78 PROTEIN THERAPY 



of the transient increase in the permeability. With this there is as- 

 sociated (2) an increase in pain and tenderness both because of the 

 increased pressure and the lowering of the threshold or nerve stimuli. 

 There will be (3) increased digestion at the focus of inflammation; if 

 there is no necrotic material present in the focus there may be no 

 evidence of increased systemic intoxication; if the amount of necrotic 

 material is large there will first result an increase in systemic in- 

 toxication when the material split down is absorbed; with more 

 complete digestion at the focus, complete detoxication may re- 

 sult. 



All these changes we associate with the focal activation that follows 

 nonspecific injections. To these must be added another factor and one 

 more complex. It concerns the observation that any cell previously 

 involved in an inflammatory reaction responds to stimuli of all kinds 

 more readily than a normal cell. Objectively we can observe this in 

 involuting skin lesions. 



The augmentation in the inflammatory reaction which we have 

 induced brings with it, as we have seen, an increased lymph flow. 

 Coincident with it there has been a relative increase in enzymes 

 protease, ereptase (peptidase) lipase, etc., an increase in the anti- 

 bodies (if the patient has been previously immunized or if the infection 

 has existed for some time), an increase in the leukocytes (after the 

 initial leukopenia), together with an increase in their phagocytic 

 activity, and an increased coagulability of the blood. The antibody, 

 the leukocytic and the enzyme alterations must exert a considerable 

 effect on an infecting agent as well as on the removal of necrotic 

 material; the tendency toward restitution to the normal would be 

 enhanced. It is this phase that we see in the so-called second or 

 positive phase. Its coincident constitutional effect that we witness in 

 the euphoria, in the lowering of the temperature, improvement of the 

 circulation, etc., is due to at least three factors (a) the destruction 

 of toxic material at the focus after the primary increase in digestive 

 activity, (b) lessened susceptibility of the cells of the body to intox- 

 ication (due to the lessened permeability), and (c) actual protoplasmic 

 stimulation (partly from the nonspecific or specific agent injected, 

 partly from the toxic material liberated from the inflammatory 

 focus). This later factor varies greatly and the clinical estima- 

 tion of the possible degree of this variation requires experience and 

 care. 



TUBERCULOUS Foci. Turning from the vascularized inflammatory 

 focus to the tubercle we find other conditions. In Schmidt's paper the 

 view emphasized is that in the general tuberculin reaction we are most 

 likely dealing with both specific and nonspecific factors, an opinion 

 similar to that which we have expressed in a previous paper. Schmidt 

 has stated this concept as follows "But it is probable that in the 

 question of specificity or nonspecificity, the placing of the one versus 



