234 WARFIELD T. LONGCOPE AND GEORGE M. MACKENZIE 



more definite evidences that the introduction of protein substances of a 

 complex nature into the human being may be followed almost immedi- 

 ately by a fairly definite train of symptoms. What information we have 

 concerning this side of the problem comes almost exclusively from observa- 

 tions made upon the deleterious effects of the intravenous -injection of 

 fluids in man. Aside from the effects produced by hemolysis, other mani- 

 festations have been observed which cannot be ascribed to this cause. 

 These effects first received widespread attention when salvarsan came to 

 be administered generally by the intravenous route and when blood 

 transfusions became popular. Previously, it had been noted that oc- 

 casionally an intravenous infusion of normal salt solution in children was 

 followed by a febrile reaction which was termed in the older literature 

 salt fever. Shortly after the general intravenous use of salvarsan, a 

 similar febrile reaction was frequently observed to follow immediately up- 

 on the administration of this drug. This chill and fever appearing either 

 in one or two hours after the administration of salvarsan was frequently 

 accompanied by headache, nausea, vomiting and pains in the back and ex- 

 tremities. The similarity of salt fever and these reactions was frequently 

 commented upon and it was finally shown by Wechselmann that most of 

 these reactions could be obviated by using freshly distilled sterile water 

 for the preparation of the salt solution or of salvarsan. He furthermore 

 demonstrated that distilled water which had stood for any length of time 

 frequently contained a growth of molds and ascribed the untoward re- 

 actions to traces of a toxic substance, thought in all probability to be 

 some form of split protein, resulting from the growth or destruction of 

 the molds in this old distilled water. Since the general use of freshly 

 distilled water for the preparations of salvarsan -and arsphenamin, the 

 frequency of these reactions (which came to be termed protein reactions) 

 has been greatly diminished. But that reactions may still occur after 

 the intravenous use of arsphenamin is still evident from a recent paper 

 by Strickler, Munson, Sidlick and Strauss. They show that fever, chills, 

 nausea, vomiting, diarrhea, pain in back and extremities may occur in 67 

 per cent of cases and moreover are as common after the intravenous in- 

 jection of arsphenamin in normal persons as they are in syphilitics. They 

 are inclined to believe that these reactions are caused by the drug itself. 

 A somewhat similar type of reaction that has been frequently ob- 

 served and extensively written about is that following the transfusion of 

 blood. The typical transfusion reaction comes on about one half hour after 

 the transfusion, and is accompanied by a sharp rise in temperature grad- 

 ually subsiding to normal in from three to eight hours ; sometimes nausea, 

 vomiting, pains in various parts of the body and skin eruptions such as urti- 

 caria and localized areas of edema. These reactions may vary considerably 

 in degree, the mildest being ushered in by a slight rise of temperature with- 

 out other symptoms, while in the more severe, the temperature may rise to 



