114 PROTEIN THERAPY 



located that it can be observed directly, as in the skin or mucous mem- 

 branes. In the deeper tissue it is made clinically evident by the 

 invariable symptomatology that follows the injections first an in- 

 crease in the evidence of pain and temperature, later a complete 

 subsidence, either transient or permanent as the case may be. 



We believe that the explanation for these phenomena is relatively 

 a simple one, although it involves at some time practically all of the 

 tissues and structures about the focus of inflammation, changes in 

 both the blood and lymph vessels and nerves, as well as in the local 

 tissues directly involved. 



With the injection there is first apparent an increased excitability 

 of the central nervous system and the sympathetic system; later this 

 subsides and ends in a period of lowered excitability. There is at 

 first apparently a direct effect on the capillaries so that they become 

 more permeable the lymph flow is increased, the tension of the 

 local inflammatory focus is greater the pain augmented. Later the 

 reverse sets in and the capillaries become less permeable. 



But in the meantime certain alterations have occurred in and 

 about the focus. We may assume for the purposes of illustration that 

 we are dealing with this early bubo a certain amount of toxic ma- 

 terial (protein split products from the necrotic tissue of the venereal 

 focus, bacterial endotoxins, perhaps soluble toxic materials from bac- 

 teria, perhaps a few bacteria themselves have filtered in along the 

 lymph channels) has been brought to the gland and has incited 

 an inflammatory reaction. This finds its expression in the hyperplasia 

 of the endothelial cells of the lymph channels, in an attraction of 

 polymorphonuclear leukocytes and the exudation of fluids into the 

 tissues. As yet there has been no necrosis. 



The tissue fluids bathing these cells contain little protease or 

 ereptase but much antiprotease (antitrypsin) so that digestive proc- 

 esses are held in abeyance. Under ordinary conditions the intensity 

 of the intoxication is therefore not diminished and tissue necrosis 

 finally results, both the fixed cells and some of the polymorphonuclear 

 leukocytes being affected. From the latter we now have the libera- 

 tion of a considerable amount of protease, sufficient to saturate and 

 thereby negate the effect of the antiferment in a circumscribed area 

 digestion begins to take place solution of tissue and fluctuation. 



If on the other hand at an early stage the patient is given a 

 nonspecific injection the focus is very promptly flooded the lymph 

 flow as measured in the thoracic duct is increased fourfold and in 

 the fluids now exuded (the permeability of the capillaries being in- 

 creased by the nonspecific injection) there is carried considerably 

 more protease as well as ereptase, while the antiferment is diminished. 

 The toxins present are not only diluted but their digestion is com- 

 menced by the enzymes. Necrosis is prevented by this effect on 

 the toxins. The capillaries now become less permeable, the fluids 



