116 INFECTION 



size of the successive doses. In order to obtain a uniform method for 

 estimating the strength of a diphtheria toxin and thus obtain compara- 

 tive values, a standard unit has been adopted, consisting of the smallest 

 amount of toxin that will kill a healthy guinea-pig weighing about 250 

 grams in from four to five days. This is known as the minimum lethal 

 dose, or dosis lethalis minimus. The technic used for determining this 

 dose is given in the chapter on Antitoxins, p. 241. 



A quick and accurate method for estimating the amount of diph- 

 theria toxin present in the body-fluids of a diphtheric patient would be 

 of value in controlling the antitoxin treatment of this infection. At 

 present the amount of antitoxin administered is regulated according to 

 the clinical condition of the patient. Uffenheimer has used a method 

 for determining the presence of toxin, consisting in injecting intra- 

 peritoneally a 250-gram guinea-pig with 0.1 to 0.4 c.c. of the patient's 

 serum, diluted with 2 to 4 c.c. of salt solution. The presence of a dis- 

 tinct doughy edema of the abdominal cavity after seventeen to twenty- 

 four hours indicates the presence of diphtheria toxin, an observation that 

 may be confirmed by making an autopsy at the end of forty-eight hours. 

 The diagnostic value of this method has not been adequately established : 

 it is doubtful if it yields any information other than is more readily 

 gained by making a good cultural examination of the patient, and it 

 does not aid in the estimation of the quantity of toxin, which is the result 

 most desired. 



Diphtheria toxins have been classified into three groups, depending 

 upon the degree of avidity for antitoxin they display, viz., prototoxin, 

 deuterotoxin, and tritotoxin. Each of these toxin groups may, in 

 whole or in part, be converted into toxoids. The prototoxin has a 

 greater affinity for the antitoxin than has the deuterotoxin, and the 

 deuterotoxin has a greater affinity for the antitoxin than has the trito- 

 toxin. The same relation is apparent with the three toxoids, which are 

 not poisonous, but which have the same power of combining with 

 antitoxin as have the toxins from which they take their origin. 



In standardizing antitoxin, it is found in general that with a perfectly 

 fresh toxin a certain amount of antitoxin will just neutralize a definite 

 amount of toxin. If older toxin is used, it is found that the toxin has 

 lost about one-half its toxic power, but retains its initial power for 

 neutralizing antitoxin. Ehrlich explained this by showing that the 

 diphtheria toxin molecule is composed of two groups one the carrier 

 of the toxic qualities, the toxophore group, which is quite labile; the 

 other uniting the whole molecule with antitoxin, being capable of neu- 



