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476 the villi and glands. As the comma bacillus does not occur in the blood, and assuming that it is the cause of cholera, we must conclude that the clinical phenomena are not the result of a septicæmia, but that they arise either from a local intestinal irritation produced by the bacillus, or from some toxin which it generates in the bowel and which is absorbed; or from a combination of these factors.* That the cholera vibrio is a powerful irritant is shown by the effect produced locally by a hypodermic injection of a virulent culture. When so injected, not only does it give rise to local œdema, but, unless precautions are taken, it causes in certain animals necrosis of the tissues and ulceration at the seat of injection. It is conceivable, therefore, that when in the course of the naturally acquired disease the bacilli proliferate in the bowel they or their products act as an irritant to the mucous membrane, and so provoke the hypercatharsis and the consequent dehydration of the tissues which are the dominating features of the disease. On the other hand, the hypodermic injection of cholera vibrio cultures is followed by smart febrile movement lasting from one to three days, evidencing the presence of a febrogenic toxin capable of producing constitutional symptoms. This fact, together with the rapid and intense prostration which, in some instances of natural cholera, appears to be out of all proportion to the amount of catharsis present, suggests that the lethal effects of the vibrio are attributable not alone to the drain of fluid from the blood and tissues but also to the absorption of a cholera toxin from the intestine. It is somewhat strange, however, if this toxin be anything more than a subsidiary element in the production of the symptoms in most instances of the naturally acquired disease, that catharsis is not one of the effects of the hypodermic introduction of the vibrio, and that fever is not an earlier and more prominent symptom in