562 ANAPHYLAXIS 



doses. Rosenau and Anderson found that animals reinjected before 

 the end of the period of incubation did not become responsive until 

 some time later. Otto has also made this observation, but the most 

 thorough study of the subject has come as the result of the researches of 

 Besredka and Steinhardt. 



Experimental Production of Anti-anaphylaxis. It has long been 

 known that the larger the first or sensitizing injection of antigen, the 

 greater must be the dose of the second or intoxicating injection, indicat- 

 ing that a large sensitizing injection introduces the factor tending to 

 produce the condition of anti-anaphylaxis. Partial desensitization, 

 or anti-anaphylaxis, may be produced by the injection of a sublethal 

 intoxicating dose of anaphylactogen during the period of incubation or 

 at its close. Quantitative relations between the size of the sensitizing, 

 intoxicating, and desensitizing doses of antigen and the period of in- 

 cubation have been worked out in a series of studies by Weil, 1 both in 

 the living guinea-pig and on the excised uterus, after the graphic method 

 of Dale. 2 Weil found that a small sensitizing dose of horse serum (0.01 

 c.c. subcutaneously) is followed by a relatively prolonged period of 

 incubation (from fourteen to sixteen days) ; that the minimal anaphy- 

 lactic or lethal dose is small (0.02 to 0.05 c.c.); that the blood, as a rule, 

 does not contain more than one sensitizing unit; and that the minimal 

 desensitizing dose is small (0.01 c.c.). Conversely, after repeated 

 large sensitizing doses (2 c.c. of serum subcutaneously on each of three 

 days in succession) the incubation period is shorter (about ten days 

 after the last injection); the minimal anaphylactic lethal dose is larger 

 (0.4 c.c.), and the minimal desensitizing dose is at least more than 0.2 

 c.c. of serum given intravenously. 



Besredka and Steinhardt observed that the refractory state could 

 easily be developed in sensitized guinea-pigs by one of the following 

 methods: (1) The intracerebral injection of 0.25 c.c. of horse serum 

 before the expiration of the period of incubation (twelve days). (2) The 

 intracerebral injection of less than the fatal dose (from 0.002 to 0.025 c.c.) 

 after the period of incubation. (3) Rectal injections of from 5 to 10 

 c.c. of serum. (4) By slowly reinjecting small amounts while the 

 animal is deeply narcotized with ether or alcohol. As shown later by 

 Rosenau and Anderson, a narcotic may mask but does not prevent the 

 occurrence of severe or fatal symptoms. Of these methods, Besredka 



1 Jour. Med. Research, 1913, 29, No. 2, 233; 1914, 30, No. 3, 299. 



2 Jour. Pharm. and Exper. Ther., 1913, iv, 167. 



