The estimation of urea and other constituents of the urine furnishes important evidence as to the influence of arsenic upon general nutrition and tissue-change, for it is clear that if the principal urinary ingredients are increased under its use, tissue-changes must be going on rapidly, and vice versa. There has been some contradiction between observers on these points. Sabelin recorded increased excretion of urea under arsenic (from 12 to 28 gr.); also marked increase in the chlorides and earthy phosphates, and proportionate diminution of uric acid - an incompletely oxidized product (hence G. See argued that the drug favored oxidation and promoted metamorphosis ("Nouv. Diet.," Art. Asthme) - he has, however, himself since withdrawn these views). Fokker published two analyses showing a slight increase of urea after 0.01-gramme doses (Schmidt's Jahrb., Bd. clviii.), and Gaeth-gens recorded the same in two dogs taking soda arseniate; also decidedly increased tissue-change under toxic doses (Centrulblatt fur Med., 1875, No. 32, s. 529, and 1876, No. 47, s. 833). Binz and Schulz, relying upon these observations, and noting also that hypodermic injection of arseni-ous acid did not produce a local caustic effect but inflammation in distant organs - e.g., the stomach - have recently argued that "this substance, in contact with living protoplasm, acts in the tissues as an oxidizing agent or carrier from one albuminous molecule to another, being converted during this process into arsenic acid, then reduced, again oxidized, and again reduced" (Centralblatt fur Med., ii., 1879; Medical Times, i., 1879). But I think the evidence insufficient for the conclusion, and all observations upon fasting animals are open to the fallacy that urea may be increased by the fasting, and consequent absorption of fat (Forster: Zeitschrift fur Biol-ogie, xi., s. 522). The dogs utilized by Gaethgens were kept many days on water only, and a careful examination of the whole question leads to the conclusion that the "tissue-change of inanition" is almost surely the explanation of what he attributed to arsenic (F. A. Falck: Archiv fur Exper. Path., August, 1877, Bd. vii.). Von Bock attributed any change he could observe to the effect of fasting (Zeitschrift fur Biologic, vii., s. 418-432), and held that arsenic acid in ordinary doses exerted no essential influence on tissue-change.

Others have concluded positively that it lessens excretion and change. Thus Lolliot, in a careful thesis, records many observations and analyses, from which he makes evident a diminution of urea and carbonic acid under arsenic; he asserts, also, that it lowers temperature, and is a "medicament d'epargne" - it lessens the activity both of nutrition and denutri-tion ("Etude Physiol. de l'Arsenic," Paris, 1868). Kohler classes it with tea, coffee, cocoa, as "sparmittel" - diminishing oxidation processes

(Handbuch der Physiol. Therapeutik, 1876). In recent experiments by Dr. Tamassia (Pavia), toxic doses of white arsenic given to animals, progressively lowered temperature up to, and after death (Medical Record, January, 1878). Animals accustomed to an arsenical ration became py-rexial and emaciated on its withdrawal, implying that some moderating power had been removed. There is still, however, a discrepancy in the observations on temperature; Harless reported a slight rise from small doses, and Billroth, gradually increasing the dose to 40 min. daily in a case of asthma, reported a febrile access in the evenings up to 101° F. (Wiener Woch., 1871, No. 44).

Schmidt and Brettschneider found the excretion of urea and of carbonic acid under arsenic diminished 20 to 40 per cent.; phosphates also diminished. Schmidt and Sttirzwage likewise report diminution of carbonic acid and urea in rabbits under minute doses (Schmidt's Jahrb., Bd. clviii., pp. 13-15), and Rabuteau states that the elimination of urea in a dog was lessened for three weeks after a few doses of arsenious acid, at one time as much as 60 per cent.; he attributes its effect in lessening tissue-change to an action on the blood-corpuscles.

I conclude that although some contradiction exists on this point between good authorities, yet the balance of recent evidence points to lessened excretion, and consequently to lessened tissue-change as an effect of arsenic.

Acute And Chronic Poisoning

Although not here concerned with cases of poisoning further than as they illustrate physiological action, we may note that if death occurs from large doses of several drachms, and in the course of a few hours, it is generally from cardiac palsy, and is preceded by excessive prostration and fainting. If 1 or 2 dr. have been taken, and the patient survives two or three days, the symptoms will be mainly those of severe gastric and intestinal inflammation, as already described, and the post-mortem appearances will correspond; while with doses of 2 to 10 gr., when the patient survives much longer, and yet dies ultimately from the effects, these will be evidenced rather in the nervous system (Hunt). If the poisoning be very chronic, and result from continued doses of 1/8 to 1/4 gr., a general irritation of the system is apparent from the symptoms of erethism or pyrexia with chills, redness of eyes and of orifices of nose and anus, vesication on palms and soles, with dryness of skin and brownish spots, pain in head and joints and abdomen, with vomiting, purging, and gradual marasmus. The soreness of mouth and salivation have sometimes suggested mercury as the poisonous agent, and sometimes the general condition has been mistaken for phthisis, or for typhoid. Gaethgens further suggests points of resemblance with diabetes and with phosphorus-poisoning (Centralblatt fur Med., 1875, Bd. xiii., p. 32, Abstract in Schmidt, 1876). An instructive case which, for a time, completely deceived the medical attendants, and yet which reveals exactly the physiological action of arsenic as we have described it -including renal and nerve-symptoms - is that of Mrs. Wooller as collated by Sir R. Christison (Edinburgh Medical Journal, 1855).