3 so Tetanus 



tion against 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 anti- 

 toxin 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 incep- 

 tion 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 ap- 

 peared 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 symptoms 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 cc. of a I : 2000 dilution of an antitoxin. If, however, the 

 antitoxin was administered four minutes after the toxin, i cc. of a 

 I : 600 dilution was required; if eight minutes after, i cc. of a i : 200 

 dilution; if fifteen minutes after, i cc. of a i : 100 dilution. He found 

 that similar but slower fixation occurred with diphtheria toxin. 



It was found by Roux and Borrelf that doses of tetanus antitoxin 

 absolutely powerless to affect the progress of the disease, when ad- 

 ministered in the ordinary manner by subcutaneous injection, read- 

 ily saved the animal if the antitoxin were injected into the brain 

 substance. 



Chauffard and Quenu,t who injected the antitoxin into the 

 cerebral substance, found that such administration brought about 

 an apparent cure in one case. 



Their observations were followed by an attempt to apply the 

 method in human medicine, and patients with tetanus were trephined 

 and the antitoxin injected beneath the dura and into the cerebral 

 substance. The results have not, however, been satisfactory, and 

 as the method cannot be looked upon as itself free from danger, it 

 has been abandoned. 



The only means of treating the disease to be recommended at 

 present is the intraspinous, intravenous and subcutaneous injection 

 of large and frequently repeated doses of the antitoxic serum. There 

 can be little doubt but that the administration must be so free as to 

 load up the patient's blood with the antitoxin in hopes that its pres- 



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

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

 t "La Presse mM.," No. 5, 1898. 



