XEPClRT OF 'l!HE HOSPITAL


'gcTc)BER 15. 1920


ANNUAL REPORT OR' THE WCRR 03 THE HOSPITAL   x

     fn the absence of Doctor Cole, who has been on

108~0 of absence since January, the following report has been

prepared with the collaboration of the other members of the

Hoopital Staff.

     The prophecy of Doctor Cole in the last anrrual
report that "men are still ready to undertake quietly the

study of disease" hae been fully Justified.   The effects of

the WEW upon the spirit of research have been tigely elimi-
nated, and the various membsrr of the Hospital Staff have
renewed their effortta with the spirit instilled by Doctor

Cole in forum yeare.

    It Is now ten yeare oince the opening of the Hospital.
A review of the work done here during the past decade wuuld seem

to Justify the eff art and money expdnded.  But far greater

resulta haveb.been accomplished than can be estimated in the
aumbsr of paper8 published, or the total patients tm&ed.
Men have been trained in the combined `bedside and IsbOratory
investigation of disease; a model hoepital for this ~pose

harr been developed.  &at reem3d a dmazn to those of u0 a0

were privpileged to be prseent during the early years has become'

a reality.  Then thqre wa8 no such place to work, and but few
                                                .

men looked forward to a career in olfnical investigation; now
many of our University Medical S&ools are modeling their med-

.  ical clinice along lines laid down in this Hospital and are
offering position8 to msn trained here, and many yuung nmn are


seeking opportiities both here and in these clinics.   It

Is a great pleasure to be able to acknowledge our indebted-

ness to our Director V.&LO has so clearly shown the way and to

all those 5a authority v&o have made the :vork materially

possible.

     The problems continued from previous years have

been pneumonia end cardiac disease; three new lines of inves-

tigation covering nearitls, measles, and acute rheumatbc fever

have been started.  The progress in each of these problems is

covered under the reports of each of the nembere of the Staff.

Dr swift

    Ihe investigat Ion of acute rheuxatic fever has been
undertaken with Doctor Boots; Doctor Miller will also collab-

orate in this problem during the coming year.  During the

past year there hare been an unusually small number of cases
of acute rheumatic fever in the various hospitals in New York.
We have therefore had only a few cases of the disease for study

In OUT wards.

from, the joints

aerobic

results

of us.

var lcsus

msthods

Blood cultures and cultures of fluid obtained

with ordinary aerobic methods and special an-

have been made with negative results; these

are in agreement wi,%h those previously obtained by one
Attempts have also been made to find antibodies to
types of non-hemolytic streptococci in the blood serum

of these patients during the course of the didease; 60 far no
antibodies have been demonstrated with the methods used.

mile these observations should be extended in order to be

conclusive 8 it seems more and more probable that streptococci
play a minor or secondary role in the production of rheumatic


fever.  As a direct corollary to this problem it vp86

shown that the inJection of both living and killed strepto-

COCCi into the Joints of rabbits is followed by the appear-

ance of antibodies in the blood serum; these immne bodies are

formed as quickly as If the bacteria are tijected into the

blood stream, and more rapidly than if they are introduced

6ubc&aXU3ou6ly or intraperltoneally.

     A new line of investigation has been started:
Attempt6 are being u&e to produce some or all of the symptoms
of the disease ln laboratory animals by inoculating them with

the blood and Joint exudate, and filtered throat Wa6hiZ'IgS ob-

tain6d from patients during the various stages of the disease.
A large number of rabbits and guinea pigs have been studied;
in sane instances distinct arthritis has resulted, in others

leslans of slighter degree have been observed.  During the

coming months the material from these animals will be subjected
to mlcroscoplc ctudy by Doctor Miller as the final criteria

URlSt be based on Studi ,of this type.

A general study of the effect of salicylatss upon

the formation of antibodies ha6 been udertaken.  The St%liCy-
late6 are ;ths dMef drugs used for the allefiatlon of the un-
pleB6a& symptoms of rheumatlsrp, but little is knmn as to

their mode of action.  In our experiments It was found that

there was somewhat slower rate of antibody formation as well
as smaller amaunt of axdibody in inoculated animals receiving
sodium salicylate than in controls; this was especially mrked
when the smount of antigen Injected was small in amount.


                             3s,

     A method for the preservation of stock cultures of

bacteria by drying them in the frozen state has been so sim-

plified that it is applicable in any laboratory.   With proper

technicrue bacteria may be preserved in this manner for several


year0.  The dangers of contamination and change in virulence

and loas of other proparties incident upon frequent transfers

of cultures can thus be largely obviated,  Bacteria kept in

this form are wick easier to ship.  It is hoped the n&hod

will have wide application in various laboratories.


Dr Avery and Dr Cullen

     During the past year Dr Avery and Dr Cullen have

been engaged in the study of the biochemistry of the intra-

cellular substances of pneumococcus-   Methods have been

devised for obtaining active solutions of cell bodies of the

bacteria with little or no resultant change in their antigen-

ic or chemioal nature; a technique has been developed for

studying the biologic aotivity of these intracellular sub-

stances apart from the living organlsc with whld`l they are

so inttitely aeeociated.   Since r;;oat metabolic processes

of the living cell are brought about by the action of ene~s

the attempt was first made to determine vthether or not tha

intracellular substances recovered from pneumococci possessed

onsyme action.  By teeting these cell-free solutions on suit-

able substrates enzymes have been readily demonstrable.   !Thet3e

enzyrr.es have been found to possess the power of actively hydro-

lysing peptcnes into skpler peptides and amino acids; of con-

verting carbohydrates into simpler products, and of splitting

esters into ?atty acids.  Evidence has been presented that

these ensymes exist preformed within the bacterial cell and axe

therefore of the nature of endoen%yx#s.   In other wcrds St has

been possible by means of sterile extracts of pneumococci to
correlate ~-any of the tictional activities of the living bac-

terial cell with the enzynotic processes of the intracellular

substances when removed from the growing organism.  Further ,

it has been shown that the optiml zone of hydrogen ion con-

centration within which these enzymes are active bears a

striking relationship to the reaction range which limits the


biologic activities of the living organism it self.

     Since the last report three papers dealing with the
nature and action of the intracellular enzymes of pneumococcus

have been accepted for publication and are now in press:

Studijs on the Intracellular Substances of Pneumococcus
------                                  -

   1, Tt;~? pL;roteolytic enzycms.

2. The lipolytic onzjmcs.

3. !RIC carbohydrate-cpl Stting enzyrces.

      Continued studies on the nature of the intracellular

substances of pneumococcw have further demonstrated the exist-

ence :vithin the bacterial cell of an enzyme or group of enzymes

rd.~ich are bacteriolytic in nature.   Minind amounts of an

aotive enzyme-containing solution of pneumococcus hen added to

a substrate of dead pneumococci of the sam or different type

cause rapid and complete dissolution of the bacterial bodies.

This bacteriolytic enzyme has been found, however, to be spe-

cific for the species, in that it is without effect ken allowed

to act under similar conditions on the dead cells of closely

allied organisms such as staphylococcus aureus and streptococcus

hemolyticus .

     Moreover, in additaon to the enzymeer described,
                                                    .

sterile solutions of the intracellular substances of pneumocoti

cus have been found to captain other active agents which marli-

fest their specific nature vPhen allowed to act on blood. l'hese

in brief are first the endohemolysin &ich causes solution Of

the red corpuscles, and secondly, a substance which is able to

transform hemoglobin into methemoglobin.  The hemolytic sub-

stance is in nature en endohemotoxin, tiich is able to exert its


                              33%


   action only after its release from the cell by disintegra-

   tion of the bacterial body.  This hemolysin, previunsly

    considered one of the most iabile of the substances of bac-

   terial origin, has been found to maintain its activity over

   a period of several ;%%eks tien obtained by the methods

    described.   Th ::atxrrro of the reactive substance of gz~eumo-

     coccLas w3iti :,?Cuc&s tin2 f c;:m&ic:> of me themoglobin has baer,

    investigated by several workers.   Considerable variance of

   opinion exists as to *ether the formation of methemoglobin

   occurs only as the result of the action of the living pneumo-

   coccus on blood, or &ether a similar transformation of hemo-

   globin can be induced by bacterial extracts and cultue

    filtrates.  The results of work already done establish the

   fact that active enzyme-containing solutions of pneumococci

   in which no living organisms are present are able under proper

   conditions to produce methsmoglobln,   The nature of the mech-

   anism of this reaction is being investigated further.

        It is felt that these studies on the biochemistry of
  the intraceilular substances of pn&mococcua are important,
   not only theoretically because of the s&led knowledge gained
  concerning the life processes of the organism, ,but also cldni-

   tally b&auae of their significance 3.n the interpretation of

   certain of the blood changes &M-I occur in pneumococcal in-
h
    fections in man,


Dr E. G. Stillman
           .-m-
    Doctor E, G. Stillman and @s Bourn have made

an extensive biological study of the hemophilic bacilli.
The small Grar; rqative heeophilic bacilli -.&ich have
gradual'ly co~t'l t:* bo considered hs belonging to one group
of organisms end to v&ich the name B. influenzae has been
given, appear in the light of the present study to be rather
a group of closely allied bacilli which have demonstrable

biologic differences.  The bacillus &ich Pfeiffer first

described end associated with clinical influenza is now
questioned as being the etiological factor in the spread of

the disease.  However, the percentage of cases in Which the
bacilluo of Pfeiffer has been recoverad i3 great enough to
indicate that this organism may be at least a secondary in-

Vader.  Since the first description of this hemephilic
bacillus in 1892 by Pfeiffer, little has been added to our
knowledge of its biological characteristics.

In this study it has been found that the hemophilic

bacilli observed divide themselves naturally into two large
groups accorddng to their ability to hemolyze Mhole blood,
The hemolytic group comprises those orgenisms originally
described as Bacillus X by Pritchett end Stillmen, end occurs

in no-1 mouths,

    Both the non-hemolyt ic and hemolytic group of hemo-
philic bacilli attain a final hydrogen ion concentration of
approximately pH 6.4 although the hemolytic group say reach

pH 5.8.  Both produce acid in dextrose, but in both groups

only certain strains ferment saccharose.  The greater ability


                   \
                                      .I. -

of the hemolytic organisms to ferment sqars may he a. basis

for further differentiation.

     A tentative classification deffnos a small s~.~Tw?
of the hemo!ytic group formed by those strains Y&I& produce

indol and gas but do not ferment saccbarose.   lhese strains

appear to ferment mgars less reac?ily md require further study

to determine whether the indol-producing strains are also gas

producers.  The @eater n\llDber of the hemolytlc strains, how-

ever, do not produce indol or gas,  but ferment saccharose.

    The noa-hemolytic organisms are subdivided into two
fairly even gruupa cwrpriaing dndol-producing and norbindol-

proclucing 8 traine.  None of the indol producers form gas in

contrast tith the hemolytio group.  With me exception, the

non-hemolytic indol-producing #trains all ferment saccharose.
A large msJ3rity of the non-indol-prorboing organbm of the

non-hemolytic type do no t f srm gas a% do not ferment sac&a-


rose 4  The lnd;l-negative strains which do form gas, with a

single oxcepi;ioiq all ferment saccl\arose.

     Tas classification-made 2n this study is merely a

tentative one.  Undoubtedly v&n the technique of these reac-

tions is more nearly perfected and a larger number of hemophil-

Ic bacilli have been studied, the group differentiations will

be more striking and regular.

     Although the number of strains of B, influensae

employed in this study is too small to warrant any definite

conclusions, it would seem that the non-hemolytic bacilli iso-

lated from persons suffering with and rzscovering from respira-

tory infections and those isolated from normal mouths during


: $1

the epidemic period show certain kioiogical dL;ii'<rCr1G3S iA8iu

those strains recovered from normal persons duing the -tinter

of 1919 to 1920.  !I"ne group of non-hewlytic hsmom!.lic

bacilli recovered from normal rxou',hs during the winter of 1919

to 1420 tilow a kigher percentage of strains which farment the

polyaaccharides, Eltose, saccharose and dextrin; more strains
                  .-.

which produce gm;. bum fener lndol-producing strains.

    55% 0. H. Robertson, &a is now on his way to
China to assume his duties in the Department of Medicine of

the Peking Union Medical College, during the past year acted

as voluntary.assistant on the Hospital Staff in the clinical

and laboratory work on pneumonia.  During the winter Doctor

Robertson completed a study with Doctor Kligler which was begun

the previous 6rmer "On the cultivation and biological charac-

teristics of Spirxkiste fibef3e~ c?ri (recurrentis) ".

In a publication last year by Lowe, Hierschfeld and

Walla& of Mt. Sinai `Hospital, a test was described for deter-

wing the type ,of pUeurWc?OCmB $n ,greumonia by meens of a blood
                          `j
react ion.  9&e test br5efly cons$sts in determining the rela-
   ., .-. ,,' ,                                      ,. 1
                _
tive rates at ti&h &ii%& b&es of p&mococci produce
                          .
.`:,c); i. iti:::`.:** ,, .,' . .                         ..,.             .i. p
                    ; , -$ * !"`;. `.`
methemoglobin Lq the laked b&od of the Lfected indi&kl,  
       ,.



laked blood is coa.nidered. .to be the same type as that prOdUC-

ing the disease,  Careful and accurate observations .on the
validity of this reaction by Doctor Robertson failed to sub-

stantiate the reliability of the test as a diagnogtLc pro-

cedure. .


     Doctor LYCQ, hose military assignment to the

Hospital during the war eventually led to his official

appointment to the Hospital Staff as Assistant Resident

physician, has resigned to assum the practise of medicine

in Boston.  During the past winter Doctor Lyon studied the

antigenic relationship of a large series of strains of B.

influenza8 in an attempt to determine &ether or not specific

differences exist among the hemo&ilio bacilli.  The recogni-

tion of biological relationhips existing between varieties of

this species of bacterium would contribute Mach to the develop-

ment of knowledge of the significance of these organisms in

respiratory disease.  Doctor Lyon's report, however, indicates

that this group of organisms shows great diversity and hetero-

geneity as far as entigenic characters are concerried.

Dr Blake:   Studies on Pneumnia.

    In completion of work previously conducted at the
q Medical School in Washington, D. C., a betai&ed study of
the histological pathology of pneumonia produced in monkeys by
intratracheal injections of pneumococcus, of Streptococcus
hemolyticus, and of Bacillus influenzae has been carried out
and an attempt has be8n made to work out the pathogenesis of

the different typ43B of

IsmB;

     Study of the

monkeys has showa that

pneumoni8. caused by th8B8 three organ-

pathology of pneumococcus pneumonia in

it iB eSSentially the sam3 as that Of

pn8umococcus looar pneumonia in man.   It haa been shown that

in monkeys the pneumococc~s invades the lung near the hilum


                                                                    -.- ,,



and spreads through the tissue by way of the interstitial

framework and lymphatics and that consolidation begins cen-

trally and spreads toward the periaery of the lung.

     Similarly it has been found that the pathology of

hemolytic streptococcus pneumonia in monkeys corresponds to

that of streptococcus interstitial and lobular pneumonia in


SUl.  The streptococcus Invades the ldng by the same paths

as the pneumococcus but the end result is different be-se

of a different tissue response to the infection and a differ-

ent effect of the organism on the tissue.

     Bacillus influensae likewise produces a distirotive

type of bronchopmumonia in monkeys similar to that produced

by B. influenzae in man.  The injection in this case primer-
ily affects the rmcoua membranes of the bronchial tree with

adjacent areas of peribronchial conaslidation.

Dr Blake and Dr Trask: Studies on Measles.

     By the intratracheal injection into monkeys of Un-
filtered nasopharyngeai wash2ngs from ceses of xmasles a rela-
tively constant group of symptoms has been induced I&&& closely

resembles those of measles in men,  Of 8 monkeys inoculated

with unfiltered washings 6 came down with this group of symp-

tOEiS.  The same reaction has been induced in two monkeys by
the intratracheal injection of filtered (Eerkefeld N)'~ashings

$rom two cases of measles.  hltumg #' these WaS4bgS sh$Wd~

,no growth after two weeka incubation.
    !The symptoms and signs induced have been constant

and definite in character:  After an incubation period of 6
to 10 days the inoculated animal becomes listless and drowsy,


the conjunctivae become injected, and small dj.screto red

spots appear on the labial mucous membranes.   These spot2

increase in number and may eventually coalesce in the course

of 2 to 4 days to form a diffuse red granular rash.   !hiS

rash is usually limited to the labial mucous membranes but

nay extend to the inside of the cheeks.   It is never pres-

ent on the roof of the mouth, soft palate or tongue.   The

individual rmcnles may or may not show the minute bluish

v&Ate centre characteristic of Koplik spots.   one to four

days after the onset an eruption of small discrete red macu-
lopawles appears on the skin, usually coming aut first on

the face.  The rash rapidly increases in the number and size
of the individual lesions and may In the course of 2 to 3 days
extend to the skin of the shoulders, upper arms, best, abdo-

men and thighs.  The rash is constant in character but varies
conside&bly in extent in different antils.   % the time th8
exanthem is fully developed l&e rash cm the mwus membranes

has begun tc) fade &nd goon hisappears,   The exanthem Sn turn
rapidly fades, sametimes wit4 a brawny deswtion, sometimes
                                      .-

wit4ollt.  By the 6th tb the ,lQt4 day after onset depending

uPon

have

dent

n$.te

t4e severity and the extent of the reaction, all eyrrqtoms
disappeared and the an&x+1 again appears well.   coinci-
tith this group of s$rrpptoms there is a constant and defi-
fall in the total leucocyte count, frequently constituting

a true leucopenia.  Symptoms of rhinitia aad bronchitis do not


occur. . Histological sections of the lesions of the skin and
mucous membranes show the characteristic picture of the corres-

ponding lesions of meastis in man.   Cultures of the blood made


both during the incubation period and during the COUTB~ cf

the r:enc';ton in a variety of media, aerobic an?. awe?obk.,

have consistently shown no growth.

       The characteristic reaction tiich foI.lozs the inoc-

ulation of monkeys with the nasoaaryngeal washings of measles

patients has been successfully transmitted from monkey to men-

key through six passages by the intratracheal inoculation of

saline emulsions of the skin and IINCOUS membranes of monkeys

killed shortly after the appearance of the exanthem.   Born
the 4th passage monkey it was also mwssfuily transmitted

to three monkeys by means of titrated blood injected intraven-

-ly.  This experiment showed the blood to be capable of

transmitting the reaction from at least the 7th to the 13th

day after intratracheal inoculation of the donor monkey.   The

reaction has furthermore been transmitted through 2 pa$Wges

by inoculation of nasopharyngeal washings of monkeys in the

early period of the reaction.   The character of the reaction

in the passage monkeys was identical with that ~&lob occGrred
in monkeys inoculated with nasopharyngealwashings of pattents.

The evidence obtained is believed to be= sufficient

to warrant the conclusion that the reaction is caused by the

virus of measles.

Dr Cohn

digitalis

action of

During.the past year the studies on the action of

were cantinuod with Doctor Levy.   In patients, the
digitalis by mouth was compared with the action of

G-stro&enthin injected intravenously,  It was found, in brief,


                             R


                                                                     \ . ..* , ,
that an effect with digitalis may occur in a little more        ' `. ,4 ;


than two hours.  After giving stro&anthin the effect may

be seen in 20 minutes or less; with digitalis the effect on

the rate of the ventricles (when the auricles are fibrillat-

ing) long outlasts that of stroaanthin in the ratlo of about

16 to 3 dage.   On the T-wave of the electrocardiogram stro-

*anthin has a slight effect or none at all.   To establish

these observations satisfactorily and to emplify them, it is

proposed to continue this study this year.   The data serve

as the basis for part of the general stuciy of the action of

digitalis on eati of several varieties of the diseased heart,

e.g. &en normal me&anism ie present) when the auricles fib-

rillate, vhen hypertensive arterial disease is involved.

      In animals, the attempt was made to ascertain

whether the change in the T-wave of the electrocardiogram
&& occurs on giving digitalis to patients is associated

with a beneficial action.  Char primsry obdect, to show that

an improvement in contraction takes place when the T-wave
Changes, was attained.  Bat the results wre unsatisfactory
in ad far that they were obtained after severe operative pro-

                          ".
cedures, and under anesthesia.  The spring was therefdre
                                                             _.
occupied wnith preparing dQgs after the method of van Leersun.

      !lJhe van Leersum method consists in placing the

c011pnon carotid artery in a situation always accessible, so

that blood pressure readings may be made of it whenever de-

s irable . *This is accomplished by an aseptic operation.

Two incisions of the skin are made, parallel to each other


                                                                      '
and to the artery itself,  !Fhe skin flap is freed and its

edges are sewed so as to include the artery in a tunnel.

The artery so prepared is now available for blood pressure

determinations by the usual means employed in man.   We

expect to make much use of animals so prepared in the study

of drugs, for the present especially of the digitalis series.

     In a series of about 15 patients suffering from

pueumonia teleroentgenograms were w.ds b;r Doctor Isvy at fre-

quent intervals during the acute stage of the disease and

Wing convalescence in order to ascertain changes in the

size of the heart.  A few of these series of plates only

have been masured.   It appears frcm the data so far availa-

ble that the method is a satisfactory one far. this purpose.

In certain instances an alteration in the siee of the heart

occurs in the acute stage of both lobar and bronchopneumonia.  .
lhis work will be continued during this winter and should be

materially facilitated by use of the bedside x-ray apparatus.

     Doctor Binqs+ has cant inued his study of the lung

volumss in *tier&s suffering from heart disease.   His results

are more fully covered else&em.

     Doctor Daisbeck, of the Flower Hospital, is pursuing

the very useful and laborious work of measuring the electro-
cardiograms of normal men (about 160).  The work rewires

such time on account of the great attention to detail neces-

sary to devote to it.  Under the circumstances, its completion

till probably be delayed f&r some time-  wlen complete, very
accurate end satisfactory data of the limits of the normal

electrocardiogram will be available.

-.

. .
I {        

   ,


1'1


     Doctor Levy and Doctor Cullen, in making big-
           --

logic assays of several lots of a commercial preparation

of G-strophanthin prior to administering it to patients,

found wide variations in potency.  Experiments XTDI under-

taken to ascertain t'ne cause of the deterioration and tc

devise a method for proparing a stable solution of the drug

for therapeutic purposes.

     I* was found that many of the glass containers

conmonly used in the laboratory and most of the glass en+

pules employed in marketing sterile solutions for hypodermic

or intravenous medication yield sufficient alkdi, on auto-

claving, to change appreciably the reaction of distilled

water toward the alkaline side.   lhis increase in alkalinity

is sufficient to render biologically inert and partially to

decompose aqueous solutions of crystalline stro&anthin in

the concentration ordinarily employed in the clinic.

' :,'

  ,:

     For clinigttl use, therefore, they found that crys-

talline strophanth3n should be dissolved in a buffer solution
(0.02 M standard @os*ate solution at pH 7.0 is satisfactory)

and mketed in hard glass ampules, thereby insuring stability
of reaction with preservation of biologii activity.

Dr Van Slvlus                                                     L:

     With Doctor Stadie the work on improvement and

revision of the methods for dotermining the blood gases has

been finished and prepared for publication.   With the exper-

ience that has been gained it is probable that these methods

are now fairly well standardized in permanent form.   The


methods revised in mare or less degree include those for

the determination of oxygen, hemoglobin, methemoglobin,

carbon dioxide, nitrogen gas and carbon monoxide.   Also the

technique has been so d.evelopcd that it is possible to deter-

mine all the gases on a single 1 cc. sample of blood.

     Doctor Stadie and Doctor Binner are engaged In a
study of the reskiration in pneumonia and in cardiac disease,

and in a study of the physiologi$al and therapeutic effects of

oxygen administration.  For the latter work they have construe-

tedan "oxygen chamber" capable of holding a patient and nurse,

and of having its oxygen content kept at any desired level,

The preliminary experiments on cyanotic cardiac and pneumonia

patients have yielded apparently striking results in change of

oxygen saturation of the blood, character. of respiration, and
puls~~ate, but as the work is still in the prelw stage

and requirer fcr jts confirmation more extensive observations,            I

it will be carrisc; o& during the coming year,,
    Doc3or bi-we: is continuing his work on respiratory
           --w

factors in heart d.iseasa,  During the spring and sumnsr he
has been engaged Ln nodifying the lung volums qthod of Funds-
guard and Van Slyke i&such a manngr that it can be used with

patienta vbbo are acuteZy ill..  In the oHgina method, t&e
subject, by 4 or 5 vigorous respirations to and from a beg

containing 2 liters of oxygen, completely mixed the air in his

lungs with the oxygen in the bag.   !be volume of air in the

lungs (lung volume) VELS calcqlated from the cowosition of the

gas mixture obtained.  The difficulty in applying the method


to ill patients 3a.y in their inability to breathe deeply.

With the ordinary respirations of which they are capable,

several minutes instead of a fraction of a minute are re-

quired to completely mix the gases, and in this t& so much

carbon dioxide develops that it causes dyspnee.   The diffi-

culty has been met by inserting between the mouth-piece of the
appsretus and the oxygen bag, a bottle containing glass beads

moistened with KCB solution.  This removes the CO2 so that it
is possible for the subject to breathe a8 long as may be necas-

sary without distress.  mn the final gas analyses are made,

the CO2 absorbed by the aMi is astimted by rinsing off the
beads, and determining the CO2 content of the wash water by
means of the apparatus originally designed In this laboratory
for CO2 determination in the blood.

     !Ihe problem to be attacked with this method is the
question of the lung volume changes ti heart disease,  Peabody

has shown that the vital capscity Is reduced, and that the ra-
duction is mora or lsss in proportion to the severity of the

cardiac condition.  .ft remains to be found whether the loss
in vital capacity is due (1) to inability to fill the lungs to

a normal total volume; (2) to a large residual air leaving rsla-

tively little room for expansion, even though total capacity is

undiminished, or (3) to an bbliteration of part of the effecti
lung mea, in prihich case it would be expected that residual air
and vital capacity vrrquld atxavp a $W&lel reduction.   Interest-

ing preliminary results have been obtained, but too few in mm-

ber to warrant conclusions.


During his experiments with the nethod Doctor

Binger made the discovery that during the breathing of the

oxygen-air mixture, oxygen.was absorbed from the lungs at a
very much greater rate than when air of onity normal oxygen

content was breathad.  !QXJ respiratory quotient nlso became
abnOr%al, the oxygen absorption being out of all proportion
to the CO2 evolution.  lhe question was raised, v&ether this
accelerated oxygen consumption is due to &ysical solution of
oxygen athiaer tension in the body fluids, or to an actual
acceleration of metabolic oxidation in the body.  This Ql66-

tion is also under investigation.  Its answer may assist in
explaining the therapeutic effect of oxygen in heart dl6eaSe

and pneumonia.

     With I!octor Austin and Doctor Cullen a study has
been begun of the blood chang;es 'in ether 6neStheSie, thBB prob-
                    ----   --
lem being a contiruation of CKW work on the general subject of

acidosis.  It; is found that during l.ight ether anesthesia the
bicarbonzts cmtent of the arterial blood falls, the carbon
dioxide tansioz. (dstwmined directly in the blood by the tono-
metric method) rises, and the hydrogen ion concentration in-

creases,  These $henomens indicate A State of uncompensated
akdOsis,- the Alkaline reserve is diminished, and the actual
reaction (hydrogen im concentration) shifts heavily towards

the acid side.  The oxygen saturation of the arterial blood
may'be increased in light anesthesia, indicating an inCr8aSed

ventilation.  !l!he latter iS not, however, sufficient to k&ap
the CO2 tension andhydrogen ion concentration of the blood


within normal limits, as it would be hspt if the respiration
gave a normally great response to the CO2 stimulus.   It

appears, thereforer, that aven in light ether anesthesia the

respiratory. center, though not entirely unresponsive to stim-

ulus, is markedly deadened.

     In deep ether anesthesia the carbon dioxide tension

in th6 arterial blood rises 6tillhigh6r, and may reach double

the normal.  Hydrogen ion concentration becomes still greater.
respiration not only fails to respond fully to the co2 stimulus,
but is in fact retarded to Such an extent that the oxygen satu-

ration in the arterial blood may fall below that normally found

in venous blood.   n?e blood also tends to become concentrated.

     Conductivity and chloride determinations in the se-

indicate only mIrute changes.  %?I6 only striking electrolytic

changes aTpear to be +.he increase in hydrogen ions and replace-
ment of part of the brcarbo,xto HC03 ions by anions of acid6 as

yet unidentified.

%a sntire picture indicates that even the initih

Stag86 of ether 6&theS~a involve a deadening of th8 raspira-

tory canter, or 8. loss of respiratory efficiency, sufficient to

permit the blood reaction to 6h:ft markedly toward6 the acid

side.  The contiit!.on steadily progressas, as anesthesia deepens,

until ventilation becomes s3 ineffj.cient that oxygenation also

fails,  Accompany~g "Lheos c';,e.l;gco is a progressive fall in the

alkaline reserve.

     The. results suggest caution in following Y. Hander-

so.21~6 plan of supplying air containing 5 or more per cent of


CO2 to patients under e?Ler , in order to prevert loss of

carbonic acid (acapnia).   D:z;r actually have an ~ccl.xx~;a-

tlon of it.  It may be tha: oqqen lack is m more impxtmt               I

factor than CO2 reteat ion and r;he accompanyj.ng acidosis.   In         1

that. case still futt:;er increasing the CO2 retention by breath-


1

1% CO2 migat whip up the partly deadened respiratory canter

!
7 8

and improve oxygenation of the blood.   If the acidosis also             1 !
                                             : I

is an important factor in the InJury that may be done by the

anesthetic, however, increasing it by breathing COIB would in-

crease the danger.  It appears that the two factors requlra

separate study.

    Doctor Austin, Doctor Edgar Stillman and Doctor van




Slyke in the study of newitis experienced trouble at the
start in applying the Ambard formula to estimate the urea-

secreting power of the kidneys.  %ey consequently directed

their attention to this point for the time, and experiments on
admals, normal men, and patients, led to the following con-

clusions: (1) Ambard andhi s collaborators, presumably because
of the inaccurate (hypobrc&te) method used in their urea deteq?
minatlons, were in error in f lnding that the rate of urea ex-
cretion rises as the squa.re of the blood urea concentration.
As a matter of fact it rises in simple direct proportion to it,

i.e., doubling the blood urea does not Quadhlple the output, as
assumed in the Ambard equation, but merely doubles the autput.
(2) The relationship between concentration of urea in urine
and rate of urea excretion assumed by Ambard holds SO loosely

that it is often difficult to ascertain any relation at all.


                                      .
            ,'                  b&


This work has led to the development of a new formula for

expressing the urea-secreting efficjency of the ki?..neys,

based on the facts that the excretion rate is proFcrt i onsl,

first to the blood urea ccnccntra.tI on, and f;econd to the

square root -of :he Lrine vclm?,   Futher work has been

done in accumulat.3zg data to ted ths accuracy of the for-

mula In normal individuals, the limits of nor-1 variation

in the results obtained tith It, and the consistency of

deviations from the normal obtained in nearitis.

      Miss Hiller in her wodk on protein analysis last

spring encountered in gelatin a nitrogenous substance in the

hexone base port ion tiich did not appear to be any of the

known amino acids. ,;It is possibly an intermediate peptide

difficult of hydrolysis by acids, but it is also possible

that a clue has `been found leading to the discovery of a

hItherto unknown mbo acid.'   It was not present in the pro-

teins examined othe? than gelatin.  It gives the pyrrol

reaction and is diff !.cu'Ft .to cryntabliae in any form yet

tried except the fiosphotungstate.  Work is being pushed to
                                                     
identify the substance.
    Ae a result of a consultation with Professor L. J.

Een&rgon of Harvard a joint piece of work was decided upon

involving Hender 9 a, Mcfsan, v&o was at that time with Hender-
son, but is now here, and some, of the men in this laboratory.

The object of the research is to establish the laws which

govern the reciprocal effects In the blo.od of oxygen end

carbon dioxide tensions, and the ;nigration of electrolytes

between the blood cells &nd the plasm under. the changing gas


temions.   It has been shown by IIttldane that, in Hendsr-

son's words `Qxygen pushes carbon dioxida out of the blood,

end carbon dioxide pushes oxygen out ".  Oxidized hemoglobin

ia a stronger acid than is reduced hemoglobin, and in cons+

qumce &en oxygen Is taken up in the lungs it provides en
acid (oxyhemoglobin) to take ths place of the CO2 which

escapes.  Convereely, when the blood passes, through the

tissues and loses oxygen, the cbenge replaces an acid (oxy-
hemoglobin) with a relatively neutral subetance (reduced

hemoglobin) and permits the blood to take up in its place an

equivalent of carbonic acid without raising its hydrogen ion

concsntrat ion by. mere then B barely measurable extent,   Sim-

ultsneouely with the gas changes, chlorlbee, csxbmtee and

water shift between

all follow definite

lated by Henderson,

to place them on an

able.   Thsy can be

the cells and the plasma.  !clle changes

laws, which have been tentatively form-
but the data for applySng them in a w'

accurate. quantitative basis are not avail-

made so only by the efforts of several mtm

working stifitanerlusly on the same blood
necessary that as11 tie determinations be

hour 09 the freeh blood semple.   Be the

samp188, since it ie

done within the came

study of reepiratory

and circulatory diseases in this Eoqital affords material for
direct asp&&ion of the theoretical information tnihich it is

hoped to gain, and as our laboratory and Henderaon~s, had both
been engaged independently in w&k leading up to this Droblem,

it seemed in every ncp~y desirable that the. collaboration sug-:

gested thru@gh Doctor McIeen by Professor Flenderscm ehould be


;, 9, `
  I
: `(

attempted.  It is expected that the work will be shared

by Doctors McLean, Austin, Cullen, Van Slyke, and J. P.

Petera, formerJy of the Cornell staff, who is entering the

laboratory as a voluntary assistant,

HOMER F. SWIFT

.