ON THE TREATMENT OF THE NIGHT-SWEATING OF

PHTHISIS.

BY WILLIAM MURRELL, M.D., M.R.C.P.,

Assistant-Physician to the Royal Hospital for Diseases of the Chest, Lecturer on Practical Physiology at the Westminster Hospital.

(Continued from Vol. xxiii. p. 430.)

XI. AMANITA MUSCARIA.

MUSCARINE is so rarely used in the treatment of disease that I offer no apology for giving a short account, compiled from various sources, of the fungus from which it is obtained.

The agaricus muscarius, amanita muscaria, fly-agaric or flyfungus-agaric mouche-is one of the largest and most beautiful of the agaricini, and well deserves the title of " imperial" applied to it by Batsch, "for the most indifferent person must be attracted by the glowing hues of its ample pileus, its regular form and tall pillar-like stipes, extremely conspicuous, even at a distance, in the shady recesses of its native woods." It is found most commonly in birch-wood, not very plentifully in England, although it is abundant in the Highlands of Scotland. Linnæus says that when infused in milk it kills flies, hence its specific name Muscarius and its popular name "Fly-agaric."

In Siberia and Kamtschatka the inhabitants use it as other nations do ardent spirits or wine, to produce intoxication. The fungi are collected in the hottest months and hung up by a string in the air to dry; some are dried on the ground and are said to be by far the most active. Those that are small, deepcoloured, and thickly-covered with warts, are said to be more powerful than those of larger size and paler colour. The usual

mode of taking the fungus is to roll it up like a bolus, and swallow it without chewing, which it is said would disorder the stomach. It is sometimes eaten fresh in soups and sauces, and then loses much of its intoxicating property. One large or two small fungi is a common dose to produce a pleasant intoxication for a whole day, particularly if water be drunk after it, which is thought to augment the narcotic principle. The desired

effect is usually produced in one or two hours. Giddiness and intoxication result from the fungus in the same way as from wine or spirits. Cheerful emotions are first produced; involuntary words and actions follow. "The natural inclinations of the individual become stimulated. The dancer executes a pas d'extravagance, the musician indulges in a song, the chatterer divulges all his secrets, the orator delivers himself of a philippic, and the mimic indulges in caricature. Erroneous impressions of size and distance are common occurrences; a straw lying in the road becomes a formidable object, to overcome which a leap is taken sufficient to clear a barrel of ale or the prostrate form of a British oak." The most singular effect of this agaricus is its influence on the urine. It is said that from time immemorial it has been known that the fungus imparts an intoxicating quality to that secretion which continues for a considerable time after taking it. For instance, a man moderately intoxicated to-day will by the next morning have slept himself sober, but (as is the custom) by taking a teacupful of his urine he will be more powerfully intoxicated than he was the preceding day by the fungus. The intoxicating property of the fungus is capable of being propagated; for every one who partakes of it has his urine similarly affected. Confirmed drunkards in Siberia preserve this as a precious liquor in case a scarcity of fungi should occur. This intoxicating property may be communicated to every person who partakes of the draught, and this with the third, fourth, and even fifth distillation. By this means, with a few fungi to commence with, a party may shut themselves in their room and indulge in a week's debauch. The passion of the Samoiedes, Ostiaks, Koraks, Kamtschadales, and other inhabitants of Eastern Asia for this species of intoxication is so great, that the poorer people drink the urine of those who have partaken of these fungi in order to induce its effects.

Numerous cases of poisoning with amanita muscaria are on record, the fungus being often mistaken for one of the edible varieties. The symptoms appear soon after the fungi have been eaten-usually in half an hour. Violent gastric and intestinal disturbance is as a rule present, but may be absent. It is not uncommon for cerebral symptoms to be the predominant feature, the patient becoming violently excited, as if intoxicated with alcohol; thus it is stated by Cosserat that a young woman who had eaten some of these fungi ran about the house in her night-gown, beating her head against the wall, and screaming like one possessed. A very interesting case of poisoning by this fungus occurred at Calcutta, and was recorded by Dr. Chevers. An accomplished gentleman of temperate habits having partaken of some mushrooms at breakfast went into court and was surprised to find that he could not control his actions; everything appeared to him ludicrous; he laughed immoderately in open court, and ridiculed in an absurd way his superior officer. After some hours he recovered, but was greatly alarmed at his attack, of which he did not suspect the cause. His physician to reassure him returned with him to luncheon, at which, among other dishes, were stewed mushrooms. Of these the patient ate, and before the meal was over he became greatly excited; every person appeared ridiculous; the most ordinary remark seemed full of fun and wit, and his laughter was immoderate. Every object appeared to him perfectly beautiful. These exaggerated sensations continued for some hours, and were put an end to by the administration of ipecacuanha, which caused him to disgorge a considerable quantity of the fungus still undigested. When larger doses have been taken the sight has been affected, things being seen dimly as through a mist, and attacks of an epileptic nature have been observed. A state of stupor ensues, in which reflex action is abolished. The pulse is, as a rule, retarded, the arteries are contracted, respiration is short and stertorous, the pupils are dilated, the extremities are cold, and death ensues from progressive loss of cardiac power. Such are the accounts given of poisoning with fly-fungus.

Various attempts have been made to isolate the active principle of the amanita muscaria, and in 1866 Letellier extracted a substance which he called Amanitine. It was not, however,

till the year 1869 that Schmiedeberg and Koppe succeeded in obtaining an alkaloid—muscarine-possessing distinctly toxic properties capable of accounting for the powerful effects witnessed in cases of poisoning by the fly-fungus. The properties

of this powerful substance have been so thoroughly investigated not only by its discoverers but by Prevost, Alizon, Lauder Brunton, Schiff, Ringer, and others, that there are few drugs with the physiological action of which we are more familiar. The proportion of alkaloid present in the fly-fungus has not been accurately determined, but the amount extracted is said seldom to exceed one-fifth per cent.

Dr. Ringer and Mr. Morshead have investigated the action on man of the muscarine prepared synthetically by Merck, of Darmstadt. They found that the smallest dose given hypodermically capable of producing symptoms was one-third of a grain, It contracted the pupil, excited profuse perspiration, free salivation, and running at the eyes and nose, and sometimes it purged and excited nausea and vomiting, with a strong desire to pass urine.

According to Schmiedeberg and Koppe a thirteenth of a grain of pure muscarine produces in the human subject myosis, loss of focalizing power, abundant secretion of saliva, determination of blood to the head, flushed face, profuse perspiration over the whole body, giddiness, anxiety, griping and rumbling in the bowels, and weight in the head. It is a curious fact that whilst muscarine given internally contracts the pupil, its topical administration dilates it-in this respect resembling gelseminum.

In the lower animals muscarine produces symptoms very similar to those observed in man. Thus in cats we have increased salivary secretion, vomiting, diarrhoea, rumbling in the bowels, staggering gait, contraction of the pupils, frequency of respiration, and dyspnoea. Dr. Lauder Brunton has shown experimentally that the dyspnoea is due to contraction of the pulmonary vessels, and that it may be antagonised by atropia.

Perhaps the most striking action of muscarine is its influence on the heart. When a drop or two of solution of muscarine, or of extract of amanita, is brought in contact with the frog's heart, it almost immediately stops in diastole. If now a drop or two of solution of atropia be applied, the pulsations are restored and

the heart goes on beating again almost as well as ever. This reaction is the best and most delicate test for muscarine. It has been shown by Dr. Ringer and myself that duboisia, puturia, and pilocarpine, all antagonise the action of muscarine on the heart.

For the last six months I have used the agaricus muscarius in the treatment of the night-sweating of phthisis. The preparation employed was a one-per-cent. solution of a liquid extract of about the consistence of treacle, which was kindly placed at my disposal by Dr. Ringer. The extract was, I understand, made in England from fungi obtained from Germany. I have treated in all twenty-six cases-sixteen men, and ten women, their ages ranging from forty-six to ten. They were all outpatients, and all were phthisical, many of them having cavities. In almost every instance the sweating was very profuse, none but well-marked cases being chosen. It was found that five minims of the one-per-cent. solution of the extract was the smallest dose on which reliance could be placed, although in some instances smaller quantities succeeded. It was usually given in a little water, three times a day, but it answers well if given only at bedtime. A good plan is to give the three doses during the night, or at intervals of about an hour before going to bed. There is usually no improvement on the first night, but on the second or third nights the sweating is distinctly less, and by the end of the week has ceased, or is at all events so slight as not to put the patient to any inconvenience. In most cases the muscarius alone was given, but in a few instances the ordinary treatment was continued. It stops the sweating without the production of any abnormal dryness of the skin. The medicine is almost tasteless, and is taken without difficulty. One patient complained that it would not keep, and went bad before the end of the week, the addition of a few drops of spirit overcame that difficulty. There is no danger in taking the medicine, for a delicate young woman of twenty-three took fifteen minims every three hours for a week, and then twenty minims every three hours for another week, without the production of any symptoms. By reference to the accompanying table, it will be seen that in almost every case-with the exception of those in which the dose was known to be too small