CHRONIC INTOXICATION DOGS. 81 



December22: 11 a.m. .received 1.0875 grams caff em, or 0.125 gram per kilo; 3p.m., 

 depressed in spirits and sick, but no other symptoms observed. 



December 23: 11.30 a. m., received 1.305 grams caffein, or 0.150 gram caffein per 

 kilo; 1.30 p. m., apparently quite sick, but no other symptoms, had good appetite. 



December 24: 10 a. m., received 0.175 gram caffein per kilo; 4 p. m., when about 

 to be fed fell over and died ; no autopsy. 



The total amount of caffein given dog 30 was 11.3458 grams, administered for a period 

 of eighteen days. The average daily amount per kilo was therefore 72 mg. Thefeces 

 became offensive when the amounts of caffein were increased to 75 mg per kilo. It 

 will be observed that in this dog the appetite was uniformly good until tne day of his 

 death. Whether or not this is the cause of his resistance to caffein will be discussed 

 later. 

 Dog 32. White, male, young. 



Although he was growing rapidly this dog's weight was constant, but he looked 

 anemic. He received a high protein diet until December 3, when the rations were 

 increased by one-third. This dog was under observation from October 26 to December 

 6 when the administration of caffein was begun. He then received 50 mg caffein 

 per kilo daily for nine days consecutively without showing any effects, when the 

 dose was increased to 75 mg per kilo, then to 100 mg per kilo. This dose was further 

 increased to 150 mg per kilo without causing symptoms, which was repeated the 

 next day. No symptoms having been observed after such amounts of caffein, 175 mg 

 per kilo were fed. This dose, however, proved fatal within two hours. Record of 

 experiment follows: 



October 26: Weight, 6.90 kilos. 



November 3: Weight, 6.90 kilos. 



November 10: Weight, 6.90 kilos. 



November 20: Weight, 6.90 kilos. 



November 29: Weight, 6.55 kilos. 



December 3: Put into cage, diet increased one-third. 



December 6, 7, 8, 9: Weight 6.30 kilos; 12.30 p. m., received 16 cc 2 per cent caffein 

 by subcutaneous injection in back, no symptoms of any kind noticed, site of injection 

 normal. 



December 10, 14: 0.05 gram caffein per kilo. 



December 15: Receivea 0.4725 gram caffein by mouth, no symptoms. 



December 16: Received 0.655 gram caffein, 0.100 gram per kilo. 



December 17: No caffein given. 



December 18: Received 0.655 gram caffein daily, 0.100 gram per kilo, no symptoms. 



December 20: Received 0.8188 gram caffein, 0.125 gram per kilo, no symptoms, 

 appetite good. 



December 21: Received 0.9825 gram caffein, 0.150 gram per kilo, somewhat uncom- 

 fortable, no other symptoms. 



December 22: Received 0.9825 gram caffein, 0.150 gram per kilo, no symptoms 

 except some uneasiness. 



December 23: 9 a. m., no symptoms, appetite good ; 11. 30 a. m., received 1.146 grams 

 caffein, 0.1759 gram per kilo; 1.30 p. m., died while making an effort to get out of cage, 

 tonic contraction of limbs observed before death. 



The amount of caffein received d urine; the entire experimental period was 9.2223 

 grams, or an average per day approximately of 80 mg per kilo, and therefore 10 per cent 

 more than dog No. 30 receivea. It will be observed that the appetite in dog No. 32 

 was likewise uniformly good, and that he received a very high protein diet which was 

 also of a very high calorific value. 



Autopsy (dog 32}. Stomach presented a severe inflammation of the mucosa, espe- 

 cially in the fundus and pyloric portions. The gastritis was more marked in pyloric 

 portion, and the inflammatory condition extended along the whole course of small 

 intestines, which presented numerous hemorrhagic areas, and a thick catarrhal exudate 

 on the mucosa. The large intestine contained quite a large number of parasites, 

 probably round worms. The liver was enlarged and the gall cyst well filled. The 

 spleen was also considerably engorged, kidneys appeared normal, other organs all 

 appeared normal. 

 Dog SI. Black spaniel, male. 



This dog had been under observation one month previous to the experiments with 

 caffein. The usual initial dose was then administered for nine days. There were no 

 signs of local irritation when the drug was given subcutaneously, but symptoms of 

 toxicity were present. These disappeared, however, when the drug was administered 

 by mouth. Tne dose was therefore increased to 75 mg per kilo. This, as will be seen, 

 proved fatal within six hours. High nitrogen diet, same as No. 30. 



November 3: Weight 10.250 kilos. 



18594 Bull. 14812 6 



