INTRO DICTION 7 



Early observations on time required for elicitation of state of 

 reactivity and on its duration: 

 The following experiments were made in order to determine 

 the optimum time interval between the injections necessary to 

 elicit the reactivity (Shwartzman, 1928/;) : 



Protocol 5 : Four areas of the skin of 6 rabbits (Nos. 48-2 to 48-6 were 

 injected with 0.25 c.c. of B. typhosus (TjJ tryptic digest culture fihrate. 

 Rabbits 48-2, 48-3, and 48-4 received intravenous injections of the filtrate two 

 hours after the skin injections. The dose was 3 c.c. per kilo of body weight. 

 No reactions were seen in these rabbits in the course of the following forty- 

 eight hours. 



Rabbits 48-5, 48-6, and 48-7 were injected intravenously with 3 c.c. of the 

 filtrate, per kilo of body weight, forty-eight hours after the skin injections. 

 The skin remained unchanged for forty-eight hours. 



Protocol 6 : The upper right areas of the skin of the abdomen of Rab- 

 bits 1-7, 1-8, 2-0, 2-6, 2-7, and 43-9 were injected with 0.25 c.c. of tryptic 

 digest Tl filtrate. Twenty-four, forty-eight, and fifty-five hours later, 0.25 c.c. 

 of the same filtrate was injected into the lower right, upper left, and lower 

 left areas of the skin of the abdomen, respectively. Fifty-six hours after the 

 first skin injection, tryptic digest Tj^ filtrate was injected intravenously into 

 these rabbits. The dose was 3 c.c, per kilo of body weight. The morning 

 following the intravenous injections, namely, fifteen hours after the intra- 

 venous injections, the following results were obtained: Rabbit 1-7 was found 

 dead and no reading was possible. Rabbits 1-8, 2-0, 2-6, 2-7. and 43-9 showed 

 no reactions in the upper right and lower left areas. Both lower right and 

 upper left areas showed very pronovuiced hemorrhagic reactions which varied 

 in size from 1 x 1 cm. to 2 x 2 cm. 



From the above experiments the follo^ving coidd be concluded: 



For the reproduction of the described phenomenon a definite 

 interval of time was required between the preparatory skin in- 

 jection and the intravenous injection of the filtrate. 



Althotigh no exact information ^vas a\'ailable on the exact ninn- 

 ber of hotns necessary for tlie preparation of the skin, neverthe- 

 less, it became obvious that two hours were insufficient and that 

 the state of reactivity did not last longer than thirty-t^vo hours. 

 The phenomenon could be invariably reproduced if an interval 

 of twenty-foin- hours \vas allowed bet^veen the skin and intra- 

 venous injections. 



It may be also noted from Protocol 6 that the skin reactivity 

 appeared as soon as eight hours after the skin-preparatory injec- 

 tion. In these animals, however, the reading of the skin reaction 

 was made fifteen hotus follo\ving the intraxenous injections, in- 



