168 PROTEIN THERAPY 



an hour following the chill. At autopsy no lesions other than those 

 of typhoid fever and a marked cloudy swelling of all parenchymatous 

 tissues and a toxic myocarditis were observed. 



The other two dangers are related to the gastro-intestinal tract. 

 When nonspecific therapy is used the intestinal tract is affected to 

 a considerable degree, depending on the severity of the reaction, the 

 agent used, etc. There is first of all an increased motility. Coinci- 

 dent with it there is an engorgement of the vessels of the bowel. Both 

 of these factors may result in an increased possibility of perfora- 

 tion and of hemorrhage. 



Clinicians who have had largest experience with the treatment of 

 typhoid fever state very definitely that these dangers are theoretical 

 rather than actual. When fatalities occur following the treatment the 

 dosage employed in producing the reaction may have been too large or 

 the agent selected not the best one for use. The injection of both 

 typhoid bacilli and also of proteoses is not followed by the styptic effect 

 that we see after milk injections, and the vaccine, too, has the added 

 disadvantage of being decidedly toxic in itself, both factors that would 

 incline one to favor any of the other agents rather than the typhoid 

 vaccine. The question of dosage is one that has not been definitely 

 settled. Of course, the massive doses of typhoid bacilli that have at 

 times been employed (1 billion and more) by American observers 

 and which were naturally followed by disasters of various kinds 

 should not be countenanced in typhoid fever, however well they may 

 be tolerated in other conditions. 



When typhoid vaccine is used only enough organisms should be 

 injected to provoke a mild reaction from 10 to 25 million and sim- 

 ilarly moderate doses with other bacterial vaccines. When relatively 

 nontoxic agents are employed such as proteoses, colloidal metals, 

 nucleins, etc., one can follow two courses. Either to give sufficient 

 to provoke a general reaction and perhaps repeat the dose after sev- 

 eral days if the fever has not been altered, or give small daily doses, 

 none of which are themselves sufficient to provoke a severe reaction. 

 Holler has used this latter method with success ; it is the method that 

 Jobling and the writer have preferred to follow when dealing with 

 typhoid fever. The immediate results may not be quite as brilliant as 

 when larger doses are used, but there is certainly much less danger 

 of precipitating some decidedly grave complication. For general 

 use we cannot too urgently emphasize these considerations. 



In order to overcome some of these potential dangers, Neustadl 

 and Marcovici usually prepared their patients, especially those that 

 had been ill for some time and in whom there were evidences of vaso- 

 motor instability, with digitalis. Jobling and the writer tried to 

 overcome the motor activity of the gastro-intestinal tract and the 



