity is diminished, roughly in proportion to the cardiac insuf-

fiolency.  Dr Binger's object is to obtain data also on the residual

air, and find whether the dimimished vital capacity la due to inabil-

ity to expire with normal completeness, or to the obliteration of

part of the aerating lung volunx3.  Results of interest are being ob-

tained, and will be reported later,

     Dr Stadie is mntinuing the studies begun last year of the

effect of oxygen breathing in pneumonia.  ,He has improved the struc-

ture of the chamber ia *I.&L the patients we placed, and perfected

the .&hods for removing the carbon dioxide and controlling the oxy-

gen tension,   His results confirm those obtained last yeat in show-

ing that cyanotic patients have the oxygen content of their blood

increased by raising the oxygen content of the air they breathe, that


.




                                `j `hs,

the cyanosis correspondingly diminishes, and usually disappears, the

rsspirat ion and pulse become slower and more nofrPa1, and the patients

a)rpaar more comfortable.  The improvement las tr only as long as oxy -

gen administraticln cant inues, removal from the chamber resulting in

an almost ImPsdiate return to the former condition.   `Ibe cuurse of

the infection appears not to be affected.  The treatment rmy, how-

ever, have value in maintaining the vitality of patients 1410 have ths

ability to overcow the infection if *ysical exhaustion is prevented.

    Dr Stadie is beginning a study of the changes ia effective '

lung volwm during convalercencle from pneumon ia, particularly with a

view to obtain informat ion concerning the changes that accon~a~ res-

ohltion.  For this purpose ha is employing the improved technique
for lung volume determination perfected by Dr Binger.

     Dr Edgar Still- is cant inking the study of nqhritia,
devoting particular attent ion to the relation of the rates of salt
and urea excretion to the blood concentration, and to other f'unctional

tests in the different types of nephritics.  At the sax~ time the.

treatment is accurately regulated with the aid of the diet kitchfm.

It is hoped that information rrrty gradually accumulate which will

assist in the objwtive differentiation' of the types of nq%ritics
and the corresponding treatments uvhidh are necessary and just if ied.
    Dr Stillrmn, as one of the details of his study, has, at

Dr Cohn's suggestion: made observations of the blood vo;lume by the

vital red method in a series of cases with hypertension, in order to
find &other there is any indication of a decrease in the volume of

the arterial system.  The results were entirely normal, however.


    Miss Hil& h&s conrpleted a carefil study of the diffemn:
           -.-.-

protein preclpitants used for blood,  in preparation for tither ex-
periments on amino acid Ny&&ogy which will rewre especial accu-.
racy in mnoval of the proteins.  The work has indicated the rela-

t$vb awl&eneas with v,Mch the different precipltants remove both
the native &oteins and the lntermedlate albumoses and peptones, and
vd 11 serve as a guide la the use of reagen to that could formtwly ba
&played only Fn a relatively uncertain xmnnm,

,        ldiss Hlller lr alas proceeding prith the wry difficult
  work of Isolating and identifying the unknowa basic amino-acid af

   gelat in.  The substance has been prepared in rus%Xi quantiti~8 in
  farm for analysis, and is now being prtqared on a larger aCel6.

Dr Cohn

     kingthe past sixmonths, the laborator 5.es in the Cen-
tral Building (Room 320) and on the sixth floor of the hospital have
been abandoned, and the new one on the eighth floor occupied in

their stead.  Under ordirar:r c!.rnlmstanc,es this ` event wu3.d merit

no c,oxment , but the `p&&g `amI preparation of tbnew rdoms m&

affer $0 nn& grater `iacil%ties,                  ,, -.
                  conserve'our energies 80 rmich more

and render experjmnt ing so muth easier as t6 compensate f'ully for
the work spent; ix+ their const,ru&tion.

     Investigations have been carried on, both on patients and.

on animla.  (1) Patients in Dr Swift18 care, suffering from acute


I
I

ohmic fever, have been studied electrocardiographically.

(%anges of two sorts have taken place in the hearts of these pat-

ients.   !tbe first concerns alterations in the auriculo-ventricular


conduction interval.   It is generally presumed that in health this

is constant or changes within narrow limits.   But it is hot un-

known that in this disease, as in sy$ilis, changes t& place in

A-V conduction in certain instances, &ich so-times lead to heart

block, especially as a late sequela.  Rut this knowledge did not

lead ua to expect changes from aaJI to day, amounting from 0.02 to

0.05 8oconds.   This oaaarrence furnishes sound cUnica1 evidence

for the belief that the rhenmat ic process my involve the heart in

its ent ire9,y , agocardiurrs as rrell as endocardinm, and In a sense per-

mits studying the qyocarddal involvement in detail.  Exactly what

lesion it is, v&~lch i8 responsible, oncj cannot say, but the nodules

described by Aschoff as dharacteristde of the disease suggest them-

selves a8 the cause of this mnifestation.  Xt is interesting to

notice that cases in vMch other evidence of continuing disease has

ceased to exist, still manifest the changes olbikh are POW described.


(.. i... .:---A ticond point-"wbridx this study has &OI& is'alteration-`i~
the form of the ventricular capgpleres id br'iif *periods Oi `time; This
involves more especially the Q R 3 group and is- indicated k the

changing he-t of the waves; alterations in the notchings *en these
are present; and deviations in the for; of that portion of the curve

wg between the Q R S group and the T-wave.   In one case espec-

ially was this chenge wked.   The downstroke of the R-wave failed

to reach the base line, but stopped Short of this and continued into


the T-wave,  It is for the morzrent of importance to recognize these

d.banges in the curlms.  That they batoken the presence of altera-

tbaa in the heart rmacla is, of collree, tnle.  But dlich fbnction

in the heart has suffered end for what reason is still obscure. The

full explanation xmst await a closer knowledge of the eiectro-ws-

iology of the heart.

     In the third place, irregu&w~ties have been encountered

in these oams.  Premture caatract ims, especially of the veutric..

U&u WWbty,,, -8 not infrequent,   In two instances trensient fib-

rilbtiorl Of the fiUZiC188 as seen.  In ano ca88 several paroxysms,

two or thr0e, mre studied.  In the other, a Sing18
ohetved, but before the return to norm1 mechanism,

interval in which for two or three day8 the ax1Hcle8

me in this case uncmmmly fortunate In being able

paroxy- was

there was aa

f lilt tered.  We

to *otogra*

the transit ion from f ibrlllation of the auricles to the normal me&+

anism.  I believe that I& hunran ~siology this observation is

unique and important.   f9 `t&3 CUP78 after th8 tit Vi%d'iCdE@ WbVe

occurring during the flbrillatory period, several more awicular

waves indicative of fibrillation appear.   Then a11 evidmce of mar-

iqllar activity vanishes.  Ihis post fibrillatory diastolic period

ie distinctly long8r than that usual ki this ca68.   Diaatole ie

interrupted by a P-wave, representat ivs of coordinate auricular con

tract ion.  It is followed by waves of normal ventricular autivity

and thereafter by a normal mechanism.  lhe curve throws light on

the f ibr illatory process.  Whatever its nature, whether due to ruul.*-
tip&e foci of stimulus production as Lewis holds, or to circus


,

i

ContractionS acc.ording to Garrey and lvIines, the process obvLmsly

terminate8 mdd0nly.   That this is less likely on MS' stqposi-

tlioo &an en that of Garrey and Mines la possible,   For the lnolrsmt

ither spaad.ation is perhaps unwarranted.

      (2) Further  stud1 es have been made with the dogs prepared

after the rrmnsr of Van I2ersu.m.  &I expevlurmts performd on an-

esthe tized dogs, it was found that with doses of g-stro@nthin and

of digitEclis equivalent to therapsut ic doses, increase of eontratr

tion, increase of blood pressure, and change in the T-warn all took

pbC8.  P&ether thee% &anges take place in the intact, unmesthe-

tieed dogs ia of course unknown.  It was thought that the dogs Fe-

pared after the Van Leersum method offered en opportunity to make

this test.  They afforded at all events en opportunity to study the

blood pressure and the T-wave change sinnltanecms3.y.   I am unable

to report on the results of these experlmnts.  The perfection of

the technique for taking the blood pressure has ccaatxmd mch tti.
The original mthod of circular cmcppreasion of the carotid tu-me1

had to be abandoned in fatror. of lateral compression,  The trafning

of the dogs to lie stil.1 for the duration of the experiment a `Rhile

not too great a trouble, has nevertheless been difficult.   Mean-

vhi1.e it is possible to report that the collect ion of control elec,-

trocardiograws and of blood pressure readings is being accomplished.

  (3) Studies itiich were rcade with Dr ~~cgwzhi on monkeys and
.

guinea pigs inoculated with 1eDtospira icteroides and leptospira

$cterohermr*ag:%e have been completed,  As in the case of yellow
fever ix?. hutqn beings, the heart rate in exper inxmtal ani~IE&3 is


slow, out of proport ion to the temperature elevation.   !Fhe mechanic

of Slowing is one of the vbole heart, that is to say, it involves the

sinus rhythm.  Irregularities were encountered but they were not sig-

`< ' ,i
I

nif icant.  Animals in *ic;h typical disease did not develop and which

were killed, did not react as the infected ones did; the heart rate

did not become slow but reuained at the narmrl level.

     ti bvy has studied the size of the heart in pnsumonia.

In a group of pneurmnia patient6 serial teleroentgenograms were uade
during the acut6 stage6 of the disease and in convalescmce. Linear

naesuremente of the cardiac dtiters and plantitrio determinations

of the size of the heart18 silhcuette have shown that in a large per-

centage of cases the heart dilates during the febrile period.   !ke

return to its normal size is gradual, lagging behind the decline of .

the pu&e and temperature curve6.   In a series of control cases,

both normal and pAhol.ogic, no significant alteration in the sine of

the heart ha6 been found over relatively long periods of time.

    For outlining the cardiac silhouette a new technique has
been devised tiich substitutes exact instrumenta delineat& for the

older free-hand method of &npleting the uutline at the base axad at

the dia@ragm.  From the x-ray plate faw points and two arcs, at
                                                                     

the riefit auricle and left oentric'le, may be directly traced.   -!Ehe

cardiac outline is completed by describing the two rerpaining EWS

wish the compass, employing as radius the distance between the two

point6 which it is desired t0 CCaieCt.   In this fashion the sector?

outlined by the arc joining these two point6 is a function of the
distance between the two points vbich are joIned, and its area varie8

I


                                                            L * . "I l.tq
therefOre, directly with this distance.  By this method the total
8ctual shadow cast by the heart on the plate i$ not the area measured.,

but a definite and constant portion of it.

     2, IYe have cant intmd the observation6 begun last year m the

u89 Of atrophanthin in the treatutmt af heart failure.  A group of

patient-6 suffering from fibrillation of the auricles has received the

drug intravenously.   In addition to the usual clinical rcethods em-

ployed, a study of the venous pressure waa made.   It hae been frond

that the venous presouFe rises ae heart failure develops, falling

rapidly with irqroveamnt in the clinical condition.  !hS veTloU PI-%*

we in nornrrl individuals in bed ranges from abmt 5 to 15 cm. of

water; in heart failure it is not uncommon to find the venou6 pressure

rice to 25 cm. of water,  After treatment with stro#mnthin, in a6

short a period as one hour, the venoua pressure ha6 fallen from this

level to 5 cm. of water with coincident relief in the patient's symp-

toas.  This study is being continued.

     3. The sarca group af patients has at different times received

digital18 by mouth.  Dosage and the rate of utiliaation of the drug

in the body have been particularly studied.   From the observat ionu of
Egglest oi it hae' become clear that large doses of digitalis rpeJt be
given by mouth dely and with therapeutic effects in 6wprisingl.y
abort time.  Our ovm studies have confflrmed these f tidings,   It ap-
gears, however, that to attempt to calculate the dose of digitalis by`

the body weight m&hod, as Eggleston rsconmentid, is di6appointing.

     The difficulty appears v&en one considers that the optirmun

therapeutic effect, v&i& may be determined easily by available crlter-

ia, is obtained in the same patient on different occasions by doses of


different magnitude and 1s observed in different patients of the

Bari. Weight after quite different amounts Of the drug.   Other mt3,hobs

for arriving at the proper dosage habe been suggested and stidied.

The amount of the wrscle of the heart has, for example, been supposed

to bear a relation

body in the belief

&ich the heart is

to the amount of the striated muscle mass in the

that striated muscle is the most active tissue

called upon to supply.   To estimate this m9s3

creatinin determinationa in the urine have been trade, for the excre-

tion Of Cmatinin is COn6taZIt and Is dependent on the VO~IUM of 6Wi-

ated muscle.  Here again

amnmt of creatinin bears

of digitalis,

in relation to

of the rate of

iod of tixe is

'Ihe 6Bme nny be said of the use of the surface area

there has been diserppodntment, for the

no constant relation to tie effective dose

digitalis dosage.  !l!ha attempt to utilize an estimate

excretion or utilization of digitalis over a lang per-

also unavailing in patients v.310 require continued digi-

talization.  In brief, there are ~EUIY unknown factors concerned in

the m8chanism of heart failure, so that it is unsound to attempt to

calculate the dosage of digitalis in terms of any one of tiem, or so

far a8 wu know now on the basis of any cmbination.   !l'he dose to be

given to a given patient at any tiwc: oi to the same patient at differ-

ent times rmst apparently still be trctimated accord_ng to criteria we

have so far found useful - the fall Lq z-at6 in auricular fibkkt ion;

the ChWg8 in the T-wave of the electrocardicgram; obvious chaxlges in

breathing; and the subjective sensations of the patient.
     4. A new Btrophanthin compound, obtained from Dr Jacobs and

fi Reidelberger of the Rockefeller Institute, has been experimented


                                                                           -

                                                               . I  IT3-s

with by Dr Lew in cats.  It is obtained from g- stro*anthin by

hydrolysis, and from the preliminary observations which have been
made in animals, appears to be less toxic, thou@ therapeutically

as effective as the mother substance.  Provided this compound can be

isolated in crystalline form by the chemists, further studies, even-

tually to include observations on patients, will be made.

     Dr Binaer has devised a method for studying accurately the

lung volupaa in individuals V&O are short of breath.   This mthod was

reported at a recent meeting of The Society for ESrperirmntal Nadicine

end Biology.  At present this method ie being applied to case8 of

cou@ensated heart disease and to oasss of heart failure in various

stages of decompensation.   Cases of auricular fibrillation lend then.-

selves admirably to this study, for the degree of decompensation Can

be controlled by digitalis therapy.  As effort is being made to cor-

relate certain eymptoms and msical signs with lung VO~ULIB kanges

both absolute and percentile.  Data are being accurmlated ht are not

yet sufficient to serve as the basis of generalization which it is
hoped will throw light on the me&anism of reduced vital capacity and

of dyspnea.

    The problem of dyswea is being studied also from the point

of view of circulatory stagnation.

     Other @uxxama of circulatory stagnat ion are being investi-

gated in patients 2nd in ani-1s.  Gf part 1rsula.r interest appear to

be:  (1) The relation of oxygen "co&e& and capcity of arterial and

venous blood,  It has been found that c.ontent and capacity bear an

inverse relat ionship in animals ir, experimentally produced anost%ila.


            .






                                                                   I


A sitilar study will, it is hoped, be undertaken to examine this re-
lat ionship in patients under conditions of anoxemia seen In heart

dieeaao.  (2) `Ihe relation of elevation of temperature to heart fail-

ure and circulatory stagnation.  An hypothesis has been found wh idh

appears to explati this relationship.   It is that the elevation of

rectal terqperature which has been fd results from faulty heat dis-

sip& ion.  nata on body temperature are being accumulated in a pre-

liminary my in a variety of pathologic states.   The facts 90 far

obtained appear to throw light m the fever ueen in heart failure and

to associate its occurrence with circulatory stagnation.

      Dr Ralsbeck bar contknred in the manner in which, as has

been reported from tlxre to time, he began to make measurements of
electrocardiograms made here of soldiers returned from France.  It is,

ar bar been pointed out, a laborious undertaking and will require some

time to complete.  His work is admirable and leads to the expectation

that its results will serve as the basis of reliable generalizations

on the dimensions of the nor-1 electrocardiogram.
     Recently we have admlnistered @nidin sul&ate, a cindhona

derivative, to patients.  Formerly guinin was nn.xch used as a cartWaG

remedy.  Recently (1918) quinidin, a steraoisomor of quinti, was in-

troduced by Frey in SchittenhelmRs clinic.   He found it effective in

converting awicular fibrillation tibo a normal cardiac mechanism in
a routine investigation of the usefulness of drugs of this series.

Since his original publication, t&e reports of 83 cases of auricular
fibrillatlon,in which the drug hss bee?. used, have been published.

In 42, or 50.6 per cent of these cases, the fibrillatory mechanism of


the lezrt is repsi'"Jz d to have been successfully rest ored to a norrral

sinus rhythm.

     lhis effect was so astonishing that Dr Levy was induced to

repeat the Gerrrran observations.  In the past few weeks the drug has

been admtnietered to four patients suffering from this condition.

All these patients were known to be SubJect to fibrillation for long

periods of time.  fn two pstientr auccem in restoring the normal

Cardiac mechanism was actually attained,  In a third, transient aur-

icular flutter followed the administration of the drug; and in the

fourth case no effect was attained.  It is possible that with increas-
ing knowledge a greater prcentage of success Is possible, especially

in cases like the ones in which auricular flutter occurred.   The dur-

ation of tie ef feet of this drug, if are nrq judge from the exper ienc*
cited in the literature, is short, lasting on the average one week to
om month; the longest case observed rermined norm1 four months. The
f iJ?st patient observed here has now maintained a normal mechanism for

ten days.  We are ktudy5ng the drug, both in patients and in -peri-

xmte.