4 a. Acute poisoning was induced in five animals whose body’s weight varied from 1000 to 9100 grm. (about 10 lbs.), by injecting from.15 (about two grains) to.27 grm. (or.03 per 1 kilo.) of cocaine, the animals dying in from 25 to 60 m. after the injection. The train of toxic symptoms was fairly uniform. For a few m. after the injection the dog either did not present anything abnormal, or fell into a kind of stupor; then appeared dilatation of pupils, restlessness, extreme dyspnoea, and acceleration of pulse, and, in 15 m., attacks of clonic spasms, lasting for half a m. or so, and alternating with paroxysms of typical Cheyne – Stokes’s breathing; later on there supervened complete general anaesthesia, dilatation of the palpebral slit, congestion of the conjunctiva, lachrymation, cyanosis, loss of consciousness, incontinence of urine and faeces, stertorous breathing, tremor of the whole body, and progressive failure and retardation of cardiac action.
4 b. Chronic poisoning was brought about in four dogs (weighing from 5600 to 8200 grm.) by injecting cocaine in doses gradually ascending from three or four (about.2 per 1 kilo.) to ten or sixteen centigrammes a day, the whole amount taken during the experiment varying from 1.08 to 7.8 grm., and death ensuing in from 43 to 107 d. The initial small doses gave rise to acceleration of breathing and pulse, fleeting (15 m.) general restlessness, also consecutive weakness of the animal’s hind limbs, mydriasis, and rise of the rectal temperature (.3 o to.5 o C.), the symptoms disappearing in about 3 h. Increased doses produced the same but more pronounced and prolonged symptoms. The 7 – centigramme doses induced sometimes manage movements of 2 or 3 m. duration, with extreme restlessness, followed in 4 hours or so by as extreme weakness and lassitude. The 8 – centigramme doses gave rise to stupor, with high dyspnoea, acceleration of the pulse, and mydriasis, of 2 – 3 hours duration. The 1 – decigramme doses caused a complete narcosis, rise of the rectal temperature (1 o C.), decrease of general sensibility, and other symptoms of acute poisoning. In two of the animals there occurred several attacks of clonic spasms. Both of them died suddenly after a convulsive paroxysm, with consecutive profound prostration. The other two sank gradually from progressive extreme cachexia (which, however, was more or less pronounced also in the former two dogs). 4 c. Morbid lesions, either in acute or in chronic poisoning by cocaine, did not represent anything characteristic or pathognomonic. A. Macroscopical examination. – In acute poisoning there were invariably found all those alterations which occur in cases of fatal asphyxia, – such as dark fluid blood, engorgement of the thoracic veins, dilatation of the right auricle and ventricle of the heart, venous congestion and oedema of the lungs, extravasations under the pleurae, pericardium, endocardium, and gastric mucous membrane, cyanotic liver, contracted spleen, moderate hyperaemia of the brain and spinal cord, and a more intense one of their meninges. The same changes were present also in those two cases of chronic poisoning which had terminated suddenly, while in the two eminently cachectic cases there were detected extreme anaemia and dryness of all organs except the brain, medulla oblongata, spinal cord, and cerebro – spinal meninges, which were intensely congested. B. Microscopical examination. – Blood did not present any structural changes. Lungs: In acute cases there was dilatation of the alveolar vessels, with extravasations and occasional collapse of the alveoli; opaque swelling of the alveolar epithelium; hyperaemia and extravasations in bronchioles. Liver: In acute poisoning there was found opaque swelling and granularity of hepatic cells; hydropic and granular degeneration of the epithelium of gall – ducts; serous infiltration of the interlobular connective tissue; engorgement of the interlobular and central veins, with occasional small – sized extravasations in their neighbourhood; and a distinct increase of glycogen in hepatic cells. (The latter statement is in accord with Professor Tarkhan – Mouravoff’s observations, according to which large doses of cocaine rapidly give rise in dogs to glycosuria of about five hours’ duration; vide the Journal dla Normal. i. Patolog. Histolog., etc., vol. vi.) In chronic intoxication, Dr. Zantchevsky found atrophy and albuminoid degeneration of hepatic cells, atrophy of the interstitial tissue, and atrophic attenuation of vascular walls. Heart presented considerable lesions in every one of the cases. In acute poisoning there was found initial signs of albuminoid degeneration of muscular fibres; minute extravasations in the subpericardial and, in a lesser degree, in the subendocardial and interstitial connective tissue; tumefaction of the endothelium of capillaries; opaque swelling and (non – fatty) granularity of many cardiac ganglia, with indistinctness of their nuclei. In cachectic chronic cases the degenerative (albuminoid and fatty) changes were still more pronounced, the muscular fibres having lost their striae and being intensely granular, while the vessels were empty and their walls atrophied; the cardiac ganglia presented extensive fatty degeneration and atrophy of their cells with vacuolization of the protoplasm, their nuclei being extremely indistinct. The medulla oblongata, especially the spinal cord, proved to have undergone still more profound alterations. In acute cases there was invariably met albuminoid degeneration of ganglionic cells of the medulla oblongata, anterior and posterior horns, Clarke’s columns and Roland’s gelatinous substance, the spinal changes being specially pronounced in the regions of the cervical and lumbar enlargements. There were found, further, dilatation of perivascular spaces, small extravasations in the gray matter, and occasionally mucoid degeneration of the epithelium of the central canal. In chronic poisoning, side by side with the same (but more intense and more extensive) degenerative lesions, there were detected hyaline degeneration of nerve – cells in the spinal gray matter, engorgement of veins and capillaries (especially in the gray substance), and such changes of vascular walls as proliferation of their nuclei and hyaline degeneration, with consecutive varicosity of the diseased vessels. All those lesions in the medulla and spinal cord had a circumscribed character, – that is, were scattered in a patch – like manner over various districts of the organs. Dr. Zantchevsky is inclined to think that ” the degenerative changes arising in the nerve – centres under the influence of cocaine may be partly explained (apart from a still obscure specific action of the alkaloid on the nerve – elements) by a disturbance in the circulation of the central nervous system, which is caused by the drug. In acute poisoning cocaine brings about, in the first instance, a rise of the blood – tension, with a consecutive diminution in the supply of arterial blood; a subsequent fall of the blood – tension and a synchronous disturbance of breathing lead to a profound alteration of the blood in regard to its gaseous ingredients: hence the altered blood becomes an additional irritant agent; and hence there arise disturbances in the nutrition and degenerative changes of the nerve – cells. ” It would be superfluous, of course, to dwell on the extreme sensibility of the nerve – tissue towards any slight deviation in the circulation or the composition of blood. In conclusion, Dr. Zantchevsky draws attention to a close similarity between the morbid lesions in the nerve – centres as found by him in the cases of cocaine – poisoning, and those detected by Dr. Cziz in cases of acute and chronic poisoning by morphia and atropia (Meditz. Pribavl. k’ Morsk. Shorn., May and June, 1883), the difference being only a quantitative one; the former are somewhat milder comparatively with the latter. Perhaps there exists a still greater similarity between the alterations caused by cocaine and those found in the nerve – centres and their blood – vessels in starvation (as described by Drs. V. Mankovsky, Lond. Medorrhinum Record, Feb., 1884, and V. Rosenbach in his St. Petersburg Inaugural Dissertation,, 1883). Judging from that analogy, Dr. Zantchevsky arrives at the general conclusion that ” the cause of these degenerative changes which occur in chronic poisoning by cocaine should be sought in disturbed nutrition of cellular elements, which, in its turn, depends upon lesions of vascular walls, caused by a direct action of the alkaloid. ” (Therap. Gazette, 1889, p. 112.)
FERRUM MURIATICUM. (see vol.ii, p.573; vol.iv, p.586)
II. 12. Dr. de la Roche and three companions (distinguished as A, B, C and D) made provings of iron. All four were healthy and robust, the youngest 21, the oldest 26 years old. All of them carefully observed their pulse m. and evening for 4 day before and 14 day after the trial. They lived in their usual manner, avoiding all excesses in the matter of stimulants. The preparation they employed was a 1/2 per cent. watery solution of ferr. sesquichlor. The 1st week they took m. and evening at 8 o’clock 15 dr., the 2nd week 30 dr. m. and evening, the 3rd and 4th weeks 30 dr. three times a d. The total quantity of the iron salt consumed by each person in 4 weeks was about 1/2 grm.
Hughes was a great writer and a scholar. He actively cooperated with Dr. T.F. Allen to compile his 'Encyclopedia' and rendered immeasurable aid to Dr. Dudgeon in translating Hahnemann's 'Materia Medica Pura' into English. In 1889 he was appointed an Editor of the 'British Homoeopathic Journal' and continued in that capacity until his demise. In 1876, Dr. Hughes was appointed as the Permanent Secretary of the Organization of the International Congress of Homoeopathy Physicians in Philadelphia. He also presided over the International Congress in London.