failed to have any further effect on either symptoms or amabæ. In the other two cases single 4-gr. doses were given during treatment, and in one ipecac by mouth had to be given to rid the stools of amœbæ.2

24

Baermann and Heinemann set 3.75 grs. as the maximum dose, and say that larger doses do not seem to be any more efficacious than 3-gr. doses. Carter 25 recommends 1/2-gr. doses, and states that small doses, as 1% gr., give the entamæbe a chance to become immune. Archibald 26 also mentions the possibility of making amœbæ emetinefast by small doses. With the same idea, I last year recommended 2- to 3-gr. doses as a routine, as advocated by James 27 in Panama, who gives 2- to 4.5-gr. doses daily. I have seen entamabæ disappear under this dosage, when smaller doses had had no effect. The only two cases I have seen so far which were absolutely refractory to emetine were both originally treated with ipecac by mouth (a most uncertain method, so far as dosage goes), and had possibly become immune to the drug.

However, the apparent advantage of large daily doses may be fallacious, as time seems to be a necessary factor in the action of emetine on amabæ. Wherry 28 showed that emetine would kill cultural amœbæ in dilutions up to 1 to 200,000 in 23 hours, while 1 to 20,000 was not amoebacidal within one hour. Rogers, working with paramecia, has shown that emetine in dilution of 1 to 1,000,000 killed in 20 hours, but did not kill in three hours. Vedder 29 found that 10 mg. emetine per kilo body weight was fatal to white rats when given on two successive days. (I have not found daily doses of emetine any more depressing than intermittent doses.) With this time element in mind, Lyons 30 advocates small doses, repeated several times daily, and reports very good results. Nogue 31 also says that two doses daily of 11⁄2 gr. each are more effective than 1 gr. once a day. Rogers recommends two injections daily of 12 gr. each, and Seal gives two injections a day of 3 gr. each. Brau 32 gives 2.5 grs. in two doses the first day, 1.75 grs. the second day, then 1.3 grs.,. then 1 gr. daily. Of the cases reviewed in the literature, 60 were given one daily dose, 16 were given both one and two daily doses, 71 were given two daily doses, and a few were given three and four daily injections. Whether large single daily doses are better than several smaller daily doses remains as yet undemonstrated.

The number of days on which emetine has been given during treatment has varied from 1 to 32, the average in 91 cases being 6.6 days. Seal, reporting 63 recoveries in adults, says two or three doses of 23 gr. bi-daily generally bring results. His longest case took five days. Carter, reporting 168 cases, seems to have gotten results in three to four days as an average.

The total amount of emetine given during treatment varied from 23 to 20 grs., the average in 100 cases being 6 grs. Seal, in 63 cases, used from 1 to 2 grs. Carter, in 120 Indians, averaged 3.5 grs., and in 39 Europeans 2 grs. to the case.

Of 87 cases reported from hospitals, the average stay in the house was 20 days, the minimum 2 days, the maximum 90 days.

Dosage in Children.-Archibald states that children are extremely tolerant toward emetine. In a child two years old he recommends 16 gr. every 12 hours for three doses. He reports two cases, one a child aged 28 months, to whom he gave 3% gr. every 24 hours, and during a relapse 1/2 gr. in 36 hours; the second was an 8-months-old. baby, to whom he gave 1/12 gr. a day until the stools were clear. Barlow 33 reports giving 1/, gr. daily for two weeks to a 16-monthsold, 21-pound baby with hæmoglobin of 40 per cent. He further reports having under treatment a native boy, aged 7 years, weight 30 pounds, hæmoglobin 5 per cent., with oedema and dilated heart from hook-worm infection, to whom he gave 1/5 gr. for two days, and then 13 gr. daily. Seal reports the recovery of four infants under one year after a couple of 1%-gr. injections, and the recovery of a 3-year-old child after 1/3 gr. Bizard reports the recovery of a 23months-old child after rectal irrigations for four days with 1/5 gr. in 100 Cc. normal salt.

V. IMMEDIATE CLINICAL RESULTS

To any one who has come through the days of treating amoebic dysentery by quinine irrigations, by appendicostomy with ice-water flushings, by irrigations with peroxide, magnesium sulphate, coal oil, or silver nitrate, and by the oral administration of 60- to 90-gr. doses of ipecac, the action of emetine seems miraculous. If emetine never effected a single permanent cure it would still be one of medicine's chief blessings because of the relief of symptoms which it affords. In from 80 to 90 per cent. of cases the griping, painful,

bloody flux, with the dead aching in the belly, back, and legs, can be stopped within a couple of days, and often after a single dose. The drug ordinarily causes no general discomfort of any sort, and only very mild irritation at the site of injection. It makes possible either continuance at, or a quick return to, work, and this is an important factor in treating mill-workers, mechanics, or negro laborers for any chronic disease. The promptness of the relief brought by emetine restores the patient's confidence after weeks of failure with the ordinary antidysenteric remedies, or after relapsing every few months for a number of years. Cheerful amoebics are unknown, for few things take the starch out of a man so quickly as a painful dysentery.

Rogers's original statement that emetine is specific has been almost universally corroborated. In tabulating from the literature 620 cases (excluding deaths), 613 are reported as cured, 7 as unimproved. The improvement in my own results since using emetine is shown in the following table:

Unfortunately, from 10 to 20 per cent. of cases are not amenable to emetine. Baermann and Heinemann concluded within a year after the appearance of Rogers's articles that some strains of the pathogenic entamoeba are emetine-fast, as some of their cases were not affected by any of the brands of emetine on the market. Both Carter and Archibald have suggested that insufficient dosage per

mitted the entamoeba to develop an immunity to emetine, and, as noted above, I have had two cases refractory to emetine, both of whom had been treated with ipecac before coming to me. Whether these cases were originally emetine-fast or became immune I am unable to say. The fact that relapses after emetine seem to be as easily controlled by the drug as the original attack does not favor the idea of immunity, but, so far as I know, there is at present neither experimental evidence nor sufficient clinical observation to settle this point.

In treating amoebic dysentery, rest in bed with a light diet is always best, and in severe cases, of course, these regulations become automatic. In laborers still at work, however, I find that a single daily injection at the office rapidly brings clinical recovery. I give 2-gr. doses, using the hypodermic tablets, as solutions of emetine, whether unsealed or in ampoules, turn yellow and become slightly acid, causing a good deal more local irritation. This treatment is continued until symptoms subside; if the stools still show amœbæ after from three to six days, I add 20- to 30-gr. doses of ipecac by mouth, in salol-coated pills, made fresh every three days, given without water, about 4 A.M. After large doses of emetine I have seen nausea and vomiting, but no serious symptoms of collapse, and none of the symptoms of an "ipecac drunk" which were often so uncomfortable and so persistent after 50- to 80-gr. doses of the crude drug. Emetine in large doses will sometimes cause several stools (possibly from relaxation), and in one hospital case these emetine stools seemed to be very much like the stools following ipecac. (On the other hand, Nogue says there are no stools for four to eight hours after emetine.)

VI. DURATION OF TREATMENT

The long and uncertain incubation period, both in original attacks and in relapses, makes the duration of treatment problematical. Baermann and Heinemann report the sudden reappearance of amœbæ in the stools with clinical relapse after 70 days in one case. In the men Walker 34 parasitized by feeding entamœbæ, the incubation period of the dysentery ran from 20 to 95 days, with an average of 64 days. He says it may be shorter than 20 or much longer than 95 days, and quotes Vincent's cases with incubation periods of 3, 6, and 11 months; so that it is difficult to say not only when a case is cured, but, if not cured, when it will relapse, as amabæ or cysts generally reappear in

the stools some time after treatment. Relapses are reported in 25 of 49 cases from which later reports are available, and out of 97 cases reported with stool examinations only 51 were amaba-free on discharge. Baermann and Heinemann recommend the giving of several doses of emetine at first, then every second or third day for four or five doses, then every three to four weeks for an indefinite time. Phillips 35 gives emetine daily for ten days or longer, then emetine or ipecac by mouth, and repeats this treatment at increasing intervals. Archibald, after the first course of emetine, gives a dose every one or two weeks for three months.

This uncertainty as to cure and to incubation period has led me to attempt to clear the stools at first, and then to tell the patient to report at once in case of relapse, when the same treatment is repeated. I see no advantage in giving emetine off and on for months, as at the beginning of an attack, when the stools contain only large trophozoites, is the opportune time for treatment. Willets 36 reports clearing the stools of 8 out of 19 non-dysenteric amoebics by the use of emetine, but does not state whether the amabæ were encysted or not. Most authors have stated emphatically that emetine has no effect on cysts. Gaide and Mouzels 37 state that emetine does not eradicate the entamœba, and advise that some local treatment in the gut be employed to help clear the stools. Carter advises the giving of 90-gr. doses for this purpose, but it has seemed to me that 20- to 30-gr. doses were large enough, when given in conjunction with emetine.

Waiting for the return of clinical symptoms, as an indication for further treatment, has its dangers, as shown by Musgrave's report of 50 autopsies on cases in which there were no dysenteric symptoms. In practice, however, I find it impossible to persuade patients either to continue treatment or to keep on bringing in stools for months after they have symptomatically recovered, so have to rely on clinical indications for further treatment.

VII. RELAPSES AND CARRIERS

That many relapses will occur is now becoming generally realized. But of the hundreds of cases reported during the last two and a half years only a small number were under observation more than a few days after clinical recovery, and their subsequent history is unknown. A smaller number still have been followed by stool examinations,