768 HENRY G. HARBOUR 



unpublished work IB arbour, Harris, and Plant have in normal fasting 

 persons found the heat production increased in two experiments in which 

 one-half gram was taken and practically unchanged in two others. These 

 experiments accord with those of Zuntz as well as of Liepelt, who with 

 large doses raised the total metabolism. Means and Aub found quinin 

 of no value in reducing the basal metabolism in exophthalmic goiter. 



/ With acetyl-salicylie acid in one gram doses there is produced in 

 normal individuals approximately a six per cent increase (Harbour and 

 Devenis). Wood and Reichert found the metabolism increased in dogs 

 after large doses of sodium salicylate, which, according to Stiihlinger, 

 also increases it in guinea pigs. 



Denis and Means found after repeated doses of sodium salicylate a 

 fifteen per cent increase in the metabolism in one out of three surgical 

 convalescents: the others exhibited no change. 



With very large doses (two to three grams) of antipyrin Liepelt suc- 

 ceeded in prodiicing a reduction in the oxygen intake varying from three 

 to seven per cent. In the carbon dioxid output was found a greater 

 diminution, probably attributable partly to retention. There was with 

 these doses no significant temperature change. Even with antipyrin, 

 however, there must often be an increase in the heat production. It 

 usually raises the temperature, for example, in normal dogs and rabbits 

 in doses which in fever are antipyretic; furthermore, it has a similar 

 and more decided effect in decerebrate rabbits. This latter finding of 

 Harbour and Deming was confirmed by Isenschmid, who also imitated 

 it with sodium salicylate. 



In fever the total metabolism is definitely depressed by therapeutic 

 doses of the antipyretics, the natural result of cooling the body. With 

 antipyrin Riethus observed reductions in, the oxygen intake varying 

 from two to thirty per cent. 



After one gram doses of acetyl-salicylie acid Harbour observed an 

 average diminution of 3.5 per cent in the heat production in associa- 

 tion with a drop of nearly 1 C. in the temperature; heat elimination is 

 greatly increased (see Fig. 4). Similar changes occur under phenacetin 

 and antipyrin. 



Quinin in fever has usually reduced the total oxidations in man and 

 animals when the temperature was affected, for example, in a case of 

 erysipelas studied by Riethus. Tuberculosis and many other febrile con- 

 ditions respond to quinin by a rise in temperature and oxidations rather 

 than by a fall. The contention that quinin, which is far from being a 

 universal antipyretic, reduces temperature primarily by diminishing the 

 heat production, certainly does not hold for human beings. 



Senta found that various antipyretics reduce the oxidations in isolated 

 muscles of mammals and birds, quinin and salicylic acid being the most 

 efficient in this respect. 



