Though the existence of bacterial anaphylaxis was demonstrated by Rosenau and Anderson (1) as early as 1907, subsequent investigators could not diminish the difficulties in producing a clear-cut anaphylactic shock with the majority of microorganisms. The main difficulty in the study of bacterial anaphylaxis is the primary toxicity of the bacterial protein. According to Doerr (2) the amount of bacterial antigen which produces shock in sensitized animals is negligibly smaller than the lethal dose for normal animals. More recently Zinsser and Parker (3) found that in guinea pigs sensitized passively with typhoid {mmune serum at least a minimal fatal dose of the typhoid extract is required to elicit in sensitized animals acute shock with death.In the study of bacterial anaphylaxis many investigators have used suspensions of organisms, not extract, so the in vivo tests are complicated by the fact that these suspensions may produce symptoms even in untreated animals. This complication can be obviated by using the Schultz-Dale method. Sherwood and Stoland (4) working with typhoid bacilli found that in some cases the sensitized uterus contracted after the addition of 0.25 cc. of bacterial extract, whereas the minimum toxic dose was 1 cc. Since the uteri of the sensitized animals failed to react in many cases, they conclude, on the basis of comparative examinations, that more positive results can be obtained with the in dvo method and that the Dale test is not a necessary criterion of sensitization. Zinsser and Mallory (5) do not share this unfavorable opinion. They find that uterine reactions, like those obtained after sensitization with proteins, can be demonstrated in guinea pigs after both active and passive sensitization against alkaline extracts of pneumococci, but "The margin between the minimum doses which contract the normal and those which contract the sensitized uteri is incomparably smaller than that obtained in analogous experiments with . . . . egg albumen." With regard to the difficulty of demonstrating bacterial anaphylaxis Zinsser and Mallory state: "it would seem to us that active sensitization is so difficult because the bacteria contain relatively little coagulable protein, and that in passive sensitization there is an apparently slower union of antibodies with the animal tissues than in the case of protein antibodies." If this assumption is right we have little hope of improving our methods for the study of bacterial anaphylaxis, the difficulties being inherent in the nature of this phenomenon. It is conceivable however, that the primary toxic substance 379 on
Topping' has demonstrated that monkeys and guinea pigs fatally infected with Rocky Mountain spotted fever can be caused to recover by the administration of hyperimmune rabbit serum. This naturally suggests that such serum may have value in the treatment of human cases. The sera prepared by Topping were made by the injection of infectious tick-tissue as antigen. We have found that a serum of high neutralizing titer can also be obtained by injecting rabbits with yolk-sac material prepared according to the method of COX.^ We have determined that this can be refined by the same chemical procedures which are useful in purifying antipneumococcal rabhit serum and removing its toxic and reaction-producing elements. In such concentrates the neutralizing titer per gram of protein is increased about 20-fold as compared with the original serum. A similar antiserum and concentrate of high neutralizing value has also been made against the Breinl strain of European typhus. Sufficient quantities of these two sera are now being prepared and refined so that a thorough clinical study of their possible effectiveness in the treatment of Rocky Mountain spotted fever and epidemic typhus fever in man can be made.
a simple and possibly a successful method to treat and control this serious epidemic disease. Before applying this method to clinical trial here in China, we have endeavored to study its effectiveness in experimental infections, So far, the results obtained seem to indicate that with the dose employed, a significant protection has been obtained by means of this immune horse serum. The exact dosage and the possible therapeutic use of the serum after the appearance of the fever are subjects now under study.Calmettel has reported that the injection of cobra venom into a mouse carcinoma brought about a very rapid disappearance of the tumor, and he suggested that cobra venom might be of value in the treatment of other tumors. Monaelesser and Taguet2 injected cobra venom into the carcinomas of man, and they reported encouraging results.Our experiments were performed for the purpose of determining the effect of cobra venom when injected into the Fujinami rat sarcoma. The minimum lethal dose of cobra venom for white rats, weighing from 150 to 250 gm. each, was found to be one cc. of a 1:10,000 dilution. The solutions of cobra venom used were prepared according to the following technic described by Calmette. A 10% solution of desiccated cobra venom in normal saline was prepared and heated at 72°C. for 30 minutes. The solution, including the precipitate which was formed, was then centrifuged, and the clear portion was placed in ampoules and kept as a stock solution.Five rats were inoculated with bits of the Fujinami rat sarcoma which reached an average size of 0.5 x 0.5 x 1 cm. in Series 1.ICalmette, A., C. R. de E'acad. de Sc., 1933, 197, 205.
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