INTRODUCTION I9 



\\ ith dilutions as high as 1 : 1000 reacted, pro\'ided the same animals 

 ^vere also prepared by injection of lower dilutions. On the other 

 hand, if higher dilutions alone were employed for preparation, 

 no reactions ^vere obtained. The only possible explanation is that 

 the more concentrated material may spread to the sites receiving 

 a lesser concentration and thus induce a state of reactivity in 

 these sites. On the other hand, no reactions result if low concen- 

 trations are employed for preparation of all the sites. Here again, 

 the richness of the lymphatic network may constitute an im- 

 portant factor in this diffusion phenomenon. 



The observations of Joukow-Werejnikow and Lipatova (1933- 

 34) suggest that the richness of the venous supply to a given 

 site may also influence the severity and size of the reactions fol- 

 loAving the intravenous injection. Thus, very severe reactions 

 were obtained mostly ^vhen the preparatory injections ^vere made 

 in jDroximity to a large subcutaneous \ein. 



(iratia and Linz (1932c) produced the phenomenon in the 

 skin of the ear. They injected 0.5 c.c. of the B. coli culture filtrate 

 intradermally and followed the pre])aration by an intravenous 

 injection of the same filtrate t^senty-foiu" hoins later. The reac- 

 tions obtained were se\ere and diffuse. 



I also foinid that with appropriate doses of the toxic material 

 for the preparatory and provocative injections, strong reactions 

 can be obtained in the ear (Shwartzman, 1935c) . The reactions 

 may be well circumscribed and intensely hemorrhagic. In some 

 instances, ho^ve\er, there is a tendency towards the generaliza- 

 tion of the reaction through the entire ear. Frequently there is 

 also obser\ed blue discoloration in j^arts of the ear not in\ol\ed 

 by the reaction. Histologically, the reaction is accompanied by 

 hemorrhage, pronounced capillary thrombosis, subsequent severe 

 necrosis and inflammation. The discolored parts showing no re- 

 action may have extensive thrombosis in the venules and no 

 hemorrhage. Comparative titrations in the skin of the ear and 

 in the abdominal Avail Avith the same material brought out the 

 fact that the skin of the ear is considerably more resistant to the 

 phenomenon than the skin of the abdomen. Ten times the provoc- 

 ative dose is recjuired if it is given into the marginal vein of the 

 ear prepared by the intradermal injection of bacterial filtrate 

 and thirty times the dose if it is given by way of the vein of the 

 non-prepared ear. The ol)\ ious interpretation of the latter is that 



