we

ATH

rey

 

REPORT OF THE HOSPITAL

 

 

1920

15

 

 
ANNUAL REPORT OF THE WORK OF THE HOSPITAL

In the absence of Doctor Cole, who has been on
leave of absence since Jamary, the following report has been
prepared with the collaboration of the other members of the
Hospital Staff.

The prophecy of Doctor Cole in the last annual
report that "men are still ready to undertake quietly the
study of disease" has been fully justified. The effects of
the war upon the spirit of research have been largely elimi-
nated, and the various members of the Hospital Staff have
renewed their efforts with the spirit instilled by Doctor
Cole in former years,

It is now ten years since the opening of the Hospital.
A review of the work done here during the past decade would seem
to justify the effort and money expdnded. But far greater
results have.been accomplished than can be estimated in the
number of papers published, or the total patients treated.
Men have been trained in the combined bedside and laboratory
| investigation of disease; ae model hospital for thie purpose
has been developed. That seemed a dream to those of us who
were privileged to be present during the early years has become
& reality. Then there was no euch place to work, and but few
men looked forward to a career in clinical invest igation; now
many of our University Medical Schools are modeling their med-
ical clinics along lines laid down in this Hospital and are

offering positions to men trained here, and many young men are

 

 

 
Ten

seeking opportunities both here and in these clinics. It
is a great pleasure to be able to ackmowledgse our indebted-
ness to our Director who has so clearly shown the way and to
all those jn authority who have made the work materially
possible.

The problems continued from previous years have
been pneumonia and cardiac disease; three new lines of inves- :
tigation covering nephritis, measles, and acute rheumatic fever
have been started. The progress in each of these problems is

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

Dr_ Swift

The investigation of acute rheumatic 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 have been an unusually small mumber 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 our wards. Blood cultures and cultures of fluid obtained
from the joints with ordinary aerobic methods and special an-
eerobic methods have been made with negative results; these —
results are in agreement with those previously obtained by one
of us. Attempts have also been made to find antibodies to
various types of non-hemolytic streptococci in the blood serum
of these patients during the course of the didease; so far no
antibodies have been demonstrated with the methods used.

While these observations should be extended in order to be
conclusive, it seems more and more probable that streptococel

play a minor or secondary role in the production of rheumatic

 

 

 

 
xs

Face

5s

fever. As a direct corollary to this problem it was

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 inmmne bodies are
formed as quickly as if the bacteria are injected into the
blood stream, and more rapidly than if they are introduced
subcutaneously or intraperitoneally.

A new line of investigation has been started:
Attempts are being made to produce some or all of the symptoms
of the disease in laboratory animals by inoculating them with
the blood and joint exudate, and filtered throat washings ob-
tained from patients during the various stages of the disease.
A large mumber of rabbits and guinea pigs have been studied;
in some instances distinct arthritis has resulted, in others
lesions of slighter degree have been observed. During the
coming months the material from these animals will be subjected
to microscopic etudy by Doctor Miller as the final criteria
mast be based on studies of this type.

A general study of the effect of salicylates upon
the formation of antibodies has been undertaken. The salicy-
lates are the chief drugs used for the allefiation of the une
pleasant symptoms of rheumatism, but little is known as to
their mode of action. In our experiments it was found that
there was somevhat slower rate of antibody formation as well
as smaller amounts of antibody in inoculated animals receiving
sodium salicylate than in controls; this was especially marked

when the amount of antigen injected was small in amount.

7o te

 

 

 
 

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
technique bacteria may be preserved in this manner for several
years. The dangers of contamination and change in virulence [ve
and loss of other properties incidant upon frequent transfers ees
of cultures can thus be largely obviated. Bacteria kept in |
this form are mich easier to ship. It is hoped the method

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 chemical nature; a technique has been developed for
studying the biologic activity of these intracellular sub-
stances apart from the living organisc with which they are
so intimately associated. Since cost metabolic processes
ef the living cell are brought about by the action of enzyres
the attempt was first made to determine whether or not the
intracellular substances recovered from pneumococci possessed
enzyce action. By testing these cell-free solutions on suit-
able substrates enzymes have been readily demonstrable. These
enzymes have been found to possess the power of actively hydro-
lyzing peptmes into simpler peptides and amino acids; of con~
verting carbohydrates into simpler products, and of splitting
esters into fatty acids, Evidence has been presented that
these enzymes exist preformed within the bacterial cell and are
therefore of the nature of endoenzymes. In other words it has
been possible by means of sterile extracts of pneumococci to
correlate uany of the functimmal activities of the living bac~
terial cell with the enzymotic processes of the intracelluler
substances when removed from the growing organism. Further,
it has been shown that the optixal zone of hydrogen ion con-
centration within which these enzymes are active bears a

striking relationship to the reaction range which limits the

 

 

 

=

parce

 

 
a _

OAR

.
~ wre
me

viologic activities of the living organism itself.

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:

Studizs on the Intracellular Substances of Pnevmococcus

1. The proteolytic enzymes.

2. The lipolytic onzjmes.

3. The carbohydrate-splitting enzymes.

Continued studies on the nature of the intracellular
substances of pneumococcus have further demonstrated the exist-
ence within the bacterial cell of an enzyme or group of enzymes
which are bacteriolytic in nature. Minimal amounts of an
active enzyme-containing solution of pneumococcus when added to
@ substrate of dead pneumococci of the same 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 when allowed
to act under similar conditions on the dead cells of closely
allied organisms such as staphylococcus aureus and streptococcus
hemolyticus. |

Moreover, in addit#on to the enzymes gescribed,
sterile solutions of the intracellular substances of pnevmococé |
cus have been found to contain other active agents which mani-
fest their specific nature when allowed to act on blood. These
in brief are first the endchemolysin vhich 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 an endohemotoxin, which is able to exert its

 
action only after its release from the cell by disintegra-
tion of the bacterial body, This hemolysin, previously
considered one of the most labile of the substances of bac-
terial origin, has been found to maintain its activity over
&@ period of several weks when obtained by the methods
described. The nature of the reactive substance of pneumo-
coccus wiich induces the fermation of methemoglobin has been

investigated by several workers. Considerable variance of

Gitte, sir niliy 6 hgie de ec ee

opinion exists as to whether the formation of methemoglobin

occurs only as the result of the action of the living pneumo-
coccus on blood, or whether a similar transformation of hemo-
globin can be induced by bacterial extracts and culture |
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 methemoglobin. The nature of the mech-
anisn of this reaction is being investigated further.

It is felt that these studies on the biochemistry of
the intracellular substances of pheumoceccus are important,
not only theoretically because of the added knowledge gained
concerning the life processes of the organism, but also clini-
cally because of their significance in the interpretation of
certain of the blood changes which a in pneumoceccal in-~

fections in man.

 
tor
tad

ae
oe
~r

“BEN
Dr E, G. Stillman

Doctor E. G. Stillman and Miss Bourn have made
an extensive biological study of the hemophilic bacilli.

The small Gram negative hemofphilic bacilli which have
gradually com> t» be considered &s belonging to oné group
of organisms and to which 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 which Pfeiffer first
described and 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
bacillus of Pfeiffer has been recovered i3 great enough to
indicate that this organism may be at least a secondary in-
vader. Since the first description of this hemophilic
bacillus in 1892 by Pfeiffer, little has been added to our
kmowiedge of its biological characteristics.

In this study it has been found that the hemophilic
bacilli observed divide themselves naturally into two large
groups according to their ability to hemolyze whole blood,
The hemolytic group comprises those organisms originally
described as Bacillus X by Pritchett and Stiliman, and occurs
in normal mouths.

Both the non-hemolytic and hemolytic group of hemo-
philic bacilli attain a final hydrogen ion concentration of
approximately pH 6.4 although the hemolytic group may reach
pH 5.8. Both produce acid in dextrose, but in both groups

only certain strains ferment saccharose. The greater ability

 

 
Be
of the hemolytic crganisms to ferment sugars may be a basis
for further differentiation.

A tentative classification defines a small suberery
of the hemolytic group formed ty those strains which produce
indol and gas Imt do not ferment saccharose. These strains
appear to ferment cugars less readily and require further study
to determine whether the inéol~producing strains are also gas
Producers. The greater mmber of the hemolytic streins, how.
ever, do not produce indol or gas, but ferment saccharose.

The non-hemolytic organisms are subdivided into two
fairly even groups comprising indol-producing and non—indol-
Producing strains. None of the indol producers form gas in
contrast with the hemolytic group. With ore exception, the
non-ehemolytic indol-producing strains all ferment saccharose.
A large majority of the non~indol-producing organisms of the
non-hemolytic type do not ferm gas anc do not ferment saccha-
rose, The indol-negative ctrainga which do form gas, with a
single exception, all ferment saccharose.

The classification made in this study is merely a
tentative one. Undoubtedly when the technique of these reac~
tions is more nearly perfected and a larger mumber of hemophil-
ic bacilli have been studied, the group differentiations will
be more striking and regular.

Although the mumber of strains of B. influenzae
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 recovering from respira-

tory infections and those isolated from normal mouths during

nw EAB gees

 

 

eee at oe

eee

i
if
i
Lf
{

the epidemic period show certain ciciogical disfercnces feu
those strains recovered from normal persons during the winter
of 1919 to 1920. The group of non-heaelytic hemophilic
bacilli recovered from normal mouths during the winter of 1919
to 1920 show a kigher percentage of strains which ferment the
polysaccharides, maltose, saccharose and dextrin; more strains

which produce gas,’. but fewer indol-producing strains.

Doctor 0. H. Robertson, who 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 summer "On the cultivation and biological charac-
teristics of Spirocraete chermeterti (recurrentis)".

In a publication last year by Low, Hierschfeld and
Wallach of Mt. Sinai Hospital, a test was described for deter-
mining the type of pneumocoeeus in pneumonia by means of a blood
reaction. The test briefly consists in determining ‘the rela-

Df ybmb oe

tive Sates at watch the three ¢ types of pneumecoces produce

methemoglobin | in the 1ekod blood of the infected. individual.
. er

The type organism vnich first proftices ‘wothemegisbin in the

laked blood is considered 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 diagnostic pro~

,

cedyre.

 
Dector Lyon, whose 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 assume the practise of medicine

in Boston. During the past winter Doctor Lyon studied the
antigenic relationship of a large series of strains of B.
influenzae in an attempt to determine whether or not specific
differences exist among the hemophilic bacilli. The recogni-
tion of biological relationships existing between varieties of
this species of bacterium would contribute much 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 antigenic characters are concerned.

Dr_ Blake: Studies on Pneumonia.

In completion of work previously conducted at the
Army Medical School in Washington, D. C., a detailed study of
the histological pathology of pneumonia produced in monkeys by
intratracheal injections of pnsumococcus, of Streptococcus
hemolyticus, and of Bacillus influenzas has been carried out
and an attempt has been made to work out the pathogenesis of
the different types of pneumonia caused by these three organ-
isms.

Study of the pathology of pneumococcus pneumonia in
monkeys has showm that it is essentially the same as that of
pneumococcus looar pneumonia in man. It has been shown that

in monkeys the pneumococeus invades the lung near the hilum

 

 

 
“a4.
and spreads through the tissue by way of the interstitial
framework and lymphatics and that consolidation begins cen-~
trally and spreads toward the periphery 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
man. The streptococcus invades the ling by the same paths
as the pneumococcus but the end result is different because
of a different tissues response to the infection and a differ~-
ent effect of the organism on the tissue.

Bacillus influenzae likewise produces a distirctive
type of bronchopneumonia in monkeys similar to that produced
by B. influenzae in man. The injection in this case primar-
ily affects the macous membranes of the bronchial tree with
adjacent areas of peribronchial consolidation.

Dr Blake and Dr Trask: Studies on Measles.

By the intratracheal injection into monkeys of un-
filtered nasopharyngeal weshings from cases of measles a rela-
tively constant group of symptors has been induced which closely
' resembles those of measles in man. Of 8 monkeys inoculated
with unfiltered washings 6 cama down with this group of symp~
toms. The same reaction has been induced in two monkeys by
the intratracheal injection of filtered (Berkefeld N) washings
from two cases of measles. Cultureg of these washings showed.
no growth after two weeks 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,

 

 

 

2 ode al RS e
ra see hee. doe ee

 
 

the conjunctivae become injected, and small discrete red
spots appear on the labial mcous membranes. These spots
increase in mumber and may eventually coalesce in the course

of 2 to 4 days to form a diffuse red grammar rash. This

 

rash is usually limited to the labial mcous membranes but
may extend to the inside of the cheeks. It is never pres-
ent on the roof of the mouth, soft palate or tongue. The
individual macules may or may not show the minute bluish

white centre characteristic of Koplik spots. One to four

 

days after the onset an eruption of small discrete red macu-
lopapules appears on the skin, usually coming out first on —
the face. The rash rapidly increases in the mumber 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, chest, abdo-
men and thighs. The rash is constant in character but varies
considerably in extent in different animals. By the time the
exanthem is fully developed the rash on the mucous membranes
has begun t6 fade and soon disappears , The exanthem in turn
rapidly fades, sometines with a brenpy desquaration, sometimes
without. By the 6th to the 10th day after onset depending
upon the severity and the extent of the reaction, all symptoms
have disappeared and the animsl again appears well. Coinci-
dent with this group of symptoms there is a constant and defi-
nite fall in the total leucocyte count, frequently constituting
a true leucopenia. Symptoms of rhinitis and 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 measles in man. Cultures of the blood made

 

 

 
both during the incubation perind and during tre coarse of
the renctton in a variety of media, aerobic and anaerobic,
have consistently shown no growth.

The characteristic reaction which follows the inoc-
ulation of monkeys with the nasopharyngeal washings of measles
patients has been successfully transmitted from monkey to mon-
' key through six passages by the intratracheal inoculation of
saline emulsions of the skin and mmcous membranes of monksys
killed shortly after the appearance of the exanthem. From
the 4th passage monkey it was also successfully transmitted
to three monkeys by means of citrated blood injected intraven-
cusly. 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 passages
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 which occurred
in monkeys inoculated with nasopharyngeal washings of patients.

The evidence obtained is believed to be sufficient
to warrant the conclusion that the reaction is caused by the

virus of measles.

Dr_ Cohn

During the past year the studies on the action of
digitalis were contimed with Doctor levy. In patients, the
action of digitalis by mouth was compared with the action of

G-strophanthin injected intravenously, It was found, in brief,

 

 
BR
that an effect with digitalis may occur ina little more cok:
than two hours. After giving strorhanthin the effect may
be seen in 20 mimtes or less; with digitalis the effect on

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

ing) long outlasts that of strophanthin in the ratio of about

 

15 to 3 days. On the T-wave of the electrocardiogram stro~
phanthin has a slight effect or none at all. To establish
these observations satisfactorily and to amplify then, 4t is
proposed to contime this study this year. The data serve
as the basis for part of the general study of the action of
digitalis on each of several varieties of the diseased heart,
e.g. when norml mechanism is present, when the auricles fib-
rillate, when hypertensive arterial disease 4s involved.

In animals, the attempt was made to ascertain
whether the change in the T-wave of the electrocardiogram
which occurs on giving digitalis to patients is associated
with a beneficial action. Our primary object, to show that
an improvement in contraction takes place when the T-wave
changes, was attained. But the results were unsatisfactory
in 80 far that they were obtained after severe operative pro-~-
cedures, and under anesthesia. The spring was therefore
occupied with preparing dogs after the method of van Leersum.

The van Leersum method eonsists in placing the
common carotid artery in a situation always accessible, so
that blood pressure readings may be made of it whenever de-
sirable. “This is accomplished by an aseptic operation.

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

 

 
“Sy -
and to the artery itself. The skin flap is freed and its 4 :
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
pneumonia teleroentgenograms were mads by Doctor levy at fre-
quent intervals during the acute stage of the disease and
during convalescence in order to ascertain changes in the
size of the heart. A few of these series of plates only
have been measured. It appears from the data so far availa-
ble that the method is a satisfactory one for this purpose.

In certain instances an alteration in the size of the heart

occurs in the acute stage of both lobar and bronchopneumonia. — : i
This work will be continued during this winter and should be
materially facilitated by use of the bedside x-ray apparatus.

Doctor Binzer has contimmed his study of the lung
volumes in patients suffering from heart disease. His results
are more fully covered elsewhere.

Doctor Raisbeck, of the Flower Hospital, is pursuing
the very useful and laborious work of measuring the electro-
cardiograms of normal men (about 160). The work requires
mach time on account of the great attention to detail neces-
sary to devote to it. Under the circumstances, its completion
will probably be delayed for some time. When complete, very
accurate and satisfactory data of the limits of the normal

electrocardiogram will be available.

 

 

 
“Ba

Doctor Levy and Doctor Cullen, in making bio-
logic assays of several lots of a commercial prenaration
of G-strophanthin prior to administering it to patients,
found wide variaticns in potency. Experiment: were under-
taken to ascertain the cause of the deterioration and to
devise a method for preparing a stable solution of the drug
for therapeutic purposes.

It was found that many of the glass containers
commonly used in the laboratory and most of the glass am-
poles employed in marketing sterile solutions for hypodermic
or intravenous medication yield sufficient alkali, on auto-
claving, to change appreciably the reaction of distilled
water toward the alkaline side. This increase in alkalinity
is sufficient to render biologically inert and partially to
decompose aqueous solutions of crystalline strophanthin in
the concentration ordinarily employed in the clinic.

For clinigal use, therefore, they found that crys-
talline strophanthin should be dissolved in a buffer solution
(0.02 M standard phosphate solution at pH 7.0 is satisfactory)
and marketed in hard glass ampules, thereby insuring stability

of reaction with preservation of biologic activity.

Dr Van Slyke | Oo
With Doctor Stadie the work on improvement and
revision of the methods for determining 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

 

 
“9Q_

metheds revised in more or less degree include those for

the determination of oxygen, hemoglobin, methemoglobin,
carbon dioxide, nitrogen gas and carbon monoxide. Also the
technique has been 80 developed that it is possibile to deter-
mine all the gasea on a Single 1 cc. sample of blood.

Doctor Stadie and Dector Binger are engaged in a

study of the respiration in pneumonia and in cardiac disease,
and in a study of the physiological and therapeutic effects of
oxygen administratim. For the latter work they have construc-
ted an “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
pulso rate, but as the work is still in the preliminary stage
and requires fcr its confirmation more extensive observations,
4t will be carrisa out during the coming year.

Doctor Binge> is contiming his work on respiratory
factors in heart disease. . During. the spring and summer he
has been engaged in modifying the lung volume method of Iunds- | t
geard and Van Slyke in such a mamner that it can be used with !
patients who are acutely il1. In the original method, the |
subject, by 4 or 5 vigorous respirations to and from a bag
containing 2 liters of oxygen, completely mixed the air in his ae

lungs with the oxygen in the bag. The volume of air in the

 

 

lungs (lung volume) was calculated from the composition of the

 

 

gas mixture obtained, The difficulty in applying the methad e
fae

ee

wee
an
“ee

~9i-

to i111 patients lay 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 tice so mich
carbon dioxide develops that it causes dyspnea. The diffi-
culty has been met by inserting between the mouth-piece of the
apparatus and the oxygen bag, a bottle containing glass beads
moistened with KOH solution. This removes the CO, so that it
is possible for the subject to breathe as long as may be neces-
sary without distress. When the final gas analyses are made,
the CO, absorbed by the alkali is estimated by rinsing off the
beads, and determining the co, content of the wash water by
means of the apparatus originally designed in this laboratory
for co, determination in the blood.

The problem to be attacked with this method is the
question of the lung volume changes in heart disease, Peabody
has shown that the vital capacity is reduced, and that the re-
duction is more or less in proportion to the severity of the
cardiac condition. It remains to be found whether the loss
‘in vital capacity is due (1) to inability to fill the lungs to
@ normal total volume; (2) to a large residual air leaving rela-
tively little room for expmmsion, even though total capacity is
undiminished, or (3) to an obliteration of part of the effectite
lung area, in which case it would be expected that residual air
and vital capacity would show a parallel reduction. Interest-
ing preliminary results have been obtained, but too few in num-

ber to warrant conclusions.

 

 

 
During his experiments with the method Doctor
Binger made the discovery that during the breathing of the
oxygen-air mixture, oxygen was absorbed from the lungs at a
very mich greater rate than when air of only normal oxygen
content was breathed. ‘The respiratory quotient also became
abnormal, the oxygen absorption being out of all proportion
to the CO, evolution. ‘The question was raised, whether this
accelerated oxygen consumption is due to physical solution of
oxygen at higher tension in the body fluids, or to an actual
acceleration of metabolic oxidation in the body. This ques-
tion is also under investigation. Its answer may assist in
explaining the therapeutic effect of oxygen in heart disease
and pneumonia.

With Doctor Austin and Doctor Cullen a study has
been begun of the blood changes in ether anesthesia, the prob-
lem being a corntiruation of our work on the general subject of
acidosis. Jt is found that during Jight ether anesthesia the
bicartonet2 content of the arterial blood falls, the carbon
dioxide tencior. (determined directly in the blood by the tono-
metric method) rises, and the hydrogen ion concentration in-
creases. These phenomena indicate a state of uncompensated
acidosis,- the alkaline reserve is diminished, and the actual
reaction (hydrogen ion concentration) shifts heavily towards
the acid side. The oxygen saturation of the arterial blood
may be increased in light anesthesia, indicating an increased
ventilation. The latter is not, however, sufficient to keep

the CO, tension and hydrogen jon concentration of the biood

z

 

 

 

a
within normal limits, as it would be kept if the respiration
gave a normally great response to the co, stinnlus. It
appears, therefore, that even in light ether anesthesia the
respiratory center, though not entirely unresponsive to stim-
ulus, is markedly dsadened.

In deep ether anesthesia the carbon dioxide tension
in the arterial blood rises still higher, and may reach double
the normal. Hydrogen ion concentration becomes still greater.
Respiration not only fails to respond fully to the co. stimmlus,
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. The blood alse tends to become concentrated.

Conductivity and chloride determinations in the serum
indicate only mirute changes. ‘The only striking electrolytic
changes appear to be the increase in hydrogen ions and replace-
ment of pert of tha bicarbonate HCO. ions by anions of acids as
yet unidentified,

Tie antire picture indicates that even the initial
stages of ether anesthesia involve a deadening of the respira~
tory center, or 8. joss of respiratory efficiency, sufficient to
permit the bleod reaction to shift markedly towards the acid
side. The condition steadily progresses, as anesthesia deepens,
until ventilotion becomes so. inefficient that oxygenation also
fails. Accompanying theso chenges is a progressive fall in the

alkaline reserve.

 

The. results suggest caution in following Y. Hender-

son's plan of supplying air containing 5 or more per cent of

|
i;
13
i
|
ce. to patients under ether, in order to prevert loss of
carbonic acid (acapnia). They actually have an accumiia-
tion of it. It may be that oxygen lack is m more important
factor than co, retention and the accowpanying acidosis. In
that case still fartier increasing the co, retention by breath-
ing co, migat whip up the partly deadened respiratory center
and improve oxygenation of the blood. If the acidosis also
is an important factor in the injury that may be done by the
anesthetic, however, increasing it by breathing CO, would in-
crease the danger. It appears that the two factors require
separate study.

Doctor Austin, Doctor Edgar Stillman and Dector Van

 

Slyke in the study of nephritis experienced trouble at the

start in applying the Ambard formula to estimate the urea-
secreting power of the kidneys. They consequently directed
their attention to this point for the time, and experiments on
animals, normal men, end patients, led to the following con-
clusions: (1) Ambard and his collaborators, presumably because
of the inaccurate (hypobrapite) method used in their urea deter-
minations, were in error in finding that the rate of urea ox~ |
cretion rises as the square 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 quadruple the output, as
assumed in the Ambard equation, but merely doubles the output.
(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.

Fr
* he

 

 

 

 

 
 

This work has led to the development of a new formula for
expressing the urea-secreting efficiency of the kicneys,
based on the facts that the excretion rate is propertional,
first to the blood urea ccncentration, and second to the
square root-of the urine velum,. Farther work has been
done in accum lat ing data to tast the accuracy of the for-
mila in normal individuals, the limits of normal variation
in the results obtained with it, and the consistency of
deviations from the normal obtained in nephritis.

Miss Hiller in her wotk on protein analysis last
spring encountered in gelatin a nitrogenous substance in the
hexone base portion which 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 unimown amino acid. It was not present in the pro-
teins examined cthe> than gelatin. It gives the pyrrol
reaction and is difficult to crystallize in any form yet
tried except the phosphotungstate. Work is being pushed to
identify the substance. :

| As a result of a consultation with Professor L. J.
Henderson of Harvard a joint piece of work was decided upon
involving Henderson, Mclean, who 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 blood of oxygen and
carbon dioxide tensions, and the migration of electrolytes

between the blood cells and the plasma under . the changing gas

 

 

 
tensions. It has been shown by Haldane that, in Hender-
son's words “Qxygen pushes carbon dioxide out of the blood,
and carbon dioxide pushes oxygen out", Oxidized hemoglobin
ie a stronger acid than is reduced hemoglobin, and in conse~
quence when oxygen te taken up in the lungs it provides an
acid (oxyhemoglobin) to take the place of the CO, which
escapes. Conversely, when the blood passes through thse
tissues and loses oxygen, the changé replaces an acid (oxy-
hemoglobin) with a relatively neutral substance (reduced
hemoglobin) and permits the blood to take up in its place an
equivalent of carbonic acid without raising ita hydrogen jon
concentration by more than 4 barely measurable extent. Sim-
ultaneously with the gas changes, chlorides, carbonates and
water ehift between the cells and the plasma, The changes
all follow definite laws, vhich have been tentatively form-
lated by Henderson, but the data for applying them in a way
to place them on an accurate. quantitative basis are not avail-
able. Thsy can be made 680 only by the efforts of several men
working simmltaneously on the same blood samples, since it is
neceseary that all dhe determinations be done within the sane
hour on the fresh blood sample. As the study of respiratory
and circulatory diseases in this Hospital affords material for
direct application of the theoretical information which it is—
hoped to gain, and as our laboratory and Henderson's had both
been engaged independently in work leading up to this problem,
it seamed in every way desirable that the collaboration. sug-

gested throfgh Doctor McLean by Professor Henderson should be

 

 

 
“OR

ros
nue.

attempted. It is expected that the work will be shared
by Doctors Mclean, Austin, Cullen, Van Slyke, and J. P.
Peters, formerly of the Cornell staff, who is entering the

laboratory as a voluntary assistant,

HOMER F, SWIFT