134 THE VENOM OF HELODERMA. 



mation of an ulcer after the injection of gastrotoxic serum, the ulcers must be 

 primarily digestive in character; and Rosenau and Anderson claim that the 

 pyloric ulcers produced through the injection of diphtheria toxin were due to 

 circulatory changes, congestion, and hemorrhage, followed by digestion. 



Although according to our observation, macroscopically and microscopi- 

 cally, hemorrhage is nearly always a concomitant of the ulcers of the stomach, 

 it is questionable whether the latter are primarily hemorrhagic. In order to 

 decide this question we introduced into the stomach of a guinea-pig 14 c.c. of a 

 4 per cent sodium-bicarbonate solution through a stomach-tube, and injected 

 the venom subcutaneously. This was the method used in the beginning. 

 Later, we gave two injections of 10 c.c., one hour apart, in order to insure 

 constant contact of the gastric mucosa with alkaline fluid. This mode of pro- 

 cedure fulfilled two indications: (1) it completely neutralized the gastric juice, 

 and (2) it constantly moistened the gastric mucosa with alkaline fluid. We 

 found that alkali markedly inhibited, and in the great majority of cases actually 

 prevented, the formation of ulcers. Thus, in 30 animals in which alkali and 

 venom were administered, 6 showed ulceration, 20 per cent ; while over 80 per 

 cent in the same number of animals in which venom alone and no alkali had 

 been given showed ulceration. Not only was this the case, but in 4 of the 6 the 

 ulceration was single, and in the other 2 animals the ulcers were very small,, 

 while in the controls the ulcers were large and multiple. Besides, in 2 of these 

 6 only 10 c.c. of alkaline fluid had been injected, and most of the fluid had prob- 

 ably passed over into the duodenum at the time the ulceration took place. 

 The quantity of alkali was, therefore, insufficient. Traumatisms caused by 

 the stomach-tube also could not be excluded. In the last series of 6 animals 

 in which the technique was most perfect, the 3 animals with toxin and alkali 

 showed absolutely no lesions, while the controls showed marked ulceration and 

 hemorrhage. 



These experiments indicate, therefore, that digestion is the primary factor 

 in the formation of these ulcers. In favor of this interpretation we may like- 

 wise cite the observation that in a number of instances, as stated above, be- 

 ginning necrosis or digestion could be observed microscopically without any 

 preceding hemorrhage. Occasionally, however, hemorrhage occurred independ- 

 ently of ulceration; but an intact epithelial layer covering such an area makes 

 it improbable that such a primary hemorrhage has much significance in the 

 production of the ulcers. Our experiments do not permit us to make any defi- 

 nite statement as to the cause of the primary digestion, but we are inclined to 

 believe that a malnutrition of certain areas of the gastric mucosa is brought 

 about by a slowing of the circulation, especially as we have observed the ulcer- 

 ation in discrete areas and with especial frequency in those animals in which 

 the phenomena of collapse were apparent. It is also possible that toxic sub- 

 stances may pass directly from the capillaries to the surrounding mucosa, 

 change the vital processes of these cells, and lower their resistance to peptic 

 digestion. Beneke's view, advocated first by Klebs, that spasm of the vessels 

 with resulting ischsemia is responsible for tissue digestion, seems improbable, 



