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WILLIAM F. PETERSEN 1095 



matter at the moment. Heubner' has used the expression "patho-biosis" for the 

 change in the cell that has at one time been the seat of some toxic (pharmacological) 

 action, the cell remaining altered and the effect being irreversible. As far as the 

 entire organism is concerned, Sachs^ finds the expression of this change in an instabil- 

 ity of the colloids. A long-continued globulinemia with an increase in non-protein 

 nitrogen and a change in the mineral constituents may persist. 



While such alterations result from the general reaction, Freund and Gottlieb-' 

 have been able to demonstrate that pharmacologically active substances appear in 

 the blood stream irrespective of the method by which the non-specific reaction is in- 

 duced. Thus, immediately after the reaction a vasodilating substance can be isolated 

 (a basic-alcohol soluble substance), while later a vasoconstricting principle can be so 

 isolated. Obviously these substances take origin in the body and seem definitely asso- 

 ciated with the increased protein destruction apparent early in the reaction.''^" Per- 

 haps they are derived from lipoidal metabolism," for both cholin and cholesterol 

 derivatives may be active on blood vessels. It is possible that they may be histamin- 

 like substances,'^ 



That the organism is fundamentally re-oriented is made evident in the change in 

 the autonomic response when aseptic pyretic agents as well as pilocarpine and adrena- 

 lin are injected. It is particularly this change in the autonomic status of the organism 

 which accounts for many of the phenomena which are to be oberved with protein 

 therapy (Engel,'-' Uhlmann,'-* Klemperer,'5 and Adler and Blumenberg.''') It might be 

 well to summarize this concept, with reference to the chain of events that follows the 

 protein injection. 



An intravenous injection of bacteria (vaccine) is followed by the rapid fixation of the 

 organisms in the reticulo-endothelial apparatus, largely in the liver and spleen. This causes 

 an immediate stimulation of these cells and, depending on the degree of toxicity, of the 

 parenchymal cells and the vascular and lymphatic endothelium of the region. A parasympa- 

 thetic status is established (splanchno-peripheral balance). '^ This involves a sympathetic 



' Heubner, W.: loc. cit. ^ Sachs, H.: loc. cil. 



3 Freund, H., and Gottlieb, R.: loc. cit. 



4Barr, D. P., Cecil, R. L, and Du Bois, E. F.: loc. cit. 



s Amstad, E.: Biochem. Zeit., 145, 168. 1924. 



^Pick, E., and Hashimoto, M.: Arch.f. exp. Path, und Pharm., 76, 89. 1914. 



'Freund, H., and Rupp, F.: ibid., 99, 137. 1923. 



* Bieling, R., and Gottschalk, A., and Isaac, S.: Kl. Wchr., 1, 1560. 1922. 



' Lohr, H. : Zeit.f. d. ges. exp. Med., 30, i and 6. 1922. 

 '" Weichardt, W., and Scholz, G.: Kl. Wchr., 2 (No. 2), 2305. 1923. 



" Mahnert, A., and Santner, A.: Arch.f. Gyn., 116, 98. 1922; also Gruenthal, R. M., and Brown, 

 G. M.: loc. cit. 



'^ Abelin, J.: Biochem. Zeit., 129, i. 1922. 



'3 Engel, D., and Kerekisa, A.: Ahs. kl. Wochen., 5, 1689. 1926. 



"• Uhlmann, R.: Zentblatt f. inn. Med., 45, 833. 1924. 



'5 Klemperer, G. : loc. cit. 



'^ Adler, A., and Blumenberg, E.: loc. cit. 



''Muller, E. F., and Petersen, W. F.: Kl. Wchr., 6, 840. 1927. 



