which will imprevo the results in this type of cases. The results of serum treatment REPORT OF THE DIRECTOR OF THE HOSPITAL. January 1915, During the last quarter reer cntients: suffering fre. ene of the fclloving wi.eaces lave “san aucitted to the Hospital for treatuent ani stucrj; acuve lovar Fnew.or.is, Cincetas, anc heart disease. A few of the patients formerly under treat- wont for aypnhilis of the central nervous system have been readmitted for short periods +o receive additional treatrent. Acute Looar Preusonia: The work on acute lobar pneumonia has been mainly a continuation of that carried on during the past uears, especially along the lines discussed ir our dast report. The number of patients admitted furing the present quartor is avout twice as large as the number admitted last year during the samo Period of time, so it seems probable that quite a large number of patients wili be available for study during the presert year. Unfortunately, so far as testing the value of the method of treatnent by reans of immune scrum i-s concernedg very few cases of Type I. have beer. admitted. On the other hand, an umusually large proportion of the patients so far admitted have been infected with pneumococci of Type II. Fur~ thee experience with the serum treatnent of cases of Type IT indicates that the value of this method of treatiient in these cases is not nearly so great as it is in the cases of Type I. This was to be expected from the experimental studies. Further efforts are being made to determine whether or not sors nodification in the method can be made in cases due to Typo I, however, continue to be very encouraging, and there seems every reason for believing that semm trearment in cases due to this type of organisa is of very great value. “hon one renemters that the nuuber cf deaths in New York, cue ro pneuvuenia caused by pnercosocei of Type I is greater tian the deaths due to dizntheria, and much greater than the total viecser of weaths due tc scarlet fever, cerebro-spinal fever, and typhoid fever combined, it is quite evident that we are Meena nen oe : “cab tai SoF - R - ' justified in Considoring this type of Pnounonia as an antity, and in feeling much Oncouraged if the méthnd employed is able to materially reduce the mortality in cases of this one type. It is planned during thea coming winter to Supply a limited Snount of sermus to several other hospitals, So that it is believed that by Spring w@ S22) obtain sufficient Statistics to permit of a definite judgement as to the therapeutic valus 0: this serum. During tho present quarter the studies of pr Dochez and Dr Avery concerning epidemiology have been extended, and the observations praviously reported have been confirmed. The report of this Study is now in press. Dr Avery's Study ef the dis ~erui have also been extended and completed, and the report will appear in the Feb- Tuary nusoer ef the Journal of schexlorxaxixet Experimental Medicine. The studies S2v6 snow tuat Practically al) the iczmune substances aré contained in the fraction of protein Precipitated by 38 to 40% armoniun sulphate. Since this Precipitate con~ tains only one 8ixth of the protein, it is evident that a method has been found for reneving a considerable amount of the protein of the serum used in treatment. This is now being carried out on a larger Scale, so that treatment may be made with such soncentrated serum. This work also has considerable pupsly scientific interest in relation to the distribution of immune bodies in the fprum protein fractions, & considerable anount of his time to the care of patients, he has had less Opportunity than Previously to carry on experimental Studies. However, he has continued his study cf the nature of the immunity in Pneunococecus mucesus infections, and it is to this eroblex: that his Sxperinental wort will be larsely devoted during the coming winter, The laboratory Studies of the Rirector cf the Hospital have been manhly “8VGCeL to a Stuly of methods of quickly Producing active dimunity and to a determi- “stlon of the best methog by which such vapid active diamunity may be obatined. It a “x fourd that if even the slightest . "Ooo ~ ved nas c vitieacy of iunune soru, in such aninni, Sor So far tested, hovver, it has besn Lipo active inmunity incide of a period of six -evised for dzcrsasing this periou, in ord for conoinins vaccination ith Passive inmunization soncemin~ tha nature of active immunity i i-portencs in order that the specific trs- due te pneumccocei of Typs Il. ye tinunt of patients wighin 3 8 of active immnity is produced, the ousl; incrcasud. With the methods bis to produce even thisslight grade cf days. It is hoped that a nothod may te er that we roy have experim:nt2l justification in our paticrts. Further knowledge h pneumococcus infecticn is esvscially of Q uffering from infsction bu rendered ners offieacious. Dr Chickering, in addition to tho caro of pationts, hae boon working with Dr Gay, and tho following is tho report by Dr Gey of the results obtained in their work. Rupore by Dr. Gay, Through tha courtesy of tie Board and of Dr Cole, the facilitior of the lvtoratctviss of ¢ for ‘chich he wishes to make grateful achno: lodgene with the assistance of Dr Chiskerinz, “ho Th: study first undertaxen dealt with tho Sutipneunioceccus serum on the addition of such a precipitetes, which could be producsd rapidly and watereclear extract of washed, alcohol~precipit therapeutic uses of either Plain or sensitized vaccines. atanioned, owing to the greeter interest awakened by another observation. «ie Hospite] heve been oxtended to Dr Gay for the past two months, His wort: has been carried on + ve will share in the publication to be mads. sss possibility of trsatment by mears of a com vination of serum and pneunococcus vaccine, or by means of a sensitized vaccine. The experinental conditions of pnoumonoccus infection in the aninals that have been tested have appanently not lent themselves particularly well to a demonstration of possible Certain suggestion have been cttained which might aventuelly lead to something of more practical significance. During the last. month, however, experiments along this line have been largely It was thought worth while to try the possible curative effect of a specific precipitate produced in an extract of pneumococci. It was found that in large volume by adding a ated and ground pnevmococei, is apparently as protective against prueunoceceus infection in mice and rabbits as an aliquot amount of the oririnal ser. This Precipitate nay further te washed in saline ang still retain its curative Properties, and in Sone instances, when freshly produced and dis- Selyad b a scall amount of alkali(maoH) wilt Stijl retaia as much curative value as vhe original senz: from which it is derived, The addition of teo Great anount of ale sli, even if it be Subsequently neutralized with HCl, may destroy the curative value. Te Sanie efiect, however, is also rpoduced by tho addition of large amounts of alkali to tho original diluted sorun. This curative precipitate contains a ver; small amount of preteins as determined fron tne total nitrogen. Vhereas the Original serum cor- tains 6 to 8° of Protein, various Speciziens of the Specific Precipitate, restored to th original voluue of Serun, have been found to Contain from .18 to ,34%, From the ob- Servations hitherto nade, it would seen that the strength of the protection afforded cy this Procinitate is not Froportionate to the Percentage of protein Present, The concentration of the precinitate in smaller voluns apparently renders it Possible to protect mice against sonewhat larger doses of the Ppneumoceccus than can be rrotected against by the whole Sérum. Tho serum fron which the Precipitate has been revoved contains much less Protective value than the original serum, although it usu~ ally contains a berceptible amount. The method for producing the maximum amount of pre:- cipitate, the Possibility of putting this precipitate into solution without destroying its protective value, and many other Problems remain to be worked out in more detail, Ye do not know, for instance, whether the precipitate itself is the protecting substance or sone other combination of antibody adherent to it. It seems evident that the pre- equally well when dissolved,and also owing to the fact that the undissolved precipitate does not protect against a type of pneunococcus other than the one against which the sorun eriployed is active, It would seen that there observations open a field of considerable interest for investigating the nature of immune bodies of various sorts, and indicate a means: of con- centrating immnne codiss ina Solution of low protein content which may be advantageously in tréatuent, not Only ef pnermonia but possibly also a? ctner infections, Dec. 4th. Curative Experiment With varyins doses of serum and Gissolved precipitate and a Tixed doses of sulture. Volume = C.5 CeCe ae Diluted serum 0.1 + Culture Preumococcus I 9g 0.05ce Survived 2 " "9,95 f Be " "0.025 n kg mn " 6.0125 . " De " " 0.00625 + 14 days 6. Dissolved precipitate O.2 +. n hoon " Survived 7. n n 0.05 . g. i" n 0.025 " o i" n 0.0125 mn 10. on q 0.00625 0 ll. Exhausted Serum O.1 " le, n " 0.05 . + 360° 13. " " 0,025 + 36° 14, Contrel + 0.05 + 20° 15. 8 + 0.0002 + 18° 16, 0 + 0.00001 + 40° 17. " + 0.000001 + yge { “*&- Diabetes: During the past quarter the efforts of Dr Allen and Dr Stillman have teen mainly directed to the treatrent of patients suffering frem diabetes, along the lines discussed by Dr Allen in his report to the Board,last April. It will be re- called that the studies on animals suffering from oxperimental diabetes led Dr Allen to believa that for the successful treatuent of dinbetes it would be important to keep sha r.tient on as low as caloric diet as possible, in the hope that the demand then nage upon the assinilative functions of the body would be reduced as far as possible, the theory being that any increased demand made on these functions, over that absclutely necessary for the supply of sufficiert energy to carry on the activities actually necessary for life, would cause a strain on the organs functioning in assimilation, in- Cluding the pancreas, and so reduce the functional power of such organs. It will be re- called that Dr Allen showed that if two dogs be each rendered diabetic fia the same grade, and that if one be fed on a high caloric diet, and the other on a low caloric viet, the one receiving the high diet would, in spite of this, lose weight, and would also become feeble, and finally die. The other one would also lose weight, but remain aprarently active and ina comparatively normal state. Twenty seven patients have now been admitted to the Hospital, suffering frou diabetes. Sixteen are still in the Hospital. The study of these patients has shown that, by the withdrawal of all food except alcohol, all patients suffering from diabetes can rapidly and completely be relieved of Slycosuria. It is also of very great impor- tance that, at the same time, the excretion of the abnormal fatty acids is also reduced to a nininum, so that, instead of the withdrawal of food causing an intensification of acidosis, it is the best means of relieving the patients from threatened acid intoxi~ cation. In order to obtain this freedom from glycosuria and acidosis, it is sometimes necessary to withhold food from the patients for a considerable length of time, in cer~ tain cases as long as @ight days. After the patient is free of glycosuria and acidosis it is then necessary to get him back to a living diet, containing a sufficient amount of the variitts kinds of food. No effort is made to have the patient increase in weight en \ . however. If he is emaciated, however, it is thought important that the weight should revain stationary. By carrying out these Simple measures, it has beon possible ina large number of the cases, to keep them free from glycosuria and acidosis and on a caloric diet of sufficient size to maintain life. It will be rorenbered that in his previous repart Dr Allen stated that he thought that by this nethod, the total metabolisr night be reduced. To test this hypothesis 2 series of calorimeter experinents have been carricd on with Dr Lusk and Dr De Bois, the patients being temporarily rerovei to the Bellevwe Hospital for this purpose. This study is still in process, but in one case, at least, a reduction of 20% in the basal .ttabolisn tas been observed, followin; treatuent as outlined. Most of the patients have shown increased tolerance to carbohydrates and protein following the procedures tescribed, though it is still impossible to say whether it is essentially greater than that observed when patients with diabetes ara made free of glycosuria and acddosis by ths Slower methods previously employod. It must be renembered, however, that with the ..thods previously used it has been impossible in many cases to render them free of ‘lycosuria and acidosis. Only further extended studes can show how great prolongation cf life may ba expected by the method employed, as coripared with that obtained by cther wethods. It is generallt assumed,however, by clinicians that in the treatment of dia~ betes it is of great importance to render patients free of glycosuria and acidosis,and that thereby tolerance nay be increased and life prolonged. It seems that the msthod proposed offers an improved way of doing this. That the total caloric values of the diet is of importance, and not merely the actual anount of slucose~producing sugars ana proteins, &s shown by the fact, now well established by these studiss, that where a patient is free of glycosuria and acidosis on a given diet, containing proteins and fats, with of without carbohydrates, the addition of a given amount of pur fat, without any change whatever in the amount of protein and carbohydrate, may cause such a patient to asain become glycosuric.e This fact together with the fact that pipaemia so often cecurs in diabetes, has suggested the importance of further study of the fat metabolism in diabetes, especially a study of the fat content of the blood. Consequently it is -%- 3G raanned that during tha coming quarter Dr MeLean and Dr Stillman will carry out furthor studies dealing with glycaemia and dipaemia. Dr Allen is also engaged in the study of the pathotogical material obtained frou experimental animals and cases of huxan dia~ betes to study further, by means of more delicate stain reactions, the finer changes in the pancreas occurring in diabetes. heart Tisease:- Studies concerning the mode of action of digitalis have been continued by Dr Cohn withthe assistant of Dr Jamieson. The studies made last year of the action of digitalis in patients with normal cardiac rhythm wibhout oedema, and with bleed pressure within normal limits, are now in press. During the present year studies are being made of the action of digitalis in patients with abnormal cardiac rhythm,and in patients in which oedema, and abnormally high blood pressure are present. Special Studies are being made of the mode of action of digitalis in patients with fever,especi-- ally in cases of pneumonia, In previous studies,in order to determine that digitalis was actually active in an individual, it has been necessary to push the administration to the point of alter- in tho heart's rhythm(heart blcok)or of inducing gastro-intestinal symptoms. These wery the nost cortain tests. In reviewing the electrocardiograms made during these studies it has been found frequently almost uniformly - that before these signs became manifest the shape of the sc~called T wave in tne electrocardiogram became altered. With greater attention to the details of calibrating the curves, it has been found that the beginning of this change can be detected easily - in two to three days ~ after giving the drug. This chage, together with a change in conduction between auricles and ventricles,which also often occurs early,offers two new,sure criteria for deciding early that digitalis is acting on the heart. By observing these signs,patients may be saved from the dis-~ agreeable effects of this forn of treatment. Ina Single instance abnormal primary negative T waves have been seen to become less negative, and later positive. These chanses persist varying lengths of time, and the curves return to their initial forn after about ten to fourteen days after stopping the digitalis. Tests of these signs in patient§ with fever(pneumonia patients) have been nade. we ba ay a , + meee -\- i vad The failure ef digitalis in these circunstcnces to lower heart rate is familiar, and its use by many persons has been discontinued. In wany €& these patiants the electso- sirdiograrhic changes alrealy :ention -lse ocevr -ftcr the accinistration of digitelic provatly after the saxe loneth of tire, ond with the soe cosage, 28 in cases of cardiac diceass. If further enveraenes berss out these observations, we cncll have velusdle ne. wethods of Jucging the value of certain stiiulants in these conditions. It nas previously been Supposed that for digitalisprep-raticn to be effecient LSeS With be. e tS LF) . faver itore than the usucl dose «as reqvirei., Dr Jamieson hes therefore couvpared the lathel dese cf evystalling strezhantiiin in nersel cets ang in cats with eperinentsl pneuucuia, induced oy insufflation. He hes feund thet in both series of onicals death cecurs aftor the sane S-otnt of the ding lias been injected;that there is no disference in the action ¢ Svropanthin in the infected and in the non-infected ani- undSe This result Pargllols the o>vservations x2do in Frvients. However,vnile the in- fectel cats Scwed well-arked consolidaticen of the lungs, tney failod to develop fever. It is possitle that the absence of fever indicates that a true intoxication, interfering with the action of digitalis,was absent,ana that,had fever been present,tha result vould lave been different. It is planned, thersfore,to rezeat these exporinents in dogs. Human hearts in which electrocardiograns have supplied evidonce that the swaller branches of the auriculo~ventricular conduction syste: had undergone pathological changes (cundle~branch lesions) have been studied in Serial sections. Structural alterations were found, but it was impossible to say definitely whether these cro to be correlated with the alterations in the electrocardiocrans, The nearts were supplied vy Dr Thonas Lewis in a state of dissection designeé for weighing the ca ities scparately, and were not quite fitted for the vUrpose of the histological Study Decauso the continuity of vce endocardium had been Scrificed. Tha failure to fing an adequate lesion tc account for the change uay lie in this circuustence. Furtuer experiments on tie distrisetion of the vagus nerves and more eszecially ci the acceleretor nerves are in Progress. It nas basn found thet the sins node doss ee Picante. etn ea ; ; ie tii a . mo ~ TK BS, net form a relay in tha path of the agus norves. The new experiments are based on the iuca that during left vagus Stisulation, th> accclerator nerves espocially are rcspon— sible for eontinucd auricular activity. Chouical Laberatory:- Tho foilvoing is a report of tho work carricd on by Dy Von Clyhe and the physicians working undsr his irmediate direction. uo Study of tho fate of the products of protcin digestion, begun tuwc years ago with Dr Moyer, and intcrruptcd last ycar in ordcor to develop reliable methods for urea deturcination in blood and tissue extracts, has becn takcn up again. fae ir Cullen and Dr NeLean have investizated the qucstion of urea formation in the livir in etheorisud dczs. Perfusion of excised livers by tho Folin school failed to yy wy wu revial an ability on the part of this orzan to transform amino acids into urea, and throvm doutt on the former vicw that the liver is the chief saat of urea formation. “orking with livo aninals at varying periods aitor rcat feodingy;howover, it has boon found that the henatic blood in every caso contains urea in greater concentration than tho portal,the increase in the urea rosulting from passage of the blood through the liver veryins in diffzrent oxperinents from 3 to 15 &. Passage of the blood through the muscig causes relatively siizht increase,usually none, Mr Eodling of Dr Carrel's department, is experinenting with portal vein fistulus in dcss. Then the experinents are successful, as promises soon to be the case, it will be pessible to follow the tire curve of the rise of anino acids in the portal blood after the ingestion of protein; by deternining at the sare tine the curve of the blood urea, the two curves may be related to the progress of the food proteins along the alimentary canzl, as shown by X-rays. It will be of interest to ascertain how soon after the in- gestion of proteins it is possible to detect the presence of their products in the blood and how scon after this the formation of urea begins. It is also of theoretical interest to ascertain whether the body begins to break absorbed amino acids into urea as soon as their ebsorption is under wey,orwhether it waits until the tissues in general have be~ cone charged with amino acids in excess. With Myr Sbeling it is also plenned to oxperinent with dogs having thoracic duct fistulas, in order to determine how important a channol the lymph is for protein ab~ sorption. Mr Cullen has assisted Dr Avery in studying the effect of immunizing horses against xtxxgz pneumonocci on the relative propostions of the different proteins in the bleod. It is of interest to determine wether the protein fraction containing the iucune bodies increases during immunization, and whether such increase in any way para- llels the protective power of the serun. Dr NcLean is making a study of kidney function in diabetas,and, in conjunction with Dr Cohn's dupartment,in heart insufficiency. The ratios of the concentrations of urea and chlorides in the blood to the rates at which these substances are elininated ty the kidney has been mathematically expressed in equations by Anbard,and Dr McLean's studies indicate that these ratios are very delicate indicators of the excretory power of the kidney. The effect on these ratios of the administration of digitalis to edenatous heart patients is striking, and it is hoped that a comparison of the results of this study with electrocardiograms nay decide the question as to whether the prinary sffect of digitalis in such cases is on the heart ot the kidney. Some of the diabetics show a pectliar,abnornally increased permeability of the kdineys to chlorides,the significance of which is still uncertain. This condition is also being ‘studied. In order that sufficiently numerous data on the blood chlorides night be ob- tained in the above work it was found necessary to devise a method which would per= nit accurate determinations with much less material than the 20c.c. required for the usual Volhard titration. Dr Van Slyke and Dr McLean have devised an iddonetric method which pernits the determination of the chlorides in ome or two c.c. of serum with an error of less than 1 part per hundred. The study of the chemical constitutidh(amino acid content) of certain food proteins, begun by Miss Vinograd last spring in conjunction with Dr Osborne of New Haven is being continued. Miss Vinograd with the collabcratiox of Dr Losee of the Lying In Hospital is oncaced in a thorough study of the Abdernalden serum reaction, using the Van Slyke enino nitrogan s:ethod in order to obtain a guantitative reasure of the extent of pro- tiolysSis occurrirg. The technique has teen so developed that an active serun usually “ives an increase of 100% or more in ariino nitrogen; so that there is no longer doubt 2S to either the occurrence, or the de-sree,of proteolysis occurring under the conditions ct the reaction. It does not appear that the reaction is very specific; but a final decision 7s to its value has not yet been reached. Recently several European writers have announced that in the most dangerous tyres of diabetes the organism loses not only its ability to burn sugar, but also its wtilaty to metabolize the alimentary amino acids. In consequence an abnormally large proportion of tho urinary nitrogen is in the form of amino acids. The determination of a..ino acids in diabetic urine is subject to peculiar pitfalls, and it appears un- certain that any of the clinicians reporting the above resulté have beon aware of them. It is planned therefore to take advantage of the diabetic material in the Hospital to octain data on this important point. RI. Cole nv