mR!f OF THE PIRECT~OF THE HOSPIT&

PF THE ROCgEFEkbER IlOgTITUTE FOR MEDICAL RESEARCH

           January 1919

To the Borrd of Scisntifio Dinoton of
The Rookofellor Irufituto for Yedioal Ro8earoh.

During the put quarter the same uonditioar

that have rortriatod the r88earch rrotititirr of the Horpital during the

put year have ~ontinuod to bo opsntirs.   In addition to the abrsnce

of many of tho daft, Dr. Van Slyke haa been ill, and conmequsntly there
haa boon little work aacomplirhed in the chmicsl laboratory, aaide fra

routine work and teaching.   Dr. Cohn ir rtill abroad eo that the work

in hla department hsr been practioally at a rtandrtlll.   Th8 interns
rtaff ha8 conrirted ent ir81y `of army of fioerr d&tailed to the Horpital.
`Thou men bre &a `kpdrary' da&y, rlbjo&t at aa) time to order8 rqnding

them 8lrewhrro.  Moat of them have had little or no tralaing in nreareh

method..  Conroqwntly it ha8 been praotioally tiporriblo for thom to . I
wwgy +y?yo8tQ~tion.~~
_..                 %, On +ccount~ of,: +ho obumtor~ of ..tho. intom,, x:..ik    ::`,
                                                                           .li' :
                                                                           `!. i
rtaff, it ,.ha8 born ko~rrruy for ths Dim&or., to- giro mwh%of I hir tiroqto
                               _'                      ' ' [:
th.8 8atu81 diagnori$ and treatment of,patisntr.in.t~~wa~8., i'!., !Y:, li~..lii?,::.
.                       .;                     `:::,
                                                                           :.

                        1 .The work, of training member8 of the amy udioal

corps bar crontinwd &wing the quarter and har mcupied a conridmablo

amount of the tto of tho rtsff.  This work, ae mentioned in the pra~iour

reportr, ham consisted of four rpecU courmo:


     I.-A course in bacteriologloal methods glron for medical off i-

aor in the Institute Laboratorisr.   The inrtmct ion of the men in tho
methods of studying the baoterlology of acute infectione has boon given
by Dr. Avery and Dr. Dooht, arrirted by Dr. Stillman, and thir haa

required a oonaid~rable amount of thoir t&no.

     1I.a 0our88 in ohmnioal methods for memborr of the 8aaitary
Corpr ham boon giron in the chemical laboratory of the Horpital.
     III.4 uouru d88igned to t8Uh waaan th@ bactoriologiaal

mothodr omplorod in th8 otiologio diagnoria of acute reapintory diSeaaO8

ha boon given during tha put quartor in the Elorpifal.   This Courao has

been under Dr. Avery and Dr. Stillman.

IV.-?nining radioti Of fiUSr8 in Cli!lioal methods.   ThOSO Offi-

Qora hav0 a180 a&ad aa intamO8.

All th888 0our888 hare now ended and it is not

likely that there will bo my further need for this kind of aatirity at

prorent.  A few of th4 army modiual off ieorr ordsrod to the Horpltal for

oliniaal Study rtlll remain, but u SOOti a8 thoy aro roplaaod by civilinns
               - .:

a88mub~8d~ and <that :the..rork of the Hospital aaa prooood iti OtdHr$y fa8hiOa        .'
                                                                           _

on00 more.  Ierorthaloar, muah roorgaxlitatioa will be neaerrary~ aad it

8oom8 adViSabl8 not to-attempt to obtain a iti1 staff at onto, nor to o tt8mpt.

to r88tm8 all tho 1iaeS of work in progrore at the opening of the war.   80

much doponds upon obtaining maofly tho right kind of mea to araid in the

work that it 80~S1dVi8ab~0 to roa\pIo tho Work and to rophca the staff


,       - ,,-j
      
; ;        3
     , :    \
    \\

gradually ar the problems develop.

_tudr of Acute RsrDiratorv Dlreappl.

             The pr8riou8 report wal Written very Boon after

tha spldamlc of influonra had made itr appoaranco in the army campr and

when it WM boglnning in Ifow York.  SIna thon, thir disease has pro-

railed to a very great extent in Pow York.  we have, theroforo, been com-

pelled by ????????????? ?? o rtond our rtudy of amto lobar pneumonia to the

study of influenra.  Indaod, the oharactor of the route pulmonary lnfoo-

tionr in Iow Tork her no changed during th4 past yoar that now typical

lobar paouaonia ?* our o xparionoo hm been largely replaaed by pulmonary

inf eotionr ocamplicating inf luoasa and by mtypioal i.nf lumations of the

lung.

                  we have

\

addttod t0 the &Hpital a UOn8idembl8

nwnber of porrona o ufforing from iafluanta in wham no astemive pulmonary

lorionr h8YS darolopad.  Thero wore largely membom of tho rtaff and work-

ing for08 of- tho InStitUtS.  'fh888 pat&k8 offorid 8xo8llent mator+al for

                    `.          .,,;; i      ,
study of tha'ri'ldor komplioated O'i& of inihionsa. . Aa' far a8 possible; "

avidont that the etiology oi tti dire&~ was unoortain.  With the &plotrd

                                 - /                           . . . .
&if Gd other w&k' koknding attsnt'ion-.it was ibviou; that hit was in&a-
                                             
                  .., . .              1 :
rib10 for us tO~hTOatigate tho &$01&y frola all standpointi.       
                                `It thore-

fore. seemod advisable for the &spits1 ,staf f to confine its attontion


mainly to the study of the ~61s of ths laflusnra bacillus in ths epidamia

and to ths investigation of the other microorganisms concerned in the pul-

monary cmplioations, leaving to members of the Laboratory Staff the

search for an unknown virus.  Dr. Amoss and Dr. Olitsky, therefore, undor-

took the latter problem, obtaining matsrial for thir investigation f ram ths

cases treatsd IA the Xospltal.  th5lr results ars given in ths report of

ths Diteator of the Laboratoriss.

?ha attempt has been made in the &mpital to

study with as great care as possibls ths predominating organimns present
in th5 throats and sputum of a11 ths Gases of influenza and pneumonia
during lifs, and to study ths bautsria prorent in tha lungs at autopsy.
It has boon ths intention to maks this stud7 with as great auautloy as

possible OA the limited number of patients coming under our obsenation.

This has involvsd a larger amount of work than might meam nso5ssary at

f irs8 sight.  There worm, at first, many tsohnioal difficulties, sspec-
iallf In the isolation of B. infhOns&.  Ws have thought it nsceseary in

all cases, in order that we might be certain that we were really dealing
with th?e organism, that: it be obtrbed in every base in pure aulturo and
    
that & orgad so obknsd be tested by all LAOWA ruthodr,
   ,-: .:, !:                                Yoreov5r,
in 6&i to ibe ~srt&n $a: t jinflu~n5a~~bacilli r5ri not being ovsrlookod,
        i;         s
It w&"nionssar~ in ma)' oanes to imake repeated a$lturss.
       .I ,,        ". ..- ., *   i"-                    With grnntor
                                 . . . . . . ._  .-,. ._ .
sxp.ri,io. and dspnoiali, with thb improrsmsnt in&thod of isolation ds-
    I
v&d 'bi                  I                "ti
  Ot;"Av&y, %f ihi52*5ntion A'11 b;;"aade' later, the dif f iaultles .

in the rtud7 ha& boon kch diminished.

                    I   Ths following tablo shows the froquenoy of ooaur-

~)AOO of inflwnsa bsoilll and othar prodaairuting orga~inms in ths camen
of influsn~r and ~~s'~onir studied IA -the Hospital during the past quarter.


   .I

  .'
.t   .`d
`.

   
    /.
   *'


._


-J

..:
_.
-3

  2
  z
.:,: *
. .S'..


In most ca555 cultures w5rs made from tha throat

and sputum, and in the cams coming to autopsy, from ths VariOw organs.

The cultures war5 made by various methods, by m0~55 inoaulation, culture

on blood agar plates and on olsats agar.   The latter method provod by

far the most 5u0055rfu1.  The most striking fact brought out 15 the frs-

qubnt oocurrsncs of B. iAflUSAs55 iA the inflUeA5a and brOAChO-pAOU!eOAis

case8.  IA the 0a505 of lobar pnsumoAla, B. influenrae has bssn encoun-

tered 1555 often thaa in tha influenra cases, snd with more nearly ths ems

frequency as in normal throats during the 51~5 period.  Esmolytic strspto-

cocci have been found very seldom, IA only two throats.  h iAtbr55tiAg

fact ie that in six cases staphylococci were present in large AUmbsr8, in

f Ire of the pneumonia aames ther rsti'the prsdominatlAg organism and seemed

to bs rssponeible for the compliaatioA.

The oliniaal featurss of the ca555 have not yet

been carefully analyred.  Bo striking alinical differeACee have been preeent

in the cases of influenra here from those described IA the cases occurring
     . A ".                                                                   ,/-.
51sewh5rer.  180 oxtsnsivo study of tho blood changes have boon undertaken.
           .,.
         4 y,          ,.. ..`.         , I , ..- _I :-
Fairly froquont blood counts have boon made in a routino ma@nor OA all oasss.
                                              1.                           . I ,_.I&
Host of ths cases have shown the leucoponia which has been generally observed.
             . , _                                                                    I
      Distribution of B. lnflusA5as in the Youthe of formal Persons
         .               5. c                                                    2) 5:  r' ; ,-

       8,     .,.i -     -' L -*.
                 u `.`,!. :, : .                              ;:`..,:,,*/ :. -,ii* ,-,t,,:'
             OA account of tho great provaloncs of B. influsn-  `:
          `_:      i'.. ,  $ : * .:: .           `. .      . `.                       I   9. 1.`
sac in the o~~se5 of pneumonia and influenta occurring in the Hospital it has
                                           .                                    
seemed of importance to determine the frequency of their occurrome in nor-

ma1 mouths during the 55515 poriod.   It was planAed to make a complete sur-
                                            i

vsy of the mouth flora of the workers and staff of the Instituts, and this
                                              .

work has been undertaken by Dr. Stillmsn, assisted by L(i58 Pritdhstt.   soms
                           


L. I- ^.- .-.- - e-b--. --._- -_-   _ .--__   _.

time war lost in developing a proper technique for isolating B. influenrab
but the work io AOW ptogreeeing at a fairly rapid rate.   DAfOrtLWLtOly

Boise Pritahett must leave to undertake her new duties at Baltimore but her ,

work will be continued by Miss Vinchell; snd it 15 hoped that by making

fairly frequent cultures, curves asp be made of the occurrence of oarrisrs

of B. influentae in the various departments during the COmiAg months.   It

15 realired that this Institute 15 not ideal for such a survey as the popu-

lation 15 somewhat shifting, and sinoe most of the pereons working here have

wide contacts outside the institution.  levsrtheless, the advantages of

making such a study where the fa.cilities for work are eo eatisfactory, and

where the residsnts U&II bo oonstantly under the ObSOtvatiOA of the iavesti-

gators, seem to outweigh the dtsadvaAtage8, and it is hoped that such a sur-

vey away throw some light on ths dlstrlbution of influenra and oorysa, and

possibly on the stiology of the dissass.

Up to the present time, a study has been made of

231 individuals.   In most instances cultures have been made only once, and
the present figures indicate roughly the conditions present in thie Iaati- '

tute dur.ing tho latter part of Z?ovembor sad December.
              `I          ,./
              Of the 231 parsons,  54 bad suffered from influensa
            / ,       
during ths past three moatha and should therotors be considered convales-

I.      ,   , . . ..I     '.*;,t -.I., . 1 _' :
oents, 177 gave AO history of having had this disoass.   From the sputum or
                               . .                            #, +
        *
throats of           '   J .*.      \       '. ,,.:
   41:p'or o&t of therm normal individuals, inf&nra bacilli have
                                                                           
bean isolated.  Of the 54 p5r50~5 in whom cultures were made during convali
                      j

e5'ce~o5 from influenta, 46 per cent shored the pr555~oe of B. influenrae in

the throat.

,

    

              Almoot one half the persons IA the Institute who

have been studied during ths past months, thsrefors, have carried B. influ-


OASW.  Whether this nido 'distribution 15 constant or Is only aseociatod


with the pr88enoe of the epidemic, only further rtudier will rhow.   The

l&tort o tudl8a indioat8, however, that the incld8ncr of thir organism in
normal throat8 at prorent ir much 1688 than it wa8 a couple of month8 ago.
Yordov8r, the dirtribution of th8 carri8rr of this organim! ha8 been intsr-

88ting.  For inrtance, in the preparation room, rher8 there w8re two con-
val8808nt Carri8r8, all of th8 right p8rronr working th8r8 carri8d thir

Organilm.  On the other hand, in th8 chsmioal laborstory, non8 of th8

work8n ~81-8 found to harbor B. influ8nta8.  Strangely 8LIOUgh, v8ry fa

carrier8 hav8 b88n found among th8 nur888 in th8 %8pital.

              ft 18 obriour that no COnolU8iOn8 rhould b8

drawn from thir rtudy, at th8 pr888nt tir8.  The line of inr88tigatlon,

hower8r, 88-8 prolmi8ing.

            Dr. Doahos and Dr. Av8ry hav8 b8en 8ngirg8d in I, .
rtudf Of th8 ptopirtiO8 Of th8 infh8nSa broilli i8Oht8d in thir &8pitti,
b8 `f8Ot Ob8@m8d whioh i8 Of mh p!WtiOal kpOrt~N8 i8 tht th8 grorth., r +
of thi8 organirnr- ia enhawed, by the addition, to a8dir of, a8rtrin roap8 of ~,,;

obromd in th8 8a80, Of h-86. pOdfiV0 Orp;mi8B8,t o 8p8Oirlly, o t~ptOOOOO~ gf,  `;;
and ~~~)moeooo~.,'.:.~Uoo~baq beo~imado;-*of;, this; obHrrrtion,iq~t~.ptoduotioa,. ?
                                         *                       q
of a 8818otinsa8dlu for.B. iaflumsaei ::Jha amdluA,,prepurd by,tlu .;,t,,7a .:
addition of, modiu oloato..to 8 por~oont meat infusion o gar, in maoh mount   -'

a8 to make th8 oonaentration of olerti 1 to 1000.  rh, initial hydrown I

ion oono8ntration of the agar rhould reprerrent 8 pH of 7.3 to 7.5.   To loo

p~t8 Of th8 rgar, while hot, th8r8 i8 added 1 OC. Of 8 8U8p8n8iOn Of rabb,ltl8

OOrpUB8108.  Becaur8 of th8 mo1-8 luxuriant growth upon thir medim, thr


COlOni Of B. iZIfh8nsa8 appsar larger and 1088 tran8lUC8nt thaa upon
ordinary blood agar, and in l8ter rtag88 of d8V8~Opmi8nt are not infmquent-

ly nucleated.  Upon this medium, the Gram negative cocci of th8 catarrh-
dlir group, 8taphylococci, and occaeionally diphtherold bacilli, grow, while
pneumooocai and o treptococci of the hemolytlc and riridexm group fail to

der8lop.  th8 ~88 of thi8 m8dium ha8 r8ry gr8atly faoilitated the 8tudy
of thr ooourrmmo and dirtribktion of B. influ8nra8.   A furth8t Ob88rYa-

tion ha8 b8en mad8 that [)sntirn oiol8t in dilution of l:lOO,OOO - 1:50,000
#till furth8r t88tIdlU th8 growth Of &%a pO8itiV8 OrQLu1i8m8, 8liminrtiXig
8taphylooOUCu8, without mat8rlally influ8noing the growth of B. infh8nsa8.
It ha8 al80 boon noted that, oontruy to the general belirf, the influmra

bIWillU8 liver for u long a period u 8ir WO8k8 in blood broth without
tXW8f8r in th; incubator at 37' C., at mm t-p@ratu@, aad at 8' Co

It h8 beon found pO88iblO t0 r&i80 th0 VinbnOO

of B. inflwn8a.8 by pa?aagw through rat8 and mic8, 80 that l/50 co. of a

34 hour blood broth oulturw will kill li rat and .OOl uo. pmro fatal for Whit8

miC8.  Und8r th880 oonditionr th8 organi8m8 are found in groat nuaborr in

being made of'the method for dotermlnlng the, hydrog8n,ion conoentrrtion of in;

OUltUI-88 Of thir 01-#~8IIi8m. , ;. .>

                       
3                            0

                    (1  A study haa boon uYkd8fiakOn to dotrrrrixm wh8th8r
or not 8. inflwnur by growth in fluid a4dia producer a rolubl8 toxin:of  .


any conrid8rable degre8 of potency.  Such rtudiee up to the prerent hav8

in the main b8en negative.  ft hae, however, b8en pO88iblO to produoe in

fluid media a rubrtanc8 of rufficient toxicity to kill white rat8 in do888

of 0.5 cc. of the bacteria-fr8e fluid.

             In the courme of bact8riologio rtudy of patient8

in the ward8 ruff8ring from infhenra, it wa8 found that in addition to the

typiual B. influ8ma4, a diffrrent Gram negative hemoglobinophillo baaillur

war pre88nt.  Thir differ8 0888ntislly from the inflUOnsa bacillur in the

following oharauterr: gr88t8r uniformity in rtaining property, marked alkalin

fementation of milk with 8Ub88qWnt p8ptoniration and active hemolysir of

blood oellr.  A furth8r rtudy of thi8 organha ir being made.

              Dr. Lyon ha8 undertaken the artificial produotion

of iaamunity in rabbit8 to virulent culture8 of B. influ8nres.   This work

ha8 not y8t progrerred far enough iOr a r8port of ths result8 to be made.

Further Study of Atypical Trpe XI Pnewnococci.

It has hem found that a cohriderabl8 number of

pneumooocoi i8olated from ca888 Of `pnOwIIOnia, 8.nd 8186 frO!E nom mouthr,

                  ,I              .A;'
rsaot' atyp&ali;`&th Tbi II' 86rW!~~~~ '                             
                   Somo'8tudy h&i b88n 6ado of thsri   `L

                                                  
    ,                                                   
organimnr by Dri k&y, the r88hir"of `which ha178 b8On pr8Giou8ly r8ptXted,

s

and which ham b8en publirhbd; "F&m a'.8tudy' of tsn' 6f $80 ' rtraino tir: "' '
Avery was 8bl8 to olag8ify them into thr88 typer, `If a, 11 b, and 11 x;

By mean8 of igglutination, abrorption and prot8etion exp8rim8nt8, the m8mb8r8

.of rub-type8 11 a and fI b were found to poa8088 immunity rOaCtiOn8 id8ntical

with all other rtraias of the homologour typee.  Sub-type II x, however,
COn8i8t8 Of a hOtOrOg8k8OU8 8Orie8 Of indspendeht strain8 whioh show8d

neither orore-agglutination nor croer-protection.

               Dr. Stillmsn ha8 colbct8d 204 strains of there


atypical typ8 II pn8umococci and ha8 made a complete rtudy with'the purpoes
of elaborating further their cla8seification on the basic of their sp8cific

relationrhipr.  The Iource of the rtraine rtudlsd nae a8 folloirr:

Lobar pneumonia

Poet-op8rat iv0 pneumonia

Yeninglt 18

Guinea pig pneumonia

~onaal mouth8

Convalescent Type I   pn8unonla


       (I         I   II        II



       a         (I   III       (I


&l8t

                 Total

77


2

1


5

100

6


3

1

6

204

             In clsrrif ying these rt rain8 agglutination and

abeorpt ion reaotionr hav8 be8n employed.  On the basir Of 8pOCifio SgglU-

ination in monovalent rabbit 8em, the 204 r$rains havr been clasrifi8d

into .twelve dirt inot group8.  Only two i straino ehow8d crooe-aggl~t inat ion

in the-, *UnO 88MI!, of i a h8tOrOlOgOlJ8; group, *and [the88 reaetione. were 8hOwn
t0 b8 &AO, t0 tho.pn88nce of minOr;8gg$Utiniao,~fOr on8 group, :.., ( : (.. (, I

              . .
  * rL    5 v.-   .`:   ; ~ Organ@ur : belonging <.t 0 CertaiVi tub-grOUp8, "(Mealy,,;
                 , `, : .t                                                              '

II a and II h,, have b8,en ancount8reQ much more frequently. in. rdation to 2v
dire888 cyld it 18 probable that the80 hare a gr8at8r pathigrnioity.  Or&an-

181~8 of th888 group8 ooour rardy in normal mouths. i Just th8 OppO8it8 $8

the oaee with organi- of certain other group8 8UCh as group8 II b, II c,

II f, and II m.  Orgfmirmr belonging in th880 group8 ar8 much BIOIV fr8qUOnt~-

ly rncountered in normal mouth8 than In a88ooiation with disease.


Biologic Cla8sificatlon of Streptococcus Hemolyticus.

     In my previous report mention wae made of the 8tudy

being carried out by Dr. Dochez and Dr. Avery on hemolytio streptococci, and

it was then stated that .evidence had been obtained that the various etrains

of hemolytic rtreptococcl differ in their immunologic reactione, and that

there organirmr may be grouped on the basir of common charactere, jurt ae i8

the ca8e with pneumococci and meningococci.   While the relationr between

the variour types of rtreptocoaci are more complex than is the care with pneu-

mocoooi, and while thOr8 bar8 b8en oonsiderable technical difficultie8 to be

overcome in working with rtreptococci due to (1) the difficulty in rendering

them virulent for mice, (2) their tendency to epontaneour agglutination, (3)

difficulty in irmnuniring animdr, neverthelesr, the work ha8 prOgts88Od favor-

ably, a considerabl8 number of 8trainr hwe now been thoroughly 8tudi8d, and

the rwultr of the inre8tigation will a0011 be ready for publication.

m of SW with A 189

.

            Th8 quarter Op8n8d on Oetob8r L, ,1918, with fifty-
                    v;*c I.              *        0
I.        ,..: ,.     L          _._ .,
'iour &philitid `patients in the Ho;d;`tbl.             , , .:   "      ,;. . .  :`; L. ,`a
                        All of them with two 8xceptionr
', .   :     ,.. (' , 3 i: \. . .   * , :      .f'.I A :, .I; I   i ., `    3, . , / *. .               ), ,. ,!-
Wbx-8 8Oldi8r8 Or 88ilOi8.  Sinor Oatob8r 1, thirt88n pati8ntr have b8en
            __ *;: ' Ij                    I
.;..'\ ;.       '2 .> .;; :.   . ; , 5  :,. ,+: 1. 1 _   \ i ,` ,.' i : L `"     "..        \>'..'. ' ,,  u iarcs'
                                                                           .

admitted to the Horpital, the numb8r of admirrionr b8ing curtailed on recount
.   : .,' ':  i ,,.. I LI ,: I' f . . .  . i,          ,    > . . . . . . ,
of th8 r808nt,8pidm'iU .of influ8nra and th8 ne8d of horpital room for th88e
                                                                     .

C&SOS.

                               :
Fifty-thres'prtientr ha08 b88n di8oharg8d from the

&I8pital during thir psriod, 80 that 88V8nt88n ryphilitic patient8 w8re in

the Horpital on the firet of January 1919.  of the fifty-thre8 patient8 dis-

charged, forty-fiv8 left a8 imprOV8d, that 18 with a nOgatiY8 ~arwrmann


reaction both in the blood and in the epinal fluid.   Four were admitted to

the Hoepital with a diagnoeie of eyphilie but were found to be not syphilitic.

Two ware traneferred to other hoapitale on account of complicating infectione,

and the only syphilitic patient who wa8 diecharged with a poeitlve laeeennann

rae a congenital ryphilitic who ie to return later for further treatment.

              &sing the month of Ootober there ocourred thr88

eevere ca888 of dOITMktO8i8 dir8ctly attributable to tr8atment with A 189.

Toward the end of Ootober, 1918, one of theee cases died of acute exfoliative

dermatiti8.   There alro occurred two ca8es of o evere acute conjunctivlts.

The occurrence of these complication8 made ?? o eem incumbent to revlre eome-

what the mode of application of the drug, 80 that since October 20th the drug

hae been given at two week interval8 in dorer of wven milligraam per kilogram

of body weight.  It hae been dlerolved in 2-t molecules of eodium hydrate and

750 partr of saline solution.

               The analyeie of reeulte presented In the October

report indloated that variation8 in alkalinity and dilution within the l%tIite

u8ed have no 8ff8ot'ori the reaction8 oocurring in the sdmini8tration of A 189;
and .thdr8foi;ii.~hi"faci~,that',during'thir quart8r"we.have 'h&i nr?reverd r8adtionr
may ,bi att r&but d`d `to'-a : 18ngthelied K`itit8rVal:%8~W8en 'dOi88$,.'* '!hk~lrngth:cidk in-
t8tval;bOtW8On~.d6$88 'ma~~br"adoo~tabf8 'tiro`for the .twd: `fdlbWing `dkdit'~otik+ -.`Y
                                                                           `.`

    .2.- .Two oa8e8 ht~~8 d8velop8d~b~tH,c~inieal and laboratory'f indiqgi' i

of central .nervoud rJphilir.undsr't~atmtmepti .but were definitely known not to':-. lr
                                               ?

have either before th8 institution of treatment.

.,        ,j `...

Tt appear8 pordble, therefore, that the diminution


in toxic effects, gained by administering A 189 at approximately half the

previour rate, may be attained at the cost of lonered therapeutic efficiency.

Owing to Dr. Van Slyks'e illnsrr and the reduced

rtaff, the rerearch aotivitiea in the chemical laboratory have been markedly

diminimhsd during tha part quarter.  Dr. Cullen hae been continuourly em-

ployed at th8 War Dsmonrtration ?brpital.   It i8 hoped that he will 80011 bo

free to reaume hi8 work here.  A ooAeid8rable amount of the rpase and faail-

itier of the ohemical l8boratorier have been ured during thr pa8t quarter by

the men of the Sanity Corps taking the cour88 in clinical laboratory method8

under the direction of Capt. EiObiA8OA.

Yirr Hiller ha8 continued the work OA which 8hO wa8

engaged with Dr. Van Slyke rhea we wa8 ooapellod to leave.  Thi8 problem

COnri8tOd iA A808rtaiAiAg th0 Optiaum AitrOgOAOU8 AUtriOnt iOr pAOW8OCOCCi.

Neither intaat protein8 Aor the amino acid8 rerulting from their complste

hydrOly8i8 appear to be M good for p~oumo~oucur media a8 8ome of the prod-
                      .,                                                            I '
uetr of psrtirl hydrolyrir. tonnod,, indef lnitoll, 'peptoad'.
    >: .                              The object of `.
                     `..      i        i *.                         8:;

the proteimpabulum in order to get it into optimum oonditioa for the ba.uter-
                        :...       ",.      . :..;.

ia to grow on.  '?h,e prelimiaarf work ha8 been a rtudy of th8 dige8tion of

cuein with trypain under accurately reproducible conditions, th8 curve of

digertion being followed b7 amino nitrogen determiAatioA8,.8o that it ir por-
Sib10 to produce at will a dig88t in which hydroly8ir ha8 reached 10, 20, 30,

or 40 per cent of completion to the amino acid stage,  The digeetion i8 8tOppOd

at the derired rtage by addition of acid, and after autoclaving the eolution

ir filtered and the hydrogen ion coAceAtration brought to the point desired


I *.,
  `.
' \  \

for pneuxnococcus culturee.   Dr. Avery is about to teet media in which

peptonee of varying degree8 of hydrolyeis,prepared a8 above darcrlbed, are

ueed as nitrogenour foode for the bacteria.

              Dr. Stadie and Capt. Robineon have been etudying

the blood garsr in patient8 with influsnra and prmumonia, the oxygen and

carbon dioxid in not only the venou8, but al80 the arterial blood being

datemined.  The method8 for the detOmiAatiOA8 are there recsntly doviaed

by Dr. Van Slyke.  Bornally the arterial blood 8eem8 to be complete15 or

almort completely, maturated with oxygen, although the number of analy808

of nomml blood 18 not 8uf fioiontly grsat to make thir certain.   Influsnra

patient8 with ayanorir frequratly show a8 low a8 75 per cent of their arterial

hsmOglObin 8aturatsd with oxygen, and in on8 fatal Cabe, Only 25 per cent,

The lomr of oxygen which the blood suffer8 in parring from arteries to vsinr

10 in ram8 oa8e8 al80 greater th8n u8ua1, indioating the probability of a slow

circulation, which in ruoh oa8eu would also be a factor in producing the cyan-

0818.  The above oOAditiOA8 are indicated rather than proven, for the work

10 in itr prelimit rtage; but it appear8 to prom180 rerults of both path-

ological and phy8iOlOgiGal interout.  The work 18 a logioal outgrovth of

*that done iti the tlorpifal a year ago by kurdsgaasd on the oxygen unraturation .
of the venoua'blood in nom1 perronr &d oardiac patienta.