while in cases where morphine is contraindicated, such as advanced kidney disease, acute gout, or certain forms of cerebral irritation, antipyrin may be given freely to allay pain. It has the great advantage over morphine that it does not cause cerebral symptoms; thus there is not any vertigo nor vomiting, and according to Professor Sée the use of the drug is not followed by sleep or nervous stimulation. Professor Lépine, however, considers that antipyrin acts both as an anodyne and a nerve stimulant, so that though it relieves pain, it at the same time quickens the intellectual faculties of the patient and renders him disinclined for sleep.

Taking his view of the action of antipyrin as an anodyne, we may say that it is diametrically opposed to morphine in that it acts as an anodyne without depressing the higher brain centers. In only two cases in which I have given antipyrin has it caused sleep, and in these instances I believe the sleep was rather the result of relief from pain than that of any somnolent action of the drug. The fact that antipyrin acts as a nerve stimulant as well as an anodyne is a decided objection to its employment when we wish to relieve pain and at the same time insure sleep. The best method in such cases is to follow the antipyrin by a hypnotic, such as chloral.

For the immediate relief of pain the drug should be used hypodermically, and, as it is very soluble in water, a fresh solution may be made by dissolving one of the tablets prepared by Burroughs & Wellcome in an equal weight of water.

The dose for an adult of antipyrin used hypodermically to relieve pain is five gains. This has been calculated by Dr. Fränkel, of Berlin, to be equivalent to one thirtieth of a grain of morphine. The dose may be repeated if the pain is not relieved. Beyond the pain caused by the injection, and a certain feeling of tension which lasts a few seconds, no bad effects have been noticed. The drug usually gives relief in from fifteen seconds to half a minute, and the effect lasts for some hours (six to eight hours-Fränkel).

As an anodyne antipyrin has been used chiefly in herpes zoster, lumbago, ataxia, hepatic and nephritic colic, acute asthma, acute rheumatism, and acute gout.

If given in sufficiently large doses it appears to give relief in the majority of cases. Dr. Fränkel gave it in all cases in which morphine appeared to be indicated, and did not meet with a single failure. Dr. Jennings, of Paris, however, side by side with

many cases successfully treated by antipyrin, mentions a case of acute gout which was influenced by the drug.

If given by the mouth as an anodyne antipyrin must be used in large doses; thus Professor Sée recommends a dram to a dram and a half in the twenty-four hours, and Professor Lépine one hundred and fifty grains divided in two doses.

In rheumatism and gout the drug appears to be both sedative and curative in its action; it not only allays the pain, but in many cases shortens the attack. Professor Sée gave it in fifteen cases of hydrarthrosis which had resisted treatment with the salicylates and also counter-irritation by the actual cautery. In all these cases he found that swelling and pain disappeared in a few days. Dr. Fränkel gave it in thirty-four cases, with the result that in all but two there was amelioration of the symptoms and shortening of the attack. In fifteen cases, however, a relapse occurred. He found that the average duration of acute rheumatism with antipyrin was twenty-five days, while with the salicylate treatment it was 35.2 days. Mr. Raymond Johnson tried antipyrin in four cases of acute rheumatism, with the result that it lowered the temperature in all, but in only one out of the four did it relieve the symptoms. The three cases which were unrelieved by antipyrin yielded to treatment with the salicylates, while in the fourth, where salicylate of soda had failed to relieve the patient, antipyrin did so.

To give relief in acute rheumatism or acute gout, large doses of antipyrin must be given, one to two drams during the twentyfour hours being a usual dose. As a rule the drug produces free sweating and rapid defervescence. In chronic rheumatism it acts in allaying the pain and shortening the course of the disease. I have given it in a large number of cases of rheumatism, and in the majority I have found it successful. It appears to me to be a remedy which at least should be tried when the salicylates fail or produce disagreeable after-effects, as they occasionally do. Most of the cases recorded in which antipyrin and the salicylate treatment have been used side by side, for the purpose of comparison, yield either to the one or the other, the refractory cases in either section usually yielding to the administration of the other drug. I have not any statistics to prove whether antipyrin is of use in preventing the secondary troubles in acute rheumatism, such as endocarditis.

Antipyrin has been used with great success in nervous disorders, and I believe it

supplies us with a specific for many neuralgic and other allied complaints. Its success in the treatment of migraine and cephalalgia is now assured, and one rarely takes up a medical periodical without finding in it the description of various cases which, after being more or less intractable to remedies for years, have yielded to antipyrin.

In Germany and France especially has this drug been used in the treatment of migraine, and to a less extent in England. During the last few months I have used it in the out-patient department and in private practice in such cases with very good results. As a rule patients return after having taken the remedy, and ask pointedly for some more of the same medicine that they had last time, a fact which stamps its value at once on one's mind.

In treating migraine with this drug, I believe the best plan is to use the remedy as a specific against the attacks, and not to administer it continuously. If the migraine be periodic, or if there be a preliminary aura, the drug should be exhibited as soon as possible before the threatened attack. Thus, if an attack be feared for the morning, antipyrin should be given at night, and if the attack still threatens in the morning, a further dose should be administered. this way the attack generally is aborted. Even if preliminary warning be absent, the medicine taken as soon as the attack comes on either aborts it or renders its symptoms less intense. In my experience it is very rare for antipyrin to fail to influence favorably an attack of migraine, and in this I am supported by almost all of those who have noted on this drug.

In

It is rarely necessary to give large doses to produce the specific effect. I generally give five to seven grains combined with alkalies and a bitter infusion, to be taken when an attack threatens, and to be repeated, if necessary, in an hour. I find that somewhat larger doses are recommended (fifteen to twenty grains), but patients rarely complain that the smaller dose fails.

I have found the drug useful also in those cases of bilious headache, which often occur in patients of full habit, who are addicted to the too frequent use of alcohol. These cases, which generally occur among women in a comfortable position in life, yield to the administration of antipyrin; I had the satisfaction of hearing a patient, who has suf fered in this way for more than ten years, state that at last a remedy had been found which relieved her. Of course the remedy does not touch the root of the evil.

In some cases of cephalalgia, antipyrin relieves for a time, but at length the patient becomes habituated to the drug, and the relief is less marked. In such cases, either the drug may be increased or antifebrin or some other of the substitutes for antipyrin may be used.

As antipyrin has so marked an influence over these nervous complaints, it seems natural to suppose that it may be useful in epilepsy.

Fraty concludes that it has a distinct influence over epilepsy akin to that manifested by the alkaline bromides, but he confesses that large doses must be given (one to two drams daily), and that in a considerable number of cases it has to be given up, owing to the malaise it produces.

I have not tried the drug in many cases of epilepsy, but I was not favorably impressed with the result when I did try it. As a sedative antipyrin has been tried in cases of nocturnal emissions, and it has been found that seven to fifteen grains administered on going to bed prevents the emission in many cases. It also acts in diminishing the excessive flow of urine which not infrequently accompanies spermatorrhea, and which arises from the hyperesthesia of the nervous system. I would venture to think that this drug may be well worth a trial in those cases which so often are found to exist in young men who have fallen into the habit of masturbation at school, and who, on coming into the world, learn the evils of it, and relinquish the habit, but in whom spermatorrhea frequently supervenes to a serious extent. I have given it in similar cases with good results, the best plan being to give ten grains of antipyrin in combination with ten grains of chloral hydrate at bed-time, the patient usually falling asleep shortly after getting into bed, and remaining asleep without disturbance till the morning.

Antipyrin was given by M. Bloch to a neurotic man with a tender spine, who was periodically overcome by attacks of drowsiness, which comes on after each meal; these were accompanied by pains in the head and debility. His condition had been improved by the use of nux vomica to some extent; but, on the exhibition of antipyrin in fifteengrain doses, given on waking and at 11 A. M., the drowsiness after a few days disappeared, and the remaining nervous symptoms abated. In this case it acted as a decided nerve stimulant.

The drug has been strongly recommended. in cases of chorea by Legroux, who con

siders it a most rapid, certain, and inoffensive remedy. He administered it in six cases, giving forty to fifty grains daily. All his cases recovered rapidly in from six to twenty-seven days. I have not had the opportunity to use it frequently in chorea, but in such cases as I have used it the movements diminished rapidly. In one child to whom I gave the drug it had to be discontinued, owing to the cardiac depression which accompanied its use.

Antipyrin has been used with success in spasmodic nervous disorders, such as hayfever and whooping-cough. Dr. Bloch tried it in a case of hay-fever in which cocaine and the bromides had been given without result. He gave it in thirty-grain doses at the hours when the attacks usually came on, and found that the drug aborted the attacks. After taking antipyrin for some weeks the disease disappeared in this case.

Sonnenberger, from an experience of seventy cases in which he used a drug in whooping-cough, concludes that it is a very useful remedy in such cases. He gave it to infants in doses of one half to one and one half grain three times a day in syrup of tolu or raspberry, increasing the dose to ten or fifteen grains for older children. The remedy must be used systematically to produce a good result in whooping-cough.

In nervous vomiting, especially in the vomiting of pregnancy, antipyrin is useful. If the vomiting be periodic, the drug should be given a few hours before the usual appearance of the attack. In sea-sickness the drug has been lauded as a specific, perhaps only to have its day as most other specifics for this disorder have had. More than one medical man has, however, recorded the debt of gratitude he owes to this remedy in crossing the Atlantic.

Antipyrin has been used as a hemostatic in cases of pulmonary hemorrhage by Dr. Olikoff. He made a solution of fifteen grains to the ounce in water, and made his patients breath through this for four or five respirations, repeating the use of it every half hour. In all the six cases tried the hemorrhage was diminished. As a hemostatic for general purposes, antipyrin is too costly a remedy to be employed lavishly, though it has been recommended for epistaxis and other forms of hemorrhage. Herpes zoster and locomotor ataxy have both been successfully treated with antipyrin. In locomotor ataxy it appears to act in alleviating the lightning pains and in giving ease to the patient rather than by altering the course of the malady.

Since antipyrin became a popular remedy many cases in which the drug has produced disagreeable effects have been recorded, though, as far as I am aware, none of these cases has ended fatally, nor have there been any symptoms which have lasted more than a few hours. The cases which I have collected (more than twelve in number) appear to me to be pure examples of idiosyncrasy. They are usually isolated cases occurring amid many others in which the same quantity of the drug was administered. They do not appear to depend on the quantity of the drug given, for in one case four grains, in another eight grains, and in a third fifteen grains of antipyrin produced symptoms of poisoning, though more than double the dose has been given in many hundreds of cases without bad effects. There is, as far as I can find, no special class of cases in which the administration of antipyrin is likely to bring on symptoms of poisoning; but, as it appears in certain individuals to cause disagreeable symptoms, regardless of dose, we are likely to hear further of this property it possesses from some of the large number of people who are now taking the drug as a preventive against sea-sickness.

The chief symptoms which manifest themselves in cases of poisoning by antipyrin are certain nervous sensations, such as restlessness, loss of memory, a feeling of general expansion of the body, and a sensation of great coldness. These are followed by swelling of the face and the appearance of an erythematous eruption resembling measles-so much like it, in fact, that those who have seen cases of antipyrin rash are careful to warn us to avoid the diagnosis of measles in patients taking antipyrin.

The chief points of difference between this rash and measles are that it appears but slightly on the face, that its chief distribution is on the extremities, that it is non-crescentic in distribution. In many cases it is not accompanied by catarrh of the eyes and nose, but in a few cases catarrh does occur, and when present it must make the differential diagnosis very difficult. sides these symptoms, antipyrin may cause diaphoresis, feebleness of the pulse, and general collapse. Gastro-enteritis occurs rarely.

Be

The antidote which removes these disagreeable effects most readily is belladonna, given either as the tincture or in the form of atropine used hypodermically (one seventieth of a grain).

Conclusions. I would venture to think that in antipyrin we have a drug which,

though suffering from a temporary overpopularity, is likely to be of use in practice. Its power of relieving migraine and other forms of cephalalgia is, in many cases, magical. As an anodyne it is particularly useful in those cases where morphine is contraindicated, especially in advanced kidney disease, acute gout, or in the bronchitis of old people. I do not think that antipyrin is at all likely to displace morphine, as this drug possesses the advantage of being much more powerful bulk for bulk, and hence is more convenient for hypodermic medication. But a trial of it should be made where morphine can not be given, or where morphine must be withheld for fear of establishing the morphine habit. In cases of longcontinued pain, in which some anodyne must be given for a period often stretching over years, antipyrin may be found useful as an occasional substitute for morphine when the patient has become habituated to the morphine, and when it otherwise would be necessary to increase the dose of this drug. I regret I have not met with a case in which I could try this, but such cases as locomotor ataxy, or cases of slow paralysis accompanied by spasm of the muscles, would be suitable ones in which to make a trial.

I do not think antipyrin will displace the alkaline salicylates in the treatment of acute rheumatism, but it is undoubtedly useful where the salicylates have failed, or where they are contra-indicated by the disagreeble effects they occasionally produce.

With regard to the objection raised against antipyrin that it not infrequently gives rise to symptoms of poisoning, I believe that such is of little value. I have given the drug in a large number of cases without meeting with any bad effects from it, and few of those who have used this drug most largely lay any stress upon this difficulty. One must be prepared to meet with cases of idiosyncrasy in the administration of this drug as one has to be with cocaine, morphine, quinine, and other drugs.

By far the most serious objection to its extended use, particularly in hospital practice, is expense. At present, its manufacture is in the hands of monopolists, and though the French chemists say they have ascertained its composition and method of preparation, no one at present has sent on the market any of the drug under its proper chemical name, which is dimethyl-oxiquinisin, a name which requires some reflection before being added to a prescription.

I have tried antifebrin as a substitute for this drug in several cases of migraine, and

though the effect does not seem so certain as when antipyrin is used, yet in many cases it has acted well. The relative expense of antifebrin is much less than that of antipyrin.-Dr. W. Tyrrell Brooks, British Medical Journal.

THE CAUSE OF SLEEP.-Sleep is not only one of the greatest luxuries we possess, but it is also one of the greatest necessities to our being. It stands in exactly the same relation to the wants of the nervous system as food does to that of the muscular-a complete deprivation of either sleep or food causes death; and a scanty supply of either, wasting and inertia. It is the sole curative agent in many an apparently hopeless disease, and the only thread, as it were, upon which life hangs; while insomnia is almost always the precursor of some dangerous malady, and a symptom sufficient to excite serious apprehension. Seeing, then, how essential sleep is to our existence, and what an important part it plays both in the relief and cure of disease, we can not inquire too much as to the means by which it is ordinarily brought about. Different opinions

have at different times been held as to its immediate cause, and arguments have been advanced to show it to be due to

(1) Anemia of brain. (2) Congestion of brain or distension of the vessels of the choroid plexus pressing on the sides of the ventricles. (3) Lessened rate of circulation.

It is our duty therefore to examine each of these different theories, and see whether the results of any other experiments can be brought forward to support or overthrow

them.

The arguments for its being due to anemia of the brain are derived from observations upon living animals in which a portion of the skull has been removed. Durham explains the cause of the anemia thus: "The results of chemical changes in the nervous matter which necessarily accompany the action of the brain-the debris, so to speak

impede the action by which they were produced, and a state of comparative anemia follows." Moore, I believe, says that "this anemia results from a contraction of the arterial trunks at the base of the brain, and of the blood-vessels of the pia mater, brought about by a stimulus originating in the ganglia of the sympathetic."

Some of the reasons put forward for its being due to congestion of the brain are: (1) Full-blooded people are always the best sleepers. (2) The recumbent position, which is supposed to induce a flow of blood to the

head, is most favorable to sleep. (3) Con. sciousness is instantly suppressed by pressure of the brain.

In order to show it to be due to a lessened rate of circulation, it is said: (1) Sluggish functions are always attended with a sluggish pulse. (2) Hibernating animals and plants during winter have a very slow circulation. (3) Sleep comes on in that posture and that period of the day when the circulation is most sluggish.

The opinion. I believe, most commonly held at the present time is, that during sleep the brain is anemic, and the experiments carried out by Durham and Hammond, together with the ophthalmoscopic observations of Hughlings-Jackson, are supposed to prove conclusively the correctness of the idea which was previously held by Blumenbach, Dendy, Fleming, and others. Unfortunately, however, the means which were taken to ascertain the state of the circulation during sleep entirely altered the conditions under which the brain is usually placed. The cranium, ordinarily speaking, is an air-tight and unyielding cavity, and consequently, from the fact of every square inch of the body being subject to a pressure of fifteen pounds, always contains the same amount of fluid; but, when once air has been allowed to gain admission, the conditions are altogether changed, and an alteration in the quantity of the cireulating fluid may readily take place.

The experiments of Kellie upon cats and dogs show these facts clearly. Some of the animals were bled to death by opening the carotid or femoral arteries, others by opening the jugular veins. In some the carotids were first tied, to diminish the quantity of blood sent to the brain, and the jugulars were then opened with the view of emptying the vessels of the brain to the greatest possible extent; while in others the jugulars were first secured to prevent as much as possible the return of the blood from the brain, and one of the carotids was then opened. From the whole inquiry, he considered it impossible to lessen the quantity of the blood in the brain by arteriotomy or venesection, and that when by profuse hemorrhages the vessels of the cranium are drained of any sensible portion of red blood there is commonly an equivalent to this spoliation in the increased circulation or effusion of serum. He made other experiments upon the effects of position immediately after death from strangulation and hanging. He also trephined a portion of the skull in some animals and then bled

them to death. In these last cases the brain was sensibly depressed, and a space left capable of containing a teaspoonful of water. The ophthalmoscopic observations of Hughlings-Jackson, instead of proving that sleep was due to anemia of the brain, to a great extent combat this idea; for it would appear that while the arteries of the optic disk are anemic, the veins are congested; and, taking this as an index of the brain circulation, we may infer that the quantity of blood in the cranium during sleep and wakefulness is more or less the same, and that the quality only becomes altered. Since, then, the quantity of blood in the brain can not be materially altered, it follows that sleep can not be due, ordinarily speaking, either to anemia or congestion; and therefore it now only remains for us to examine the third cause assigned, viz., lessened rate of circulation. First, then, it is an admitted fact that the quantity of arterial blood supplied to an organ varies directly in proportion to its activity. This applies to the brain in common with all other parts of the human frame. The only difference between the circulation of the brain and that of other organs is, that the total quantity of blood (venous and arterial blood combined) always remains the same. Now, to cause an increased supply of blood to a part, there must be both an increased vis a fronte and vis a tergo, or, in other words, a greater attractive and propelling force. A diminished supply is always, under ordinary circumstances, the result of a lesser demand. The various functional and morbid conditions which may cause an insufficient supply of arterial blood in the brain are:

(1) Weakness, dilation, fatty or valvular disease of the heart. Ossification of the blood-vessels or aneurism. (3) Tumors pressing upon the arteries or veins. (4) Altered state of the blood. (5) Diseases of the lungs. (6) Impure atmosphere. And in all these there is more or less tendency to sleep.

Let us now examine the circumstances under which sleep usually comes on, and then take into consideration the various causes which, generally speaking, banish and induce it.

It comes on, for the most part, at that time of the day and in that position in which the circulation is most sluggish, viz., at night, and in the horizontal posture. As a rule the pulse becomes slower toward evening, and, moreover, is less frequent in the horizontal than in the erect position; consequently these two circumstances, inasmuch as they favor a slow circulation, favor