monia of the same type, were noted. The decision is inconclusive from lack of a sufficient number of cases to warrant more than preliminary deductions, and for the reason that some of the material was of far-advanced pneumonia, complicated pneumonia, and the pneumonia of particularly poor subjects like alcoholics, a class of cases that should, except for a most far-reaching trial of the serum's virtue, be excluded. The one particular impression gained by the use of this product was the remarkable manner in which it aborted or cut short what apparently were beginning typical attacks of lobar pneumonia.

Cerebrospinal Meningitis.

Another conquest of the biologic therapeutist greatly to be desired is that of cerebrospinal meningitis which, in sweeping epidemics. in insidious

sporadicalness, has made itself a dreaded Scourge among the civilized races, particularly of the north temperate zone. Activity in this direction has not been fruitful to the present time. For example, during the Silesian epidemic of cerebrospinal meningitis in 1905 Göppert treated eight patients with a serum obtained from Doyen in Paris, with apparently detrimental effects in all of them. This serum, when examined by v. Lingelsheim was found to be devoid of any agglutinative action on the meningococcus. Kolle and Wasserman have produced an antimeningococcic scrum which has been tested for its agglutination, and for its opsonic power in rabbits. So far as I can learn the clinical usage of this product has not been reported. Flexner, from the Rockefeller Institute, and several workers in the research laboratory of the municipal health department of New York, have made immunizing experiments in various animals and have tested the serum in experimental meningitis of guinea-pigs and monkeys.

My personal efforts which are now

given publicity only in a preliminary manner, have extended to the test in four cases, of the serum from a horse treated with the poisons obtained from the meningococcus by a method already published. This serum certainly differs from the reported action of Doyen's, as it is highly agglutinative for meningococci and, though employed in large, subcutaneous doses, aroused in none of the patients harmful effects except a slight and transient serum reaction. There seems to be an agreement on the part of the several Detroit physicians through whose kindness I obtained access to these cases that a prompt and beneficial influence on the nervous symptoms (delirium, stupor, coma, restlessness, etc.), followed the administration of the serum. In the first case, one of the fulminant variety which I saw with Dr. P. B. Taylor within twelve hours of its terrific onset, the patient was able to leave her bed in three weeks and has made a perfect recovery with the exception of total deafness. The other cases which were kindly placed at my disposal by Dr. P. C. McEwen and Dr. W. G. Hutchinson were more advanced in the disease (7 to 10 days). One of these has made a surprising recovery after passing through the hydrocephalic stage of subacute meningitis. The two other patients died after removal from the hospital, where one was apparently on the road to restoration. This meager material would seem to indicate that the serum in question possesses antitoxic properties, but in its present form is powerless to check the progressive bacterial infection. I am in hopes that some improvement or combination may be secured whereby the antitoxic effects of a serum for cerebrospinal meningitis can be reinforced in the direction of an antibacterial property.

Gonorrhea.

Serum therapy has not yet conquered

the ravages of the gonococcus, though interest in this alluring possibility has recently been revived by the report of J. C. Torrey on the production of an antigonococcus serum from rabbits, and of Rogers concerning the use of this serum in gonorrheal rheumatism. Both in the employment of rabbits' serum in these experiments and in those of Beebe and Rogers who injected the serum of specially treated rabbits in patients with exophthalmic goiter, a peculiar and very troublesome reaction followed, seemingly induced by the blood serum of this animal. Undoubtedly this objection will be largely obviated if the horse can be successfully treated with the gonococcus or its products, and I look with hopeful anticipation to an early date in which such a serum will be available for the treatment of gonorrheal rheumatism, and, along a different line, I believe we shall soon enjoy a specific and satisfactory biologic therapy for the various manifestations of subacute and of chronic gonorrheal infections.

Technic of Serum Injections.

My contact with physicans at the bedside indicates that a few words about wellestablished features in the technic of serum injections may not be out of place. The mistake of injection into the muscles, especially of the buttock or limbs, should be avoided as unnecessarily painful; and for the preferable subcutaneous injections the site of election is the loin or flank where, if one penetrates the proper layer of tissue a quantity of serum of 40 cc. to 60 cc. and even more, can, if necessary, be inserted through at single puncture with no particular discomfort to the patient, and with only a diffuse temporary and moderate swelling. Then there still exists the fallacy about the danger of air injection which was thoroughly exploded several years ago by McClintock and others.

Intravenous injection of serums is in

dicated wherever there is a necessity for prompt action, as in advanced and even apparently hopeless cases of diphtheria, in tetanus, and in septicaemias. With the convenience afforded by the ready-to-inject devices. of American serum establishments, direct intravenous injection is not especially difficult. The sterile needle with its rubber connection is inserted in the chosen vein (median cephalic or basilic preferably) rendered prominent by light bandage of the arm, and when the flow of blood announces the success of this maneuver the serum-containing syringe, with its contents heated to approximate the body temperature, is attached and the injection completed.

Rectal and Oral Administration.

Rectal administration of curative serums, especially those which are designed for use in chronic diseases, is gradually obtaining more extensive trial. Experimental investigations upon laboratory animals have given no definite information as to the possibility of obtaining through the rectum an absorption of the particular antibodies contained in the serum, indeed, my own tests in this direction indicate that antidiphtheric serum per rectum in dogs does not afford protection against diphtheria toxin subsequently injected through the skin. But on the other hand, competent clinicians in increasing number record beneficial effects where serums like the antistreptococcic are used per rectum in treating chronic streptococcus infections. Added to this testimony is the advantage that horse's serum by the rectum does not excite the more severe serum reactions observed in subcutaneous injection. The practice of using these rectal injections when the bowel has been emptied by a laxative and flushed, and of diluting the serum with two or more times its bulk of normal salt solution seems to me excellent.

It is not improbable that further clinical experience will confirm the claim of those whose habit it is to give curative serums by the mouth, especially under circumstances where subcutaneous injection is impossible or where no especial urgency exists. As an extreme exponent of this method of serum medication is Paton, who uses weak antidiphtheric serum per os in many kinds of infectious and other diseases irrespective of the offending microorganism; and who claims that beneficial results accrue from the increased tissue resistance and the leucocytosis provoked by antidiphtheric serum administered in teaspoonful doses at frequent intervals.

Hypersensibility to Serum.

The annoying reactions which follow the use of serums, and the happily rare accident of sudden death have been in

vestigated along new lines of late. I cannot do more on this occasion than to call attention to the exhaustive studies of v. Pirquet and Shick on the "serum disease" as they style the various sequels of serum injection, and of Rosenau and Anderson from the Hygienic Laboratory of the U. S. Public Health and Marine Hospital Service who have experimentally investigated the subject of hypersensibility to horse's serum in laboratory animals. But one conclusion must be impressed on practicing physicians namely, that serum reactions and accidents are due to the foreign serum itself and have no relation to the particular antibodies (antidiphtheric, antitetanic, etc.,) contained in the serum. Further, it has been shown that the "refined and concentrated" diphtheric antitoxin is quite as capable of arousing the peculiar reaction in guinea pigs as is the whole native horse's serum.

ARTICULAR

The theory that acute articular rheumatism is due to an excess of lactic or uric acid in the blood had to give way to the researches of bacteriologists. The disease is now regarded by authorities as belonging in the class of infectious diseases, since many indications strongly point to its being of microbic origin. The exact nature, of the microorganism has not been definitely determined, but that it, if there be a specific one, is a micrococcus is quite well established.

*Read before the Section on Medicine at the Jackson meeting of the Michigan State Medical Society, May 23-25. 1906,

Wasserman, Menzer, Malkoff, Westphal and Allaria believe the microörganism to be a streptococcus or a diplococcus. Poynton and Paine are of the opinion that it is a diplococcus, while Tribolet and Walker and Ryffel consider the bacterium which has been designated as the Micrococcus Rheumaticus, as the specific organism causing the disease.

Clinical experience teaches that a polyarthritis often follows tonsilitis, infected wounds, septicemia, boils, scarlet fever and other infectious diseases. This,

with the various bacteriologic findings, seems to indicate that the disease may be caused by a variety of microörganisms, probably all belonging to the same species.

The exact nature of the infection not having been definitely determined, the rationale of using streptolytic serum in rheumatism may be questioned. In this regard it is well to consider that nature's method seems to indicate that immune serums have a larger field of application than the specific infections caused by the organisms in their production.

O'Malley1 and Raynard2 report favorable results with antidiphtheric serum in treating pneumonia. Huber and Wolff report favorable results with the

serum in treating cerebrospinal meningitis. Lopez reports an extensive experience with marked beneficial results in treating "scarlet fever, tonsilitis, quinsy, etc.," with the same serum. Dr. Gottman, of Detroit, informs me that he has had four years' experience with the same serum in treating scarlet fever, usually with good results. I have repeatedly used antidiphtheric serum in scarlet fever and non-diphtheric throat infections for more than six years, with unquestionably good results. Ogli reports favorable results with an antistreptococcic serum in endocarditis. Dr. J. W. Foss in his report of mixed infection in tuberculosis treated with streptolytic serum says that "staphylococci disappear in almost the same ratio as streptococci." Others who have used streptolytic serum in mixed tuberculous infection have made the same observa

tion.

The practitioner is not so vitally concerned as to how these serums cure diseases; practical results are what he is primarily looking for. Acute articular rheumatism, like other infectious diseases, varies in severity in proportion to the resisting power of the individual and the virulence of the invading or

ganism, which produces mild types in some, and malignant types in others. When the mild types are met with it is often difficult to determine whether the inflammatory condition of the joints is caused by an infection or from other influences. For all practical purposes, however, we are safe in considering inflamed joints with a tendency of the inflammation to shift to other joints, associated with pain and fever, as being due to rheumatic infection.

Under the conventional treatment the results are not satisfactory. Clinicians differ in opinion as to the value of the salicylates, some ascribing specific action to them while others consider them merely sedatives, relieving pain. While a large majority of cases recover in from one to six weeks, the tendency to relapse is recognized. These relapses in many cases are so frequent and occur at such short intervals that the joints become enlarged and crippled from inflammatory deposits and adhesions, the condition becoming chronic. In other cases, the treatment is so inefficient that the inflammation in some of the involved joints lapses from the acute into the chronic state resulting in deformed, enlarged and painful joints. It is in preventing these relapses and prolonged cases, by instituting more efficient treatment in the acute stage, that the hope of avoiding cripples from rheumatism must be looked for.

These chronic cases are often erroneously diagnosed as "arthritis deformans," simply beause the joints become enlarged and deformed. In articular rheumatism, lapsing into the chronic state, the seat of the trouble is primarily in the soft parts, associated with swelling, effusion and adhesions extending into the bony structure, causing enlarged, deformed joints. In arthritis deformans the original seat of the trouble is the bony structure with a distinct persistent tendency of the bones to become en

larged and encroach upon the mobility of the joint, while the soft parts are not much involved. There is not much pain when the parts are at rest, and little or no fever is present. In chronic rheumatism the infection of the joint becomes chronic in the same manner as we have cases of chronic erysipelas and other intractable infections.

Heart infection, under the conventional treatment, is one of the most serious complications of acute articular rheumatism and unfortunately is quite frequent. From reliable statistics it appears that about one-third of the cases so treated are left with a crippled heart. In this regard the efficiency of the serum treatment is clearly shown. Of my 24 cases of acute rheumatic fever treated with streptolytic serum, but two developed heart complications. One oc

curred in a child two weeks after the joint infections subsided, which had yielded very promptly after two 10 c. cm. doses of the serum, each given hypodermically. Forty c. cm. of serum were given per rectum for the heart complication. The condition of the heart gradually improved, resulting in a good recovery. I feel certain that if more serum had been given at the start, the heart trouble would have been prevented.

The other case occurred in a boy, aged 16, subsequent to a slight relapse, which took place two weeks after recovery from the initial attack. There was no treatment given during this relapse, the inflammation subsiding spontaneously.

Examination of the heart at this time revealed nothing abnormal. The boy was not seen until some months after that, when the heart trouble was discovered. The heart infection probably developed from lingering germs after the relapse. If serum had been given at the time of the relapse this complication might have been avoided.

The length of time required to effect a recovery with the serum treatment

varies. In acute cases the earlier in the course of the disease the treatment is started, the better, corresponding in this regard with serum therapeutics in other diseases. When the treatment is started during the first or second day, recovery usually takes place in a few days-the disease is aborted. In cases of longer standing it will require from one to two weeks' treatment. Where the conventional treatment has been used for one or more weeks without improvement, the results from the use of the serum vary, some patients recovering very promptly, while others require from three to four weeks attention, but they always recover.

The treatment is usually started with an initial dose of 20 c. cm, of the serum followed with 10 c. cm. every day thereafter, until the inflammatory condition subsides. In severe cases, 20 c. cm. should be given every day. In cases where there is considerable elevation of temperature the serum is tolerated better than in mild cases. So more serum can be given without producing a disagreeable reaction. A good index as to the tolerance of the serum is the amount of local inflammation produced by the serum from the previous injection. If there is considerable inflammation and swelling at the site where the serum was injected the previous day, the indication is that the patient does not tolerate the serum well, and if the treatment is pushed, will develop a disagreeable urticaria. In these cases the serum should be given per rectum. I have had some experience with the rectal use of the serum and find it quite efficient, although not as positive as the subcutaneous method. In acute cases I have particularly noticed that when additional joints become involved after the treatment is started, the inflammation in these joints does not last long. In persistent cases the inflammation may start anew in joints that have recovered, but if so, it always subsides in a