EXPERIMENTAL PRODUCTION OF GASTRIC ULCER. 129 



acutely from the injection showed lesions of the stomach. Turck failed to pro- 

 duce gastric ulcer by injection of the diphtheria toxin into the stomach-wall; 

 only minute hemorrhagic foci were found in the duodenum. He also failed to 

 produce gastric ulcer by the introduction of the toxin into the mesenteric ves- 

 sels. He obtained, however, in ten weeks, necrosis in the duodenum and near 

 the pylorus. Rosenau and Anderson produce these changes by direct subcu- 

 taneous injection of the diphtheria toxin in a dose sufficient to cause the acute 

 death of the animal. AVhen the toxin is completely neutralized by antitoxin 

 the stomach shows no lesions. Lesions may occur in infections with Bacillus 

 diphtheria: as well as through the action of the toxins. These pathologic 

 changes — ulceration and hemorrhage — always occur at the pylorus and are 

 found in 50 per cent of the animals dying within 24 hours and in 75 per cent of 

 those dying between the third and fourth day after the injection. They enum- 

 erate the steps in the formation of the ulcer: (1) congestion, (2) hemorrhage, 

 (3) digestion. 



These observations represent more or less acute conditions in which toxic 

 agents are at work. Indirectly they have, as will be shown, some bearing on 

 our work. 



METHOD OF PRODUCING ACUTE TOXIC ULCER OF THE STOMACH. 



The beginning of our investigation was the observation that the subcu- 

 taneous injection of the venom of the Gila monster {Heloderma suspedum) into 

 guinea-pigs frequently produced ulceration and hemorrhage of the stomach. 

 The dose of venom necessary to produce this change depended on the toxicity 

 of the venom, and as this constantly fluctuates, the dose must vary with the 

 toxicity. In the beginning of our experiments we found that 1 c.c. of fresh 

 venom, diluted in the proportion of 1 part of venom to 19 parts of normal salt 

 solution, was sufficient to cause death in from 2 to 4 hours after the animal had 

 reached a state of marked intoxication. Later on, however, as much as 1.5 to 

 3 c.c. of diluted fresh venom was occasionally required for the purpose. The 

 dose of dried venom which exhibited approximately the same toxicity was from 

 12 to 15 mg., and a much greater dose was frequently given. The average 

 weight of the animals employed in our experiments was from 350 to 400 grams. 

 In larger animals the dose must be increased in proportion to the increase in 

 weight. 



It is very important that the animal should be in a state of marked intoxi- 

 cation and remain in such a condition for a period of at least an hour. Under 

 such circumstances the animal is in a stuporous condition or has tremors, con- 

 vulsions, or later actual paralysis. This condition of intoxication is the most 

 important factor in the production of gastric ulcer; the dose of venom must be 

 chosen accordingly and the injections repeated with sufficient frequency to 

 insure the continuance of such an effect for a certain time. Following these 

 rules, we were able to produce gastric ulceration in 35 out of 41 animals injected 

 with venom alone — a little over 85 per cent. Of the 15 per cent in which no 

 change or only a doubtful change was visible, several had received insufficient 

 doses, and in the case of several others the toxicity of the venom had been 



