REPORT OF TEZ DIRE-~$I&OF TX HOSFFI'AL
                         - . -- --..L--

April 21, 1923


REPORT OF `XE `JORK OF THE HO&TAD.

April 1923.

   During the period covered by this report patients suffering from
the following named disease8 have been admitted to the hospital and

various problema relatix to t3eae diseases have been studied: Heart

Disease, Nephri tie, Acute Rheumatic Fever, Chicken-pox, Acute Respl-

ratory Infections.

Heart Disease. (Reoort of Dr. Cohn.)

Dr. Cohn. Dr. Stewart and Dr. l.hxra.

   With Dr. Murray, a study of muscle contraction has been begun.

It is the general object of this research to arrive at some description
of the behavior of muscle relative to certain changes in the life history

of ,this tissue and to the nature of its environment under various cir-

Wmstancea.  .Ae*`&iteria of `behavior we count on iti Lreactfon in. tex&si'.

       - .

of growkh, of rite'& of contrictile'power .  !?he method of' a@roa&ing
            '                       
this problem has gikn UB much c&cern for,                     ,"Y >!f
              `- eo far as h&an'ih&ology

                  
in espeoial'.is"concerned, muscle xxx.9 b& regarded from tw'b &pect$;"`?iret
its relation to the process of ageing tid senescence; md'second its "'

relation to the processes of disease.   It is increased information on

these matters in particular at which we tiish to arrive.   In the second

case there are included at least two phases; that involved in hypertrophy


118

of the fibre and that involved in increase of ite length.

It seemed desirable to study first the relation to ageing.

h'or this purpose It is admntageous to confine the investigation especi-

ally at first to a single species, such as the fowl, since material is

readily available throughout embryonic as well as in post-embryonic life.

Fle were glzd to make this choice not only on this account but because of

the great experience with it which Dr. Carrel has accumulated and which

he has placed unreservedly at our disposal.

Ve have, in the first place, devoted considerable time to

becoring familiar with our material.   In choosing the direction of our

work we thought It irqortant firet to learn the influence of age on the

rata of growth of tissue.   In a sense this is not unlike that aspect

of the subject which Dr. Carrel ham developed In studying the inhibiting

influence on growth of plasma taJcen f ram fowl of increasing ages.  In our

worh, we are on the other hand, studying the rate of growth of which the

tissue is capbie at varies life periods.  Vith this, we hope to

to compare certain other proparties of heart muscle, more directly

cerned with aontraetioa,                   .'

be able

con-

.I

    .?n' our early experiments t#e planted the tissue in hanging `drape
composed of ohioken pla~miz and of extrtlct -de of ahicken embryos, e&i
fragment being placed on rqtca covsrs closed in by separate hall'& ground

glass cells.  Later, so that we might assume a like influenbe of a number

of variables, we planted a number af fragments (5 to 20) in the same rbedium

on &rge mica OO+era, su$pported on large dishes (Gabritschewski). mie

gave us the opportunity of ,&vera.ging the performance of a mmber of frsg-

ments and of studying the d;eviation,of each fram this average. We found

that, although this nrst'nod lent itself tro the comtnact:on of 3 cux!ve of

growth, the rate qf growth dacreg~in$ tith the age of ihe embryo, the de-


viations oi individual experirrents from the average were greater than we

supposed could `oe nccoutod for by varintlons: in techzique from one tb

cLnot?ier experiment.

      Tne basis of the differences appears to lie in the nature of

the eggs with which we were suElied.  `Jo halve accordingly sought and ob-

twined the cordial cooperation of IIr. J. G. Meb'o, who has supplied us with

the eggs we require.  Xth this help vie have succeeded in eliminating

zertsin errors.  Ve nvtr knaw exactly the histor;- and age of the hens, the

eggs of which we exzmlne; we -know the tir;le at which the eggs are laid; we
receive the eggs daily, within 24 `hours of the time they are laid. ThesO

are the eggs we ai`8 now utilitin; IrJt the> have not been available long

enough to permit us to rz?ort the reerlts.

      Directly corzeztad with this study, we are estimating the
water content of the tissue through em3ryonl; life. The embryos are

weighed before and after dq:ing.  in measurements already made, it was
found, just as in the case of tissue growth, that a curve could be con-
structed showing a relation between age and growth of the embryo as a

whole.  But here again it was thought desirable to carry on the work with

more accurately known -3&tsrial,  For this reason the work was postponed

until now, when the eggs already referred to supplied by the Webb Fam

h.a+e become available ;'

`-

We hope to tilats these studiesl

at different ages aind' also.`to 
             certah other

fore begu td' study rbyfhic

of two sorts.  In the first
`conditions of tiegu5 culture

contraction.

to the' hiatoiogy o&x&& -
                      *
functioni; Ve h&3 therei'
For t'nis we have preparations

it was our object to learn whether under the
a preparation could be obtained to serve as

               A
a reliable control.  Fragments of tissue were taken from the hearts of

embqros at vaiious ages, and were planted in a medium consisting of chicken


plzsna and OmbqTotic tissue cxtxxt.   Vlc h:rvo so f w not c:qerir.lented

74th types of media, of irrirptio2, 01' oi 7sri3tiono in oxgyen tension
r.or with the results of trzmspIon:i~ the tissue fre~uontl: to new codia.
Go do not 'rt;low ho:{ long tissue r~;::r live c-her, these Ixtcrs ;lro tzken into

accoui1t.  Fragmsnts of tisscz h~vg '~oen t;='.:zn frOL tLo ti7s auricles 3nd

froa the ventricles, csyeci:-.l.l, the loft 023.   In these xlturds, cer-

t&n fragments, usually r30ru 9x-a lxif I";-OLI each cl' the60 localities, con-

trxted; they context for periods of Yr.a rmging fror-1 ono

dhy6.  It iS U6\;31 for them t0 COZItims t0 30 F3 f0: Six to
it is ~nuoual for thx to do 60 for a loss j?ori!xi. usU?liy

COntrXt il6 6oon 36 they a?e pL:lted; sonetixes they 20 not

to fiftosn

ei&ht sp;

tho f mEtints

begin until

after a lapee of two to three daJ6.  Often the rata slows after o fm

days, but later rises a@n.  \7e hzvo r,oticod th?.t tho rate at which

cLuricular tissue contracts is greater than that t&en frcnri the ventricles.

There soems 3160 to be a difference in

right and left auricles.  Re have done

effect of alteration of tex2~erature on

the rate of contraction between

a few oqerirxnts to observe the

rate and have seen that in these.

fragmsnts terrrperature exerts an influen&3 on rlzte, an effect frequmtly.m, :,.
. observed by otheos in other preparations,,  T?e are, however, not yet able
So say whether in our preparations the rate increases with temperature,:. ~,
according to the lavish of 3 simple chez&xal reactio-n.  The diff 8rences in

behavior of auricles and ventriclea,- and the possSble difference noticed.,
between the fmo auricles, suggest either that these diPferances hdicsta
differences in the structure of the muscle tak.en from vwious regions of

the heart, or that the dif ferencss observed depend on the Tresence of other
tissues such a6 ganglion cells or nerve tissue ir.co:Toratsd in the rnx.cu~ar

stmcture.  Theee are zztters for futulrs study. They recall those observrt-

tions in erlbryology bearins or- the 3.zwanderi;lg of ganglion cells Into the


                         I f
                                                             b `6
                                                                           ?? o
                                                    121

heart muscle.  Ag to thht eifaLt tif' ,;;`ne 7)r3:`e:u:e of these cells on the f-xc-

tion of the heart nxocle e.7 a;?xt fron .~he Eony&?.tm of e.lec crocardj ograms,

littla or nothing 5 s Inns-37.

      In c.ddition v.3 qwclie.vs j ? tu b:; jxpc;-L~~t for 111 Lo st-&:dy the

rate Of the vrhole hezrt i? t11e jn\;zc, ZZ.OY,TO wkiie tbi~ is SC! li ?&idturbed

in the egg or, at 1enRt) dir, t x'cxl LLS little as FoEsiblc .  ?:`ri~ +hirr we so?e

enploylng the galvc-nometri:: methoe cf regiTteri.ng the !.eart. hec';s.  %le

method h3s been used before nox, br.t 1 f h;~c, beail 11~36 tc :,kq~$r  the for-n of

the electric c-xve whicS is obtzinscl.   Lf -:t lo act an? ion ks b%en attached

to the ~USBtiCZl of rate.   3u.t it i8 this funf:tio~: Of ',k;r. mWi.l.e WtliCb t0

us ia martant in the attempt to establish those ra?fLtions to other func-

tions, s'cch a8 metabolic. rate, to which rcI'crer.se tis alrece been r&de in

discussing growth, age and tissue density.                                 I
      The subject8 which I have mentioned cover a wider field then cm

be inves:igoted irrnedlntely.  I have described them so as to indicate the

point of view from which trt thb present time we are ap?rozching this problen.
Having arrived at these general views and explored the possibilities tiforded
to us by our nlaterial, we intend first to m&e the me&uremenis which we hope

                   
will perzxit us to constzxct grov;th curves ; next to learn &he natural I&& bf '
the heart d&ing e&&on& life; md next to ascertain' the &lidit~ ;bf those
                                                                           -
pr8lininary obse'mations, already keflrred to, on rate exhibited bi tissue
frq various porti&s of the heart,
                         ,     and the influence of tekperntura upon it.

                                                                 
                     .                                                              ::

      With Doctor Stewart experiments are in progrem on dogo with
t;?e view to producizq valvular lesions in them so t'kat inTorm=Ltidn on certain
circulatory problems connected with the volme and minute outputs and with

the rate of flow, may be gained.  Lesibns of the val.ves in dogs that survive

ltapts of uourse been zade, notably with Such pieces of apparatus as the VSIVU-

lotme,  It was our infhntion to use this instmment, although the precise


                                                                     1:      r*4
                        I 3
                                          p;i 22

lesions to be obtained with it ccrtld not be predicted.   Meawhile, duritlg tho

auturrrn (1922) , a notice ,lppeared in the 3ourrxz~l of the American Medical Ae-

sociation by Graham and Allen stating th3t they hc?.d mclde and used an =Lppsr~Zs

not unlike R cystoscope with which it is possible,

heart through one or the other auricle, to cut tho

wh9t one is cutting.   The inatmment used by them

when introduced into the

valves and to see precisely

VJZLS not available at the

time.  Accordingly we set to work to devise one here snd have now succeeded in

producing one which meets our requirements,  g fving a large field of vision in

the area of opemtion.   So far Doctor Stewart has suoceeded In operating

auccesafully on two dog8 which tive survived.   The risks of the operation

are great as Graham and Allen reported.  We also found this to be true during

the tims when the intracardioscope ~8 being perfected.   Since then. subae-

quent operations have shown that the danger8 appear not to be unduly great.

The =Leeptic technique ir, aa is ~911 known, difficult of attalrzmnt because

of the prolonged ad

the heart, The dog8

is reason to believe

wide eqosure of the pleural cavity in the approach to
so far operated on have survived 10 and 7 tiys.  There

that wa shall succeed in preparing the sort of dog re-

quired for our

        It

or& to bring

subsequent studies .

is however not enough merely to produce a valvular defect in

1 . .

&I&it a state `of `chronio heart failure as other exrperimentero,

I,

notkbly C&&g: &g poi&d 6ut `, `If is `the usual &&&) and `it was' `.  ?`I(.
                                                                         ,~: .,... :.    $1,
                    /                                                           
rniti` here; t&t'%he `hegre&.`of fai& `titer injuring the valve eithei i9 ex- .:`:I:
                                                                           `i
                                         . . .    (L .", `..I        I
tre&e resuitirig `&m&,' in death `"or &at heart failur9.i&ils entirely'<9 ap-  ."'

                                                                           ..I,        *,
                                                                           .,  :"
pear.  f;n view a? the faot that this is still likely to bs our experienoe, we '
mesa to resort to the devite of subjecting the anirmla which survive the op-

erations to one of several procedures, notably to work on a

meanwhile we have studied the effect of another method. We

to producing valve lesions, to caus9 the muscle of the doge

treadmill. But

plan, in addition

to degenerate.


In rcbbits a vGriet+y of agen-Ls injure the !loart 1;111sclc, hut them is m Yet

little ex?rience in this direction in dogs.

     Yro have rcoorted in the first in&once to the use of diphtheria

toxiu, and have met r/i-Lb ,-esults VII: did not anticipate.   A number of control

measurements were first obtained such as electrocardiogrcms, X-ray photo-

graphs and the

body vreight ot

ill, failed to

body weight,   It \:as found that if 0.0016 cc. per kilo of

diphtheria toxin was injected intravenously the dogs became

eat, lost weight and died.  The duration of life after in-

jection was from 3*to 7& daya.  During this time it was noticed that the

okin of thu dogs became discolored, the urine took on a yellovr-br0v.n color

due to bile, the red cells undenrent changes ao that in the smear they pre-

sented marked variation in shtpe and size.  Very striking ~/its the reduction

in the size of the hearts.  This was determined from x-ray plates by mea2ur-

ing the site of the hearts with the pknimeter.  In vion of the fact that

after the injeotions the animals failed to eat, it waa thought necessary to

exclude the posslbillty that the reduction in site was due to starvation.

Y!ith this phenomenon we vlere familiar from studios made in casea of diabetes

mellitus treated by the method of undernourishment. 178 starved dogs accard-

ingly for the same period ot time (4 days) in the course ot which reduotion

in siae after injaotion had been observed, and found that starvation of this

duration produ'ced no.greater change in the eize of the hearts- than oould be
accouked for by the inaccuracy of the method, which Dr. Levy pointed out.:. :

Thor iwxta of the same dogs subsequently

was inj@tted.  Other dogs then received

and survived.  These dogs failed to show

showed reduction in size when toxin

diphtheria toxin 0.001 oc.per kilo

those changes in the size of the

cardiac eilhouette which have already been described in the case of the dogs

which died.  Ye have in progress expkrimenta designed to datermini: whether

in dogs receiving doses of diphtheria toxin large enough to cause death,


the chaxge in the henrt xca is due to a sir~ljit: in bloom;. trolume, to blco?,

destruction, or to charge in the heart muscls itself,

     Autopsies were rslde of the dogs, the hearts and kidneys being

taken for further studies.  The hearts were dissected and weighed by
the method of Filler with the modifications reconmendad by Wilson a&

Herrmann.  We thought it of value to do this first to complete the

measurementa bearing on the reduction In the size of tha hearts In com-

parlson with the body weight and aecon- 3 to learn whether the changes

found in certain of the electrocardiograms denoted an alteration in the

relative weights of the two ventricles.    Theee studies as well 3s the

study of the microscopic anstaoy of the haart muscle and of the kidneys

are not yet complete.

     In addition to these methods (valve injury and diphtheris
toxication) of bringing about changes in the heart and consequently

in-

in

the circulation, ne design to excise portions of the kidney.   In this

phase of our study we think It eeceesnry to come to definite conclusions

on the ralatige value of various methodsof taking blood pressure %n dogs

by indirect *ana.:  After w expsriments.with varieties of apparatus

applied,bot,h to the carotid artery, by the method of Van Leemm, ,and to

`the femoral artery,. we have finrrlly concluded to abandon the method. of! ,:;.,

Van Leersum and to adopt: the.method. of indirect measurement of. blood pres-

sure in the femotil 'artery.  Thesq method8 have of'course been compared

with the direct method.                                                      .-, ..,
               In taking the pressure of the femoral artery we

find the method of Rolls the most @isfactory. The method is essentially

the me thoct of Erlanger .   Thare is added a' record of the levels of the

mercury column snd a modification of the device which magnifies the ex-

cursions of the vessel wall.  It may be pointed out that any method of tak-

ing blood pressure in dogs, requires careful interpretation because of the


1           fluctwtions which are known to occur from day to day.

?!e ore accordingly in tha early stage of this stud:;. What

has so fsr been accomplished is in t,ho direction of disposing of cer-

i
z
; t

trrln preliminary  technicnl difficulties.

     We have admitted patients to the hospital 2nd hove been in-

tens ted in stu&ying tb3 from t210 points of view.   It nas shown by

Cohn iand Sevy ,  that In dogs dose:: of digitalis presumed.' to bs com-

parable to doses used in the clinic, doses which in xy cnse do not

kill intact dogs, were nevertheless sufficisnt to increase the degres

of contraction of the vantricular unxcle, when this Is measured by

the myocardiosra?h of Roy ztnd Adomi .  To loam whether XI effect on

the contraction of the ventricular muscla occura rrlso in man under

therapeutic conditions 1s a mztter of importance for its own sake, bat

more especially since th8 view is comonly held that this action doas

not take place, that the use of digitalis in man is confined to its

effect on auriculo-ventricular ccnduction, an effect which is seen in

the reduct'ian of the ventricular rate in fibrillation of the auricl&.
To teat `tiis'lr2tter of ac`tion on the muscle in man is' diff'icult. We
repbrt now a plan we. have `adopted in order to test this possibility.
By ?r.ea$ of t& X-ray the' left border of. the left vantricle wan be pho-
. t'~g~+&;. -                                                            
      If ia a single' record. the excursion of. this border. from'

                                                                     
the &a&lic to the systolic position could be photographed and me&
       ;i
sured, b&`ih fhk control period and' in the period when the heart is

under the influence of digitalis, a compcLrison between the two maasura-
men& should Indicate whether' the drug has produced an effect.  There

am naturally precauthns to be taken in estimating tha value of such

measurements, for'dfgitalis may Ime an influence on cardiac rate, and

altwattww $n rata are ., as is well Iz~own, ' of importance in bringing


                         1 . i> 1
                                                   '.) $
                                              `36
                                                                        a.u

about changes in the volume mztput per beat of the heart and conssquently

in the excursion of any given point in the csrdiac surface.

     In attempting to ILL* such msursments we hizvc followed the plan

of Goett In constructing Q. moving X-ray camera (Fig. 1). Betwaen the pn-

tient and the mbving plate there is a lead screen.  In this screen there

is cut a slit 1.0 cz. high and about 17 to 18 cm. wide.   By this means

there is exposed to the moving plate only 1.0 cm. of the left border of

the left ventricle and 1.0 cm. of the right border of the right auricle.

`178 photograph only the shad@.-1s which pass through the 1.0 cm. slot, `Ihe

enct position which Is photogrr?phed in this mnner is lmown by photo-
graphing the whole cheat at the same time in the us-1 way, (Fig-21, this

plate being placed betwean the individa1 and the lead screen.  The X-ray

plate is drawn upward by a motor behind the alit. The excursions of

single portions of about 1.0 cm. of the two cardieo borders then oppecrr

as saw-toothed or wavy lines (Fig.?i), the outer points representing the

position of the portion exposed in diastole; the bsse of the trough its

position in sys tole .  The difference between these points is the measure

of the systolia excursion of thi8 fr%tion of the heart's border.   In

these curves oan be

tolic an3 diaetolio

tkne wd the pha8sr

seen the rate of change of position both of the sys-

pr~ceeaes at the point studie&,   We record both the

of rtespiration by photograph5ng the movement 8 of le-

vers hung apposite the slot, between the Lny tube and the lead screen.

`Iha shadows of these levers appear in the fonn of continuous ourdss. We

are non m&ing successful photographs by this method.  Wa have au yet no

data to report dealing with our problem.

      A second study concerns the inability of digitalis in certain

cases of heart failure in which there is edema to relieve this condition.

Thesa are cases in which the Mdneys  are zactive, for by means of diuretics,


P.- .,.:

,,..`.
:, p <
-, - ,_\. `._

126 a


126 b


such as theocin, marked increase in %he cutput 02 urine Is obtsired.

though the effect Is temporary ; and in which the heart, or at lext c. 1,.
inhibitory apparatus is affected hy digitalis action, as is evident bj

the contlrRl#d effect of this drug on the rate of the ventricles when the

auricles Jr3 fibrillating.  The failure is apparently due to the absence

of

to

90

muscular action of the drug.  The group of patient6 which corresponds

this description ie lergo and the reasons for the failure of digitalis

affect them is unknown.  fn thi8 study we are attempting to understar.d

this group and to learn the nature of the factors which are involved.

,

? m . (Including Report of Work Carried on in the Chemical Laboratory

jR013ort of Dr. VN, !

Br, Van S.ldm. Dr. w. Dr. Lsnder. Dr. Salveaen,&J&_ti~,
k. Neil1 and Miss Hilley.
'
Cw3nosis.

    A review and theoretical consideration of the cauaee of cyanosis

has been prepared for publication by Lundsgaard and Van Slyke.  Lundagaard

had previously demonstrated that the factor responsible for the production

of cya2loeis is the concentration of reduced hemoglobin in the capillary
blood, and our study resolved itself into an investigation of the cpmti-

tative effects of the factor6 contributory thereto.  The contributory
factors are (1) I , the degree of oxygen unsaturation of tins arterie&: r
blood coming from aerated lung areas, (2) $$ 1 the proportion of blood
gass$ng frm tb right heart to the left through unaerateb &annels, (3)

D
,I the oxygen cPnsur.?ption in the capillaries, (4) 15: , the total hemo-

globin content.  In effectiveness in causing the presence of reduced

,.I

hemoglobin in the capillary blood, these fouk factors ra& in the order

named.  For example an increase of 50 per cent of the distance between
normal and maximum in each fsctor Increases the capillary reduced heno-


Slob-in content from t%e ~o~nzl, expressed in grams per 100 cc. of bl.:od.,

$0 3.3, 6.4, 4.5, and 2.8, respectively, 4 to 6 being the range NIL wi,,r:-

cyanosis usurrlly becorf.es visible.   5'he corr.Yined effect of the fxt.ars

`was found to be expressibie by the equation

        C=T+ WD
        `1
                      1   0-x

There are various other factors which modify the coloration. Such Ire

local akin vascularity, picentation, thickness of epidermis.

      `Ihe main clinical conditions in which cyanosis is a symptom

have been considered in connection with the causative and modifying fnc-

tors present, and attempts have been rzde to estimate the functional and

matomical significance of the cyanosis in certain of these conditions.

?fephri t i q.

In the nephritis work Linder and Lundsgaard have continued

their studies of blood grotein and blootiolune chances.   They find in
glcmerular n?-:`-.ri$:s and nanhrosis (term used in the sense of Volhard
and Fahr) that the total pfoteiti content of the plasma is usually reduced
L

helm the normal; it varies from 3..5 to 5.5 grams per 100 cc. compared

with the norrral 6. to 7.  In all the cases of these two types studied CL

fall in the a1bumin
       globulin  ratio below the normal occurred.   Since albumin

is the protein chiefly excreted in the urine, the readiest explanation for
its relative (and usually absolute) deficit in the plasma is direct loss

by excretion.  Whether this is the entire explanation is uncertain, how-

ever.  The excretion of albumin and globumin in the urine of these patients

is being studied with the above point in view.

In cases of nephrosclerosis. and functional albumirmria the plasma

proteins were .normal .


    The ggge.s_f, theW .&KC c_o.n.c3nt~~-t_i_on_-o~-~xoteins in the Ilarmq
content observe8 in many nephritics hzzs been an object of speculation

sines the tins of Bright.  Thsre were two possibilities: either tilers

?;ao 3 loss of protein from ths body, or the blood was diluted with ra-

tnined water (hydremic @thora).   In order to obtain data that might

lead to a decision, blood volums deterA.~tiona, by Keith, Rowntree,

and Gemghty'a "Vital Rod" n&hod repelted at intervals over varying
periods cf time have been performed on patients with low plasma pro-

teins.  In no instances, even when there was gre:t edetu, has the blood

volu~o been found abnormally high. `i!e have thus far had no cases in

*.v'ni:.h a Flethorlc hydrenia existed.   The lovv protein content appears

due ontirel:r to A diminution In tho total amount of plasr;u proteins in

the bod&r.   Tim 1at ter ) calculated from the protein concentration and
the plasma vol~~e, have been found to be about 3.5 grams per kilo body

weight in nom1 subjects.  In the nephritics with lam plasma protein

concentration the f imre varied between 1.5 ati 3 .O grams.

     In some cases a riss towards normal of the L,otal plasma pro-

teins was observed to accompany clinical improvement.   The increase in

plasma proteins did not o~cxr

. does not aspear probable that

In the production of edezna.

Chemistry of the Blood.

until after edema had disappeared.
   It

the low plasma protein content is a factor

    With Dr. Nell1 the details have been Derfected f'or utilizing

the? "constant volume'* blood gas apparatus for all blood gas analyses,
`& gases are extracted in the same manner wed with the fox%er %onstant

pressurel' apparatus.  The measuremen% a-;` t'ne gas, however, is based on

tine principle of redcci.-,
           `-- iC, to an arbitrarily chosen, convenient, defi-
nite vok-.ie (5 cc,, 2 cc., gr 0.5 CC.), and measuriq on a mercury mano-


meter the pressurs which the ssaa exert -,vhen csnra-acsd to that volum?.

I

Thti mount of gas present is pro?ortional to the pressure.   In the forme,.

a?paratua the pressure of measurement was constant (at atmospheric), the

usa of gas being measured by the volume.  In the present apparatus the

volums is sons tnnt , the mass of gas being measured by the pressure.   A

great gairi in accuracy is 03taline2, because we can mw chooss conditions

af zensnrement such that the error in measuring the volume Of gas shall
be no greater than the error in measuring the pressure, e.g. with the

volume of gas at 5 cc., as in our most accurate CO2 determinations, and
the pressure to be measured at 200 to 300 mm. of mercury, both volume and
pressure can be measured to 1 part per 1000, and the sum of errors in
both measurements is only 2 parta per 1000.  The manipulation of the ap-

paratus is so simple thau b this degree of accurac;r is, In fact, attained*

in our routine determinations.  Refinement to tiiis point wae forced upon

us in order to obtain data fran which 1ve could determine the effeat of

oxygenation and reduction on the base binding power of heizoglobin.

     As reported in October, we found that at pR 7.4 the sodim salt

of oxyheonoglobin binds 2.15, reduced hemoglobin .1,47 equivalents of Na per
mbleculs of hemoglobin,`the difference being 0.68 equivalents of alkali;

i.e. %f reduced hemoglobin is o-*genated, its acidit:? is aiu@aented. so `that'

it binde:at the `same pH 0.68 more quivalents of, Na'per moleuule: However>
we found that in blood the change fiam complete reduction to oqgenation
lmreaskd the all& bound by proteins only by.0.56, Instead of 0.68 equld

valents per molecule of hemoglobfn.   This difference we w%re unable to

explain at the time.

    We believe, however, that it ie now completely explained. !-iataC~
ings, h'elll, and Barrington have found that in hemol?rzed blood the same.
effect of oxygen3tion is obtained as 13 the solutions of pure sodium hem+


x

                                       .

                                                    f L. f"
                             1.J 9 * if 1

globiuate.  The fGmerl!,r 3jc-5rv~3d 3i.f f e-?!ncs %:,1 tit-leer. the solution c&L tnz'

blooi i; t:\erafo;-e >ttribuk.jle to t,te cotii*lt;;p>ieLt jf' <he het;oglcbl~ ii1

tile cells  05 the blood.
    Vcn Sl;lke, RI, and iJcLazn in Poking (ir work reported below)

sho7/ed 5i-c t wher, the EI~~~ p:i cf blood IS $ .4C tta cell pII is only 7.26.

And at 7.23 the ozygemtior. of p-x-e sodium herr,oglobi=te increases t'ne

IlaJsb by only 0.62 imtecd of C.% equi..-alents.   This accounted for half

the obsormd difference between whole blood ar.d y.ze solutions.  The other

hdf was due 20 some other factore, WI? of kmm differences between cell
contents and XaKo solutions the nost etrikinl; is the fact tLat all the
alkali in the cells is P; rather them Na (in hezoljrzed blood the aUcali o
?? ??? ????  ?e accordingly determined the effect of oxygenation in go-
1Ltiona of potasalm hmoglobdmte ati found the same value as in blood,
when the pH differmce between cells and serzn is Included in the calcu&-

tion.  `The effect of oxygenation and reduction on the acid-base balame of
the blocd is one ro:e ph:~aiolo&c?l phencmenon v:hich has become explain-

able on a physicoc'nerr,ical basis.

     The work doile in Peking vms a development of the work on the
physical chorzistry of tine blood on which this laboratory is engaged. It
has been kaovm that, at normal pH the chloride and bicarbonate in the cells
are only about hal? as concentrated ae in the semm although both Cl'  and
XCO; pass readily through the cell walls,  On the other hand the hydrogen
ion concentration is greater in the cells than in tile serum although the
cell membranes appear po;neable to Hf  ions.  By 60x33 rx3chanism it was

lumwn that the Cl and HC03  distrilmtion is so regulated that it enables the
                                    

indiffusible cell buffers (heiAoglobiz) to act through the cell wall and as-

sist ir, maintaining the neutralit, v of the serum wit'? nearly the SWEJ degree

CT efficiency that the hemoglobia would  exer C were it di.rectl;- dissolved in


                          I B
                              -.; :'
                                                 132

the se FL.1 ,  !:s hid no e::pl?+nations, other thnrl Titzlistiz ones, for these
F'ncnonena, nor for the faot thz.t use of CO2  t ensions caused the cells to take

nxter from the sel'um.  The discover;r of the ixgnitude of the ;?ou.nts ef al-

ksli with which hemoglobin combines, nnL the r;rezt effect of chx-@nrJ p9 on

the alkali combined, indicated the nnnner in which a common. explanation could

be found for the above phenomena, in the basis of the Knox 1~s of soiutions.

The solution xas obtained by ccrcbining the three physicochemlcal laws which

govern the distribution of electrolytes between solutions at osmotic equili-

ir',UE On tLJG S2&33 Of a membrane, whic'n 13 pcrr:.a.rLblo for only part of the

i 3w prescl;.  These laws r.my be expensed, for the conditions found in the

blOCl,  as f ollo~;..s.

      T
      - I  For Ble:trig. nsutmllt~ cations 2nd anions must be oqyal at re-
actions as near ,the n*utrai point a; the bl.oo% :!* and CR'  ions are negli-

gible, and the baoe 1s coabi~sd Frtly wit5 monovalcn*, anions (Cl' and iiC0; ) ,
                                                                           L

partly with grotcir,.   TkqFesxting the concxltration of total cell bnse

ah+3 c,  that of th; xcno3icnt anions as  ;A--
                    L I c, t%t of the negative13
                                                          - .-

ionized prntein,or protein combined with alkali, as l?:!2 , and similar values
j.n the aerux as `c33, )            we have, assum'ing complete electro-

lytic diasozia%ioz.,

,,' ,   XI *  According -lo -n's law, when electrolyte solutions are separated

by a mem3rane permeable for only part of the ions, the nonovalent permeable

ions so distribute tkemseti?es that the ration of the concentration of any anion

in the cell to the concentration of the san9 anion in the semL~ is the same as
t&t of any ot&r anioq and the raci?rocal of that of any cation.   For the


permeable ions in blood therefore, we have the following distribution

- 1
H+- s
L ..   $1' ! c =IkC?$ c =pj
        I-)       .                C    = r;

the letter r being used to indicate tha cmnon ratio.

  111. For omotic eq&itv between cell contents and serum the con-

centrations of osmotically active ions and molecules in each must approxi-

mate .cpdity.  We found that the tit of osmo!&& !ZgWntra!&XI i8 cot

the ratio' +::$E i%:Bw but -%a--= 8o that P'J

represellts the equivalents of chloride %r kilo of water in the cells,

not the chloride per liter of cells.  The total concentration of the
bsaotlcally active substmcee in the bez?uz -xay be repreeented as 2 Lx
+ CBI';
   ,8' since the salts represented by Ba, are dissociated into two
O~Otitilly aCtiVe iOnS a+ end AH , while the protein Salt PPI di81
sociatea into iord of rrhich onlg one LrJ+I , hzs important ,osmatic acti-
vity, [P'[, having so tittle that it xay be neglected.   In the wee of the
cell conteaks we'muet add t<, `the, ck&otic activity of, the, kekttdlytss that

of the hstnbgiobi& which ie &IA l/l0 6f `khe fbba&;. Therefok, if the
betli~tic cmc t ti " .
     en rri. on6 iA cklle &2d% a4rk.1 Ue evrfn We have

The Wrmracy of thie equatiti v&s da&m&rated by analyses df ~611s and

   By .odmbining the above eq-utions we obtain f inall:? -one which '
e~pyesses $&g ralatioashig betveer, the- @%Wtrolvte di8tri'XLtion and thf%

&li bound b.. +r th 8 ?Aocd ;>rotei%, tiz.


This equntlon was tested quantiktively by analysis of the serum

and cells of blood after it h4 been mbjccted to vnryfni COzVtensions.  It

was found to agree ne.-rly withh t3e limit of experimental error in H+ ,
ci ( and HCOj    ratios.

     The water distribution was calculated as folLvs: the equation

cf osmotically active subsknces may be written ts

or if we use (B)s to lnd?cate the sem base,  (Bjc the cell base, etc.,
peer-k;iiow sf- blood, we ma:? {vi-i te it as

2 (a)  - (B?) + (Hb)
      C           C           C  , or
   c-$0) C

(H20) s  2 (aIs -
-u       (BP) s
039) c  2 WC -  (fHc  + (=d c .                 

The distribution of water bitween serum and cells was found wittin the
limits of ajlalytical error to be related to the amount of base bound b.

the cell proteins in the aanner indicated by the last of the above equa-

tions.

    It appears probable that tine &a&s gr)tterl?iq the distribution of
salts and water between intracellular and extracellular fluids in the blood
also govern the distribution in other parts of the body, between tissue

cells and exudate, for exaz-?Jla.  The study is being extended in t'nis direc-


tian, an1 it is hoped that it my assist in explaining

di;turbances that underlie such conditions as edem.

Acute Respiratory Diseases.

Drs. Cole. Averv. Mor~an,khl r.z-& Stillman.

the ph;~sicochemical

     The admission of ptients h=cs not been ccnfined to those suffer-

ing from lobm pneumorria but Ftients suffarirg frm various types of the

milder mute respircrtol?J inf'ectiono hzve also beer. abitted for stwiy.

Through a combination of the clinical stud:p of these p&Li%::ts and mora in-

tensive laboratory Investigations M atterqt is being made to differentiate
more clearly the various typos of infection of the respiratoqr tract and to

learn more corxerning the .mture of the in,Pective agents concerned in the

primary locus of infection and tho moee of invar,:cn of the lungs.  Further

analysis is being mde 05 the phenomena of infection with pneumococci ati

the process of recovery.

I)acterial Incitant of Acute Upaer Resgiratorf Tract Infection
                                                    --p--.&*

Dr. Mortar. and Dr. Averv.

Stuaes directed

baoteria of' this type from

toward the isolation. of 3. pneumoaintes or other

the nasal secretions have been continued. The

technic followed in this

itskir 2nd Gates in their

study has been

investigations

essentially that described by Ol-

on the bacteriology of epj,demic -

influenza.  In ;t;la 54 spec3mens of naao pharyngeal seoretions from 45

individuals have heen examined by cultural and animal procedures. ,In 17
instances the washings came from the nose and throat or* _mtients in T.vhom
the diagnosis of clinical influenza seemed certain or highly probable.

l?ne n&o pharyageaf washings from 16 individuals sufferiK from acute co&-

ryza, a%nusitis or bronchitis were similarly studied .-,r3. of the remaining

individuals dnvestigated 5 were suffering from lobar pneumonia and 7 were

frea from respiratory infection.


.

133

     From none of these 45 individuals has 2. pneumosintes been re-

cdGered.  On the other `hand, during the study of these 54 specimens of

filtered naso pharyngeal secretions, 23 strains of sr~all C-ram negative,

anaerobic bacilli have Seen isolated.  From one case of probable influanza

en identical organism was isolated on four successive examinations at

weekly inten-1s.  All etrni:x recovered thus far apparently belong to
a heterogenous group or` orgznisz; which are closely allied to 3. pneumo-

sintes ht are serologically listinct.

    Of the 23 strairre of these pneumosintes-like orpnisms, 15 zere
obtained from the 17 cases of supposed influenza; 6 strains from the 16
pationte with %olds", (coryza sinusitis, etc.) ani 4 strains fran t'ne 7

normal individuals; f rQ;1 the filtered sp.rtum and .naso pharmeal washings
from 5 patients with lobar pneumonia no organisms of this type were iso-

lated.

At present the sf@ffoance of these organisms 13 the causation

of mild infe&ions of the upper respiratory tract

certain.  Their relation to each other and to 33.

clear.  Zkperiments to determine their antigenic

carried out.  Serological

this group because of .ths

taneoualy in nomal serum

investigations are exceedingly difficult within
tendency of these bacteria to agglutinate sP;on*

and in salt mixtures.

me&%1 Nature and bmnolonical Pro>erties of Specific Substances,oc
$3x3umocot3~us Orida.

Dr. Avery and Dr. SeidelberaQ.                                      c
    In 1917 Dr. Dochea and Dr. Avery shov;ed t'hat whenever pneumo-

must be regarded as un-

pneubosintes is not

relationships are being

cocci are grown in fluid media, there is present in ",ize cu1tm-e fluid, even

during the early hours of

growth, a substaxe IV%.C~ reacts specCI'icai,ly with

antipeumococcus serm of tine hmolo~o715 typ.  23s (scl:~-213) w.ibstxme


                                                137

is &mom trzbl.3 In --. '
           LAAt-;re filtrate; dariizl: the iriitinl grcx-:th

phase of the orgmis-x , that i&, cluring th3 period oi' their maxim

rate of multiplicntion when lit tlo or no cell death ozd disintogrs-

tion is occurring.  The formtion of this soluble sy,ecific material

by pneumococcl on growth in VI tro, suggested the pro'oability of

an cx-&ogous subat-ncs bcir-* `t f cm-&l on grmth of the orgsnism in

tlm an-1 b0d.v.   Zmzfne'. ion of the blood 2nd urine of ex?eri-

mentally infected m&mLs gave prool of the presence of this sub-
stafice in considerable quantities in thb bcdy fluids, following
intraperitoneal infection with pnemococcus, fn other r:or2:3, this
soluble nrrterltrl elaborated at the focus of the disease rsadily
diffuses throughout the body, is taken up in the blood, posses the
kidney nnd appears in the urine unchanged in specificity.   Shi-

larly a study of the serum of patients suffering from lobar pneu-
monia has revealed a substance of like nature in the circulating

.

blood during the cv~sa of the disease in mn. l?urthermore, exmi-
natton of the urine of patients having pneumonia due %o pneumococcus
types I, 11 and III has shown that fn approximately two thirds: of
the cases, this epeo2fically reacting b6dy Is excret6d init& urine
in quantities readily demonstrable by preuipi tin tests, and it& Ime, `2.

,.,,

also been found U&t-the.ambUnt bf preckpitabie substance in the
urine s&m to bs a measure of the eemrity of the infectioh

    Xa the earlier: studies by Doohez and Avery certaidfrcts

Were ascsrtained concerning ths chemical clmr&Cteristi2S Of tfii3

subs tame.  ft was fcmnd that the specific substance is not destro:-sd
by boiling; that it is cesdily soluble in water, and precipitabls Ln

au6 to F alcohol and ether; that it is preci$tated by c0110idd iron,

and does not dialyze through parchment ; that the nasolo~iosl react:cx

                                                                   _- .~.

C


                                           t             ?  rl. /I
                                               .-i i 1
                                                     138

of the substnncc am not affected by proteolytic digestion by trypsin.

Since this substance is easily soluble, therrzos table and type specific

it seerr.ed an ideal bxis for the >e&nin:: of a study of the relation
between bacterial specificity and chenical constitution. l'he Present

report deals with the work done in this direction.

      As the no& abundant sources of the soluble specific substance

appezed to be an 8 day old, autolyzed broth culture, this mterial

has been ueed for r=.ost of the work.  The organism used wa9 the Tspe II

pneumococcus .   It was found that when the broth was concentrated on

the water bath to one tenth of its oolme and then treated with nlco-

ho1 or xetone, a separation into two layers occurred.  Zy addition

of the precipitating agent until the upper layer no longer gave 3 tur-

bidi ty with ~IZEIUI&I se-, the specific soluble substance could be con-

centrated in the leer layer, leaving in the upper layer a large pro-

portion of the coloring r.?attar, peptones, and other inpurities, dartvetd

from the broth.  In this way the active mterial f rax 75 to 100 liters
of broth culture could be concentrated 3nto a vc3um of about 1.5 UtoB .
tithe? purification consisted in dilution and repeated precipitation
with acetone or alcohol, first from the neutral solution, and finally

after acidification with acetic acid.  Careful fractional precipi tat ian

In the later stages resulted in the removal of Inactive fractions, as
ft was a simple Elatter to redilrsolve a portion of each precipitate and

test with Smmne serum.  In this way it was possible in W~etal instances,

without the use of other reagents, to isolate small amoxmts of highly

reactive material whidh no lower gave the biuret reaction and no longer

precipitated phoophotungstic acid, one of the best ptocipitants for

dt rogenou8 compounds.  Under the most favorable condition8 the yield
was 10 milligrams of dried active substance per liter of broth used.


                          I  t `"y
                                                                           ._ I I
                                                                .          `! -
                                                                          `., ,9

In other cases, however, In order to obtain products of the same degree

of purity 5.t. was found necessary to precipitate the nitrogenous &nxci-
ties fixt with phosphotungstic acid, ncrcuric choloride, or neutral

lead acetate, or to leave them behind by precipitating the soluble 6ub-
stance (and other gums) by saturation with ammoniun sulfate.

     The best sroduc';; qbt?inzd in this way caused a precipitate

to form in tho homologous ~IZA~I~ sonx~ when the dried substance in a
solqltlon of aa great aa 1 part to 2,530,000 was added to the serum.
On th.e othsr hand, no trace of clouding occurred when tha Bubstance,

evgn in high concentration, was added to the hoterologous serum.  This

conoentrntsd and purified substance t:s>refore is exquisitely typa s?ec-

if$c.  The further study of this purified substance showed it to be free
from substances giving the blurst re?ction, St rotated the plane of

polarized lAgI& about  31 o to the right, gnvo the Xoliach test for car-
bohydratae, in the hiGheGt dilution at :7!Ach Gpocific precipitation OC-

curred, (a point r&ear tLe limit of d?licacy lor the Molisch reaction,)
and yielded reducing sugars on bydroJys:l s v:ith acid.  The finding8

are mxmnarlzed in the accompanying kble:


Table T.

Sum.ary of the Troperties of Varioue Prspaxlions of the Soluble
    Specdfic Eubstanze of Pneu;;lccoccu~ Type IX.

Prcpn. Total
  I
.-
LO.   I 2.
      L ("

4 t

4*ti

8 iTl

9

11

15

6.1

4.7

2.9

6.6

2.1

2.0

.rolys

1.3

;      -

Red'g
sugars.
o/o

tFrom urine.
tlPrepn. 4 repurified.
FFrom dissolved pneumococci.

s P

$0 o/o

_ -- I

1.5

  1.0

1.8

0.9

Spec-
ific
Rotation

F.l D

-20.60

t19.8O

-8.60

+31.6*

~30.8~

Pptn.!vith
IERIWM

serum

.._ _. -  -- --

80,000

640 (000

1,250,000

640,000

2,500,OOO

2,500,OOO

_.__._--

11, lisck:

-. ___

32': cr?
   t  _

640, cou

----we

1,250,OOO

1,250,OOO

,_ __.._. .._


bM.lo Prcpzration 8 was der.S-ICC'. f Yom wa;hod Type II pnsumococci vr'h;r..L 17-X

been diosclved in antiformin.  TcY ziso yCcl5 CL re?xcil*~ subs&ice6 C~I

hydrolysis.

     slnco the sper;(,fic. 3cIublo :~,`,stc;u:: r,: tI.2 ?y-po II pneumococcu3

aspears, in Its present stat3 6:' puxty, to consist largsly of a Folyeac-

charide, it was of interest t; dQteL%inr:, Jf ?ossibls, the sugar from

which the complex molecule is b-A.1 t 3;~.  1 scczlingly -00 mg. of Prepara-

tion 15 were hydrolyzed by hoatirg 7 SG-LJX on the water bath in 0.5 2

hydrochloride rcid.  Although the act.iv7 J naiicr.1.21 WEILL L,iA! iered

acid at room teqenture for 56 ho=lrs, tn%+.ir,, x the water Lath

suited in the disappearance of the specific reaction with kreuno

and the appearance of reducing sugars.   The hydrolyzed. sol.u.t.ion

treated In the cold with pherprlhydrazine and sodi-m acetate, and

by t'l.n

rc-

38~Jm,

VJaS

a5 no

hydrazoce separated, was then baated on the water bath.  In a vzry shor.2

time a crystalline osazone separated.  Although the amount was very small,

it was posalble to recrystalllxe the oeazone.  Its melting point was then

1900, shcwdng that It was the o8asone of a herose.  tian diSSolved,in
midine and tioohol it rotated the p'iane of polarized Xght to the left,.,

a phsnmenon characteristic of the osazone of glucose.  U-nfortunately the

axNunt of substance wa8 too ~nal.1 to peruit the quantitative 88 tination

of the optical actavity, and conclusive proof that gl'uoose is the sugar
from which the golysaccharide is built up must await the purification of yore

mterizl, which ia XUY,V under way.

It will also be attempted to carry the purification of the so!.ubie

substance still further, in order to establish wit.h certaintyz whether t.hs

carbohydrate reactions are due to the soluble substance itself, as now seems

highly probable I or are simply due to an admixed impurity.


      Studies have also been undertaken to learn more concerning the

c3cnical nnd irmmnologicazl properties of the protein constitutents of the

pneumococcus cells.  To obtain the bacterial protein ELB free as possible

from +he other constitutents of the cell, including the type specific

non- protein soluble substance, the following ne thod has been employed.

     From bouillon cultures of actively grmlng pnoumococci, the
cells are removed by csntrifugation and resuspended in l/10 volume of

salt solution.  Solution of bacterial bodies is kmediately offeoted by

the addition of the minimum lytic amount of bile

carrying out the reactlCn in the cold. Ram the

solution, freed frm cell detritus by filtration

and autolysis reduced by

clear, slightly tiknline

or cent rifugation the

protcin is pr&cipitated by dilute acetic acid, the white floculont pre-

cipitate ie washod with distilled writer several timee, redlsaolved in

waak alk;cline solution and again precipitated by acid. The process is

repeated several t&es to rid tne protein of the soluble substance al-

ready referred to, and the fin-L1 precipitate rapidly washed with acetone

and than dry ether and dried in vacua.   Yhe product thus obtained in a

f om of a white powder, is readily soluble in &.lute alkali and gives

qualitatively all the protein reactions: Biuret, Millon, phosphorus, eta.
The qu;zntitative klysis of this substance is being undertaken as rapidly
                             

aa sufficient purified material is available.  9hQ kIYmlnOlogical rhdy OS

this eubetsme, while it is not yet compkte, hae gfelded most interesting
                           *                                        .

P66Iif.t6.  It has been found that when a solution of this substanoe is added

to anti-pneumococcus immune serran precipitation occurs.  Bo precipitation,
                                                                           '.

Occurs with ant&mm ~roducsd by immarnization with bacteria other than

pncumococcus .  It is, therefore, a specific pne~.~~~ococcns substance. The

remarkable fact, however, has HUM developed that this precipitation occurs

no matter which type of anti-pneumococous sem 3.6 employed.  It is there-

fore, although species specific, apparentljr not ti;q~t,-' ;pwific. Kmrun.Lzr.e-


I

                                                  l43  2 I- !
                                                  i . j /;
                                                                           1

tion of animals with this pneumococcus protein substance is now undsr WCs'
but conclusive results have mt hen obteirw3.
    These studies hxve resulted in observations r!hich indicate that
immunity to pnoumococcus is rclzted to two ontirol:j distinct bacterial

substances.  One of then is a protein, immunity to which is very specific
as regards pneumococcus hut is entirely non-specific 3s reg:rrrds tme.  The
second substsnce is nonprotein in nature, in its present state of puri-
fication possosses the propertice of CL carbohydrztc, and is to a very

high degree type cpocific.  This second substance when injected alone is

apparently non-antlgenic.  These facts have su3r;cstcd entirely new oon-

cept ions concerning pneumococcus inrzuni tl r vrhkh xmy explain a number of

obscure facts , includihg the changes of 6pecif icS ty of pneu2ococcus with

changes of virulence.  The further study of this problem is now in pro-

gress.

g8 a8 Portaltidf Entm for Dactcria in Xnfectioa in Mice.

Dr. knest Stillman.

    In the previuue, report it was stated that when mice are ex-
posed to an atmosphere abntaining cultures oI @ bacteria in the form of a
fine mist, the bacteria readily penetratea &nto the lower respiratory

tract. Pneuuococ~i whiuh have reached the lungs as a result of this pro==
cedure usually disappear witiiin a few hours and give rise to no infection. '

Attempts

chilling

to low3r

to cause `infection to occur uIore frequently by meana such as

and exposure to cold were without result.  It was then attempted
local resistance by inducing slight injuries to t'ne CZJC~XS meX?VaM

by inhaling ether, alcohol,

sand or talc in the form of

the frequency of infection.

and atmospheres containing finely di.vided s`z-7 i,d

dust.  The procedure, however, did mt increzae

It was found that mice could be easily intoxi-

cated by breathing an atmosphere containing alcohol ard that, if the mice,


while under tna ir5lmnce of ;Icohoi, were allowed to inhale an ntrnosphe-:f:-

containing pmumococci in suapcxim t'hcro nas a mrkced rise in the inclciz.*e

of pnc-JI~lococc-~s 3ept iCm!lii\. .   ,!s the direct inhalation of an alcoholic at-

:..:oz?herc zliE;ilt alter the respiratory rmcosa and this might explain the in-
c?oasod froqumcy of infection, cico rlerz i&o:;icatcd by injecting a l@

alcoholic sol-ltion intraperitonoally.   3hen mice v:ere intoxicated by this

means and were them exposed to an ntmosphoro containing pneurnococci in sus-

pension there was a definite increase In th3 incidence of fatal scFticmi3,

but not 38 peat nn increase as in the series of mica vfnlc'n had inkzlc;d

L?lcohol.  In other oxperinents mice were first intoxicated by nn injsction

of alcohol intmpcritoneally; they wore than exposed to an ataosphoro con-

fz.inin;: 2. influonzr,e in suapcnsio3, and than they were allomd tc ir-halc

air contniniw pncunococcus culture in the form of spray.  In thasa nici,

the incidsnco oi' pnomococcus infection ma almost as high as In the nice

intoxicate& kLv izhalstion of alcohca znd thon exposed to the air containjns

prlcumococci.  A 6tti.p of the tietological changes which occur in the 1m.g~

followLng tha irihalstion of an atmosphere containing influenza bacilli and

pnemococci has alsc besn undertaken.  Apparent l:* definite pathological

changas ia the 1~~s occur a8 a result of the inhalation of 3. influenzae.

    Pronw of Fneumococci Modified bs Gzutit nc: in l&;-une Seng31 aa
                                                                --

by Growiz in LIedia Cmtainins Bile.

Dr. Dahl.

    It was previous~ dsnonstrated by K&S Stz$o:- norking in this
lab&tory that when pneumococci are cultivated repeatedly in media contain-

ixg homologous m sawn the bacteria decrease markedly in virulence an?.

the:7 also bccom much less sepcific ic their innunify reac"uions.  Dr. Avery

has also shown that when pneuzococci me grmn in media coztA.ting ninuta

XT:C.,~S of bile the bacteria becocos resistant to t!:e bile, and by gradur.' :J:


by this observer ati 31~0 by ot;-,er o that thg im.mity roaponss in anirm3.s

r'ollov;ing the injection of theac modifisd bnctcria differe fro;3 t&t fol-

lotnricg tho injection of vimlent pneumococci. L otviy bps hew unde?txa

for the purpose of extending those obsorvctions aad if possible of e::si".in-

in< tha msults obtaimd.  The obeervatio;;s of Xi88 Stryker have be% cc&-

obtained which posseos a2-;lost no virulence Zor mi.x snd vrhizh Piicx`I IILCIG

type 3peoific:ty.

3y ropeatad cultivation in media ccntainia~ bile cultwcs of

pcouuocccci hrsve also Seo,-i obta2ned c:Xcb r2f2:j grmi r2a.dil:r ir. SC2 bile.

These culture8 have also practiaall:r lost their virulence a-i f;~s s>eci-

;`icity .

    &&nals tl-re now being imuuiized to tSees modif ied cultures and
                           *                        ; . .                      "
studies are being made of the properties of Ike serum.  The renulta of these

studies are not yet conclusive,

Acute Fb~lc Fever.  (Report of Dr+ Swift o )

Dr. Swift. Dr. llobta and Dr. Miller.

     l2ao ttypes of rheumatio fever studied ~~~:-in~ the Fe t six nor;tho

`have been nostly of tIm mI+zcute and chrozic form; and practical& all

of the patients have szffered f rm carditis .  As znti oned in previous re-

ports the chronic fom of ths disease seem to be derznding more and r;lore

of o-m at tention .


:*.  1 ;-,. I
      I L'

I.46

Znbreetlng c~zdcal marrifestat~, not previously mcounteted

by us, tive been sldn rashes .  Four patients with akin lesions, cOmnOtiy
classified under the term, Erythema multifonne, have been seen recently.

In two instances, these nshes have almost constantly been observed for

two or three months; this we cmsider another indication of the per-

eietence of the infection.  Ip anothar patient the relapsea have been
actqxmied by recurrence6 of the mytherm.  Three or four patients have
had numerous eubcutaneous nodules which have furnished UII mterial for

histopatho~ogical studies a8 well a8 for hmcubtion. me are now 1-0.

moving apall pieces of the jo%nt ccrpsuls and periarticular tissue for

hiato~thologlcal study.  Ue have also written to various pathologista
in &gland and in thio country requesting material from fatal cases of

rheumatic fever and chorea.

Ar far as I know, them is no caqrehensive study of the pa-

tholoe of rheumatic fever.  The hiatopathology of the nryocarditis is

well lqrawn. The pathology of the ruboutaneoua nodules is fairly well
studied; that of the j&t, &r&G &ute &tls and of the brain in
                                i             `. `
ohorea patients iB m&gerly d&&&d.  xi, a# ~0 believi, all of them
                                                             
X.eslons are due to a GCUIXIO~ etioi& age*, t&m must be sane korrela-
                  ,)I .`. .I..,,.'                                     . .       .
                                        .-.

tion b&men the tkke rsepbsirrso'~~ the v&we organo. me feel thEid
                            

bo determined by bietopathologlcal &diem.
           ..'                   ~      ,.                           . .
  Obaemationt3 on relation to Lukooytosis to the aotivZty of
hfeotion ha thf388 patients have been cont$nued.  'Ibe group of rheumatic
fever -Wants amen ir, the winter of 19214922 has been followrrd this

                                                           
winter. b3st year ths patient0 were suffering f&i abtive infection;
this year they wtsra nearly all a**r&tly well.  Our results indicate

   `>
   .. ,,
"3.
  t
   .,


that when the white blood count remins consistently below 8,000 the

prognosis is rnach more favorable than when it is above this figure.

The leukocyte curve is, therefore, a valuable aid in prognosis: in the

acute infection if leukocytosis persists while the patient is under the
influence of anti-rhematic drugs it serves as .sn indication for the
continuation of these remedies even though the patient is free from

symptoms; and in the sub-acute and chronic form

sistent leukocytosis sex~es as an indication for

supportive treatment.   We feel that the results

along this line will be helpful to practitioners

fever patients.

of the disease a per-

continued rest, and

of our investigations

in treati% rheumatic

.

    The cUnica1 study of neocinchophen (or tolysin) baa been

continued.  `here La I#) duubt that this dxug is a valuable addition to

our therapeutic armementarium, because in most instances marked anti-

pyretic and anti-arthritiC effects can be obtained with doses that are

practically nun-toxic.  The recent armuuncemeat of Barbour and Lozensky
that enormous doses of tolysin could be given to dogs and other labora-

tory animals without

administer too large

distinct evidence of

`be observed with the

Balicylates.

producing toric syqptoms may lead practitioners to

amounts to patients.  OTe have occasionally observed

renal irritation tn patients; so the seme care must

use of this drug as with the *older and cheaper

    Dr. Boots and I have ccqleted a series of experiments upon

the subject of joint sensitization.  Hersy and Faber have previously
claimed that the joints of ax&r&s may be rendered more sensitive to

invasion of bacteria f tern the blood stream if the joints are previously

injected with small amounts of killed streptococci or with extracts

pqared from these microorganisms,  The recent work of ~esredka And of


I

Gay indicates that lnmuni zation of tissues riizay result from local treatment

with small smounts of vaccine.  5s is the opposite of Harry's and

Faber's point of view.  Our work has failed to demonstrate any hoper-

sensitiveness of joints injected with either vaccine or bacterial ex-

tracts.  Joints so treated were about as liable to involvement a~ the other

joints of the same animal following the Intravenous inoculation of these

animals with living streptococci.

     Mrs. )[ancefield and X have been tryins to determine the presence

of isrsune bodies qainst non-hemolytic streptooocci in the blood of lieu-

xsstia fever patients and comparing them with similar reaction in patients

suffering from streptococcus viridans endocarditis.  This work is still

in the preliminary stage as the methods previously developed do not seem

to be sensitive enoqh to detect lm concentrations of immune bodies, such

as possibly exist in patients with the first-named disease.  178 are also

tryi% to develop methods for the demonstration of antigenlc substances

in exudates.  If such antizenic substances could be demonstrated i.n the

arthritic fluid. and pleural exudates, we would have a substance with which

to test for immune bodies in the serum of patients with more doubtful

conditions, and to demonetrate the unity or JAurality of the rheumatic

infection.

   Dr. Miller and f are c~tinuing our efforts to'animalise the

virus of. rheumatic fever.  Ae sources of virus we have used (1) the heart
valves f&m a fataL case; (2) the subcutaneous nodules excised from a

patient with arthritis, chorea an& extensive subcutaneous nodules; (3) the

joint fluid obtained from the knees of patients during the early. stages

of the disease.  Rabbits have been the test animals. First the eyes were
used; but it has been impossible consistently to obtain lesions differing

very markedly from those Incited in controls.


    Recently, attempts have been made to carry the infection thrgu&

successive inoculations of rabbits' testicles,  In several instnnoos diffuse

testicular lesions have been induced in series of rabbits with material far

enough removed from the ori@nal hurrun source to insure us that tissue from

a heterologous species was not responsible for the injury.

     An extensive series of controls la ncwr beinr: Obesmsd, PralleliW3

those inoculated with rhbuxatfc mcrtericrl.  trtrile it 18 too early to report

any conclusive results, we can state that in several instance8 we have @-
tained microecopic lesion8 much more severe in the nrheumatic series"

than in the controls.

       (Report of Dr. Rivers.)

Dr. Rivsro and Dr. Till&t:

     l[n undertaking a study of the contagious diseases occurring in

children, varicells was chosen as

lcnving r0asona :

    1.  If produced in a-15,

the one with which to begin for the f ol-

there would be a more or le8s character-

iatic leeion to identify it.

2.  There are at least three other diue@see, vaocinia, m=riola and
  alaetrim, with which it can be ~c+patid.

?? o  Relatively little,zatte$tiQn has previously been given to the       
   iliscsss3.

4.  there ie dt present a g-at deal of.inte?est in ell`dis&ses that
  prodwe vesicles in the skin.                                         
                                          

5.  fa spite. of ite'mildness this bibahe laay hold `the key to the
  uabrstanding of more seriou!3 dW3s$ear.

,

The report will be rpsde under th& he&da:    

A.  study of vaccinia 5n rabbits.

3.  CUnical at** of cases af varicella in the hospital.

C.  Results Qf attempts tQ produce ParZcella in animals.

A. Studv of %ccW~ in Rabbit%.

The study of vacoinb was undertaken in order to learn the proper


methods of handling a virus .which -.  the one causing varicella

might be expected to resemble.  It was attempted to answer the following

questions: l.- Can vaccine virus injected intravenously be made to lo-

calize in the skin by 6hcLvi~ and irritation?   Calmette and Guerin

clnimed it could be done.  T/e have confirmed their observations. 2.- Does

vaccine virus get into the blood when M animal is vaccinrrted on the skin
and, if it does, can it be recovered f ran the blood in denonetrable am-
ountis? Ohtawara says the virus gets into the blood and that he was able
to recover it by putting the blood of a vaccinated rabbit into the testi-

cles of a normal rabbit and after four to six days removing the teeticles,
grinding them up end testing for the virus on the skin of a normal rabbit .

j7e have confizzed and extended th.I.8 work.  3.. IThat ie the appe3nnce

Qf ttse C31,1 iaChSi~ in VECCiaia?  Rabbi tsl eyes rera ime+?+& tit2

vaccina virus ati tsslored at different times, langin: fras seventeen ?xnc5

to fourteen days.   %briOUB fixativek

ployed, Including vital dyes. We are

called inclusions or vaccine bodies.

and stainiq methods have been em-

now familiar with what have been

It sBems from our observations that

there a%3 several classes of inclusions arising in different ways and that

the izaolusions men wader oertatn conditions of fixation and staining are

not always the wne as those pcben after other fikativea and Btains have
been used or the sums aa those seen in fresh unskned cella, or 5n f reeh

cells s%alned with vi$a dyes.  ~~hlSiQZB3 tft8l.l hld.i88 'XQplQfi~ Vital
dyes in fresh no-1 tissues uannot be applied to pathological cor,ditions,

such as the vaccinated corma. Under these circumstances diseased or dead

cells are present even in the freshest specimens collected under the best

conditions .  For instance, mitochondria in normal cells do not stain with
brilliant cresyl blue (in proper dilution) but do stzin as soon as the

cell dies.  This dye also reacts differently to fat drozlats and vacuoles,


depending upon whether the cells are dead or alive    Such differences

21~0 occur when Nile blue sulphate is ua&i.  (See Lewis' article in

&.I. Jour. ,Inat .)  Idi tochondria, apparently undergo marked changes in

the cells of a vaccinated cornea.  They become swollen, veaiculated and

clumped in various parts of the cell, eapeciall;t around the nucleus or

around certain inclusions.  This has been demonstrated with brilliant

cresyl blue and janus e;reen in fresh specimens and with anilin fuchsin

2nd methyl green after proper fixation.

Qt&cal s&+&f of cases of
J.                   Varicelln in the Hosri tax.

     Twenty-seven patients with varicolla tive been admitted since

the ward was opened,  No instance of herpes zoster and mricelln oc-

curring in the same family at or about the SCUZE time has been noted.

The clinical stuCtie5 can be discussed under the following headings.

    1.  The blood picture.

2.  Effect of trauma or hyperemin on the localization of the er.Ipt-
   ione in the skin.

   3.  Allergy.

   4.   The skin lesions.

       1 .- !&? blood aicture was followed in twenty-two caBe8 and the

findings are summarized aa follows:
                          

     a.  Leukopenia {below 7,000) occurred in four cases.

   b.  mbite blood cells were normal (7,000 to 9,000) in seven case6,

                         , .,

c.  A leukocytoeis (above 9,000) occurred in
   wa8 never marked,  The highest count was
  was between 10,000 and 11,000.

d.  delve patients had an eosinophilia of 4

eleverl cases.  This
14,000; the average

per cent or more.

The eosinophiles reaohed 12 per cent in one instance.
The increase of these cells car?e during convalescence. The
stools were examined but no prasites or ova were found.

2 .-  The effect of Traum or &meremia an the Localization of the

eruDtion.

The localization of t:le engtion qas certainly Mluenceh by


                                            I.52

                                                      c
trauma or hypeTemfa in three cases.  0-m patient hxd an almost confl~-
ent eruption beneath adhesive plnoter applied to the ankles fo relieve

the pain of CL chronic arthritis.   The patient had had a Schick test

recently and the erupt&on appeared earlier at the site of injection

and the veeiclee were much larger and more numerous than elsewhere.

In another patient the eruption was most marked beneath the napkin which

gave evidence of not being; chmpd ve;y frequentl:*. In a third Tntient,
Q boy who b9ore soft collrre with hip necktie drwm very tight, there

was a narrow bad of vesicles around his neck just beneath t?le tie.

These observations seem to indicate clearly that the virus ie di660nir~-

ted through the blood stream and localizee especially where the skin

is irritated.  Similar observations have been mentioned casu&ly b:: a

fen writers in regard to varlcella and partlculerly in regard to measles
by Pirquet and in regard to var1ol.a by Schick and others. Attmpte
were made to induce thie localizatfon after patient6 were admitted to
the hospital by irritating the skin in certain areas. ft has been i=ri-

possible, however, to induce this localization under these cmdition6.

It seems that the irritation must be present before the rash makes it6

appearance.
     Theas facts nay have ~txm retitionsh$p to the ocourrenoe of
herpes aoster md varicella in the 66.1~6 patient at the Iiane time. They
may also have a bearing oh the eases reported in %he literature In which
following attempts to vabdinate against varicella with fresh vesicle
lymph, vesicles have later appeared at the site of vaccination. In

the majority of these cams a nild general eruption appeared at the sam

tim9.

        3 .- Allerm.  No allergic resgonse hne been demonstrated in

patients recently recovered from varicella f ollowiq the application of

fresh vesicle fluid to the scarified skin. T'nis xay indicate tL?"t the


virus is no: v2r-y cunceatlsted in th3 VdSiG?X .flJid..

    4 .-  .St~~nf..t-~-.~~~~S:"Jicns.

a.   Vesicle f lu+.J,.  Vesicle fluid was coilsctac; from lesions at

different stages of dcvolopment and a cytological study was made in fresh

unstained specimens, in fresh spcimons stained. w;th differen vital dyes

ani fat stains, and in qeoimens fixed and stained In r.any ways. Thera

are only a few cells in the fluid from youq vesicles snd these consist

mostly of swollen epithelial cells and only an occasional giant cell.

Only a few inclusions are seen at this time. Later the cells become more

ruxrou and are of various kinds.  lhany are under,-oing depner3tioC

characterized by fatty or lig6idal c:`haqes and coagulation necrosis.

T'h3 mitochmdria exhibit a &awe in size, shape and locstion in rn~ny of

the cells that show degeneration.  ht this time mny so-c?lIlsd inclusions

aan bo mde out.  In addition to the cytoplasmlc chcnges, there are also

profound alterations in the nuclei.

b,  m. &all pieces of skin have been removed at various stages

in the development of rizncules, papules and vesicles, and have been fixed,

staineCt, and studied in wany wa;*s.  The following fat ts are worth z-ding:

  (1) There occur a definite reaction around the small blood vessels

in the corium just beneath the epidermis. This i's probably the ear$ieet
lesidn. '

  (2)  !bre is a marked fatty far lipoidal degeneration of the epi-

dermal cells as shown by s&Ian iii and osmic acid methods. Apparently no

one has stressed this type of degeneration of the cells in the diser,ses in

which so many cell inclwions are found, certainly not in varicella.

  (3) There are changes in the mitochondria, as swelling, vesiculation

an& clmiping .

(4) There are cell inclusions, which, after certain fixatives and


stains resemble vasciw bJditx.  T"esa are not, so :-xzzr3us, hmever, aS

in vnccinia . Some of the grarules ani bodies seen in degemrating cells

after treatment with certain fixatives a3d sk3ins may b9 directly related

to fatty or li~oidal changes or they my even represent altered ;nitochon-

dria.

C, Attempts to Turnit Varicslla.

Nost of the experimen*QJ work with varicella has bean limited

to attempts to vaccinate normal children with fre;ih vesicle lynph. In

the majority of instances the results have been negative or, when posi-

tive, open to criticism because of irnpro?er controls.  IEn all previoue

atteqts to trcuidt thf3 dAsease4 to ankals tb restits day be cozzaidared

negnt ive .  In these sxperimente wesicla lym_bh ems mloyed and the skin

or eye of the animal used as the place of Inoculation.

In undertaking the present attempts to transmit varicella to

animala we were guided by the following considerations.

It has seemed that the virus night be present in at least one of

the following locations.  It might be present in the vesicle lymph, in the
                          -

hsso-pharyngeal oecretLonk (&cially~ early in the disease) in the.spinal
                                             .
fluid, or la the'blocdi A'&~knte'~arrs therefok made with material from
                   I .
                    A     I- .                                   .     ,' ;
all of theai s&et~ ati mo&ys a#d &bits kre ti&d for the tests. Mwe-
                           

over, it seemed c&t& that the sitk of injection of `the'irifedted material
                   .,        
mmld be of great isrpokbncie. Therefore the vims was Injected into the
                                             _

animals in various places a& in various ways.  The following are some of

the procedures oarried out:

   1.  Utiiltersd naeopharyngealwashfngs were injected intratracheally

into monkeys.  The skin over the abdomen was shaved shortly afterwards.

   2.  Vesicle fluid was scratched into the eyes and the skinof poung

rabbits and young monkeys.

  .--. -._-~ ---. -    _      .__ --.. _-. _


3.  Vesicle fluid was injected in',0 the bsalr,z cf young rab'uits and

monkeys and into the trachea of monkeys.

4.   Spinal fluid from a patient with vorlcella ~~a5 injected subsra-

chnbidally and intravenously into a morkey.  The skin over the abdomen was

shaved and scarified.

   5.  Unfiltered nasal washings were injected into the trachea of

monkeys and blood was injected into the veins at the same time.  The skin

over the abdomen was shaved and irritated.

   6.  Blocd from varicella patient0 was injected intracerebrally into

rabbits.

   7.   10 cc. of uncitrated blood from varicella patients was injected

intravenously into rabbits.  The skin war shaved and Scarified in @tea

i-diately after the injection.

In all of these experiments the results were negative or very

doubtful,  It seemed inadvisable, therefcre, to proceed furthsr along these

lines.

                           I

Certain clinical observations previously mentioned, however, gave

a &.UO which when fallowed up have yielded more aubcessful results .  It has

been stated tbat'in certain paiients <he localization of the leaion has

Strongly indica~dd that' the'vhn;le iS preeent in the blood ia consi'derab&e
concentrabion, at least krly in the dit&se. Moreover, the extent of the

eruption may bear no relation to the concentration of the pirxs in the blood.

On the other hand, all the experiments previously made suggest that the vi-

rus qqf b@ in very small amounts in the vesicles.

     Experiments with vaocinia have indicated that the testicles of

rabbits is an excellent place for propagating a foreign virus of thie type.

IA view of theee considerations It was decided to zxake a serious

attempt to transmit the u$p~q. by iqjeqting apnsidera,ble amounts of blood


directly from the patient; into thz t;stic:les ox i=ttbits and to persist
                                                          /
in the attempts to anim.di;;e the vlx; by rc?ccltr;3. t rxsfor, even though

no lesions were evident on tho first t;-o.nt;fe:.  Zlsod WLJ tharafore ob-

tainod fr0;3 a patient early in tine disease an12 `ocfore coilplation occurred
two cubic centimeters were injected into oath testicle of a rabbit. AZI

irrrxdiate reaction occuxed and the swolllnC: ncrsisted eA the testicles

bocane hard and fixx. Ilf ter five days these tostlcles were removed,
up in salt solution and 0.5 cc. to 1.5 cc. of the emulsion was injected
into the testicles of other rabbits. In further transfers inocul?tix

of the testicular matorinl was za.de not only into the testicles but 03

the scarif ied skin and scsrif ied cornea of rabbits.  Tko results were

qtite st rikin; .  Lesions much resembling tho30 of vaccinis. were obt-.izoi

in a number of mbbits, both in the skin and in `,he eyo.
     A considerable number of experiments similar to the a`3ovc Love

now bcon carrisd out.  Xatorial `has bs.cn obtain-d from fivs ptixto and

pO8itivo results have nuvf 3~sn obtafnod br this method with the r:a:crFal

frcsn throo of the cas~a.  ,It la ovidont that 5f the virus of vcrice1l.a
has boon obtainod it cloetIfg+ roe~smblos that of ttrrccinia a&d variola.
    Eqorimcnt s to siW$j the occurrcncc of ixmxnity and t;lc relation
df this irJaunfty to that or' vaccinia am new under way but dofinits coti

elusions oamot be drawn at tha prosont time.   It is insend to 20ntifiuo

this study, to

chal~tarie tic

Xl3Vf knOWlOdg0,

learn mora concetin;; the aatv.ro of the virus and tho

lesions produced.  Many possible applications of this

au& ~18 vaccination against tha disoaso in children, are,

of courso, obvious.  Tne possibility of application of a similar mctlvhol

in the study of other infecti- disoascs, such as alastrim and evea

measles, sugg3sts itself .


T:r  3irAr
1_.    "r Cw.d Dr. 3row.

     The w-Jo& on OXy&Zi\ VIompy in ~L3'2,r.ii *.x:lr- LntG?I+.l?t3d *a;* the

tiortuzuto accident in which ths chm>c;- wts dostro: zd. Dr. Sir&or sthrlzd

;.t once to plan a new c'nrznbzr - the >,laxa for which ars nova r,oi?Qiztc.  `k

chuxr.lbor is to ba built ol" X-I&I iron with ~1~s arid shmt iron sidss. 15

is to bc located on th3 4th floor of tha hospital In rooa 405, fomrly

usc:d for hydra therapy ovipnznt . A small 2 c-~bici'fmtohcl of th3 ckmbcr

ha3 bocn built and t3stod and found sufficicfitly leak tight. The rux:

ch.mbsr is to bo fir:, proof ati 13 l&c ti@t C.S it cm bs tado.   Thi3

should considerably rcduco tho cost or' operation.  All v;i rlnz alzci othor

GOUICOS of oncr~y will ba kapt outeido the oxygc;l rich st;;losphcro. This

hm involved numarous nzw problems and c.rplr?insth? dzla;- in start% OF-

cr3tions.  Th:, chambcrrrhould bo ccmploteG by e;?riq.

       Vi'o have boon fort.;LMto this 2::ar in ha-tin, v3x-y fz.7 cases of

p nOumOnia with C~~IIOB~S - the ones in whiA oxygen therapy appmrs to be

or' so much benefit.  A fow caeos have bezn treated by o:qqn insufflation

with a nasal catheter.  This zthod, while it aomcttimss gives good practical

rasults, does not servo as a substitute for tho osygen chamber and affords

no 0pportunAt~ for studying the opt i=n;L1 dosage of ox~~gant

      %orimonta have boan made with a bod tent constrcctod of rub-

3arizod'canvas such as mod for the constru&ion of air-cmft. This tent

is easily portable ad should prove to bz of use in hams and in suck

hospitals as am unabls to have `chambers.  ?ho tent is not yet mad;: lo:-

USC.  ThO COnStxctica 09 it has "awn uklertaken by thz Conmcticut L2.l:

Craft Company under the directicn of Dr. 3inser.

kid-3asc Eauilibriux in Pnmonia.

      cl~scl,v related to t!T& probles of <isturbsd rospiratcqy fur,ction


in pneumonia ie the qlestj.on of the state of f&c `,lo~d ahd the p,zsam

or abacnco of acidosis.  Co3ain inv,zstLga.tors (`PIeris 3t 21) bolizve

they have dononct Ftcd the sxistcilcc of acid0;l.s j I; ?n>i::cnia ad h.q,vo

rocorrzzsndsd thn routino us3 of codi-&. bicsrborztr, fol- the ~ur~>oso 0:

incroa~ing the CO2 binding ~CWX of th3 blood.
CO2 absorpticn cur;z: XL cAc..Acztod tho pl! 02

nssumod constant.   xr.gcr, !iastings f.nd Ejoill

,fi,rc , of Int,:Icd. Jan,1923,1 ,a nrtj,cl~ d.oscS.bir,g ths UZliO%d rgsUlt8
which may follow tho lndiecrirdnato -.ISO of SC~~IXI bicaz-bomt3.  Tin3 par-

ticular caeo WEUS ono in which the kidneys could net oxcrotc bicarboratz.
There was rotoatlon of the salt and a concuni~ar,t ~3 ocrio~ rotmtlor.
of wator resulting In cdma or' tho lungo, hydzot::orax and goaomli;od

atiarca - with profound cyanosis ati rapid ard ~hall.cr.v brcathin;.  TX

case was browht to th3 hO8pital in this state.  Invosti~ation of tk

arterial blood showed a pror.our.ccd alkalosls and anoxcnia.  Th5 pa:ixl:

W98 treated in tho oxygen chamber

course stopsed.  There was akmst

WCll.

and bicarbonate atiinietration ?vas of

imodiato recovery. %%a patierit is now

    This pointed to tho desirz-.bility of reinvostig3ing the ccSdition

of acid-b;se brknco in pnomonis by more d$.mct, cethode.  Ikstings and
Neill, Morgan and I)inggr hzm studied the nrtcricLl blood of ~1. sorim of

c3sos of pneumonia - mzking direct observations of oxygen and CC, ccntent
and canabining power and hydrogen ion concsnt:ation by bo?h the eloct?o-

=letric and colormetric methods.  170 3viden$e of L:CidOsLs h-s 'oee1-l fcrx?.

Iiuna Volume stucQg.

Metho&: (3) TYe method for swing lung volume in indivi&--1s stif ezir--;
from shortness of breath hzs becz doscribcd and t'n~ report vi.11 s?L&',;-

zpl;anr i@ the Journal of E;~qorfnenta~ E,iedicine .


  (b) The studies on p zfiznts wi';h i;Cai*t disl:?..s-: arc com2letod ~r.1

nn xticlo on this work tis box submitted for publlcstion In the Jourcx4

of Expcrincntal ModiAnz.  In brief tho findings ~.ro aa fol1ov.s: `I'he

reduction in the vitd c-psicty of Cc lungs obszrvsd in corditions of

heart fsllurc is gonozlly nosooirrtai with a reduction in the total lung

c3pacit.y and In the ao-called mid-capacity 3.a ~11. No zvidcncc of cm-

physcma has boon found - 3 condition dcncribcd in tho forclgn litcratxz.

In the ox-ly czscs whom reduction 02 vital c(rpLity is sll@:t thcrc

ie an incrcasc in residu31 air - often sufflclal; 50 oxplaln tho dim-

iniehcd vital czpacity. In tho cases of long st-.rZ.ng with xx&cod cvi-

dcnoo of congestion in tho pulmonxy circulcrtl?,n th;rc is ua~lly J ra-

duction in rosidu31 air os wcli.  The cmxm and signifizncc of czch

one: of thaso volurno chzrqoa h3s boon fully discussod and the rolctione

which they boar to the gzncnl prwblcm of dyepms.

Lunu Volum Sttiios in Lob-a Pnmuonia.

Dr. Dinrror and Dr. Drcqy.

     Tho intimto relation which appozrod to exist b2twocn rodnction

of lung VOlumB 2nd dyspnca Sndicatad tho dosirabflity of studying this .

condition in loba pneanonia where we ?a?c,w that a, good doal of tho air

content of ,,tho lung my bo roplrrced by eolid material Lznd where tho surfzco

through whichztho ,rospir%tory ~50s diffuso is disaased.  To study .n con-
aition, fn which thb,,:dlsocrsod &ato gradwlly disappears and rcvorts to. I

nom1 sacmed an adrair&le opportmity for learning SW.? axect facts about
tho pathological physiology of roepirat ion.

     Now a study of raspiration in the pneumonia J+ticnt is %A ozm

tromoly difficult cLfftir as any obstruction or rcsist%ncc immodittcly

mrias tha typo of breathing.  Furttrermorc, it xis ncccssary to got

gnphic curves of rcapircttions while the patient WJS broxthfng stmosph?ric


ctir.  3y mcdifyir4 3 LxrgL? 30 Lita- Tissot Sl;iXLEtCt uld providir,g for
continuous rcaovnl of CO2 and xpply of O2 zt the r1'3-to ?f conoumption,

it was possiblz to sOruT such trxings .  This m?ds it fczsiblc to mcas-

ur'3 tho voluzno of nir fn ttc lung!3 2t 2ny given ph2.se of xspirstion.

3ccauso of the rclatlvo constaxy of tila cxpiratoq position as compared

to the inssiratory - 1x1~5 vclur.~~s hr,v:: been ncnsurod at this position i.e.

the volume of air rxxinln;; in the lu~;s at the end of CL Guict cxpir.-.tory

excursion is being studied. `Ikro appears to bz =L dcflnitc relation bct-

wecn this vclluz znd the type of broathi% ,n.nd perhaps - though this irk

not yet certain - to tha appoarsnco of aoxcmia and cyaosi 8.  ThOOC

otudios are bzlng aado throughout tha course of the disc?sc and the C~XI~CS

during resolution znd conmlcsconco are being noted.  The work is not

yet c3fflclontly advanced to pcxmit of gonomliz=tions.

     A serica of normal individuals arc bclq studied as ~11. 3%~

mothod has noti baon pcrfcctcd to a vary fatisf-ctoxy dcgroc of czccursc:~.

Dtiations of 100 cc. in 2 litcra are mzxincll - roproeonting tL maxima3

error of 5s.  The sa~o rolatione appozr, to obtain in normals 1 .o. the depth

and rata of pulmonzq ventilatibn eeems in some way related to the VO~UIX

of air bn the 1-g at the and of nom~~l oxpircrtion 5 which, of course, is

a functibn of the B~&LLOO arca of respiratory opitholi;nz.

     An effort is baing mado to correlrte the size of the ra

CXpiratorv lwln ~olum with some other physicc?l measurement s-&a 5s sur-
face area (from the DuZois Height, Weight formula) or chest mozuromcnt -

in ardor to ba able to predict u&t n lung

individual.

&port of the Patholonist. (Dr. &anch)

VO~URM shoulri bs for any giixr-

Tha routino pathological work has included 9 autopsies, t%e


rcorgcnization of thp ~.lusca ,md the mning of 3 pnt`noiogicnl lnborrrtory

23 n ur,it

`2 cast of

bncillus,

the oLrly

including the twining of 3 tcr2hnici.m.  One of th? a;Uto~siCs,

r;ubxute b?x:crinl cndozsrditis due to a hmolytic hmophylic

hr.3 been wri ttcn up f o:- publicsfion with Dr. Xillnr .

Apart fron t50 .zbovc lvork th\: c:licf i.;tcxst has centnrcd around

2athologicnl lcoims of pnsur;ccccc;a; grax.anlr ,

In ordor to obtain cm3 insight into tho cellular reactions pro-

ducod by this orgmicm xndor varying corxiitions, a mmbor of guinx piy

wcro first used.  Subcutmcouc injection Y:XI cqloycd on the assmption

that pncuruonic= Is 3 collulitis. Dy this ncthod :rlso dor;ago can bc occur.;-

tcly mcxmrcd, tine per$oda readily tzkzn Into account, xd th3 bin e-sily

runovcd at diffcront intcrmls for hiotologlcal cxazin".tion and inprcssion

silLc.2rs.  The diffcrcnco of rcxtion in intonalty par tine period in 1rmu.n.o

and older rmimls could be rosdily compared with stock znd young xim.ls.

     Vith this bsckground wo have prococdcd to study tho asrly his-

tological losione in the lung.  Matcrlal uo& hcrc was obtcfnod from r.tice

sprayed by Dr. Stlllmm in hia work including those r;pEycd with pncmo-

cocci, nlcohol and pnoumococci, influenza bacillus nnd ~T~~OCOCC~, etc.

pu Further material was also obtrrined frm DC?., hvary and FlorgcLn in their work

on intro-tracheal injection of rabbits with nzaopharyngeal washings and

  suspensione of infected crushed rabbit lungs.  This study is still in

progress.