Of the 145 positive cases only 26, or 18 per cent., gave symptoms or signs of syphilis. He does not state the nature of the antigens used, their degree of dilution, nor does he give the degree of intensity of the positive reactions. Of the 145 positive cases seen one to three months post partum, 115 remained positive; one former positive case was doubtful; six former doubtful cases were still doubtful; two former doubtful negative cases became doubtful, and one former negative case was positive.

A. M. Judd of New York found in a series of cases that primary cases of less than two weeks' duration are negative; of more than four weeks' duration positive in 75 per cent. of cases; that 90 per cent. of secondary cases with symptoms are positive; but that only 75 per cent. of the same type of cases without symptoms are positive; and that tertiary cases with or without symptoms show positive reactions in 75 per cent. of all tested. He also observes that lobar pneumonia frequently shows a positive Wassermann within a few days after the crisis; and that 20 per cent. of cases of malaria untreated and with pyrexia show a positive test. He makes no mention of post partum tests, however; and in fact, literature is very barren upon this phase of the subject. E. P. Davis calls attention also to the frequent occurrence of the positive phase of the Wassermann test in eclampsia and advanced toxemia of pregnancy. It may occur, also, he states, in cases where the general health may be otherwise seriously disturbed.

Of considerable interest in this connection and in contrast to literature on this subject (although the number of cases here mentioned are too few for any conclusions) are a few observations made at the Massachusetts Homœopathic Hospital, Robinson Memorial Department. The writer's attention was drawn to the occurrence of negative reactions three to twelve days post partum in all but one of nine cases who had shown one to three months ante partum three plus or four plus reactions, Going over the records of the other two services to October 1, 1916, the same change of reaction is noted in all but one of nine cases recorded, one other case positive ante partum not being tested post partum.

These observations with the others previously mentioned would seem to indicate that considerably more must be accomplished in the perfection of the Wassermann test in its application to pregnancy. Explanation of these variations have been numerous. The Wassermann test is fundamentally not a true antigen-antibody reaction. Probably the explanation lies in the well-known fact that all the ferments, especially the proteolytic ferments, are increased in both syphilis and pregnancy, and

that distinction at present may at times be difficult until more detailed work on the proteolytic ferments is accomplished.

In view of these facts, one naturally considers the question of the real importance of the Wassermann test in pregnancy, and also whether there may be at hand other practical means of diagnosis of syphilis; especially in the infant. Davis suggests that in the new-born the only truly reliable test is microscopic determination of the spirochete pallide in the blood from the umbilical vein and in the tissues about the cord. A Wassermann test of the blood from the umbilical vein is not only not conclusive but not even reliable. A microscopic examination is a comparatively simple procedure for the trained man and will decide many cases which might be in doubt clinically and serologically.

J. M. Slemons suggests another method which, although not always practical, is nevertheless of decided interest. He teases with dilute hydrochloric acid fresh chorionic villi, which show distinctly different histologic structure in the normal and in the syphilitic states. The villi of a luetic chorion appear abnormally large, opaque, and of irregular shape with swollen ends. The pathology is a proliferative inflammation of the blood vessels. If these villi be suspicious, a hardened and stained section of placenta must be studied and a Wassermann reaction in the blood determined. All should be done, he claims, in premature, macerated, or still-born infants. In his series of 390 cases he notes that a positive Wassermann finds corresponding specific changes in the villi in 95 per cent. of cases. The Wassermann reaction is therefore a test of very great auxiliary value, although it must be considered in the light of clinical evidence; and if doubt still exists, further tests must be summoned into service. A persistent strongly positive reaction means practically always syphilis, while a negative test does not rule out infection nor does it always indicate a cure of the disease previously existent. It must truly be said, however, that in spite of its limitations, syphilography without a Wassermann test would today be as medical diagnosis without a stethoscope or sphygmomanometer.

One cannot bear upon the subject of hereditary syphilis without recalling the so-called laws of Colles and Profeta, which may be stated briefly that when a mother gives birth to a syphilitic child the mother may suckle that child without being herself infected with syphilis, but that the child may give the disease to another; and that, if a mother who manifests symptoms of syphilis gives birth to a child which shows no taint, such a child is immune and may suckle the mother with impunity. In the light of modern investigation it is evident that

these theories are no longer tenable. The immunity of the mother in Colles' law and of the child in Profeta's law is only apparent. Neither can contract the disease because each already has it in latent form, by reason of the presence of syphilitic antigens in the blood of the child and similar antigens in the blood and breast-milk of the mother. From a sociological as well as a medical standpoint this is an item of importance that can not be overestimated.

SUMMARY

1. Syphilis is today a tremendously vital subject, both sociologically and medically, and one of the chief points of attacks in the expectant mother.

2. Latent syphilis is far more prevalent than we have had reason to suppose.

3. The Wassermann reaction, in spite of some limitations, is a very vital factor in determining syphilis on a large scale.

4. Considerable research remains to be carried out for the perfection of the Wassermann test in order to clarify some apparent discrepancies which now exist.

5. The laws of Colles and Profeta are no longer tenable in the light of modern knowledge.

6. For the benefit of society as a whole, as well as the patients themselves, every possible step should be taken to determine the presence or absence of syphilis in the pregnant woman, especially in the case clinically suspicious, and in all cases of premature, macerated, or still-born children.

54 Huntley Road.

BIBLIOGRAPHY

1. Syphilis in the mother and infant. Bulletin of the Lying-in Hospital of New York, x, 243.

2. Fullerton, E. U.: Significance of syphilis in obstetrics. Obstet., lxxiv, 23.

Am. Jour.

3. Commiskey, L. J. J.: A preliminary report of the routine Wassermann reaction in hospital obstetrics. Am. Jour. Obstet., lxxiii, 676.

4. Judd, A. M.: Wassermann reaction in pregnancy. Am. Jour. Med. Sc., cli, 836.

5. Davis, E. P.: Syphilis in relation to obstetrics. Am. Jour. Obstet., Ixxiii, 769.

6. Slemons, J. M.: Syphilis and obstetrics. Med. Record, xcii, 16.

TOXICITY OF SALVARSAN (ARSPHENAMIN) SUBSTITUTES

HELMUTH ULRICH, M.D., Boston, Mass.

The supply in this country of the original salvarsan and neo-salvarsan was exhausted soon after the beginning of the war. This shortage was temporarily relieved by a special shipment of accumulated stock from Holland and later by the arrival of a certain quantity of the drug on the merchant submarine Deutschland. There has been, however, no original salvarsan available for many months, at least not in the open market.

Substitutes began to make their appearance very early; among the first to be sold extensively in this country was a product labeled diarsenol, manufactured by the Synthetic Drug Company of Toronto, Canada. My early experience with this product was not particularly fortunate, many of the cases to whom it was given showing rather severe toxic reactions, both immediate and late. Flushing of face and rapid pulse, followed by fallor, very weak or imperceptible pulse, faintness or actual loss of consciousness with muscular twitchings, were among the symptoms developing immediately after or even during the drug infusion; the later attacks, occurring usually a few hours afterward, were chiefly gastro-intestinal: nausea, vomiting, abdominal pain, diarrhoea. Published reports showed that others had similar experiences. I discontinued using diarsenol because of this evidence of its toxicity, but later tried it again and have used it occasionally for several months with no or occasionally but slight disturbance. With neo-diarsenol, put upon the market later by the same firm as a substitute for neo-salvarsan, I have had no experience, but toxic effects have been reported.

The first salvarsan substitute made in the United States was produced at the Dermatological Research Laboratories in Philadelphia under an agreement with the American branch of Farbwerke-Hoechst Co., when the supply of salvarsan was used. up. This product bears the name arseno-benzol. It was withdrawn from the market when salvarsan became again temporarily purchasable, but is now once more being sold. The technic of its preparation for infusion differs slightly from that used with salvarsan. I have found arseno-benzol very satisfactory, both as to results obtained and the minimum toxicity displayed by it.

Quite recently another American-made substitute was offered for sale. This is manufactured by Farbwerke-Hoechst Co. of New York, the distributing house of the original salvarsan. They claim that this product, for which the name salvarsan has

been retained, is manufactured in accordance with instructions received at the parent firm in Hoechst a.M., and that it is, therefore, identical with original salvarsan. A shipment of this drug received by me recently contained 0.4 g. ampuls, lot DJB, and 0.3 g. ampuls, lot B X B. The contents of several

of these ampuls caused most alarming immediate reactions: extreme pallor, perspiration, thready or imperceptible pulse; twice unconsciousness with muscular twitchings and tonic spasm; in one case involuntary urination; and in another case loss of memory and mild delirium lasting twenty-four hours.

The attacks usually began during the infusion and lasted but a few minutes. Late gastro-intestinal symptoms sometimes appeared, but these were mild and resembled those produced at times by other substitutes and by salvarsan itself. Subsequent infusions of arseno-benzol or diarsenol given to these patients had no unusual toxic effects.

Not all of the ampuls of this shipment caused such severe reactions; several of the infusions were followed by no symp