JOHN A. KOLMER 1103 



4. The possible production of antibodies by releasing antigenic substances from 

 the parasites. 



5, The stimulation of processes of oxidation; the production of hyperemia and 

 stimulation of reparative processes; the production of leukocytosis and mobilization 

 of proteolytic, lipolytic, and diastatic enzymes capable of interfering with the nutri- 

 tion or otherwise crippling invading organisms, etc. 



And the mechanism of organotropic or toxic effects of chemical agents for the 

 body cells in general or of a particular group is likewise far from being the simple 

 matter of union by chemo-receptors, involving as it does the subjects of absorption, 

 elimination, distribution, fate, and other complex pharmacological and toxicological 

 effects, the production of toxic lesions and symptoms being by one or more of the 

 following processes: 



1. By immediate reactions in the blood like agglutination or lysis of erythrocytes, 

 precipitation of plasma proteins or salts, with the production of colloidal shock re- 

 actions, embolism, etc. 



2. By direct chemical interaction between the compound or drug as administered 

 or after some transformation in the body, with some protoplasmic constituent of the 

 fixed body cells, resulting in the death or crippling of the latter by interference 

 with vital processes. Or by some physical or physico-chemical interaction with the 

 protoplasmic colloids of cells, involving precipitation, coagulation, changes in electri- 

 cal charge, etc., either mechanism involving the body cells as a whole or particular 

 groups and centers by reason of special afi&nities or through the function of elimina- 

 tion. 



3. By producing excessive hyperemia, cellular infiltrations, and other tissue 

 changes; by promoting excessive enzymic activity with the production of toxic sub- 

 stances from dead or devitalized body cells or parasites; by promoting or stimulating 

 the activities of parasites, as in the Jarisch-Herxheimer reactions of syphilis, etc. 



A study of the toxicity of a chemical compound or drug, therefore, in relation to 

 chemotherapy, may be not only a matter of simply determining the minimal lethal 

 or maximal tolerated doses per kilogram of body weight for the lower animals, but 

 under certain circumstances involves a study of its pharmacological and toxicological 

 effects for human beings and especially for sick human beings, which brings into play 

 far more complex processes than are met with in healthy lower animals. 



LOCALIZED vs. GENERALIZED BACTERIAL INFECTIONS IN RELATION 

 TO CHEMOTHERAPY 



It is readily apparent that the principles and mechanism of the chemotherapy of 

 localized bacterial infections by the direct application of disinfectant substances are 

 quite different from those concerned in generalized or systemic infections requiring 

 the injection of the disinfectant into the blood or its absorption from the gastro- 

 intestinal canal, muscles, or subcutaneous tissues. From the standpoint of chemo- 

 therapy, a localized infection may be defined as one confined to a certain organ or 

 tissue and accessible by direct or topical application of a chemical disinfectant. It 

 may be a localized infection in the strict sense of being a tissue or organ directly or 



