CLINICAL SIGNIFICANCE OF ANAPHYLAXIS 431 



protein solution there is a distinct gain for safety in the use of 

 such preparations. Endeavors to produce potent antitoxic sera by 

 chemical or physical methods without any sensitizing properties have 

 thus been unsuccessful. 



On the other hand, the knowledge gained by animal experimen- 

 tation regarding the influence upon the anaphylactic manifestations 

 exerted by various methods of administering the antigen has led to 

 results which have proven of much value, both in the immuniza- 

 tion of experimental animals and in human serum therapy. Prob- 

 ably the most carefully studied of these methods is the one which 

 Besredka 14 has recommended on the basis of his work on antianaphy- 

 laxis in animals. He found that sensitized guinea pigs could be 

 injected with quantities of serum amounting to about one half or 

 less of the fatal dose without showing symptoms, and subsequently, 

 at intervals of 2 to 5 minutes, further injections of the serum could 

 be given, the total amount five to twenty times exceeding the lethal 

 dose without causing symptoms of any kind. From these experi- 

 ments he has developed a method of serum injections the principle 

 of which is very simply a division of dose. In lieu of injecting into 

 an animal or man the entire quantity of serum at once, small, gradu- 

 ally increasing amounts are administered in two, three, or more 

 doses, the intervals varying from five minutes to several hours, ac- 

 cording to the necessities of speed indicated by clinical considera- 

 tions. The process as applied to man consists, then, in preceding 

 the injection of the larger quantity of the serum by one or two sub- 

 cutaneous injections of smaller amounts. With this principle well 

 defined it would be quite unwise to lay down definite rules of quan- 

 tity or interval at present, since in no instance will it be possible 

 to estimate the exact condition of susceptibility of the particular 

 case. It goes without saying that the precautions should be par- 

 ticularly respected in children in whom the relation of 5 or 10 c. c. 

 of serum volumes to the body weight approaches the dangerous pro- 

 portions dealt with in animal experiments. 



Besredka has also shown that if the rectum of a sensitive animal 

 is cleaned out by enema, and a relatively large amount of the an- 

 tigen then introduced, an injection may be given in within twelve to 

 twenty-four hours later without danger, however delicate the hyper- 

 susceptibility of the animal has been. This method apparently 

 must depend upon a slow, gradual absorption of antigen, and would 

 seem to furnish a most convenient and advisable method to apply in 

 man. 



14 Besredka. Ann. de I'Inst. Past., Vol. 24, 1910; C. E. de la Soc. de 

 BioL, 65, 1908, p. 478; C. E. de la Soc. de BioL, Vol. 66, 1909, p. 125; ibid., 

 67, 1909, p. 266; C. E. de I'Acad, des Sc., Vol. 150, 1910, p. 1456; ref. Bun. 

 de I'Inst. Past., Vol. 8, 1910, p. 735. 



