4. In an experiment by MM. Flander and Denger, 3 decigrammes of arsenious acid were introduced under the skin of a sheep; symptoms of poisoning very soon manifested themselves, and in 5 d. the animal died. Autopsy showed pleuro-pneumonia with effusion of r. side. (Ann. d’Hygiene Publ., April, 1843, p. 469.)
5. Arsenious and arsenic acids were given to animals in small doses, so that they lived from 3 to 6 d. Liver was always found considerably enlarged and very fatty. Fat was not diffused through substance of organ. In each acinus three zones were distinguishable, -an external, pale and red; a middle, dull yellow; a central zone, of comparatively trifling extent, and appearing as a reddish point. Microscopic examination showed that it was in middle zone that cells were enlarged and filled with fat-globules of various size. Kidneys were much enlarged, tubuli completely filled with fat-globules, and wherever epithelium still existed its cells also were full of similar globules. Muscular fibres of heart and diaphragm had also undergo a fatty tongue. Epithelial cells lining glands of mucous membrane were often enlarged, and sometimes contained a quantity of fat. When large doses of arsenious acid were given to rabbits, so as to kill them in 20-28 h., liver was found fatty, but far was diffused through substance of organ, so that change was not so definite as in more chronic cases. (SAIKOWSKY, quoted in N. Syd. Soc. ‘s Year-book for 1867 from Virchow’s Archiv, xxxiv, 73. GIES found same, with changes in bones analogous to those of chronic phosphoric poisoning. In long bones was a special thick layer of bone between epiphysis and shaft; shaft also was thicker, and in bones such as ribs and vertebra structure was more dense and harder to divide than in normal animals; the new structure was true bone, but bone corpuscles and Haversian canals were smaller than average. If doses were increased beyond a certain point resorption of bone occurred, and symptoms of poisoning set in. Gies does not accept the view of increased stimulus being given to bone formation, but rather that of diminution of tissue change, and hence increased deposit and insufficient removal of organic particles. [ “I conclude that although some contradiction exists on this point between good authorities, yet the balance of recent evidence points to lessened exertion and consequent lessened tissue-change, as an effect of A.] (PHILLIPS.)
6 a. MM. Caillot de Poncy and Ch. Livon have lately experimented on chronic arsenical poisoning. The effect of the addition of small quantities of A. to the diet of cats was not at first to cause any disturbance in the general health; indeed, they ate more, became fat, and seemed generally to be in exceedingly good health. After a time, however, they began to lose flesh, became affected with diarrhoea, lost appetite, became languid, and finally died in a state of anemia and emaciation. At the necropsy all the muscles, including the heart, were extremely pale; liver, lungs, and kidneys presented all the naked-eye signs of fatty degeneration; the mesenteric glands also were swollen, and showed same change- a lesion not previously observed.
6 b. Cornil and Brault found, in acute poisoning, the pulmonary capillaries dilated and distended with blood, and the endothelial layers invaded by large fatty granulations. Hemorrhages were seen at certain points, and many alveoli were filled by degenerated cells, giving rise to the naked-eye appearance of pale islets. The mesenteric glands appeared as large yellowish-white masses of caseous aspect. The microscope showed that the peripheral parts of the glands were invaded by fatty degeneration, which was not limited to the follicles. (Brit. Journ. of Hom., xlii, 90.)
7 a. Considerable doses of A. given for a length of time produce fatty degeneration of the liver and other organs, and cause the glycogen to disappear from the liver, so that puncture of the fourth ventricle no longer produces glycosuria.
7 b. Minute doses appear to increase rapidity of pulse; larger doses diminish pulse and blood-pressure. In frogs the heart is slowed, and finally stands still in diastole. This stoppage of the heart appears to be due to paralysis of the motor ganglia, as the muscular substance will still continue to contract upon direct irritation. In warm-blooded animals it appears to prolong the irritability of the heart so that it will still continue to beat for many hours after the death of the animal. According to Runtzer, this is due to retardation of the vital processes in the mammalian heart, so that it comes to resemble that of a cold-blooded animal. A. diminishes the blood pressure from the beginning. This appears to be due partly to diminished activity of the heart, but chiefly to paralysis of the splanchnics allowing the abdominal vessels to dilate. (BRUNTON, Pharmacology (1885), sub voce.)
8. DELAFOND has noted the almost immediate production (in less than 2 h.) of false membranes, sometimes so compact that they may be removed in one piece, like a hollow cylinder, on internal surface of small intestines in horses poisoned by A. (Amer Journ. of Medorrhinum Sc., N. S., vi, 495. Lolliot noted a similar occurrence in one only of the smaller animals poisoned by him. See his Etude Physiologique de l’Arsenicum, 1868.)
9. Two cats lapped up milk vomited by a patient who had taken a large dose of A. with fatal results. One died in great suffering the following day; the other was very sick, refused all food for 7 d., and became thoroughly emaciated. On 9th d. all hair came off save that on face; surface continued quite bare for 2 months; hair then began to grow, and in 9 months cat was covered with a beautiful silky fur, but only half the length of its former coat. (Brit. Medorrhinum Journ., 1856, p. 17.)
10 a. In frogs, according to Sklarek, in about 5 m. after poisoning by arsenic acid, the animal lies flat, with extended extremities and without breathing. Pinching, or other irritation, excites neither reflex action nor voluntary motion, though much voluntary power remains, since, on lifting the animal, or withdrawing a leg, or turning the frog on its back, it displays active voluntary movements. In a short time, however, the animal becomes completely paralyzed. A., therefore, paralyses first sensation and reflex action, and some time afterwards voluntary power. In cold weather I find that sensation and reflex action persist as long as, or longer than, voluntary power. Sklarek attributes the general paralysis to the action of A. on the cord. [ Vulpian has been able to ascertain, in a dog which he had made to swallow considerable doses of A., the existence of an acute myelitis. (L’Art. Medorrhinum, xIiii, 49.) ] My own experiments confirm this statement; but they also show that A. is a paralyser of the motor and sensory nerves, and of the muscles; in fact, it is a protoplasmic poison, destroying the functional activity, first of the central nervous system, next of the nerves, and last of the muscles.
10 b. In our experiments published in the Journ of Physiology for 1878, Dr. Murrell and I found that A., like tart. emetic, produced desquamation in frogs. After poisoning with only 1/10000 of the weight of the animal, desquamation begins on the trunk in about 5 h., on the legs in about 8 h. The cuticle strips off in large pieces, so readily that mere handling of the animal detaches it. Does A. affect all epithelial structures in this way? I think so. Miss Nunn has shown that it so affects the cornea; and after acute poisoning the bowels are found filled with a rice-water fluid consisting of epithelial flakes, and the epithelial cells are choked with granules, some being in a state of advanced fatty degeneration; and these changes occur even when the poison is injected into a vein. (RINGER, op. cit., sub voce.)
11. An examination of a series of sections taken from different parts of the body at different intervals after the (hypodermic) injection of the poison shows that the general effect of arsenious acid on the epidermis is to cause a degeneration and partial solution of the protoplasm of the cells, whereby (1) the whole epidermis becomes loosened from the subjacent derm; (2) the cells of the Malpighian become incoherent so that the whole layer collapses, and its well-known architectural features become obscured; and (3) the intermediate layer separates from the Malpighian layer below, and at times from the corneous layer above. The corneous and intermediate layers are thus desquamated, sometimes separately, sometimes-and perhaps most frequently-together. In no case, even in those of most extreme or most lengthened poisoning, have I ever seen the Malpighian layer actually cast off during life; it always remains attached (although loosely) to the derm, in a manner I shall presently describe.
It is obvious from the foregoing account that the A. first attacks the lowermost or innermost portion of the epiderm, that its action advances from the derm outwards…. I have never observed any excess of the fluids excreted by the skin generally as the result of arsenical poisoning, and it is impossible to explain the changes described above as merely or even chiefly due to an excessive discharge of fluids from the cutaneous blood- vessels or lymphatics loosening and separating the cells. All the facts go to prove that the changes are the result of the A. acting directly on the epidermic cell, which, with its diminished cell-substance and shrunken muscles, presents a striking analogy with the secreting cells of a salivary gland which has been stimulated to exhaustion; and I shall probably not go for wrong in regarding the changes of the former as the consequences of an action of the poison not wholly unlike an excessive, in fact a lethal, stimulation, by which the destructive changes of the protoplasm are hurried on beyond the reparative power of the constructive stages. The stimulation is obviously of a peculiar kind. One marked effect of the stimulation of undifferentiated protoplasm is to forward and accelerate processes of growth. I have looked diligently for indications, such as double nuclei, &c., of multiplications in the epidermic cells, but always in vain. (NUNN, Journ of Physiology, 1878.)
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.