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Obstipation---Stasis---Autotoxemia

claims victims by the score.

INTEROL SECURES RESULTS IN HANDS THAT

KNOW HOW-AND WHEN–TO USE INTEROL

Obtainable of your druggist.

Booklet on request.

VAN HORN and SAW TELL

15 and 17 East 40th Street

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THE RESULTS OBTAINED WITH

WITH SALVARSAN INTRAVENOUSLY AND WITH AUTO-SALVARSANIZED SERUM INTRASPINOUSLY IN TREATMENT OF SYPHILIS OF THE CENTRAL NERVOUS SYSTEM

By RICHARD DEXTER, M. D. The treatment of syphilis in general and of syphilis of the central nervous system in particular, has undergone marked and radical changes in the past five years. These changes depend for their being upon the epoch-making discoveries of Schaudinn, Wassermann and Ehrlich, together with a host of other workers, too numerous to mention, who have each contributed some part to our ever-increasing knowledge of the disease processes of syphilis. The introduction of Ehrlich's salvarsan opened a new field in the treatment of syphilis. The early results were in many instances unsatisfactory, but today we can frankly state that this drug has been a tremendous addition to the efficient treatment of the disease.

Among the most important changes in our viewpoint in regard to syphilis has been the new and now well-substantiated conception of the so-called parasyphilitic condition. Previous to the discovery of the spirocheta pallida by Schaudinn, tabes dorsalis and general paresis were considered to take their origin from the injuries of a pre-existing and long dead syphilis. The idea that they were due to the presence of an actual living organism and that they were simply a part of the active disease process of syphilis, was never generally admitted. The intensive study of the activities of the spirocheta pallida in the body which has taken up so great a part of the medical advance during the past 15 years has shown us, beyond peradventure of a doubt, that there is no parasyphilis, that each involvement of the nervous system by the spirocheta pallida is but another manifestation of the disease process of syphilis, and as such may be amenable to antisyphilitic treatment to a greater or less degree.

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We wish to discuss certain aspects of the treatment of syphilis of the central nervous system and to cite cases from our own experience. The conclusion that the pathological conditions involving the central nervous system were parasyphilitic and therefore beyond the reach of therapy, was based upon two observations: first, that in almost all cases history or physical examination pointed to a syphilitic infection which was no longer active, and, second, that under the old methods of treatment little benefit was to be expected from antiluetic treatment. Occasional cases of early and stormy involvement improved under mercury and the iodides, but tabes dorsalis and general paresis were usually unaffected by all forms of therapy. Our present knowledge of the protective and selective action of the structures which guard the central nervous system will explain this observation. It is known that very few drugs are excreted into the cerebro-spinal fluid, and it is probable that the mechanism which gives rise to the cerebrospinal fluid exerts an actual selective action for substances circulating in the blood stream. Therefore, lesions which are situated within reach of the blood strea'n may be affected by drugs which are carried to them by this route, but as far as the meninges and their adjacent structures are concerned, therapy which depends upon the blood stream for its distribution is notably inefficient. The work of Flexner on epidermic cerebrospinal meningitis, the various studies on the excretion of drugs and dyes into the cerebrospinal fluid, and more recently the work of Adler, Swift, Hallo and others on the excretion of arsenic into the subarachnoid space, all go to substantiate the fact that but very few drugs are excreted into the subarachnoid space.

Previous to 1912 the introduction of salvarsan or neosalvarsan directly into the subarachnoid space had been attempted by Marinesco* and others without any noteworthy results, except those of meningeal irritation. In 1912 Swift and Ellis described a method whereby arsenic in the form of salvarsan might be brought into close contact with the meninges, without danger to the patient. Their technic is briefly as follows: 50 c.c. of blood is removed with aseptic precaution from the arm vein of a patient who has received salvarsan one-half hour previously. The serum is separated from the clot by a rapid centrifugalization. The serum is pipetted off the clot, care being exerted to leave no red cells or fibrin in the serum. This serum is then diluted to either

а

40 per cent, 50 per cent or 60 per cent with sterile normal salt solution and treated in a water bath at 56° C. for one-half hour. It is usually planned to have from 25 cc. to 30 cc. of the serumsalt mixture. Lumbar puncture is performed after the method described in the preceding paper of my co-worker, Doctor Cummer, and 15 cc. of spinal fluid are drawn off. The serum-salt mixture is then introduced into the subarachnoid space. The barrel of a 20 cc. Luer syringe fitted with rubber tubing and a slip joint is used for a funnel through which the fluid is introduced. The serum is allowed to flow into the subarachnoid space by gravity. The patient lies with the foot of the bed elevated for 3 or 4 hours, and is required to stay in bed for at least 24 hours from the time of intraspinal injection.

Other methods for the introduction of salvarsan and neosalvarsan into the spinal fluid have been suggested, notably the method of Ravaut," and Udo J. Wile's' modification of this procedure. By this method small doses of neosalvarsan were introduced into the subarachnoid space, either dissolved in spinal fluid or in a solution isotonic with the spinal fluid. While the therapeutic effect of this method has been satisfactory enough, the procedure is frequently accomplished by very marked signs of irritation of the spinal cord, referred to the region of bladder and rectal control. For this reason the method has never come into general use.

The method described by Ogilvie is an attempt to reproduce the chain of events in the Swift-Ellis method in vitro instead of in vivo. The blood is obtained by venipuncture and separated in the usual way. Minute doses of salvarsan, ranging between a quarter and a half milligram, are added to the serum. This serum-salvarsan mixture is allowed to incubate at body temperature for one-half hour. The serum is then treated exactly like the autosalvarsanized serum and injected in the same manner. Those who have used the Ogilvie technic claim excellent results for it. Though it has been found to be, on the whole, somewhat more irritating than the original Swift-Ellis niethod, it is claimed that more accurate dosage can be obtained, and this is undoubtedly true. Draper' has found that it is not possible to give more than four doses of serum prepared in this manner without producing irritative symptoms. On the other hand, by using the Swift-Ellis technic the patient not only receives the intraspinal treatment but has the added advantage of the intravenous injec

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