30 ANAPHYLAXIS AND ANTI-ANAPHYLAXIS 



anaphylactic shock, while in reality those symptoms 

 are due to coagulation and subsequent embolism. 

 Now, these accidents are never to be feared when the 

 subdural route is employed. If this latter is a trifle 

 less effective than the venous route it is more satis- 

 factory than the intraperitoneal route, and incom- 

 parably more so than the subcutaneous route. 



The following concrete example will suppl}-- a 

 satisfactory estimate of these differences in sensitive- 

 ness. Guinea-pigs sensitised to serum were inocu- 

 lated with a test injection after the necessary in- 

 terval had elapsed: they exhibited grave or lethal 

 anaphylactic symptoms with 0*05 to o-i c.c. serum 

 introduced intravenously. To produce the same 

 effect subdurally 0-07 to 0-125 c.c. is needed. With 

 intraperitoneal injection the guinea-pigs only reacted 

 in half the cases, and even then a dose of 5 to 6 c.c. 

 was necessary. The same dose injected subcutan- 

 eously rarely gave rise to serious or lethal symptoms. 



As we have pointed out, our preference from the 

 outset has all been for the subdural test. We have 

 discovered that in the case of the guinea-pig one 

 cannot inject more than 0-25 c.c. of the fluid into 

 one hemisphere without setting up symptoms due to 

 compression; this is the dose, therefore, that we have 

 been in the habit of employing in all our experiments. 



Toxicity of Sera. — In the course of our experiments 

 we have noted that the sensitiveness of guinea-pigs 

 to serum is far from being uniform, and that sera of 

 various origins set up more or less severe reactions. 

 In the case of the same serum, however, the intensity 

 of the reaction is in direct ratio to the dose injected. 



This finding, which nowadays appears so natural, 

 was not so simple at the time of its discovery. This 

 suggested to us the idea of graduating the dosage of 

 therapeutic and normal sera.* The test for this 



1 Annales de I'lnstitut Pasteur. 1909, xxiii., January. 



