paper is illustrated by many figures showing an interruption in the development and the failure in many places of the union of the two systems. An extraordinary feature is that they may remain stationary for years, and then somewhat rapidly increase in size. This has been the case with two patients I have studied, and Dr. Alfred King, of Portland, Maine, noted within three years rapid growth. They may remain of very moderate size until middle life. The condition is consistent with robust health for many years.

Early and common symptoms are pain and hemorrhage, which lead to the diagnosis of stone. Hæmaturia may be a predominant feature for years, and it has to be borne in mind that this is one of the causes of obscure recurring hemorrhage. In 1907 I saw a lady, aged 60, who had led a life of unusual physical vigor. From childhood she had had at intervals hæmaturia, for which she had consulted numerous physicians on the continent and in this country. She had many letters about her case, in which she herself took a very intelligent interest. The bleeding had recurred at intervals of about eight months. She did not think that from her girlhood she had ever passed six months without an attack. One of her physiciansI suspect Sir William Gull-told her not to bother as it was of no more moment than nose-bleeding. I could not get from her that he used the term renal epistaxis, which has been attributed to him. When I saw her the diagnosis was simple enough-enormous bilateral tumors, with irregular surfaces, sclerotic arteries, colossal heart, with apex beat in the axilla, low specific gravity of the urine, and oncoming uræmia, of which a few weeks later she died.

Hæmaturia has been present in five out of the six cases in adults of which I have notes. The urine usually presents the features characteristic of chronic interstitial nephritis-constant low specific gravity, with a slight trace of albumin, hyaline tube casts, and there may be constantly a small number of red blood-corpuscles. Associated with these are the usual cardiovascular changes of chronic nephritis sclerotic arteries, high tension, except in the last stages, and hypertrophy of the heart. These features have been well marked in four of the six cases. In one, as I have already mentioned, the enlargement of the heart was enormous. I do not know that I have ever felt an apex beat so powerful or so far to the left. On the other

hand, in the cases at present under observation, the cardiovascular changes are not marked, and at post-mortem in the first case the heart was not at all enlarged.

The physical signs are distinctive. No other condition gives the same picture of bilaterally enlarged kidneys with numerous elevated projections, and usually one kidney is much larger than the other. Occasionally, when unilateral, it would be difficult to distinguish the condition from hydronephrosis. In the second case the passage of calculi would suggest an ordinary hydronephrosis, but I do not think it at all likely, as the urine is clear, except during the spells of hæmaturia, and she has never passed pus. The type of dendritic calculus may be associated with progressive increase in the size of the kidneys and a gradual onset of chronic interstitial nephritis, with sclerotic arteries and enlarged heart. There may be no colic, extraordinarily little pyelitis, and progressive hydronephrosis may follow. In such cases the tumors are not very large, and I think it much more likely that this patient has bilateral cystic kidneys complicated with calculi.

When affecting one kidney the tumor has been mistaken for an ovarian. In rare instances, as I have already mentioned, it is unilateral, but, as a rule, both kidneys are involved, so that removal of one deprives the patient of so much valuable secreting tissue. A fatal uræmia has followed the removal of the larger of two cystic kidneys, so that surgeons now make it a rule to examine both organs before attempting to remove one.

PISO and Marcgraf,1 in their work on the natural history of Brazil (Amsterdam, 1648), first described the ipecacuanha plant as a remedy for dysentery. A little later it came into use in Europe under the title "Radix Antidysenterica." 2 Helvetius cured the Dauphin with a secret preparation composed mostly of ipecac,3 and the French Government bought the remedy and made it public in 1688. For the next two centuries ipecac was alternately praised and condemned in the treatment of dysentery, the favor in which it was held depending probably whether it was used in the amabic or in the bacillary type. In the last few years Manson in England, Rogers in India, and Brem in Panama have again firmly established its popularity in the treatment of amoebic dysentery.

Pelletier, in 1817, extracted an active principle from powdered ipecac which he named emetine, and with Magendie recommended its use instead of the crude drug. In 1829 Lomax Bardsley used emetine successfully in dysentery, and in 1891 Tull Walsh 5 used emetine combined with mercuric iodide, reporting 34 cases. However, as Douglas says, this knowledge passed from the ken of medical men, and it was only after amoebic dysentery had been singled out as a distinct disease and had been put on a sound etiological basis by the work of Schaudinn, Viereck, and others that Vedder undertook to investigate the effect of ipecac and emetine on amabæ. Vedder, in 1911, showed that emetine would kill amœbæ in cultures in dilutions of 1 to 50,000 up to 1 to 200,000. Rogers, after seeing Vedder's work, applied it clinically by injecting emetine hydro

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chloride subcutaneously, and in June, 1912, announced his first results. In the two and a half years that have since elapsed numerous reports have testified to the correctness of Rogers's first impression, that emetine is practically a specific against the pathogenic entamoeba. (Walker has shown there is only one.)

II. COMPOSITION OF EMETINE

The alkaloid first isolated by Pelletier was, according to Low," an extract composed of mixed alkaloids, and he therefore designates the pure alkaloid as emetina. Lyons 10 warns that emetin, a resinoid, is also on the market. The United States Dispensatory says that emetine is an amorphous, white powder forming crystalline salts with the halogens and with nitric acid. The hydrochloride is the salt ordinarily used, as it is the most easily soluble, requiring about 1 Cc. of water to dissolve 1 gr.

The formula of emetine hydrochloride is variously given by different authors, most of them referring to the work of Paul and Crownley.11 Merck, 12 who makes his emetine according to Paul, advertises the formula C30H44N2O4: 2HC1: 2H2O, containing 92 per cent. of the anhydrous salt.

III. METHODS OF ADMINISTRATION

Most workers have followed Rogers in using the drug subcutaneously, and this is undoubtedly the simplest and most satisfactory method. However, in very urgent cases, Rogers 13 has given it intravenously in 12- and 1-gr. doses, dissolved in 5 Cc. normal salt, with good results. Baermann and Heinemann 14 recommend that treatment be started with either subcutaneous or intravenous injections, and place the maximum dose to be given intravenously at 150 mg. per 60 kg. body weight, reporting alarming symptoms when larger doses were used. Rogers himself,15 reporting on the toxicity of emetine, shows that in the rabbit the equivalent of 10 grs. per 70 kg. body weight, when injected subcutaneously, gave no symptoms, but that 4 grs. per 70 kg. body weight intravenously caused death within one minute. It would hardly seem probably that the advantage of giving emetine intravenously could compensate for the added risk.

Emetine has been frequently tried out by mouth, and keratincoated tabloids are on the market. Unfortunately, emetine retains in some degree the local action of crude ipecac, and, according to both Low and Keng,16 the tabloids cause vomiting, while Rogers says emetine should never be used orally in serious cases. reports the death of a six-year-old child, presumably from emetine, after 14 gr. by mouth.

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Le Blanc 18 has used emetine successfully both by mouth and by colonic irrigations with one quart of 1 to 10,000 to 1 to 5000 solution. Bizard 19 also has used rectal irrigations of 1/5 gr. in 100 Cc. normal salt in a 23-months-old child, but Thiroux, in discussing the case, quotes Chauffard as having seen emetine irrigations following subcutaneous injections cause flux. Guillemet 20 and Seguin 21 each reports a case treated by hypos and irrigations of emetine.

IV. DOSAGE

Rogers recommends that in adults 1 gr. be given every 24 hours for three or four days. In 500 cases tabulated from the literature with respect to the amount given in 24 hours, it was found that 234 received from 1 to 1 gr., and 266 from 1 to 2 grs.; but it is impossible to tell from these clinical reports whether the larger doses were any more effective than the smaller ones.

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Orticoni 22 gave a case 2.5-gr. doses during a relapse after treatment with smaller doses, and it again cleared up. Maurras and Hervier 23 gave single daily injections of 2.5 grs. to a case that was later discharged clinically well. I gave repeated 2.5-gr. doses to a woman who has remained clinically well for 15 months. In another case who relapsed three months after 2-gr. doses I repeated the treatment with 2- and 3-gr. doses, and he has remained well for 12 months. In three patients Baermann and Heinemann gave single intravenous injections of 3, 4, 5, and 6 grs., respectively. The first case was amoeba-free at autopsy, 17 days later. The other two recovered clinically, becoming carriers, but the cysts from these two cases failed to infect kittens. I have given 4-gr. subcutaneous injections in three cases; in the first case the dose had been increased to 2.4 grs. without effect, and the 4-gr. dose cleared up the symptoms and stools for the first time in months, but within ten days the case relapsed and daily 4-gr. doses of emetine combined with 30 grs. of ipecac by mouth