THE HOSPITAL OF THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH, 63 -, / b SSrn STRKET AND AVENUE A, NEW YORK ,, .tr _" - ., \ i April 4, 1914. lo the Board of Soientlfio Directors of the Hookefeller Inetituta for Lledloal Reaearoh, ;entlemen I - The Dlreotor of the Hospital haa the honor to submit the following re- Iort of the work oarried on In the hospital during the paat quarterr- Pneumonia: During the paat quarter thirty-five patients suffering from pneumonia h&ve been treated in the hoepital. This la not ae large a number ae it was hoped light be admitted during this aeaaon* During the past week, owing probably to newspaper publloity, thera has been a marked inoreaee in the number of aclmims)ione. The etudy of the type of organism oonoerned in eaoh oaoe has been zontinued, and it has been found quite poeslble and fairly easy to determine readily the type of organism oonoerned In the Individual oaae. During the present winter, of the fifty oases treated, only about twenty peroent have been caused by organisms of type I, while almost forty perasnt have been due to organiama of type II. who- ther or not this indioatee a greater prevalenoe of pneumonia due to this latter type of organism during the present winter in New York than during last tinter, it ie diffioult to aay from our limited experienoe. Our previous experienoe in regard to the relative severity' of the condition in oaae6 due to the different types hae been oonfirmed. The oaeea treated with the type I aerum have all done well, and the experimental and olinidal evidenoe indioates that this sort& is of therapeutio value. The effeot of the type II serum, however, has not been ISO s&isfaofory,.einoe four of the patienta'^' fully treated with thie serum have 'died. The reeultn.were diffioult to understand until further study of the serum used ahowed that its proteotive-power In animals was muoh lower than that of the serum employed laet year. All of the type II serum used for treatment has been obtained from the first horse immunieed and from whioh all the serum used for treatment last year'was obtained. It ie not known why this horee, whioh was previously able to yield a potent serum, now faila to do 80~ but it is known that horses yielding anti-toxic sera and also those produoing other anti-bacterial sera may gradually lose their power to produce effeotive kera. The reason why no other type II serum was available for treatment was beoause the aeoond horse, whose immunization was oommenoed last summer, developed a ohronio joint in- fection and had to be sent to the farm. We also now have another horse in process of immunization with organisms of type II, and also a horse whioh is being immunized to organisms of both type I and type II. The serum of this latter horse now shows ISroteotive power against both types of organisms as high in each oase as we have ever found with a monovalent serum* This serum is now ready for use* Dr. Avery has oontinued his efforts to oonaentrate the serum on a large scale, but so far without very eatisfaotory results. The experimental work has shown that the proteotive substances are largely aontained In the euglobulln fraotion, as ,btained by the salting out method, and also are present in the so-oalled insoluble globulin preoipitated from the diluted serum by oarbon dioxide. However, it has been found so far that the loss of immune substanoes in filtering , eta., when these methods are employed on a large soale, is too great to justify their use, Modifloations, however, are being made and it is hoped that a satlsfaatory method may be worked out. Dr. Dooher end Dr. Avery have oarrlsd on studies conoerning the various types of pneumoooooi in relation 'to the mode of Infection and epidemiology of the disease. Dr. Doohec Is oarrylng on a oomparative study of pneumoooooi present In the mouths of normal individuals. A large number of strains have so far been Isolated from the mouths of fifteen normal indlvlduals. In only one instanoe has an organism of the fixed types I, II or III, be& isolated, In this inetanoe an organism of type :I was isolated from the'mouth of th'ct wife of a'patient with pneumonia dbe'to I.:. an organism of this type. Further'nork, of oourse, may show that these f&id types , occur in not-& mouths'muoh more frequently than the results so far would indioate. ,' Rabbits are being immtinited to varibus strains isolated from normal mouths, in order , ( to learn more of'their antigenio properties. Dr. Avery is studying the persistenoe of the pneumoooooi of the various types in the sputum of oonvalesoents. The evidenoe so far indioates that the pneumo- cocci of fixed types can usually be found in the mouth or sputum no longer than a few weeks after reoovery* Later only organisms of the type found in normal mouths are present. It is of great importance to learn whether or not the organisms p-sent in pneumonia are simply displaced by these latter organlam, or whether possibly a transformation may have taken place. In order to aid in determining this point, the antigenio relationshipa of/a number of the organism ieolated during the disease, I , to those found in the same mouths after recovery, are being studied. Dr. Avery is also studying the behavior of tho various speoifio type strains of pneumoooooi in the different oarbohydrate media. Dr. Chiokering has been studying the time of appearanoe and diaappear- anoe of agglutinine in the blood of patients Buffering from pneumonia. In untreated casea the agglutinlne appear only about the time of orisiB, though in 8ome oases they mtty be delayed until a later period. In the treated oases the agglutinine appear muoh earlier. The presence of agglutfnins, therefore, ie not of muoh value in de- termining the type of organism oonoerned, but the demonstration of agglutlnins may be of some importanoe in prognosis. Furthermore, this etudy will offer oonfirma- tory evldenoe of the etiologioal relationship of the type of organism isolated in the oases where the organisms are only obtained from the sputum. Dr. Zaoharias is about to undertake a atudy of the hydrogon ion oon- oentration of the blood in pneumonia by the eleatrometria method. The relation of the reaotion of the blood to its oxygen and oarbonio aoid oontent xi11 be studied. She relation of the degree of aoidoeia lndioated by the inareaaed ammonia exoretion in pneumonia will alao be oonaidered, in order to determine whether the aoidoeia indicated by urine analyeia really oorreaponda to an inoreeeed aoidity of the blood. The study of the produotion of methaemoglobin by pneumoooaoi has been oontinued, and aleo the study of the toxins produoed by theee organisms* It has been found that by freezing the pneumoaooof and drying in vaouum while froren and then making up in ealt solution, the resulting solution ie toxia for guinea pigs, and the same effects are produoed as by the injeotion of the bile extraot. Fur- ther evidenae haa therefore been brought that the toxia eubstanae ie pre-formed in the bodiee of the baateria and set free upon their dieaolution. The method aleo permits large amount8 of toxin being obtained and preserved, 80 that experiment8 msy be oarried on from day to day with toxin8 of equal strength. Diabetks * The following is a verbatim oopy of the report caoeivad from Dr. Allen. . P While in aertain inatanaes Dr. Allen has allowed his enthusiasm to lead him to draw oonolusionsAnot yst,,,justi ied, yet it is very evi- dent that he has a definite and W interesting point of view. The results ob- hined in the one patient so far treated are most striking and very promising. Heport from Dr. Allen WorL has been oontinued along the paths previously outlined. The progress along a few of the prinoipal lines may be SLInUnariZed as followsS- I. Produotion of Diabetes o ?? By simple removal of panoreatia tissue:- The results in a long series OP dogs are oonstant. The newly observed relation between panoreas and body-weight also holds good, i.e., large dogs have less panoreas in proportion to body-weight than small dogs, and beaome diabetio from removal of a oorresponding smaller fraotion of the panorsas. Large oats, on the oontrnry, have as muah pan- areas in proportion to body-weight as small oats , and similar fraotions must be re- moved in order to aeuse diabetes. The "apparent" sugar tolersnoe is not an Index of susoeptibillty to diabetes. For example, large dogs normally have as high a sugar toleranoe as amall dogs. Monkeys have a low sugar toleranae, and in pigs the apparent tolersnoe is almost nil, as Carlson reported. But if one attempts to maintain a oontinuous glyaosurla in these animals, the 'orgsnism responds by assimilating even the largest quantities of between apparent and real toleranoe. psnoreasr a pig now under observation glyoosuria: but.the glyoosuria ia now will probably be the result in suoh a has thus far prevented a satisfaotory Even takes sugars thus illustrating the differenoe after removal of seven-eighths of the 500 gms. gluoose daily with only slight oontinuoue and inoreasing, and true diabetsa predisposed animal. Pressure of other work series of experiments with partial panorsateo- tomy in speoies other than dogs and oats, though the monkey and pig promise to be highly important (espeaially for the problem of aaidosis) when time oan be devoted to them. B. By diet:- It is now safely established that dogs and oats can be predisposed to diabetes by removal of suitable portion8 of panoreas, and that oarbo- hydrate-rioh diet will then aat as an exciting aause of diabetes. When the pan- cream re , + ant is of oertain size, the animal is glyaosuria-free on meat diet, but