154 PROTEIN THERAPY 



purpose, made up as follows: 10 loops of fresh typhoid culture were 

 suspended in 10 c.c. of human typhoid convalescent serum and in- 

 cubated for 5 or 6 hours. The organisms were then centrifuged from 

 the serum, washed three times in physiological salt solution, suspended 

 in 100 c.c. of physiological salt solution with 0.3% phenol and finally 

 shaken for 1 hour. The vaccine was not heated. Of this emulsion 

 0.5 c.c. was diluted in a syringeful of saline before injection and the 

 whole slowly injected intravenously. 



In most of Ichikawa 's cases a single injection sufficed to terminate 

 the febrile course of the disease; in some the result was not quite so 

 marked. After the critical drop in the temperature the temperature 

 would again rise in these cases, usually remaining intermittent in type 

 and much lower than before. The general condition of these latter pa- 

 tients was always much better after than before the injection. In the 

 refractory cases the injection was usually repeated once and even twice 

 until the desired result was obtained. 



Ichikawa assumed that the effect on the temperature curve was 

 due to a mobilization of antibodies that had been formed in the cells 

 during the course of the infection but had not been thrown into the 

 general circulation until the vaccine was injected intravenously. 



The mortality in this first series was 11%, rather high in itself, 

 but not in comparison to the death rate in untreated cases in the Osaka 

 Hospital, which was around 30%. 



Ichikawa did not observe any ill effects from the vaccine injec- 

 tion; indeed he considers it unjustifiable to neglect the advantages 

 of intravenous therapy merely because certain inherent dangers are, 

 theoretically, to be considered. He watched particularly for cardio- 

 vascular changes but did not have any collapse cases, and hemorrhages 

 were less frequent in his vaccinated cases than in the untreated. In 

 a few cases he did observe hemorrhages from 1 to 3 days after the 

 injections; usually they were slight and not alarming in character. 

 In two cases he observed hemoptysis, twice nose-bleeding, and in two 

 cases hemorrhages into the skin, but they were all mild in character 

 and did not recur. The reaction that occurred chill, fever to 40 

 C., relatively high pulse, occasional nausea, dyspnea, etc. was 

 transient; even the increased temperature never persisted over 24 

 hours. 



Hetero vaccines. Kraus and Mazza reported their work in 1914 

 in which not only the results obtained with intravenous injection of 

 typhoid vaccine in typhoid fever was described, but the use of hetero- 

 vaccines was taken up. Ichikawa had previously noticed that with 

 typhoid vaccine he could treat paratyphoid fever just as well as 

 typhoid. Kraus and Mazza found that colon vaccine did just as 

 well, and besides reported on the effect of the intravenous injection 

 of such vaccines in puerperal infection, where relatively long stand- 

 ing infections were promptly terminated and the disease process 



