PRACTICAL APPLICATIONS 363 



reach the bacteria. In these the use of citrates or citric acid (as 

 recommended by Wright) is occasionally of great value. 



The mode of action of antistreptococcic serum is still quite 

 uncertain, and its use is purely empirical. Probably in most 

 cases it acts as a bacteriolytic substance. Wright has suggested 

 that it may contain free toxin, and so act as a vaccine ; but the 

 fact that it will passively immunize animals treated with it is 

 adverse to this supposition. It is prepared by gradually immuniz- 

 ing horses and other animals until they can withstand large doses 

 of the living organisms. The differences between the various 

 brands mainly arise from the nature of the culture used for the 

 purpose. The earlier sera to be prepared were procured by the 

 injection of a single strain of streptococcus isolated from a case 

 of erysipelas, puerperal fever, etc. It was found, however, that 

 this serum was not successful in every case, and attempts were 

 made to improve it. Starting from the supposition that the 

 reason for the non-success was the fact that the streptococcus 

 used was not exactly the same variety as that causing the infec- 

 tion in the patient, polyvalent sera were prepared by treating horses 

 with cultures from many various sources, and it is sera of this 

 nature that are now in general use. Another explanation was 

 that the cultures used were not of sufficient virulence, and as 

 antibodies to an attenuated organism may not act against the 

 same culture when the virulence is exalted, strains of great 

 potency were obtained by means of passage through rabbits. Yet 

 a third method has been adopted, based on the fact that an 

 organism which is highly virulent for one animal may be harmless 

 to another species. Here passage is avoided, and the cultures 

 used in the immunization of the horse are taken direct from 

 human disease, and are used soon after isolation '.., before 

 virulence has been lost by prolonged cultivation in vitro. There 

 is no very clear evidence that any special advantage attaches to 

 any of the sera thus prepared ; in any given case it is a matter of 

 chance which sample will prove successful. The criterion as to 

 the suitability of a given sample of serum is purely an empirical 

 one. The patient's pulse, temperature, nervous condition, etc., 

 should be watched with the closest attention, and any definite 

 improvement occurring within the first twenty-four (and usually 

 within the first four) hours of the first doses should be an indica- 

 tion to continue with the use of the same brand of serum. In 

 some cases each injection causes a slight but definite rise of 



