THE LANCET,] SCIENTIFIC INVESTIGATIONS INTO THE CAUSES OF CHOLERA. of the species. This had two advantages: 1st, it was undoubtedly true mucor racemosus; and, 2nd, it was derived from a place which cholera had not visited. Some of this material was, on the 7th October, set for development in a watch-glass containing some solution of grape-sugar. Previous to preparing the cultivation, some of the material was examined microscopically, and was found to consist of mycelial threads, sporangia containing spores, and numerous free spores. On examining the cultivation on the following day the same elements were visible, but many of the spores had germinated, sending out one or more fine filaments, which in some cases were slightly branched. (See Fig. 3.) The next day's examination showed FIG. 3. vation), development of the young plants was seen to have advanced greatly. The dilatations were now no longer solitary, but were arranged in chains, and were also much increased in size. Many of the dilatations were seen to have a double contour (see Fig. 5), due to the contraction of the FIG. 5. ان considerably increased development in the filaments, which were now much branched and frequently marked by dilatations of a more or less round or oval form. In some places filaments were seen proceeding from spores contained in capsules which were still entire. (See Fig. 4.) On this point Prof. De Bary remarked that though, as a general rule, the Fig. 4. contained protoplasm, caused by osmosis arising from the density of the surrounding medium. This double contour disappeared on the addition of a little distilled water to the medium. In the mycelial filaments, and more especially in the dilatations, were numerous globular bodies. These were in some places disposed with a certain amount of regularity, while in others they were irregularly heaped together. The nature of these bodies (see Fig. 6) had now to be ascer FIG. 6. ། sporangia ruptured before the germination of the contained spores, yet it frequently happened that these germinated within an entire sporangium, thrusting out their filaments through its walls. (See Fig. 4.) The dilatations noticed above are analogous to the tubers of the potato, being capable of giving origin to new individuals after the rest of the plant to which they belong has died. They vary extremely in size, presenting in this a marked contrast to spores, which are very constant in this respect. tained. With a view to this, ether was added, and their fatty nature clearly demonstrated by their disappearance under its influence. At this date young sporangia appeared for the first time. They were seen in various conditions: some borne on filaments; others detached; and others in which the peridium had ruptured, with partial escape of the spores, or even totally disappeared, leaving only the columella attached to the extremity of the filament. It was in some cases a matter of some difficulty to distinguish a detached sporangium containing spores from a dilatation containing oil-globules. Here again, however, the application of ether settled the question; the oil-globules disappearing, whilst the spores remained unchanged. In the same field as the mucor plants, some specimens of penicillium were visible; but in no case could the same plant be seen to bear mucor sporangia and penicillous heads. Dr. De Bary here, again, insisted on the necessity of only drawing conclusions as to development, and the identity of various forms where one could trace them unmistakably arising from the same spore. All the specimens of mucor growth which had as yet appeared were colourless; and Prof. De Bary now proceeded to take means to secure coloured specimens. Whilst doing this, he remarked that, as in higher plants so in fungi, At this stage of the proceedings small portions of the material from the watch-glass were placed on two object-colour is a matter of very minor importance, and one which glasses, and, after being carefully examined microscopically, introduced into the common isolating apparatus. On the fourth day of observation (the third of culti cannot always be caused to vary at all. In mucor racemosus, however, a brown or yellowish colour can almost always be obtained empirically by the addition of an am organic connexion affording no grounds for such a conclusion. 6. That the use of reagents is absolutely necessary in order to escape from constant sources of fallacy. Fourth. Observations on Urocystis occulta.-Prof. De Bary considered that a familiarity with this species was of importance, considering that Prof. Hallier had in his publications maintained that the fungus which he found on riceleaves, and which he considers peculiar to cholera, was a urocystis. He accordingly showed specimens of various plants affected with urocystis, remarking, in passing, that rye was the only grass known to be affected by a species of this genus-viz., urocystis occulta. A specimen of rye so affected was next taken, and some of the fungus removed from it, and examined microscopically. It now appeared to consist of brown angular cells, which were either solitary or aggregated into masses, the constituent cells of which overlapped one another. (Fig. 9.) Each of these cells had a FIG. 9. as to be easily recognised again after the geography of the preparation had been clearly ascertained. This preparation was now introduced into the cultivating apparatus. On examining it twenty-four hours later, the spores were seen to be still in connexion with their cyst, but to have sent out numerous branched filaments, which were marked by dilatation, and formed an abundant mycelium. (Fig. 8.) More nutritive fluid was now added, which caused the spores to swell out, rupture the cyst more completely, and escape from it, leaving it empty, with the exception of a single ungerminated spore, which remained within it. (Fig. 8.) The specimens undergoing coloration now showed various tinges of brown and yellow, and an abundant development of oil-globules. They also afforded examples of a peculiar form of gemmation often occurring in mucor dilatations. General conclusions resulting from the above series of observations.-1. Mucor spores, on germinating, invariably give rise to plants of mucor, whether they be exposed to air or not, and whatever be the chemical reaction of their surrounding medium. But 2. The relative proportion which ordinary mycelial threads, chains of saccules, and sporangia bear to one another varies with these accidents. 3. Coloration may be induced at will by the addition of ammoniacal salts to the soil of the cultivation. 4. The spores may germinate either before or after the rupture of their containing cyst or sporangium. 5. When, in any cultivation, various forms of fungi are observed in the same microscopic field, it does not follow that they have a common origin; mere coexistence without varying number of cellular processes connected with it, which were rendered very manifest on the cautious addition of strong sulphuric acid. This reagent destroyed the colouring matter in some degree, and so allowed the relations of the small cells to the large ones to be more clearly seen. Preparations illustrative of its development were now shown corresponding with the figures in Prof. De Bary's paper on Cholera Fungi, and clearly demonstrating the difference in its germination from that described by Hallier as occurring in his cholera cysts. 66 Fifth. Probable nature of the bodies found on rice-leaves by Prof. Hallier, and considered by him to be the cysts of the cholera fungus.-Prof. De Bary stated that as he had not seen preparations of these cysts he could only judge of their nature from the figures of them published by Prof. Hallier in his Phyto-pathology." In his opinion the figure seems much more to resemble a pleospora than a urocystis. With a view to substantiating this opinion, he first showed some of Tulasne's plates of Pleospora, and then, sending out to the Botanical Garden, procured one or two dead or dying plants. These presented numerous small, dark subcuticular markings. A portion of cuticle so affected was now examined microscopically: it was seen to present numerous dark-brown cellular masses of pleospora, closely resembling those figured by Hallier as cholera cysts. There were also numerous mycelial filaments, some free spores, and here and there a few detached cells adhering to one another, and presenting a faint resemblance to urocystis, but without its cellular projections. As Prof. Hallier has now abandoned his views as to the similarity, if not identity, of his cholera cysts and urocystis, it is unnecessary to enter farther into the matter here. Sixth. "Micrococcus" and yeast-cells.-On examining the mucor-cultivation on the 8th October, Dr. De Bary pointed out numerous small cells which were either separate or in chains, and also numerous aggregations of smaller bodies (appearing as minute granules x 300), some of which were in active movement. The larger cells he stated to be yeastcells, whilst the smaller were bacteria or schizomycetes, which are included by Prof. Hallier under his comprehensive term "micrococcus." Dr. De Bary next proceeded to discuss the nature of yeastcells. He defined them as being "fungal cells immersed in fluid, and increasing by a repeated process of gemmation; the new cells either becoming detached, or remaining connected in chains of various extent. Such cells are derived from various fungi, and closely resemble one another in appearance. They differ from one another, 1st, as regards their physiological action, as shown by the various kinds of fermentation which they induce; and, 2nd, as regards the fungi developed from them, under circumstances favourable to the normal development of the species." Experiments with a view to determining the species to which a given yeast-cell belongs are beset with many difficulties. Even if a single cell be isolated, it is almost impossible to be certain that it is a bonâ-fide yeast-cell, and not a spore which has become mixed with the yeast. On this point Prof. De Bary remarked that "modern mycology" derives yeast from everything; taking a large quantity of material, and concluding when yeast-cells appear in it that they necessarily have originated from some special constituent in the material, whereas the spores of various fungi may have been present and have simultaneously given origin to yeast-cells. "As well might one introduce a stone with the material, and conclude on the appearance of yeast-cells that they had taken origin from the stone." The Bacteria were next examined; and Prof. De Bary explained his views regarding them, as stated in his paper on Cholera Fungi, entering at some length into the grounds on which he founds his opinion as to their being algal and not fungal in their nature. During the next few days both yeast-cells and bacteria increased greatly in quantity; but there was no evidence of the development of the one form into the other. Prof. Hallier states that micrococcus is produced, whenever a spore is introduced into a suitable fluid, by a peculiar species of development. Prof. De Bary believes that this is not the case. With regard to this question, Prof. De Bary stated that no doubt, if spores are sown (even in distilled water), bacterial forms are found on examination, either at once or at some later period. If the distilled water employed have been kept for any time (however carefully), bacteria will be visible at once; for it is only freshly-distilled water that is free from them. Prof. De Bary stated that he has never seen the formation of micrococcus from the spores of any fungus, though he has often seen bacterial forms in the fluid in which such spores may be. He has made careful observations on penicillium (one of Hallier's micrococcusforming fungi), and has seen: 1st. Cases in which the spores germinated. 2nd. Cases in which they did not germinate. 3rd. Cases in which they ruptured. In none of these cases has he ever seen the formation of micrococcus. When spores are cultivated, they either germinate, or do not germinate; and in either case schizomycetous forms appear sooner or later. If the spores do not germinate, they may burst, and the granules of the protoplasm escaping may mingle with the surrounding fluid and schizomycetes, and of course the latter tend to accumulate to the greatest degree in the neighbourhood of such granules-i. e., in the situation where they can obtain most nourishment. Whenever a cultivation of spores is undertaken, they are almost certain to carry with them the germs of bacteria, schizomycetes-i. e., as these bodies naturally exist in greatest abundance in the same situation as are suitable to fungi, and from the rapidity of their multiplication, one or two germs will soon give rise to an immense number of individuals. Seventh. Oidium lactis and 66 Cylindrotanium cholera Asiatica."-Professor De Bary considered that an acquaintance with oidium lactis and its forms was desirable on account of Thome's observations on the so-called cylindrotænium cholera Astaticæ. (Vide Virchow's " Archiv," Bd. xxxviii.) Accordingly he showed specimens of oidium, and set spores of it, to be developed for future examination. The specimens showed it in various stages of growth and development (Fig. 10, a), showing mycelium and spores, some of which adhered to one another in zig-zag chains, while others were separate and scattered over the field of the microscope. Dr. Thome's figures of cylindrotanium were now compared with these forms, and a most close accordance was at once manifest between them. In connexion with this subject, Professor De Bary remarks on the extreme frequency of the occurrence of oidium [JAN. 9, 1869. 41 THERE is no subject on which the lamented Trousseau shed more of the light of genius than that of the terrible kind of facial neuralgia to which he gave the name epileptiform." The picture of that disease which came from his hands is wonderfully vivid, and wonderfully like the original, even if somewhat too sharply defined; and there is suggestiveness in the view which led him to call the disease "epileptiform," although the name itself be, as it unquestionably is, unfortunate. It was a pity, namely, to tempt ordinary thinkers to dwell more closely on the spasmodic manner of onset of the pains than on the remarkable constitutional and family history which distinguishes the victims of the disease; but, on the other hand, the word "epileptiform" may serve to call attention to the real and important family connexion which there is between epilepsy and certain forms of facial neuralgia. As regards the treatment, however, of this dreadful disease, Trousseau appears to me to have done the reverse of good by the precepts which he laid down. I say this with the diffidence one must feel in criticising so able a teacher; but also with a firmness of conviction that has been produced by undeniable, observed facts. Trousseau describes, with the brilliant eloquence so peculiarly his own, the tragic prospect which the sufferer from spasmodic tic has before him; how hopeless it is that he should obtain a cure, and how certain that any relief obtained by remedies will be followed by a return of all his sufferings. He lays it down as an absolute law that we are to expect nothing but a temporary respite or alleviation; and he then proceeds to say that this minor amount of good is to be procured by very large and increasing doses of opium better than by any other means. I observe that various later writers have followed in the same sense; but I am so en tirely convinced that the principle laid down is wrong, that Now I believe that a very much better result than this may be obtained if the malady be treated, from an early stage, according to the following plan:-1. Counter-irritation of a peculiar kind. 2. Nutritive tonics. 3. Subcutaneous injection of morphia, or of atropia, according to circumstances. treatment which are within the reach of every practitioner. It is necessary to state, however, that for those who are so circumstanced as to be able to provide themselves with proper apparatus for the generation of a constant galvanic current, the prospects of effecting good in even the most seemingly hopeless cases of spasmodic facial tic are very greatly increased. Not to dwell, now, on my own more limited experience, I maintain that it is impossible for any candid person to study carefully the treatise of Benedikt* without coming to the conclusion that we have in the constant current a remedy capable of effecting much more, in these severe cases, than any treatment by drugs, or any other means. A low-tension current from a Daniell's battery (using from five to fifteen cells, according to circumstances) applied daily in séances of a few minutes, appears sometimes to entirely arrest facial neuralgia of the worst type, and commencing under the most unfavourable omens. Especially may we indulge hope, as it seems to me, in regard to the results which may be obtained from the galvanisation of the sympathetic, in cases which would otherwise afford no rational hopes of more than the most trifling amendment. But on this point I have not space to dwell at length, and any very condensed account of this mode of treatment would be likely to mislead. To those who possess the requisite preliminary knowledge of electricity and electro-physiology, and also the opportunities of providing themselves with the somewhat expensive and troublesome luxury of a really effective constant battery, I would urge the necessity of a careful study of the English treatise of Althaus, and the German treatises of Remak, Benedikt, and Meyer, upon the medical uses of electricity. They will find facts therein which will at once arrest their attention, and engage them seriously in a most important branch of the therapeutics of nerve-pain. Wimpole-street, January, 1869. PAPERS ON BY SYDNEY RINGER, M.D., I.-ACONITE AND ITS PREPARATIONS. Or all the drugs we possess, there are certainly none more valuable than aconite. Its virtues by most persons are only beginning to be appreciated, but it is not difficult to foresee that in a short time it will be most extensively employed in the diseases immediately to be noticed. 1. Counter-irritation, to be useful in epileptiform facial tic, should not be applied to the branches of the fifth, but to those of the occipital nerve, at the nape of the neck. A blister in the former situation is as often hurtful as useful: in the latter, it is sometimes strikingly effective in gaining a short respite. And this is of very great consequence in THE THERAPEUTIC ACTION OF DRUGS. this awful disease; for the mere fact of such pain being allowed to continue is itself of the worst possible omen. 2. The assiduous use of cod-liver oil, or of some fatty substitute for it, should be insisted on from the first, and is of the highest consequence. 3. Subcutaneous injection places us in a totally different position towards the use of opium in spasmodic tic. There is no longer any excuse for the use of enormous doses of opium from the first. It will be sufficient to commence with the use of one-sixth of a grain of morphia twice daily, increasing this, if necessary, to one-fourth and one-half a grain; and, in rare cases, to one grain. If this produces, along with the other measures, a notable remission of the pain, it should be cautiously and steadily decreased, as circumstances may admit. In cases where morphia fails, atropia may be tried, in doses commencing at one-sixtieth of a grain. The injection of a less quantity than this would probably be useless in severe tic. Hopeless as was the cure of the form of neuralgia which I have now described, under Trousseau's plan, or any other which might be directed to the object of deeply narcotising the patient, the prospect is by no means so cheerless when the subcutaneous injection is employed, with the precautions above mentioned. Although I cannot say that I have ever seen a positive and complete cure of a facial neuralgia setting in under the conditions which have been described as peculiar to this disease, it is certain that the experience of those who have used the subcutaneous method extensively has proved that the attacks may be kept at bay, and their severity greatly mitigated when they occur; with this general result-that the setting in of a facial tic in the latter period of life, even in a patient whose family and constitutional history is of the worst augury, is no longer a fatal warning of life-long and scarce endurable misery. The economy in the necessary use of opium effected by the use of hypodermic rather than gastric administration is enormous ; and this not merely for the purpose of producing a given effect by a single dose, but also (which is most important in regard to the preservation of digestion and nutrition) with regard to the rate of increase in the doses. In the above remarks I have only referred to methods of As external applications, the liniment or ointment is used to relieve pain. They appear to possess power over pain of different kinds. In the neuralgias of the brow or face these applications are sometimes of the greatest use, and often relieve, either permanently or temporally, the distressing pain of these complaints. But while in many instances their effects are immediate and permanent, yet it must be confessed that in the majority of cases the pain is unaffected. Neither can we, with our present knowledge, predict with any certainty the cases in which the application will be useful, or those in which it will fail. This much, however, is ascertained, that those neuralgias which depend on decayed teeth or diseased bone, or on tumours pressing on the nerves, are beyond the control of aconite. But these are not the only forms of neuralgia over which aconite cannot prevail. No doubt in some instances the failure can be explained by the badness of the preparation; but even when this is excellent, it is not uncommon for the pain to remain unabated after the application. As, however, no harm can possibly follow their employment, they should always be tried; and if unsuccessful, then recourse can be had to other modes of treatment. If aconite suc ceeds at all, it will succeed at once; and hence, if no relief is speedily obtained, it is useless to continue its employment. The preparation should be sufficiently strong to produce * Elektrotherapie. Von Dr. Moritz Benedikt, Wien., 1868. THE LANCET,] DR. SYDNEY RINGER ON ACONITE AND ITS PREPARATIONS. decided numbness and tingling in the skin over which it is rubbed; and, where of service, these sensations replace the pain, which does not return when the effects of the aconite have worn off. The ointment and liniment should be applied with friction, which very greatly heightens their activity. Of the ointment, a piece the size of a pea or bean should be rubbed into the skin till it has disappeared. Care should be taken while using these powerful and poisonous applications that they are not rubbed into wounds or cracks of the skin, nor brought into contact with absorbent tissues, such as mucous membranes and the conjunctiva of the eye. Spinal irritation and intercostal neuralgia may in many instances be removed by aconite ointment, and sciatica sometimes yields to the same remedy. The former complaints are better treated by the belladonna preparations. When employed internally, the following sensations are experienced, the graver appearances and symptoms occurring only when a considerable dose has been taken. There is first a feeling of warmth at the pit of the stomach, with sometimes nausea and vomiting. The feeling of warmth spreads over the body, and there is soon perceived tingling of the lips and tongue and adjoining parts; the uvula with the tongue feels as if it were swollen, and too large for the mouth, and deglutition is frequent. If the dose has been a large one, the tingling and numbness are felt in the tips of the fingers, and thence spread over the whole body, and are accompanied by diminished sensibility and some muscular weakness, which, if the dose is a considerable one, becomes extreme, and is one of the most prominent and important symptoms of the drug. On the circulation and organs of respiration its action is most noteworthy. With moderate doses the number of the heart's beats are much lessened, and may sink to 40 or 36 in the minute. After a larger and dangerous dose, the pulse rises in frequency, and may become irregular. With some persons such irregularity follows even a small quantity of the medicine. Whether the frequency be increased or lessened, the pulse always loses strength, and hence the circulation is retarded. The effects on respiration are very similar. By moderate doses the breathing grows slower; but after large and poisonous quantities it is often short and hurried. During the administration of aconite cutting pains are often complained of in the joints and other parts of the body, and there sometimes breaks out on the skin an eruption of itching vesicles. Delirium occurs in some cases, but often after fatal doses the mind remains clear to the last. In some cases which have ended in death there has been found blindness, and deafness, with loss of speech. When death is produced by this drug, the muscular weakness is extreme, and frequent faintings occur. Death from aconite appears to be due to syncope. On account of its power to diminish sensibility, aconite has been used internally in various painful diseases; but other remedies have, for the most part, superseded it for the relief of pain. It is on account of its power to control inflammation and subdue the accompanying fever that aconite is to be the most esteemed. The power of this drug over inflammation is little less than marvellous. It can sometimes at once cut short the inflammation. It does not remove the products of inflammation when these are formed, but, by controlling the disease, it prevents the formation of these, and so saves the tissues from further injury. It is therefore in the early stage of inflammation that the good effects of this plant are most conspicuous; still, although the disease may have progressed to some extent, and have injured the organs by the formation of new and diseased products, while the inflammation is extending aconite does good. It is useful wherever there is acute inflammation of any tissues of the body. The good it accomplishes can be shown both by the amelioration of the symptoms, and, still better, by the changes it effects in the inflamed tissues when these are visible, as in pharyngitis, tonsillitis, &c. As might be expected, the results of aconite are most apparent when the inflammation is not extensive, or not very severe, as in the catarrh of children, or in tonsillitis, or in acute sore-throat. In these comparatively mild diseases, especially if the aconite be given in the earliest stage of the inflammation, when the chill is still on the patient, the following consequences will very generally be witnessed In a few hours the skin, which before was dry, [JAN. 9, 1869. 43 At the hot, and burning, becomes comfortably moist; and, in a little time longer, it is bathed in a profuse perspiration, which may be so great that drops of sweat run down the face and chest. With this appearance of sweat many of the distressing sensations-such as the restlessness, chilliness, or heat and dryness of the skin-are removed. same time the quickened pulse is much reduced in frequency, and, in a period of twenty-four to forty-eight hours, it and the temperature have reached their natural state. It is rare that a quinsy or acute sore-throat, if caught at the commencement, cannot be disposed of in twenty-four to forty-eight hours. The sweating may continue for a few days after the decline of the fever on slight provocations; but it then ceases. The appearance of the inflamed part also exhibits, in a striking degree, the beneficial effects of the drug. Thus large, livid, red, glazed, and dry tonsils may often in twenty-four hours have their appearance completely altered. If the medicine has been given before much lymph has been formed in these organs, in the time named the swelling and most of the redness will have disappeared, and the mucous membrane will have that look which proves the acute inflammation to have subsided-namely, it has become moist, and is bathed with mucus or pus. If just at this stage some strong astringent-such as glycerine of tannin-be applied, most of the remaining diseased appearance and the pain, if it continues, will be removed. Such are the visible effects of aconite on inflamed tonsils, &c. These statements are not exaggerations; but the simple truth, as may be witnessed by those who will employ the aconite in the way to be immediately mentioned. Its effects on catarrhal croup are as conspicuous. In a few hours the urgent dyspnoea is removed; and in a short time longer the fever is subdued. Severe colds, in, which there is much chilliness with great aching of the limbs, with a hot, dry skin, and quick pulse, may be equally well treated by aconite. So, indeed, may all the slighter forms of inflammation. The effects of this valuable drug, though not so rapid, are equally important on pneumonia, pleurisy, and the graver inflammations. These diseases may be considerably curtailed, and made much milder, if aconite is employed. Its influence on inflammation has been ascribed by most observers to its power over the heart; and, as they truly point out, the remedy is found to be of most use in the sthenic forms of the disease; and where there is great weakness and the heart beats feebly, unless care is taken, it may do harm. The method of employing the drug has much to do with its success. As already said, it should, where possible, be given at the very beginning of the disease. Every hour is of importance; the use of the medicine should never be delayed. Of the tincture, half a drop, or a drop in a teaspoonful of water, should be given every ten minutes or quarter of an hour for two hours, and afterwards be continued every hour. If there be much prostration, and the pulse be feeble and weak, a still smaller dose will best be given. It is not inappropriate to mention here what signal service the thermometer may render in enabling us to decide whether aconite should be given or not. When called to see a patient, and when the symptoms and physical signs are not sufficiently developed to decide whether an acute inflammation of some deep-seated part has, set in or not, this instrument will often decide the doubt. No acute inflammation can exist without preternatural heat of the body. Hence, if in a doubtful case the temperature, after a careful investigation, be found natural, the case is not one for aconite; while, on the other hand, if the symptoms, although doubtful, indicate an inflammation, the presence of an increased heat of the body will very considerably add to the probability of its existence, and will so indicate the advisability of employing aconite. Another instance may be mentioned. After scarlet fever, as is well known, acute inflammation of the kidneys is very liable to occur. This would at once be indicated by a rise in the temperature of the body. It is therefore desirable to direct the friends of such patients to observe, night and morning, the temperature; and if this should rise beyond limits of health, they should at once commence the administration of aconite, and not allow some hours to elapse before the patient can be seen by the medical attendant. It is true the fever may depend on some other complaint than |