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.

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NITRATE OF AMYL.

Nitrate of amyl, C, H1, 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-urca:

"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.

In order to determine the difference of action of the two ureas, 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 anesthetic 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).

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 anesthesia, 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 anæsthesia, 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 anaesthetic.

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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. In 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

fluid, in vapour, forty-six times for short operations on the human subject, and in the average of cases have produced the required insensibility within fifty seconds. In one instance insensibility was produced, a firm tooth was extracted, and perfect recovery occurred in forty seconds. As yet there has neither been vomiting nor other untoward symptom during the administration.

There is, however, a peculiarity in the action of this vapour to which I ought carefully to refer, viz. that insensibility from it intensifies after the inhalation of it is withdrawn. Thus in administering, whenever there is the least indication of its effects, such as winking of the eyelids or drop of the hand, the sign is given to stop the administration. The operator may now wait a few seconds and then proceed. The inhaler I have constructed for the administration of this new anæsthetic is before the Meeting. It is a simple hollow cone made of leather, and is furnished with two light silken valves for entrance of air and exit of vapour and breath. It is lined with domette set on a light frame or ring of metal. When the inhaler is not in use it forms a case for holding safely, in a bottle, four fluid-ounces of the anaesthetic liquid. This quantity is sufficient for twenty operations, of from one and a half to three minutes' duration, two drachms being the amount necessary for an operation not exceeding three minutes' duration.

The vapour described above will become, I believe, should experience confirm its safety, of general application as an anesthetic for short operations; for long operations it will probably not replace the heavier anaesthetics. I am indebted to Mr. Ernest Chapman for the suggestion of the abbreviated name hydramyle.

PHYSIOLOGICAL NOTES.

In the course of the researches detailed in the preceding pages I have again, as in previous researches, been led to notice certain simple facts which lie in the path of inquiry, and which, though not necessarily belonging to it, are too prominent to be passed by without notice. I shall therefore offer a few notes bearing on three topics; and this the more readily, because it is rarely the case that so many eminent physiologists as are now present, each one interested in the subjects to be named, meet together to take part in discussion.

EFFECT OF SOME NARCOTIC VAPOURS ON THE MINUTE CIRCULATION OF THE BLOOD.

I have taken occasion several times to observe the effect of narcotic vapours on the minute circulation of the blood. I prefer to use the term "minute circulation" because it embraces the minute arterial and venous, as well as the capillary circulation.

In these researches the web of the foot of the frog was selected for observation, and I think on the whole with advantage. The following particulars were carried out in every case :—

(a) A large healthy frog was chosen, and one in which the web was very clear. (b) The same microscopic power, and that low-the inch or half-inch object-glass and A eye-piece (Ross)-was always employed. (c) The temperature of the air was kept the same during periods of observation, and the work was conducted during the same hours each day, viz. between the hours of 2 and 5 P.M. (d) The observations were never hurried; they occupied an average of three hours each, and every change of scene in the vessels through the various stages of narcotism and of recovery were carefully and systema

tically noted. (e) The animals were placed for narcotism in the small glass chamber now before the Members. The chamber as it is was finally constructed, after many essays, by my friend Dr. Sedgwick, and it answered admirably. The animal was placed, without any restraint, in the chamber; one foot was then gently drawn out on to the stage attached to the chamber, and the web was extended over the small glass plate. The animal being thus prepared, the web was brought under the microscope and the circulation examined. (f) The part of the circulation to be observed was so selected as to include a good view of an artery, a vein, and the smaller intermediate capillary vessels. (g) When the natural condition of the circulation was well observed the chamber was closed by the sliding cover, and through it the narcotic vapour, the effect of which upon the circulation was to be investigated, was gently passed. The vapour was driven over with hand-bellows from a small Junker's apparatus, manufactured by Messrs. Krohne and Sesemann *. By counting the strokes of the bellows it was possible to maintain the same current of vapour at all times. (h) And lastly, the web was sustained in the same condition of moisture, so as to prevent errors of observation due to evaporation from the tissues.

Such were the precautions taken; and I am inclined to think they were sufficient, although it will be a great satisfaction to me and an aid in my future labours to hear of any amendments or additions that may be suggested. The narcotic vapours used in the research were hydramyle, chloroform, bichloride of methylene, and absolute ether. In some particulars these acted precisely in a similar way, in other particulars they acted in a way more or less peculiar to themselves.

The first fact I would notice as common to the action of all the vapours used is, that no obvious change in the physical characters of the blood-corpuscles, red or white, was ever observable; neither was there any noticeable difference in the relationships of the red and white corpuscles to each other. The red corpuscles held their ways so long as there was motion in the centre of the blood-streams, while the white ones rolled along by the sides of vessels in the same manner as they did before the narcotism.

Another fact common to the action of all the vapours used was, that the first sign of arrested movement of the circulation commenced in every case on the venous side of the circulation, and consisted of a sort of pulsation or to-and-fro movement of the current through the vein; soon upon this the venous current became obviously slower and the vein dilated, while the arterial current remained, often for a long time, unchanged.

In every case the minute circulation remained long in force after the respiration had entirely ceased, and after all evidence of the continuance of life had entirely ceased. On the average the animals ceased to breathe for one hour and thirty minutes after the deep narcotism had set in; yet all the while the minute circulation was still playing with more or less of efficiency, and so long as it continued the chances of recovery were nearly certain. The cessation of the minute circulation was, on the other hand, the sign and proof of irrevocable death.

There was still another effect common to all the narcotics used. The circulation through the capillaries often stopped altogether, and for considerable intervals of time, when the reduction of the circulatory power was greatest. Under this condition the circulation, such as it was, was maintained by the arteries, in which the blood moved to and fro with occasional slow steady * Dr. Richardson here fitted up the apparatus, including small chamber, hand-bellows, and Junker's bottle, and showed the method by which it was worked.