EFFECTS OF CERTAIN DRUGS AND POISONS 779 



the percentage of heat lost in the vaporization of water from the lungs 

 and skin was not significantly altered by caffein. 



Bod [i Temperature. Binz appears to have discovered that caffein 

 hyperthermia, which is not usually intense, regularly results when con- 

 siderable doses are administered to animals and man. Pilcher found 

 that the lowered temperature of moderate, but not of deep narcosis, could 

 be successfully combated with cafFcin. Karelkin states that the temper- 

 ature increase is much greater in thyroidectomized than in normal 

 dogs. The diuretic effect, which concentrates the blood, is probably re- 

 sponsible for the rise in temperature, but this should be determined by 

 experiment. 



Mandel observed a correlation between purin excretion and tempera- 

 ture-fall in fevers. He produced fever in monkeys by xanthin injections; 

 xanthin, if given with salicylate, failed to raise the temperature. 



Total Metabolism. Edward Smith in 1859 by a very large number 

 of carefully conducted experiments established the fact that caffein in- 

 creases the carbon dioxid output. The rise obtained was anywhere from 

 fifteen to thirty per cent. Reichert by direct calorimetry in dogs observed 

 greater increases in the heat production. Using more, modern methods 

 Edsall and Means, and Higgins and Means found increases varying from 

 three to fourteen per cent. 



Means, Aub and DuBois observed in four normal subjects receiving 8.6 

 milligrams per kilo of caffein alkaloid an increase of from seven to 

 twenty-three per cent in the basal metabolism. In these elaborate in- 

 vestigations the independent methods of direct and indirect calorimetry 

 gave results which agreed within one per cent. 



F. G. Benedict and Carpenter (6) found that approximately three hun- 

 dred and twenty-five grains of hot coffee will increase the basal metabolism 

 eight to nine per cent. 



Nitrogen Metabolism. C. Voit concluded from his experiments that 

 caffein did not alter the nitrogen balance, although there was possibly 

 some increase in the urea excretion. Ribaut found the nitrogen excre- 

 tion in man but little changed, while it was moderately increased in dogs. 

 In three of their subjects Means, Aub and DuBois found an increase in 

 nitrogen elimination varying from six to thirty-seven per cent. This was 

 attributed to the diuresis. 



Farr and Welker state that theocin decreases the nitrogen excretion' 

 in both health and renal disease. 



Creatin and creatinin elimination were found but slightly altered by 

 Salant and Rieger. 



Purin Metabolism. Mendel and Wardell have shown that the addi- 

 tion of strong coffee infusion to a purin-free diet causes a marked increase 

 in the excretion of uric acid. This increase was not obtained from de- 

 caffeinated coffee. The increase was found equal to the quantity of uric 



