HEMOLYTIC ACTIVITY OF SOLUTIONS OF ARSPHENAMIN AND NEO-ARSPHENAMIN
Journal of the American Medical Association
Several years ago, Peabody12 stated that the develop¬ ment of acidosis bears little relation to the accumula¬ tion of nonprotein nitrogen in the blood or to the phenolsulphonephthalein output, although he pointed out that in the terminal stages of uremia there may be a high grade acidosis. Our experience likewise leads us to believe that there are many cases of nephritis with considerable nitrogen retention that show little acidosis ; but this certainly is not true of the more advanced cases.
... e advanced cases. From the data reported in Table 1 , it would appear that all fatal cases of chronic nephritis with marked nitrogen retention show a severe acidosis, sufficient in some instances to be the actual cause of death. What part acidosis plays in the clinical symptoms of so-called uremia is difficult to answer. Patients with pronounced acidosis present a somewhat different clin¬ ical picture ; but until we possess additional informa¬ tion regarding the cause of uremie symptoms, whether they are due to a toxic base such as methylguanidin, to a deficiency in calcium, or to something else, it will not be possible to clear up this problem satisfactorily. Palmer and Henderson, Sellards, Peabody and Whit¬ ney, in the papers previously referred to, have given illuminating discussions of the acidosis problem in nephritis. So far as the acidosis goes, it is now possi¬ ble to obtain very reliable information from the carbon dioxid combining power of the blood plasma with the relatively simple Van Slyke method ; and furthermore, the administration of alkali can be particularly well controlled with this method. Acidosis is a fairly prominent feature of many cases of acute nephritis, and is present in severe form in all terminal cases with marked nitrogen retention. CONCLUSIONS All fatal cases of chronic nephritis with marked nitrogen retention show a severe acidosis, sufficient in many instances to be the actual cause of death. In some cases of acute nephritis and acute exacerba¬ tion of chronic nephritis the distress is apparently due to the acidosis, since the judicious use of sodium bicarbonate results in general clinical improvement. With the rise in the carbon dioxid combining power of the blood, the dyspnea and hyperpnea disappear. 12. Peabody, F. W.: Clinical Studies on the Respiration, II, The Acidosis of Chronic Nephritis, Arch. Int. Med. 16:955 (Dec.) 1915. Child Surveys.-The need for surveys to reveal exactly what a child ought to have in order to be properly reared and what his chances are for getting it under present conditions is one of the topics emphasized in the seventh annual report of the chief of the Children's Bureau of the U. S. Department of Labor. Special investigations made by the Children's Bureau in three American cities show how babies have suffered as a result of the advance in the price of milk. In Baltimore, of 728 children between 2 and 7 years of age, only 29 per cent, are now having fresh milk to drink, as against 60 per cent, a year ago; in Washington, half of those between 2 and 7 years visited by the public health nurses were receiv¬ ing no fresh milk to drink; and in New Orleans conditions were even worse. Studies of the type recommended by the chief of the Children's Bureau would seek to determine all a child's needs. They would be based on actual living con¬ ditions in various types of communities; and would accord¬ ingly have a practical and not merely a theoretical value. Through them mothers would obtain an authoritative state¬ ment concerning the basic needs of growing children, and communities would be given an insight into the way in which those needs may be met. In the preparation of solutions of arsphenamin and neo-arsphenamin for administration by intravenous injection, sterile freshly distilled water or saline solutions (generally 0.4 per cent. sodium chlorid in distilled water) are commonly employed as solvents ; the solution of arsphenamin so prepared is acid and highly toxic and requires neutralization with an alkali before administration, 15 per cent. solution of sodium hydroxid being commonly used for this purpose. On the addition of sodium hydroxid, the solution becomes very turbid, owing to the precipitation of the insoluble base of arsphenamin ; with the further addition of alkali, the solution is neutralized and "clears," with the formation of the soluble monosodium salt. The addition of still more alkali to this clear solution (usually one third of the amount required for neutralization and clearing) results in the hydrogen atoms of both hydroxyls becoming replaced with sodium, and the production of a disodium salt of arsphenamin. Ehrlich originally advised the administration of the monosodium salt (solutions neutralized with sodium hydroxid just to the point of neutralization and clearing), but recently the tendency has been to add a little excess of alkali with the production or partial production of the diso¬ dium salt, which has been regarded as somewhat less toxic. Solutions of neo-arsphenamin, being neutral, do not require the addition of alkali. While the causes and nature of the reactions fol-loAving the intravenous injection of arsphenamin and neo-arsphenamin are not as yet definitely known, one of us (Kolmer) with Schamberg, Raiziss and Weiss1 has recently shown that solutions of arsphenamin in water possess hemolytic properties, and that this factor may exert some influence in the pathogenesis of the untoward symptoms following intravenous injections of arsphenamin. Solutions of neo-arsphenamin were reported as being practically devoid of hemolytic properties. HEMOLYTIC ACTIVITY OF ARSPHENAMIN The hemolytic activity of solutions of arsphenamin in water may be ascribe 1 to three factors, namely, ( 1 ) the direct hemolytic activity of arsphenamin ; (2) the hemolytic activity of nonisotonic solvents (water or hypotonie saline solutions), and (3) the hemolytic activity of sodium hydroxid, especially when used in excess for the production of the disodium salt. When arsphenamin is dissolved in water and the solution is neutralized with sodium hydroxid, some sodium chlorid is produced but never enough to render the solution isotonic; 0.1 gm. of arsphenamin dissolved in water and neutralized with sufficient sodium hydroxid to produce the monosodium or disodium salt yields about 0.0247 gm. of sodium chlorid. For the From the Dermatological Research Laboratories.