Antitoxin 



409 



almost any multiple of the fatal dose, but the quantity 

 needed, in proportion to the body-weight, to save an animal 

 from the unknown quantity of toxin being manufactured 

 in its body increases so enormously with the day or hour 

 of the disease as to make the dose, which increases millions 

 of times where that of diphtheria antitoxin increases but 

 tenfold, a matter of difficulty and uncertainty. Nocard 

 also called attention to the fact that the existence of tetanus 

 cannot be known until a sufficient toxemia to produce 

 spasms exists, and that therefore it is impossible to attack 

 the disease in its inception or to begin the treatment until too 

 late to effect a cure. At this point it is well to recall Nocard 's 

 experiment with the sheep in whose blood so much toxin 

 was already present when symptoms first appeared, that 

 the amputation of their infected tails could not save them. 



The explanation of this inability of the antitoxin to effect 

 a cure when administered after development of the symp- 

 toms of tetanus is probably found in a ready fixation of the 

 toxin in the bodies of the infected animals. This is well 

 shown by the experiments of Donitz,* who found that if a 

 mixture of toxin and antitoxin were made before injection 

 into an animal, twelve minimum fatal doses were neutralized 

 by i c.c. of a i : 2000 dilution of an antitoxin. If, however, 

 the antitoxin was administered four minutes after the 

 toxin, i c.c. of a i : 600 dilution was required; if eight 

 minutes after, i c.c. of a i : 200 dilution; if fifteen minutes 

 after, i c.c. of a i : 100 dilution. He found that similar 

 but slower fixation occurred with diphtheria toxin. 



It was found by Roux and Borrel f that doses of tetanus 

 antitoxin absolutely powerless to affect the progress of the 

 disease, when administered in the ordinary manner by 

 subcutaneous injection, readily saved the animal if the 

 antitoxin were injected into the brain substance. 



This observation was followed by a ready application to 

 human medicine, and patients with tetanus were trephined 

 and the antitoxin injected beneath the dura and into the 

 cerebral substance. The results attained have not, how- 

 ever, been satisfactory, and the method cannot be looked 

 upon as itself free from danger. 



ChaufTard and Quenu,J who injected the antitoxin into 



* Reference 18, in "Jour, of Hygiene," vol. n, No. 2, in Ritchie's 

 article. 



t "Ann. de 1'Inst. Pasteur," 1898, No. 4. 

 J "La Presse med.," No. 5, 1898. 



