1912] Malarial Pigment in Malarial Paroxysm 109 



This subject of acquired tolerance has been taken up largely 

 to emphasize the importance to be attached to results obtained 

 from properly adjusted initial doses of hematin, but also to 

 explain the apparent discrepancies in the results from any 

 series of hematin injections. It is the initial injection, with 

 but few exceptions, that gives the maximum temperature reac- 

 tion obtainable with a given dose of hematin until the series 

 of injections has been extended to such a degree as to permit 

 of the acquirement of a tolerance in highly susceptible animals 

 or to cause a break in the early acquired tolerance of more 

 resistant animals. When such conditions supervene, the tem- 

 perature reaction may again increase and show an even greater 

 response than with the initial injection (table I, animals 9 

 and 18). 



SUMMARY. 



The paroxysm of hematin intoxication in the rabbit un- 

 doubtedly presents many features of striking similarity to the 

 paroxysm of human malaria ; still one must hesitate to apply 

 such results unreservedly in an attempt to identify the causative 

 agent of the malarial paroxysm. When, in addition to the 

 character of the paroxysm, we consider the sequence of events 

 in the two instances, the analogy becomes so close that it seems 

 impossible to regard the matter as a mere coincidence. The 

 injection of hematin, especially in fractional doses, is in a 

 measure comparable to the liberation of hematin into the 

 human circulation by the malarial parasite. In these experi- 

 ments, both solution and finely divided suspensions of hematin 

 have been found equally effective in eliciting the phenomena 

 of the paroxysm, and while it seems possible that a portion of 

 the malarial pigment might be dissolved in the alkaline human 

 serum, such an assumption is probably not essential. 



It might be objected that the toxic action of foreign hematin 

 thus injected into the circulation would probably be greater 

 than that of hematin derived from an animal's own blood, but 

 as far as I have been able to determine, this objection does not 

 seem valid, as rabbit hematin, dog hematin, and ox hematin 



