supplied with abundance of air, and well protected from cold. The introduction of the vapour was so moderated that the same quantity was made to undergo diffusion each day.

The first fact that became well established was, that cold and a low barometric pressure greatly assisted the action of the vapour, and frequently led to sudden death from congestion of lung and accumulation of fluid in the bronchial tubes.

A second fact, of singular interest, was the degree to which recovery from extreme congestion of lung would take place, on simply withdrawing the animal from the influence of the agent. When the lungs were so obstructed that what is called rale from accumulation of mucous fluid in the bronchial surface was most marked, there was invariably a rapid recovery on removal to fresh and warm air.

A third fact relating to the lesions induced, beyond mere congestive lesions, is also of deep interest. The lesions were primarily all of one kind; they were hæmorrhagic, and consisted of red spots and patches, in which blood was effused and coagulated in the connective tissue. The position of the hæmorrhage was singular. In three cases it was only in the extreme point of the apices of the lungs; in four other cases lower portions of lung were involved, but in these the apices were the seats also of hæmorrhagic disease. It would appear, in fact, as if these points of lung were least resistant to the force of the circulation.

In the animals observed these distinct hæmorrhagic changes were usually fatal, so that the further result of the local neural paralysis could not be carried out as could be wished. In two cases, nevertheless, we had other results worth recording.

In one instance there was clearly an oedema of the lung structure: in another the pleural membrane was raised in four or five granulated points, round each of which there was effused blood. Dr. Sedgwick, who took the lungs of this animal for careful microscopic inspection, reported to me that there were plastic exudations in various parts of both lungs, and that the granulations of which I have spoken consisted of effused plasma beneath the pleura.

I am well content to leave these observations as I have written them

above, with but two observations more. It has been suggested by an accomplished and acute English physician, Dr. Eade, of Norwich, that pulmonary consumption may be primarily due to pulmonary vascular paralysis. My experiments do not enable me at this stage to endorse Dr. Eade's hypothesis as to the primary origin of consumption, but certainly they indicate to what extent nervous deficiency will go in favouring the hæmorrhages, congestions, and exudations which attend tubercular disease. The concluding observation this year with nitrite of amyl relates to the fact that the nitrite atmosphere, when it is not too much charged with the vapour, exerts a certain curative effect. Three rabbits were brought to me with a skin disease resembling lepra in man. They were emaciated and feeble, the fur on the back along the whole length of the spine had been cast off, and the skin was covered over this part with white ashy scales.

Placing these animals in an atmosphere of nitrite of amyl, I noticed that, as the agent took effect, the scaly white skin on the back became red and flushed. In a day or two the scales disappeared, the fur began to extend, and the general health to improve. In a month all the animals had entirely recovered.

There are many local conditions of disease in man and other animals in

which the essence of cure lies in reestablishing a good capillary circulation. It may be, therefore, that by administering the nitrite of amyl, or the other organic nitrites, secundum artem, we may make them further agents in the cure of disease, and thereby add another progress to physiological as distinguished from empirical medicine.

NITRATE OF ETHYL.

In one of my previous Reports I touched incidentally on certain of the nitrates of the organic series of compounds. These substances differ from the nitrites simply in that they contain an additional equivalent of oxygen. It is a very interesting study to follow the difference of physiological action upon so simple a change of chemical constitution; and this year I studied once more this difference from two of the representatives of the nitrate series, viz. from nitrate of ethyl and nitrate of amyl.

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Nitrate of ethyl, to which I first refer, is a fluid, almost colourless, and yielding an agreeable odorous vapour. It has a specific gravity of 1·112, a boiling-point of 85° C. (185° F.), and a vapour-density of 45. Its composition is C, H, NO,. It is made by dropping 10 grms. of absolute alcohol into 20 grms. of colourless concentrate nitric acid in a platinum vessel surrounded by a freezing-mixture. Mr. Ernest Chapman was kind enough to make me a fine specimen of this nitrate, with which my experiments have been conducted.

Nitrate of ethyl was used in experiment, physiologically, in 1848, by the late distinguished Professor of Midwifery in the University of Edinburgh, Sir James Simpson. Sir James considered that it possessed some anaesthetic properties. It has for many years, I may.say centuries, also been used in medicine, in combination with alcohol, under the name of nitric ether, and so employed has been considered valuable for its diuretic properties.

I find, on using it in the undiluted form, that it may be introduced into the system either by inhalation, by hypodermic injection, or by the stomach, and that the effects which follow its administration in large doses are closely analogous to those induced by nitrite of amyl, i. e. it produces rapid action of the heart, some pulsation of the vessels of the head, flushing of the face, and muscular prostration. In the strict sense of the word, it is not an anesthetic; when administered in an extreme dose, there is no evidence of insensibility, until death is imminent. In all cases the motor force is overcome completely long before the sensory organs are influenced. The paralysis of the vessels is slower than from nitrite of amyl; the danger of using the agent is consequently much less; and as the effects are more prolonged, the substance becomes very manageable in medical practice.

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When the administration of the nitrate is carried up to death, the condition induced in all the vascular organs is an intense congestion. this congestion the lungs and the kidneys specially share; and I think there is no doubt that the well known diuretic action of the substance is due altogether to the paralysis of the renal vessels it produces. It alters much less than the nitrites the colour of the blood, interferes in no way with the process of coagulation, and is eliminated rapidly from the body both by the lungs and the kidneys. Administered to the production of complete prostration, it reduces the animal temperature in a definite degree. In pigeons the temperature goes down five and even six degrees, in rabbits three degrees, and in guineapigs from two to three degrees. Like the nitrites, nitrate of ethyl reduces the tetanic spasm of strychnia; and I would suggest that in tetanus, and other acute diseases of spasmodic character, it might be used

with great advantage; but it must be given for this purpose in very different proportions to those in which it is now commonly prescribed. The best plan would be to administer it by inhalation until a decided influence over the motor action is manifested. In pharmacy it would be convenient to keep the nitrite in the pure and simple state, leaving the dilution of it, in alcohol, to the judgment of the physician.

NITRATE OF AMYL.

Nitrate of amyl, C, H,, NO,, is a pale amber-coloured fluid, of not very agreeable odour. It has a specific gravity of 0.992, a boiling-point of 138° C. (280° F.), and a vapour-density of 66°. It is made by acting with strong nitric acid, 30 grms., on urea nitrate, 10 grms., adding afterwards 40 grms. of pure amylic alcohol. I am again indebted to Mr. Ernest Chapman for a specimen of nitrate of amyl, freed as far as possible from nitrate of butyl, from all trace of which it can with difficulty be separated.

In the nitrate of amyl we have a substance differing chemically from nitrite of amyl in having an additional equivalent of oxygen, and differing physically in that it is heavier and of higher boiling-point. It enters the body readily by all channels, and in its general effects it agrees with the nitrite, except that a longer time is required for the development of symptoms from it, and a longer time is demanded for the process of recovery from its influence. The quantity necessary to produce decisive results is the same as with the nitrite; but the nitrate is not so pleasant a substance to administer, and when administered by inhalation is not so conveniently applied. Whether the nitrate of amyl has any real advantages over the nitrite is a question on which I would prefer not to speak at length, until larger opportunities than I have yet had of proving it have been afforded me.

SULPHO-UREA.

In my last Report I treated on the physiological properties of certain of the organic sulphur compounds, viz. sulphur alcohol, mercaptan, and sulphide of ethyl. Recently a very curious and interesting sulphur compound has come before me for experiment; I mean a crystalline substance known by the name of sulpho-urea. Sulpho-urea was first made, I believe, by Prof. Reynolds, and it has since been produced in London, in Dr. Thudichum's laboratory, by Mr. Charles Stewart, to whom I am indebted for the specimens with which I have conducted my researches. Unfortunately the manufacture is difficult, owing to the necessity for many recystallizations, so that I have only been able to work with six drachms; but the results, as far as they go, deserve notice. Mr. Stewart has kindly given me the following note in regard to the preparation of sulpho-urea :

"About a kilogram of pure ammonium sulphocyanate is dried at 100° C., powdered, and dried again. Slight loss by sublimation occurs. When perfectly dry, it is heated gradually by a paraffin bath to 170° C., and maintained at that temperature for two hours. The mass is then allowed to cool to 110° C., treated with one and a half times its bulk of boiling water, decanted from a small quantity of black matter (it is impossible to filter it, as it destroys paper filters), and set aside to crystallize. The crystals are long, fibrous, satiny needles; they are drained, pressed strongly in Hessian cloth, and purified by recrystallization from water. The product is then dissolved in boiling alcohol, filtered from a little ammonium sulphate which remains undissolved, and set aside to crystallize. Two more crystallizations from alcohol

render it practically free from sulphocyanate. The crystals from alcohol are hard, opaque, white prisms: from water they are long, fibrous, silky needles. Both forms are anhydrous." I present specimens of both varieties.

"From the mother liquors more of the urea may be recovered by the same process. The last mother liquors, containing mainly sulphur urea, but also much sulphocyanide, may be evaporated down, and heated again to 170°, as above, with fresh sulphocyanide of ammonium, to furnish more urea."

Sulpho-urea is much less soluble in water than ordinary urea, requiring twice its own weight, at 60° F., for solution. It has a saline bitter taste, compared by some to the taste of magnesian sulphate. It differs simply from ordinary urea in that in it sulphur replaces oxygen.

REP

OF THE

RY

Sulpho-ureal NIVERSITY

CN

NH}

S

CALIFORNIA

In order to determine the difference of action of the two urcas, a series of comparative experiments were carried out. The results may be thus epitomized :

On frogs and rabbits sulpho-urea differs materially from common urea in its action, i. e. when used in the same quantities. The first produces definite convulsive action, with coma and convulsion; the second produces, in frogs, coma without convulsion, and in rabbits nothing more than a slight and gentle soporific condition, which lasts for a very short time, and can be broken at any moment by the simple act of moving or calling out to the animal.

In frogs sulpho-urea induces the saline cataract, common urea does not. To produce any decided physiological effect with sulpho-urea, the proportion used must not be less than thirty grains to the pound weight of the animal. In three experiments in which it was administered to young rabbits, to the extent of producing slight soporific effects, it reduced the animal temperature two degrees Fahrenheit within the interval of an hour.

The impression I have gathered in respect of sulpho-urea is, that it is a saline narcotic, and as such it may prove of use in medicine; but the great point of physiological interest in connexion with it lies in the difference indicated, by its means, between the action of oxygen and sulphur in combination with the same elements, C, N, H, in the same form. The difference may be due to the difference of weight, or it may be due to difference of solubility; the elements, oxygen and sulphur, producing the distinction by virtue of their physical qualities of weight or solubility; or it may be due to the special qualities of the elements. I offer these thoughts as again bearing upon the general question of chemical composition in relation to the physiological action of chemical substances.

CHLOR-ETHYLIDENE-MONOCHLORURETTED CHLORIDE OF ETHYLE.

In the year 1852 Dr. John Snow introduced as an anesthetic the monochloruretted chloride of ethyle. He administered the vapour of this substance many times to the inferior animals and to the human subject, and he came to the conclusion that the vapour was equivalent in value to chloroform, and had an advantage over chloroform, viz. that it rarely if ever produced vomiting; it did not usually excite the stomach, he observed, even if it were administered after food. In 1870 the distinguished Liebreich, who evidently was not aware of Snow's research, reintroduced this anæsthetic under the name of chlor-ethylidene. Chlor-ethylidene yields a sweet etherial vapour,

less pungent than vapour of chloroform, but still pungent; the vapour burns in air. The specific gravity of the fluid is 1.174, the vapour-density 49, the boiling-point 64° C. (149° F.). The composition is C, H, Cl. It differs from Dutch liquid, which in other respects it resembles, in not being decomposed by an alcoholic solution of potassa (Snow).

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I had already seen chlor-ethylidene in use in 1852, and had added Snow's memoir upon it (during the writing of which, by the way, he was taken with his fatal seizure) in my edition of his works on anæsthesia, published in 1858; but since the subject has come up again I have travelled once more over the same ground. I obtained a specimen of chlor-ethylidene, administered it several times for the production of anesthesia, and am bound to say of it that it is a very good anaesthetic. It resembles bichloride of methylene very much in its action, produces vomiting as rarely, but is less rapid than the bichloride, being of higher boiling-point and yielding a heavier vapour.

On inferior animals I find that when carried to extremity it arrests the respiration before it arrests the action of the heart; and I also find that recovery from its extremest effects is comparatively easy. In one of my lectures during the past winter session I restored life in a rabbit, by careful artificial respiration, seven minutes and a half after all signs of natural respiration had been abolished by the vapour of chlor-ethylidene.

I would give to chlor-ethylidene a prominent place amongst anæsthetics. It would take the place of either chloroform or bichloride of methylene efficiently; it is safer than chloroform, and excites vomiting less frequently; it is less rapid in action than methylene bichloride, not more effective, and possesses, I think, about the same value in matter of safety.

HYDRAMYLE.

At the Meeting of the Association at Exeter I placed before this Section a fluid called hydride of amyl. The fluid had a specific gravity of 625, and it boiled at 30° C. (86° F.). Its composition was stated to be C, H,, H. I described then that this vapour was a quickly acting anæsthetic.

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During the present year I have experimented largely again with this hydride, with the view of rendering it applicable for the production of rapid anæsthetic sleep, for short operations, such as extraction of teeth. this research I found one or two difficulties in the way. The fluid was too light to be manageable on every occasion; that is to say, it escaped from the inhaler, as a gas, by the mere warmth of the breath, and the vapour had also an odour which to the majority of persons was objectionable.

I set to work to obviate these difficulties, first by slightly weighting the fluid, and secondly by making an inhaler that should more effectually restrain the liquid as it was undergoing evaporation. In both attempts I have succeeded well.

In making good bichloride of methylene we put finely pulverized zinc into a retort and pour upon it absolute alcohol and chloroform, using afterwards a heat not exceeding 120° F., in order to distil over the product. I modified this process by diluting the mixture of chloroform and alcohol with eight times the volume of hydride of amyl. This mixture is poured upon the zinc, with the result of an instant vehement action without any application of heat; after a free evolution of gas, which lasts some minutes, there distils by this method a fluid which contains pure hydride of amyl and pure bichloride of methylene. If the distillation be carried on at 98° F., the fluid that comes over has the specific gravity of ordinary ether (720), a most agreeable odour, and rapid anæsthetic action. I have now administered this