—These are required in every case of diphtheria showing any marked degree of constitutional depres sion, most of all in septic cases. The pulse and the general condition of the patient are the guides in their adminis tration.
The best of all is, undoubtedly, alcohol. A child of three or four years can take at least 1 ounce of whisky or brandy in twenty-four hours. It should be given diluted with from 4 to 6 parts of water. In the severe cases the quantity of alco hol may be increased to several times the amount named above. It is best to give it apart from the food, as the patient may decline to take the stimulant, and may be led to refuse the food because of its admixture. Next to alcohol, strych nine is of most value. The / 1. no part of a grain may be given every two or three hours to an infant one year old; twice that amount to a three-year-old. The drug may be pushed till the deep reflexes show an exaggeration. Digitalis and like cardiac stimulants may be called for by the condition of the heart, but most reliance is to be put in alcohol and strychnine.
Antitoxin.—The antitoxin treatment of diphtheria has been in general use the world over for the past three years, and in that time has won for itself the right to be regarded as a specific.
[The history of the introduction of the diphtheria antitoxin may be found in Welch's article in the "Transactions of the Association of American Physicians" for 1895, page 313, and in brief in the article on "Diphtheria" in volume i of the ANNUAL OF THE UNIVERSAL MED ICAL SCIENCES for 1S96.] The antitoxin is derived from the blood of horses that have been sub jected to repeated inoculations of in creasing doses of the toxins produced by the diphtheria bacillus. The course of treatment usually occupies several months. When immunity has been thor oughly established in a horse, the blood is drawn from a jugular vein into steril ized vessels and allowed to clot. The clear serum is then siphoned off into small sterilized bottles, each of which contains sufficient antitoxin for one dose and is preserved by the addition of cam phor or carbolic acid in small quantity. The antitoxin thus prepared is a clear, limpid fluid, having the color of blood serum. If kept in a cool, dark place, it remains clear and is efficient for several months. After a year it begins to lose some of its power. Often before this time the serum becomes turbid and is unfit for use. The strength of the serum is expressed in terms of an arbitrary unit, dependent upon its power to neu tralize definite quantities of diphtheria toxins. Upon each bottle of antitoxin is indicated the number of antitoxin units which it contains.
Little is yet known of the nature or method of action of the antitoxin. Ac cording to one theory, its action is purely chemical, neutralizing the diphtheria toxins present in the blood; according to another, it acts by increasing the re sisting power of the cells of the body to the diphtheria toxins.
With the object of investigating the local antidotal effect of antitoxin, doses of this were injected in certain cases with crude toxin. Three series of experi ments made on guinea-pigs: (1) with toxin alone, (2) with toxin and a half neutralizing dose (as regards its lethal activity) of antitoxin, and (3) with toxin and a fully-neutralizing dose (as regards its lethal activity) of antitoxin. Of the series treated with toxin alone, the earliest section to show undoubted (edema was the 51/2-hour one. It was more marked in the 24-hour one. The fixed connective-tissue cells in all periods, from 1 to 24 hours, appeared swelled. At no period were there discernible signs of fragmentation of the nucleus nor of proliferation of the cells. The number of wandering cells seemed to vary di rectly- with the length of the period up to 24 hours. In 1-hour and 2-hour sec tions the majority showed almost a uni form staining with hminatoxylin. Frag mentation of nucleus was seen most markedly in 24-hour sections, though it was also seen, but to a less degree, in 10 'A-hour sections. In cells apparently endothelial in character the chromatin net-work stained faintly with hmmatoxy lin, but was distinct. They were present in all sections, perhaps in greatest num bers in the latest ones. In most sec tions there were signs of cloudy swelling of the superficial muscular fibres. In the second series treated with toxin and a half-neutralizing dose of antitoxin it was impossible to be sure of the reality of cedema before 51/2 hours after injec tion. This period was increased up to 24 hours. Connective-tissue fixed cells ap peared swelled in twenty minutes' sec tion, and this swelling was present in all sections. Tbe changes in the wandering cells seemed to be similar to those in Series 1. The results of the third series treated with toxin and fully-neutraliz ing dose of antitoxin were practically the same as in the second series. The points elucidated by this research seem to be: (1) that the cellular changes are degenerative, anct that there is no indi cation of proliferation of affected cells; and (2) that antitoxin, whatever may be its antagonistic effect generally, does not locally act as a chemical antidote to the toxin. J. J. Douglas (Brit. Med. Jour., Sept. 3, '98).