4. .
                        FZ?OX OF THE                     ' :!
                                                                           i

                 DTP%-?TOP OF TUE ESGSPITAL OF

                 TX2 RCCKEiXUR f:!STITUTE.

                   April 1915.

     Acut 3 tobar Pzemonia.  During the Guartar f art;--three pat ionts auf f sring
irw. nc*lte lobar pzmmonia have been a&.,itted to the Hospital.  This numb& is some-

::hnt IarGar than the number a&it-ted during the same period last year.  Of these f
;atimte ten v3re dus to pneumococci of type 1,  All the patiants of this type were

treatad `and all raoovered.  110 obearvations have been made to change our former con-
clusions a8 to the efficacy of Benxm of type I. in case8 due to type f infection.
Win-, the present :;inter only a part of the case6 due to type II have been treated

vi i'.h ir.xur*e B anlzr..  The resu&ts have not been Batiafactory.   There hae been no evi-

!Y.CT tk;Rt the eeru~ has ha5 any rely znarked ef feet.  At the preeent time we are

:.ot + xeat%g Cam8 3~0 to this tgte of orgsnisn with immune seTurn*
    Small amounts of the ~3rm of type 1 hava been sent to the Brigham HoBpi-
:s: in-. Eoeton, the Presbyterian iiospital in Xew York, and to Dr Hanes of Richmond.
`?;o:ts 012 fhe results obtxinsd have not yet been received.  ff the type I serum is

+.o te sant out and to be usad more or lass indiscrtiinately, an important question

is as to the

the 8eruLl 80

considerable

th& use of a

rinistere&

overcome the

use of preeervat ives.  No preservatives have been employed in any of

far uesd.  It is obvious that the use of such serum is accompanied by

danger,  Considerable study will have to be made to determine whether

preservative is practical, where such large amounts of serum are ad-

A practical method of concentration of the Berum would, to Borne extent

dif f icultiee.  The study of methods of concentration by %--Avery ad by

Dr Gay and Dr Chickering has been of great theoretical interest,but,BO far, these

studies do not seem to be of practical application.  The method employed by Dr Avery

rsquires very e::tetaive handli:;g of the se-, with corresponding danger of contami-

;;a'! on s -and a Coctsntrat2on of ouly about four times is obtained. The concentration

ci serum by this mat::od described by 27x- Gay and Dr Chickering has demonstrated the


- 2-

j'fiiiity Of obtaining the immune ZOdieB in very

l+S SO !Z,07iiini; t0 urhom factors, oamot be

small amounts of protein,but the

constantly obtained, and in many

: chura such results are obtained there is considerable loss in the immune sub-

. .a
"`", eo that the method practically would be ver; expensive.  Tmportant pr-inciples,
: r, ham been demonstrated by these investigations and it is quite possible that
-:iCSi application may be mada of them.  The Important fact, howsver, has been de-

iried now beyond any do ' uh t that the 1iPIit to the practical application of thio forrp
::.-ra?y is dependent upon the degree of infection.  If the info&ion ie of a certain

", no amOUst Of immune Berum will protect, and concentration of immune bodies is

..`, practical advantager  Ubservatione rhich vo have made, however, indicate that,
1. t;ic coccentratioo of immne bodies in a given 8ennn may not furnlBh better pro-

:?
-. r. than is obtained by the unconcentrated serum, it may be poeBible to produce
. of ;ii$aer grades of protection, possibly depending upon the so-called avidity of

:.-.s Sodies for the bacteria.

   The therapeutic treatment of cases of type 1 now B~O~B to have reached a

.t: ma-*
< I 1. "  stage, while the treetment of pneumonia due to other types is still in a

: :; a-qerinen:al condition.  T:te Nea York Boatd of Health is now preparingmse~'W of
2 1 ar.d Serum of type 1 is 3eing prepared by Dr &swis at the Phipps InetitUts, Phib '

1phia.  Commeraial houses have desired our co-dperatioa fn the preparation Of sex1up
~3 have discouraged their taking up this matter at the present tkoe.  A more d*
                                                                           .

-Isa accowif of the exact nature of the work on pneumonia follows.
  Observatiorrrs dealing with the occurrence of pneanococcl of various f&s in

mouths of healthy persons, and in those of persons sick and conv&ment from Pneu-

*.!.s are being COnBhntly carried on by Dr Dochet and Dr Avery.  lhn,mty familieB ia

:h one or more members have been sick of pneumonia have been quite thoroughly studied,

.-; ai$ht of thsse families one or more healthy members have been disaooered to be
. . .

.hrs of pneumococci of a fixed type.   In all the so-called carriers so far d*
inA the type cf organism has been the same as that responsible for the OaBe Of


                     -39                                     L I i

y-P%miia i.? t:;s family.  Zkese carriers i-eve b3ex followed wherever possible until

+ 1
b.`C: fimd rirule::f type of ~~U~~COCC~S LisapPearsd fron the sputum. The longest

: ;rlad duricg whick heaithy persons have so far bean found to carry the fixed type of

~jl':~nis~ Las been forty days; the shortast t;wnty-one days; the average approximately

th:*it;- days.  In none of these carriers that have bean observed has pneumonia daval-

qd.  Three instances of pnaumonoccus infection oocurring in individuals In contact

ritk C&S00 of pr.a~~onia, however, &-;a been observed and studied.  In each case the

ty?e of org.anism isolated corresponded to the type found in the case considered as tha

sxirc3 Oi - infection.  firthar Studie6 have been made concerning the length Of time

hA:-!Yig :o;:ral58cence, during :vhich patients r:`,th pneumonia harbour in their mouths tha

ih33 Viml3-A types of peumoao::i.  The longest period during which the patient has

:a..-:ied %.e ynsurroco;cus oi t. \e fixad type has been ninety days, and the shortest Period

tas 3tzc &aloe da:*s;%ha average has baan about twenty-nine days.

Studies concerning the mode of action of antipn9umoooccus Berum are being

zade.  Dr Avery has shown that Than a mixture of pneumococcl and anti-pnaumococcus

SWE.I is iralia no bacteriolytic or bactaricldal action could be observed. mhen,howevar,
;aLtes sre made from the nisture at short intervals of time, there can be demonstrated

a sell-defined inhibition of growth during a period of about six hours.  This ratarda-

tion of growth is not dependent upon agglutination, slnca it may occur in dilutions Of

serum in which no agglutination of the organism occurs, and it is not completa~y SPSCi-

fit for the' different types, while agglutination, on the other hand, Is vary ~paoifi~~
This phenomenon has suggested tlja$ part of the action of the serum may ba dua to in-"-

hibifion Of certain metabolic activities of the bacteria,  We had previously found that

i-a:Xla sarum when mixed with pnaumococci did not inhibit the power of the lattar to
Froduze net5emoglobln.  Later observations, however, have shorn that if the bacteria
and aarum are allowed to remainpn contact with one another at 3'i'C for two hours bafora

L.
"&I? !lemoglobin is added, no methemoglobin formation occurs, 80' that tha sarUm aPParantly

dO.>S ~ossass t:ia power 0. 4 iaibiting this functional activity of pnaumOCoCcd


         ..-_ _ . - --                            r- 2
                                                         j ._
                    -.                                 .  I.

         -49

    Dr Dcchst and Dr Xvery ara making observation to determine whether or not
tile SSXUTL irhibito cartain digestiva and fer~entative properties of the pnawnocoocus,
sspocisliy the fomation of amino acid from protein, and the fermentation of various

carbohydrates.  It has been found that vhen the normal curves of these types of acti-
yity have been datarmlnsd, whan lmtmana serum 1s added to comparable mixtures there is
clther com?late or partial inhibltion.  It is possible, therefore, that a part of tha
action of lrzuna senn~ may be due to the ir.hibition of fannantativa processes, which
`cactsria carry on In the medium lmmadiatsly surrounding them, which processas sra naca+
5~' for tha llfa of the bacteria,  Experiments indicata,howavar, that tha lnhibltloa
of t!Iesa EiCti:titie8 of the rneumococcl are not absolutely specific as regards 5aI-a of
ths diffarsnt types in relation to the corresponding organisms.

    Dr Avery hse made a study of the ralationship of the fennantativa reactions
of +.hs diff3rsr.t tnes of pnaumooocci to the antigenie differences.  A large number
of strains of the different types have been studied, but no wall-defined differences
ir. the fannantativa activity of the members of the different groups could be detarminad.

   Dr Zhickaring has continued the work corrjeanoed by him and Dr Gay on the spaci-
+`ic precipitation of a&ibodies from antipneumococcus serum by bacterial extracts.Thair
Conjoint wbrk has already been published. Various methods of produaing the bacterial
extracts have been triad, but the use of large amounts of acetone aa employed by Dr
tfan Siyke and others in the precipitation of f.amenta, has proved to be of the greatest

value.  Dried -acetone-precipitated bacterial substances go into solution much more
saeily than the bacterial substances prepared in other ways*  The fractional employ-
nent of bacterial extracts in the precipitation of immune serum has been found to be
SffSC?iQe in completely removing the protective substances from the saru%  To remove
the bacterial protein from the serurz precipftate, the best method has been found to

WXliSt in extractinS the praci~ltats tllth normal saline, after the addition of weak

a1Zalie, as sodium carbonate, heating and shaking.
trifugalization contains only;a vary small amount of

The supernatant fluid after can-

protaln and apparently protects


- .-
.r _ .i.in.: the tOXizit;* of t>6 extracts in vzrious anic;ale, under V8riOt.N ConddtiOnS.

sdrii!;is',ratiol; 0: such axtracts has yet been made to patients, but the experimonta
!icnte that there Is little danger cf `their FroducinC toxic effects,  stUdie6 have

No

in-

3190

'-"' rr.ade to Ceterxdna the duration of the irz.unity follovfing the addnistration of
L ::.r

dxacto J End also the possibility of proiuzin; si.il;:lt active, as r:eil as paseitfa, b-

:`LzdityJ by mews thf suck axtract6.  Apparently pastivs immunity, rrhe+.her obtaited by
Ale ;erum or precipitates J kas disa?Feared at the end of abo;t five dats, kAt aftor
LYV Jays when the extracts ace used eli5F.t Srades of ac:ive immunity are Been*
. -.*

    Studies are be1r.g zarried on by Dr Cole with the assistance of liss Stroker

;;; ;i; hV6 f3r ?helr ob jscts first J the determination of the difference between active

.`:-i Fassive PE$UEIOCCC:UB inm~hity, and secondly, the production of more ef fectiva im-

!`.
. . ..t  Serxz.  37 careful quaSftative stu2ies i:, mice it has been found that by the pro-

-s:$ion of very slight grades e,i active iznunity the degree of effec? obtained from in-

:.UJ senzm is very markedly ir.xeased, muc!l more markedly titan can be accounted for by

-. :k:le aciition of the t=o fsctoCs.  Second, by treating animals vith daily doses of

:i;rSr;: bacteria, combining t%ese doees of bacteria with an amount of iuvmrne serum suf-.

ficient to pzotsct tha animal, it has bsen dlound poaeible to produce within three or

1:~ weeks such immunity in rab'cite that the serum will protect mice against doses Of

*virulent culture as high as 1 to 1.5 cb o., whereas horse serum, obtained by the ozIdinary

rethod of iIUmUXhf.ZatiOn, 0ven after six months, or 6ven after one yearts treataentJ is

iible to

;cst is

protect against no more t`na .l or at most .2 C.C. of virulent culture. A

now in process of imxunizatiol;, and if the serum of this animal proves stfica-
                                                               .

;ious, we shall proceed with the kxmization of horses by thnc new method,

2. Col-ln,   nmrt J?iseaaa.

    It is r,a-.-~;c;r@ll7 tiel!.eved that the form of the elact?ocardiogram remains con-

:tx:it ir. human beings for long periocla of time.  Ir-, a:r+r:tiente on knimals it has been


  . . .

                                                 I'- TS
                                                d 8
                                                 t \ >'
-6-

found that its Fern! can be altered by the application of heat to the apex or base of
*-+- ventricle, by the application of muscarin to the surface of the heart, and by the
".I.,

.tld-ation of the vagua nerve.  In studying the curves of patients to whom digitalis

1; 74 .-a,-
   ,>A b Y.b we have found that under the tnfluence of this drug the form of the electro-
:' :.iio;r% ia also changed.  The change takes place in that part of the curve ini

chM betaeen the R and the end of the T wave.  The T cave flattens and later becomes

ir.x?r~cd in the greater number of our patients.  It is a general rule that lnvarsion
:f tliQ T vave depends on the fact that the apical portions of the ventricular muscle
Ire, relatively, electrically more active than the base.  Digitalis evidently ha6 the

;:"W oi kringing about this state.   :?e have discovered this ef feet of digitalis in
: Jay and a half to two days after beginning the administration by mouth.  It OUtlaSt 6

LX adcinistration by five to twenty-&/o days.  If the presence of the electrical
:l:ar.ce actually means that the drug is still present in the heart muscle, it becomes
:kw why digitalis action in patients comes on EIO promptly when a second course of
:xstment 18 begun ten days after the first ended, for after so long a period Complete

::irination is usually believed to have taken place.
    Te have utilized this aigu of change in T waves in studying
flxlation of failing heart a in pneumonia.  In pneumonia, especially

the question of

among acute in-

i-Cions, the value of digitalis as a stimulant has been much debated.   The first

;oint we though, which should be decided, was whether there was a way of detemining
.:.a3 digitalis was exerting an irrfluence. It was clear, from our own and from the ex-

yriences of others, that to judge by its effect on the rate of the
`6 found in the elect&cardiograms of pneumonia patients what the T

1s it does In the non-febrile.  The chan~a takes place in about the

heart was valuele~sq

wave changed just

same length of time,

sn;l it requires about the same amount of the drug to ppoducs it. Ve have,' therefore,

3 Lleans of telling that digitalis does produce an ef feet.  Xntbhe group 02 patients

3 livelop auricular flutter or fibrillation, EL rhythm of the heart, which develops

.;aAaneously in pnem,onia, digitaLis is beneficial.
                 .                    The rate of the heart, when


rises to a grant height.  bizitalis has the power of re-

in them, by blockin, n the auricular impulses, just as it

*:CS in nor-febrile patients having these tfyythm5.   Vhether it is

- = rlythas is normal, we are not yet able to say,
..a.

    Dr Jamieson has attempted in another way to find whether

beneficial when

there is a liffer-

:r.ca bebeer, the action of digitalis in pneumonia and the non-febrile state-  He in-
!Lcted crystalline strophantin(ouabaine) fntravenouslp into dogs and cats, to ffnd the

Animal lethal dose per kilogram.  In thir hs followed the method of Hatcher

,lc ston.  Then he injected a number of dogs and cats with virulent cultures
::.C:Ci by the nthod of hsufflation,  Fhen the animale were at the height of

h?,lse, he injeated strop3anthin into them in the same way as in the control-

*; +
. ..I. the zAnlma1 lethal dose per kilocram was the ssm in the infected as in

and Eg-

of pneu-

the di-

He found

the non-

ir,fscted animals, 8.1 rcgn. in cats and 0.12 mgm. in dogs.  Post nortem the lungs.

Cf the animals were seen to be consolidated,
    The conc'lusion is dram from the observations in patients and from the ep
:~r~onts in infected animals, that digitalis or strophanthin, may be expected t0 ast

is tine same way.

   Dr Cohn carried out experiments, sozle time ago, In dogs which showed certain
suite Definite diffemaves between the action of the right and the left vagus nerves-
ke nain difference was that stimulation of the right acted more esjmcially on ths

me-r?aker, while stimulation of the left acted norr especially on &ri&O-Ventri-

cular cond;letion.  Experiments were next carried out to see what influence the sj~-~o-
auricular node, usually accepted as the pace-maker of the heart, exerted on this dif-

ference.  The sims node was therefore destoryed in the jaws of a clamp.   It was
found that Stimulating the vague nerve still showed about the ssme differences `as

t.sio:-8, except that stimulating the left vagus nerve caused a greater effect on the

pats--z.*a2lng fua:ct<on than it did before destoaying the node. This effect differed

- 7 t :Y"t , befcre claqing, the auricles continued to beat during stimulation, after

:lanpin.~ they ceased,  It appeared, therefore, that an inf'lue$ce which caused the


.z
. - ::cls to conf inue to contraA z&z-An? Loft -?agxs atixlati~n had besn destroyed; The

-*
. . ; : .c. ..t Tas thareforg r:sde to discover r&&her the accelerators provided this stimulus,

. ..;: -*:a:*e accordifigly cut ina number of eqerimcts, sometimes the right, somefimos

  1 SC&
.livI and so3;iatiues t 0th.  Cuttiq thex producoi no influence on the usual differ-

  .
..a. ~r~t*i:sac the vagua nerccs.
    . .                 Vhat nechanisr it is zhith is affected -.-r en t!?e S-A

.- i.6
  : 2   `cstroped, has not ye', beer, ascertained.
   TLe &u3y of the a.ctj.on of dif_italin in patients suiforini; from heart disease

53ine contimed.  The action of the dn!g 5s F,eing stu3ies on rate of the beats,on

I L. `aztion, blood pressure, diuresls, arrd its affect OS the electrocardiograms Fomer

:c:to have dealt with it3 txtion in pagients !laving sitrple form of disease.   Ve are

`,a :ol.lsctir.g data in Lore cocplicsted form in vhicf; abnomal rhyt'ms, high blood

c xr3, oebrza, and d:qsnosa are fcund.  Experimnts in animls are going on, plaa-

: to cnrrelate t'i.e cl-nn;;?s chic !i take plnve in the aisebshape and weight of the heart

.__ =.`* -?ariouo can9ltions with the electrocardiographic curves.  The sha?e and size are

1: .f:.ed by
         X-rar 01 servat ior, - tile wcl-,l;t, post nortern.   These animals are to be

: Il?d tnilar t:le conddtion of strain, as when dogs mxs on the tread-nill., and also in

. :=xnso of artificial valvular lesions.  The influence of di$talis on them is

-3 to ba studfei.

Study of Diabetes.

Up to the present tim forty-one patients with diabetes

..-.'.'f! Laer. trented.in this hospital.
                        a        Tine results of treatment of patients, IQ to the

r:9sent, are as follows:  Total number of patients treated, forty-one. Number of

:xthB, five.  Of these, trio were deaths in soma shortly after entering the hospital;
::.c patient with a sever cardia lesion died of `heart failure, shortly after enteririg
.j hospital; one boy died following a break in diet; one man recently died after

.x-al xocths of declire in spite of +,rmtnent, and autopsy showed caseous(tubercular)

~. -*'.r,cr,ia.
. . . .-_    TWO &her patients treated lx coma wera brought 0113 of coma. Of several

  -a--`-
1 r:c) rweiveci -2lcsa 50 coma, ::02e 7ent into coma.  Two patients have left the hos-


                                                 * -8-1
                                                  , . .'
                                                  ; i
-9 -

..i c>..x2 pertilssion or inotrwztions,
I                      nftar several months of treatment and improve-

. (9~ of these left because he imagined hinaelf well.)  Tmnty patients have been

rz3i in satisf sctor$ condition, freo from glycosuria and acidosis. Several of

  `e;.~ ci=iidrab, ran:inc from seven to seventeen years of ase.  Two patients have

: d c-.dre to
         k   trenkinp, diet, but have rs-entarsd the hospital in better condition

t first, and have tesn cieared up more easily than at first.  One other patient

.>I 1 ;>.t rala>se oaing to the advice of another physician that he eat bread.  Other-

I rqorZC ahoz aoztinuod f rsedon f ror.: i;lycos!\ria or symptor:s.   This includes

.,-street, tl;e first c,atient, yrhose case was ona of the severest. The remaining
   . _

.."C :-*
      L tha hoqital are kept sugar-free and ap?arsntly kproving.

   TLe rcutine study of these patients, involvinh 3s it does a very large number

. .izq.l enaiyses of urine, requires much ?ime and labour.   Under the section

_ 5 :'rort t%e Cfierzical Laboratory' is Given a description of the studies of act-

: ~.!~t:ii ars being made.

   Cr St.tllman is also studying the blood sugar in a series of cases, especially

ii:rer.ze to the relation between the concentration of sugar in the blood and rate

V:::retioz is the urine.

   As will be remembered, the theoretical. basis of the treatment employed is

* pancreatic function may be spared by
I

.: s -:las based on the changes observed ih

i'. , i:  The studies in animals are being

diminishing.body mass and metabolic activity.
depancreatiasd animals, under varying condi-
continued, parralel to the studies in .patienta

.tiallp depancreatixed animals are being subjected to conditions which alter body     :

2 or mtabolic activity. It is hoped by such observations to obtain evidence in

.0:.-t of the theoretical deductions on which the treatment is based.

   Dr Ailen has previously bmught experimental evidencx in favour of the view
:. !:lood sugar exists in a different physical state in diabetic and non-diabetic ani-

:, .  Experiments are nom unde r rvay and obseraat ions are being made having for their

.;a% the demonstration of SW> physical differences.


                                          c? *-
                                                      L l:,'
                                              ._ ..- .

                           - 10 -

   The study of norpkol~gical changes in the Islands of Langerhans occurring

l:`~etlc ?ni.mals and in patients is being continued.  The large amount of materiel

z.1::olr; in Eli. steps of the disease, as v:ell as of fresh ~IX:BX naterial, affords

  :. _ ,F::icsal opportunity for the study of this problem.
   It is no-.- planned during the surxler to publish the material SC far obtained

:o;x. of a ?:cno;;raFh.  This 7111 inzluiie (a)a report of the animal experir;snts

    .y A .r  `d;ie
  -v-u.    `;a310 for tile propossd modification in tke treetnent of diabetes; (b)

   . . l- V.Lcl.
     *. -; .,-
   d.      of 5h;e r.thod of `trsatmsnt s.3d reports of clinical cases treated.
   Studies conzentin;: tl:e Nature of Acidosis and eapeoially Acidosis ir. Diabetes,

    Dr VT.:; Sly?:e, Dr Stillman and I?r Cullen have undertaken a study oi acidosis

: :;`~~ds.  ?ralimir.n~y work by Dr Van Siyke and Dr Stiilman has indicated that the

:-:f.~?.=tion or' the sadon dioried tension, 0. * the alveolrrr air is one of the most

  1.1 ia ~:ethods
       .I       , if not the most vaiuable method, of determining the actual condi-

. . `. f t'r.o Tatlent, as re;ards acidosis.  A vary large number of observations of al-

t-L;' co2 -Lension in the patients with diabetes has been made by Dr Stilti, by a
.`-:d `?hiz3 is quite simple, but seems to yield accurate and comparable results, at
. .

It 11: >a+.ia!lts not cmdose, and vho can be &aught a very sirqle procsdure-  Dr Van

:!a and IIr Cullan then tidertook the problem of determining the changes in the blood
.i::l corresponds to the changes in alveolar carbon dioxide, in order that the inter-
:,Mion of the latter determinations might be put on a firm scientifio basis. I&
..`lan has gone on'with the work commenced by Dr Zacharias last year, the direct de-
::::icatior of hydrogen ion concentration in the blooffl by electrometric methods, and

isvaloped the method for tha present purpose.  It had already been shown by             -.
.::1.?Lis axd ct%ers that in acidosis the actual hydrogen ion concentration of the blood

Lx-Goes l:`.ttle or no change and Xr Cullen has confirmed these observations.   It thez

.:.L.J~ t3at iC, might be possible to determine by this method whether or not the reserve

-`:~iid%y of the blood in such zasss vjas decreased.  To determine this two r&hods

. -3 hem employed aid by- these methods it has been possible to determine that such de*-


ereaes in reserve alkaU.Mty is actually pr&,snt.  First, when a given amount of  : I, ., ...Bi,G:
                                                                           ;..,
Xl is added to the plasma of a case of acidosb, the acidity developed, as measured        `1
                                                                           `-I.*

                                                                           "i
                                                                       `.: .,&.
:I :he hydrogen ion concentration with the electrometric method, is much greater than   ^,?
                                                                           `.;.

ken nomal plasma is treated in the sane r;ay.  As an example of +esults?the hydrogen
iw concentra+ioza obtained after addUg one volume of -& H Cl to the plama from a
sevsre case of arriboei~ `k&t? `one hundred end fifty times as great as the hydrogen ion   .-it-
                                                                           i. ..,-j
                            .                                                                   .G.   ..,+
:oocectration of *nomk `pl&ba `i!&Sarly treated.                                       I..  1 .2,:'
                                                                           `.A.
                                                                           . *`
                                                                           _ .+,.I
  Sedond, & vftn-`si& `has b&n abIg to shoff t&t the ability of the-plasma 1. "1 .p'%
                                                                           .-..a*

to fix carbon dioxide which, `of course, depsnde on the amount of reserve alkalis, b .     '

                        - _ .A(
        ,.* _ ._           ~*$y ,,4 ?.>~A
such fox& ae ~~aij;iL,~~oephate"iih&.c~bonatd, f;`&duced 5.n acid'osi,s;- fn ord*t~~~~ $g$$
                                                                   : :.mA.<
                                                                           `- ,.  . s-4,:.`,+%* 119
dmon*tAta `th~e~`facfr..~i~~s"~abn `&&kry .to develop `i me&d, which ha@ ~&Xl$~~~~~$
                                                                 . .                   , .I A-. &;--<i
                            "..`,                                             : < _ *$y'v-~~-.
plif ied `60' is -to &&"&&i&e ,&lb frqmnt d&&&nations possible. The method,&$&$Z
                         # -                                                 - .,. .+s.&,-.~
       v-r' ,.                            "  _..     _ `.   ,                                 
                                                                           , ,..... q?~*. f
                                                                           4r 1.I-b&


;.z the result 05 which the CO2 gas immediately leaves the solutioh,                        ,:,
                                      The mercury is ,I    .., ,Y.
                                                                           .-`&:
                                                                           . ,j    -: _I .:
%n let back into the pipette, and the volume of CO2 read off on the upper stem,on.      i .? ,".>

                                                          <                            ,. i ,, `.:y
                                                                           -4
                                                                           $.>.

Xsf; a scale is etc'ned. Duplicate resuits rar& vary by nom than one per cent;        7 `"-`-<,
                                    ' `- `,-`I!

Noti Pbx%i binds 75 per cent of its volume of COz. In cases of acidosis

2-3 fF;,ure may be a8 low as 2c) per cent.  This nan and simple technique for detemining '

`.il3 CCI 2 capacity of the plasm provides a clinical method for the neasurenent of aci- :.  . . ..`.z
                                                                         r ,,I;:

331s dire&ly 4-r; the .blood itself,                                                             . *..*.rr;
              In a series of cases there are now being deters I $?z
                                                                           -`._

:-b-d A.z.xltaneou8lp,- firi& thi alveolar COz;,.                                         $3
                    second, the alk&ne reserve of th
                               

tion of horstie,`against':pne'~~~.`on ~thd~~`til~tive~ pi6portions of -the?dif fereht .,"_.*...: -.`a"`%."
                                  ,protein$

          . .._..
fn,the seti.. `;*


XSU;tS obtained have not indicated t'hat through huntration, at least with pnemo-- '

;occi,one Or other of the protein fractions is increased over the nomad.  Thether a        "
:ki!.ar critical study of the effects obtained by inmmization of horses to diphtheria   qc
                                                                           ,_.I'
                                                                           .L1,
                                                                           >-a
toxir; nil1 yield similar results,contrary to those non generally held true, cannot be    ,'  `I
                                                                           ,.
                                                                           : '

m+,ed but these observe&Ions throw some doubt on present conceptions.                     ,
                                                                           ^ .,
                                                                                i
   The study of the -ax&o acid content ol certain proteins, which Dr Van Slyke     .i, 1.
                             .I.$

and Jme Vimgrad began, over a pear, ago,                                             I,'

                               r' j      In callabamtion with Professor Osborne of  -.;zi
hv fIbvm, had reached a satisfactory conaluaion.                            "4
                            m point of htereet whiah he  ' `"`? ":'
                                                   , _ .; :,,L$

finally been settled cone&m the" content of iliadin, the principal wheat protei&in b ' ~*"`~$
                                                                           .
bine, one 6f the amino,. aafds which the work of Osborne and Mendel has shown to. be `,"' `:   .- ..,, ,:
                                      :`?$$

      `, : Budy. of ,the
        ,`.,        . Abderhaldan -reaction;-:.blJtt~~lsse Vinograd.
         `,'                  1:: ."     
of the Lying` In. H&$&,`3T has,;,b'&- t&t i&,& _                         /

       .i ,,.I ,_         ; ,' F   ;'   ml.. I      `, \I The &,thod eEployea; has
         ., -..            .' .,  :, ..`..   ,. `5..
de:emining the, increase,S in .+             -

8amn.  They are by no mais &aracterietic of pregnant sera. Secon&,.`such pm+


-._.

-.  .

                                                                           * 1
                                                                           ,
                      - 14'9

`2 .:ic enzmeE digast not only placenta protein, but other proteins as well.  Third,cn

' I a-.-Wage the enzymes in the sera of pregant nomen are somewhat more active% than
.;

.LSS in the sera of noi -pregnant Totlen an, of normal men.  The individual variations,

.- ..,-,
_  4 in the latter cover nearly, if not quite, as great a range as those of the

:I c ? rregant 7.:onen.  In certain IatholoSical conciitions,norsover, as in Pnetlflonia,

-, rlr.:.t:y ths most active digestive action is seen.  No evidence, therefore, of the

s 3-s oi a spscific enzyme in the serum of

.>n'; qxan'itntive variations observed in the
. .

;:t iz r,3r:.:al anci pathological sera, ae well

promant women has been obtained. The

amount of the non-specific ferment pra-

as in the sera of prqnant women, indi-

:-ltj that the B'oderhalden reaction is unreliable for the diagnosis of pregXU%ACY-

Pith the assistance of Dr Losee at the Lying In Hospital, studies on the to%!-

. ..in of pregnancy have been carried out.  The most

:oxdas has beon that of Ening,according to which

:iciency.   The chemical evidence for this was the

concrete theory comeming these

the toxenias are due to liver insuf-

increase of non-determined nitrogen

i:. the urine, nhich Ening attributed to excreted amino acids, which were supposed to

:.~vs secaped nozmal catabolism because of the inefficient liver.  Direct determinations

C: :Ila amino acids, aa ~11 as the other nitrogenous constituenta, not only in the urine
`..A also in the blood, have bean made, and the amino acid content in both has been fold
rU.                                 . .       -.

w be absolutely nomal,  The results make Ewing's hypothesis untenable. The abnormali

ties of the urinary nitrogen appear to be, as surmised several years ago by Underhill

of Nsv Have% the abnormalities of hunger, and nothing more,

Studies in Nephritis.    Dr ?lcLean has continued his study

         purpose cases of cardiac disease admitted

tion, and ha8 used for this

for study and, in addition,

types have been admitted in

a small number of cases safiering fraia nephritic of varicka

order that studies may be carried out cn them.  Dr McLean

of kidney func-

to the Hospital

kas continued his study of the ratios between the concentration of chloride and urea

ic the blood and the rates of eitcretior.  o f these subsLvan(;es in the u-he..   The method

3: estimating the excretory efficiency of the kidne$ in this manner has been reduced


- 15 -

tcl a rracticai basis Ly Cr ::ct,ean?, so that the xsuits are expressed in per

sf noxal eff icier,cy*  The labour oi calcxla'vion has been reduced to a minimi

centaGe

um by

;-.:-.
A L 1 :J 1x-.= a slide rule for zhe purpose, -hich enables oze to pcrfom the otherwise              1 ,y
                                                                           ! !.

-.,. c..;i-.3t prolon,ad calculation in a fey; seconds.   The l-.&hod for detsrmination of     ;
                                                                           I fi

",.1
_.I- J. -.les i:; szall a;.our.ts of plasma h;is been further sirplified by Dr McLean SO that

.'
_ . rist~lts c?n naiily be obtained rrithin a half hour after the blcod has been drawn.

-.

is rla~:.~ed to continue this study of nephritis, ccployin[; this method in compari-    ,;I;
I.                                                                           i
                                     q
: " A-, : J ti; ox:ler no+.hoIs Cor detenining kidney function,         . I