WILLIAM F. PETERSEN 1097 



typhoid fever is one of the few acute diseases in which protein therapy has yielded 

 particularly interesting results that are of importance for the bacteriologist from the 

 theoretical point of view. 



In approximately one-third of the cases after protein therapy, patients recover 

 by crisis. The patient's temperature returns to normal, the spleen becomes small, 

 the rose spots disappear, bacteria disappear from stool and urine. In another third 

 the patients are improved — i.e., the sensorium becomes clearer, appetite is improved, 

 the temperature range lowered. In the other one-third there is practically no change 

 in the clinical condition. 



How is an abrupt termination to be explained? 



When we inject the non-specific agent into the blood stream the reticulo-endo- 

 thelial cells immediately fix the formed particles (bacteria) or the foreign colloidal 

 material. Depending on the relative toxicity of the injected substance, the cells are 

 variously stimulated. The vascular endothelium of the splanchnic area participates, 

 and because of its remarkable structure, there is a great increase in the passage of the 

 larger molecular aggregates from the blood to the lymph spaces. Antibodies which 

 have heretofore been concentrated to a greater degree in the blood' enter the splanch- 

 nic lymphatic bed. With them go enzymes and complement. The typhoid bacteria 

 are therefore suddenly subjected to lytic processes and may be destroyed, partly or 

 completely. Their rapid destruction may however entail further production and 

 liberation of endotoxic material. If great in amount, the injury to the patient may be 

 such that death may take place. If only moderate in amount, but with complete 

 destruction of the bacteria, termination of the disease by crisis occurs. 



But how can we explain those cases in which crisis does not occur, in which the 

 patient merely gives evidence of improvement? Here evidently the complete destruc- 

 tion of the infectious agent has not taken place, but the reaction of the host has changed.'^ 

 The same amount of intoxication now no longer brings about an equally intensive 

 response on the part of the body. 



It is at once apparent that in typhoid we are dealing with an infection that is 

 peculiar in its localization and particularly favorable for non-specific therapy from 

 the theoretical side. But this does not necessarily hold true for other localized in- 

 fections (lobar pneumonia, for instance) or a septicemia. Generally, protein therapy 

 in such cases does little good; sometimes it may be harmful. But here again clinical 

 experience has demonstrated that at times a prompt and spectacular recovery may 

 take place after some non-specific injection even in a septicemia. 



How are we to explain the mechanism? 



A sudden increase in antibody titre in the body fluids? A sudden enhancement of 

 the activity of the reticulo-endothelial system with fixation and digestion? Enzyme 

 mobilization and accelerated digestion of bacterial or tissue toxins? A change in the 

 acid-base equilibrium of the cells, the tissues becoming more alkaline after the primary 

 increase in acidity — with a general sympathetic status of the organism? The accumu- 

 lation of leukocytes in the splanchnic region with greater destruction of bacteria? 

 The release of fresh leukocytes from the bone marrow? Any and all of them may be 



' Becht, F. C, and Luckhart, A.: Amer. Jour. Physiol., 40, 366. 1916. 



" Burmeister, J.; Zeit.f, kl. Med., 95, 237. 1922. 



