From the arsenic treatment of chorea, G. M. Swift has seen the following: hemorrhage from stomach, hemorrhage from kidneys, conjunctivitis, neuritis, serious anemia, and tedious gastrointestinal inflammation with albumin in the urine. Similar reports have come from others from the use of arsenic in chorea, pernicious anemia, etc. Oliver reports brown pigmentation in children treated for chorea. Heffter asserts that in cases of chronic poisoning arsenic is always to be found in the hair.

Death has occurred from 1 grain of arsenic trioxide (Kun-kel) and from 1/2 ounce of Fowler's solution administered in a period of four days (Taylor).

In the medicinal use of arsenic, the first indications of cumulative poisoning are usually puffiness under the eyes, nausea, diarrhea, abdominal cramps, headache, and coryza.

The treatment of chronic poisoning is stoppage of the drug or removal of the patient from the arsenic-bearing substances, and attention to the general health. Potassium iodide is often given, but Oliver says that iodide increases the pigmentation of the skin, and does not promote the elimination of the drug.

Therapeutics

Locally

Arsenic trioxide is employed in the form of a paste as a caustic for lupus and superficial epitheliomata; it is very slow in action and very painful. It is used by dentists to destroy the nerves of teeth by setting up in them an inflammatory reaction.

Internally, arsenic preparations are used: (1) In diseases of the blood or blood-making organs, as chlorosis, pernicious anemia, leukemia, Hodgkin's disease, chronic malaria. (2) In certain bone and joint diseases of obscure origin, as chronic rheumatism, rheumatoid arthritis, osteitis deformans, osteomalacia, and rickets. (3) In nervous conditions, as chorea, hay-fever, and spasmodic asthma. Swift says it does more harm than good in chorea. (4) In chronic non-parasitic skin diseases (not in acute inflammatory skin diseases). (5) In any run-down conditions with anemia and poor nutrition. Von Noorden and others have found arsenic preparations useless in diabetes, though Salkowski reported that in animals poisoned by arsenic no artificial diabetes could be produced by puncture of the fourth ventricle or by curare. Arkin and Korper (1916) state that arsenic has no specific action in tuberculosis.

The organic preparations have been employed in trypanosomiasis, Vincent's angina, relapsing fever, syphilis, leprosy, pellagra, malaria, splenic anemia, leukemia, etc., with varying results. It is claimed that arseno-phenyl-glycin is the best in trypanosomiasis (Wendelstadt, Roehl). Atoxyl has a very strong tendency to produce optic nerve atrophy and permanent blindness.

Administration

Arsenic trioxide is generally used with iron or strychnine in pills or as an elixir. Fowler's solution is mostly employed by itself in doses by drops, one drop from a bottle lip or standard dropper being practically one minim. Through some fallacy it has become customary to begin with a small dose, say three drops three times a day, and to increase the dose each day by a drop or two until the patient shows the first signs of cumulative poisoning. But the harmful metabolic effects of the drug contraindicate such a method of administration; and there are numerous instances of neuritis and other toxic manifestations which bear witness to the inadvisability of giving this drug to its physiologic limit.

Salvarsan And Neosalvarsan

In syphilis these are the remedies of choice, the dose being regularly followed by a prompt subsidence of any acute manifestations of the disease. Yet in most cases they are not completely curative and must be alternated or combined with the mercury treatment. Not only do they act in the primary and secondary stages, but according to Fordyce "in all the active manifestations of late syphilis the therapeutic effect is almost as intense as in the early contagious period." Neosalvarsan is more easily administered and less irritating to the veins, but it is less efficient than salvarsan. Fox states that while the symptomatic value of neosalvarsan is only slightly less than that of salvarsan, its total value, estimated serologically, is considerably less. Adler has shown that after intravenous doses of salvarsan, arsenic is present in the blood usually for thirty-six to forty-eight hours and occasionally for many days, and Stuhmer's experiments demonstrate that the greater part of the salvarsan becomes stored in lungs, liver, and spleen, and that from these depots it is doled out again to the blood. The arsenic is excreted by the kidneys and intestines.

These drugs are regularly administered intravenously, the dose of neosalvarsan being one and one-half times that of salvar-san. The subcutaneous and intramuscular routes have practically been abandoned for salvarsan because of its destructive action on the tissues; but for neosalvarsan they are still employed, and there are a number of reports from army surgeons in Europe of excellent immediate therapeutic effects thus obtained.

In cerebrospinal syphilis, and to a less extent in locomotor ataxia and general paresis, additional clinical improvement has followed the intraspinous use of salvarsanized serum. This method, introduced by Robertson of Edinburgh, has been brought into general clinical use by Swift, Ellis, and Draper. These investigators all now advocate fortifying by a minute amount of added salvarsan. The method given by Draper is as follows: At weekly intervals 0.3-0.6 gm. of salvarsan is given intravenously, and followed forty minutes later by the withdrawal of about 50 c.c. of blood. This is centrifuged, and the serum after heating at 560 C. for thirty minutes is introduced into the spinal canal the same day. The dose is 20 to 25 c.c. of 100 per cent. serum or 30 c.c. of 50 per cent. serum. Salvarsan up to 0.0005 gm. may be added in vitro before the injection, or may be added to serum obtained from blood withdrawn before the intravenous administration of the drug. Though several authors have claimed that quite as much arsenic reaches the spinal canal after simple intravenous administration, the researches of Camp, Hall, and others would suggest that this is not the case. In 17 cases Camp administered 0.6 gm. of salvarsan intravenously, and on testing the spinal fluid fifteen minutes to forty hours later found arsenic present in only one case. Hall at twenty-four hours found arsenic present in the spinal fluid in 2 cases and absent in 4, and after neosalvarsan found arsenic absent at one and a half, six, and twenty-four hours. On the other hand, it is to be noted that the arsenic readily disappears from the spinal fluid, for after intraspinal injections of 3 mg. of neosalvarsan in simple solution only 4 out of 7 spinal fluids showed arsenic at ten hours, and only 1 out of 10 at twenty-four hours (Hall). The method of administering neosalvarsan intraspinally in simple solution mixed with cerebrospinal fluid is not approved, as it has been the cause of a number of deaths and of paralysis of the lower limbs, probably because the amount employed has been too large or the dilution insufficient.