HYPERSUSCEPTIBILITY 225 



vestigation of these substances has had an important bearing on the 

 development of theories of anaphylaxis, because if these can be com- 

 pared to the supposed toxic substance of anaphylaxis it would seem 

 reasonable to suppose that anaphylaxis has as its basis a colloidal dis- 

 turbance. Many of those who have worked with these substances 

 have not been strict in their use of the term anaphylaxis and have 

 depended in large part on the clinical manifestations following the injec- 

 tions of these agents. From time to time certain investigators have 

 indicated that more intimate study would prove that anaphylaxis and 

 the phenomena following the injection of these colloids are not identi- 

 cal. Manwaring and Crowe, for example, found that occasionally there 

 appears in anaphylaxis occlusion of pulmonary blood-vessels by thrombi 

 and used the term pseudo-anaphylaxis. The problem has recently been 

 investigated extensively by Hanzlik and Karsner. The experiments 

 in this series oi studies were controlled by gross and microscopic studies 

 of the viscera of the animals after death. More than thirty colloidal 

 agents were studied by a variety of methods, including intravenous 

 injection, studies of perfused organs, protection by atropin and epi- 

 nephrin, as well as test-tube studies of the action of the agents upon 

 blood-corpuscles. Many of the agents studied produce serious dis- 

 turbances of circulation and others produce equally serious disturb- 

 ances of respiration. In the case of none of these colloids was it 

 possible to demonstrate that the clinical and morbid anatomical phe- 

 nomena, taken collectively, are identical with those of anaphylaxis. 

 The symptoms provoked can all be explained on grounds other than 

 the assumption that we are dealing with anaphylaxis. Even in the case 

 of agar, where bronchial constriction and pulmonary distention are well 

 marked, the common occurrence of thrombi both in the living animal 

 and in perfused lungs definitely excludes an identity with anaphylaxis. 

 These phenomena may, therefore, be considered as of colloidal nature 

 and may well be referred to as " colloid shock." Pepton produces symp- 

 toms and signs more nearly like those of true anaphylaxis than the other 

 substances studied, but the fact that pepton more frequently produces 

 thrombosis, hemorrhage and edema of the lungs than is the case in true 

 anaphylaxis, would place pepton poisoning in the group of ana- 

 phylactoid rather than anaphylactic phenomena. Similarly the injec- 

 tion of primarily toxic sera such as ox serum and eel serum into the 

 guinea-pig produces certain circulatory disturbance with hemorrhage 

 and edema. It seems probable that the toxicity of some of the sub- 

 stances of protein nature or the decomposition products of protein may 

 depend for their activity upon the presence of histamine. The poison- 

 ous character of histamine depends in no way upon previous sensitiza- 

 tion, is primarily toxic and therefore may be included as anaphylactoid 

 in its action. 



Summary. With a strict adherence to the conception that ana- 

 phylaxis constitutes that state of hypersusceptibilityto a given substance, 

 which has been induced by a previous injection of the same substance 

 we may conclude that the mode of the second injection determines the 

 15 



