1912'] Malarial Pigment in Malarial Paroxysm 107 



however, larger doses, e. g., ten cubic centimeters per kilo, are 

 given, phenomena simulating the picture of hematin intoxica- 

 tion may be elicited, but the changes are not so definite or con- 

 stant. 



If now we correlate these symptoms with the temperature 

 curve, we find that the elevation of temperature during the first 

 stage is slight, and that the second stage of the paroxysm cor- 

 responds closely with the period of rising temperature, the in- 

 itial drop coinciding sharply with the vascular dilatation and 

 flushing of the ears and the elevation of the surface temper- 

 ature. The third or hot stage, as previously noted, corresponds 

 to the duration of the temperature above normal. 



As in the case of the temperature, all other phenomena of 

 hematin intoxication seem to be exaggerated when a given dose 

 of hematin is divided into several fractional doses, the cycle 

 of phenomena following closely consequent changes in the tem- 

 perature curve. 



It must be pointed out, however, that the prominence of 

 these paroxysmal phenomena and the degree of elevation of the 

 temperature are by no means always parallel. The toxic par- 

 oxysmal phenomena may be present to a high degree in an ani- 

 mal that shows only a slight elevation of temperature, and in 

 most instances such a condition is to be regarded as evidence 

 of over-intoxication. 



Acquired Resistance. — Early in the course of these experi- 

 ments it became evident that repeated injections of a given dose 

 of hematin in the same animal did not give uniform results. 

 The results, however, were of such a nature as to suggest that 

 the animal acquired a certain degree of tolerance which, in 

 turn, might be broken when the intoxication was pushed suffi- 

 ciently. To determine this point the following experiment was 

 carried out. 



Experiment. — Four rabbits, weighing respectively i,6oo, 1,650, 1,790, and 

 1,840 grams, were injected on ten successive days with a solution of ox 

 hematin containing 5 mg. of hematin to i c.c. The first two animals 

 received 10 mg. of hematin per kilo of body weight, and the other two 

 received 15 mg. per kilo. Rectal temperatures were recorded every half 

 hour. 



The results are shown in text-figure 4. In a is shown the 



