PROTEIN SENSITIZATION OR ANAPHYLAXIS 259 



the most thorough study of it have come from the researches 

 of Besredka and Steinhardt. 



Theobald Smith 1 stated that the guinea-pigs which had 

 received the largest doses of diphtheria toxin-antitoxin 

 mixture more frequently survived the second dose than 

 those that received smaller doses. Rosenau and Anderson 2 

 found that animals to which they gave reinjections before 

 the end of the period of incubation (before twelve days) 

 were not responsive when another reinjection was made 

 at the end of twelve days, and that a longer period than 

 another twelve days had to pass before they became respon- 

 sive. All who have tested this point in serum anaphylaxis 

 have found that the larger the sensitizing doses employed, 

 the longer must be the period before typical anaphylactic 

 shock appears on reinjection. Moreover, all who have 

 experimented with anaphylactic shock, whatever the antigen 

 employed, and whatever the avenue of administration, 

 have found that animals which survive the first reinjection 

 are for a time thereafter, which is variable, refractory to a 

 second reinjection. Besredka and Steinhardt observed 

 that it was easy to develop the refractory state in guinea-pigs 

 by either of the following methods: (1) The intracerebral 

 injection of 0.25 c.c. of horse serum before the expiration 

 of the period of incubation (twelve days). (2) The intra- 

 cerebral injection of less than the fatal dose (^5- to -f^ c.c.) 

 after the period of incubation. (3) The intraperitoneal 

 injection of 5 c.c., after the period of incubation. The last 

 method seems to apply only to French guinea-pigs, which, 

 as we have already stated, are not so easily sensitized as 

 those of other countries. (4) Rectal injections. The rectum 

 is cleansed with a glycerin-enema and then 10 c.c. of a 

 dilution of serum with an equal volume of normal salt 

 solution is injected. This never affects sensitized guinea- 

 pigs, and after twelve hours they generally prove refractory 

 to poisonous doses given intracerebrally. Besredka 3 secures 



1 Jour. med. Research, 1904, xxii, 3. 



2 Hygienic Laboratory Bulletin, 1906. No. 29. 



3 Kraus and Levaditi, Handbuch d. Ergeb. d. Immunitatsforschung, 

 Erganzungsband, i. 



