vii KATABOLIC CONSTITUENTS OF UEINE 389 



obtained uric acid from a variety of other tissues and organs : 

 brain, kidneys, liver, gastro-intestinal mucous membrane, lungs, 

 thynuis, muscles, etc. 



That uric acid arises from nuclein, not merely in vitro as 

 Fischer showed but also in vivo, was demonstrated by Horbaczewski 

 on man by administration of nuclein, which produced an increase 

 of uric acid in the urine. He also showed that the increase of 

 uric acid coincided with an increase of leucocytes in the blood, 

 which suggests that the circulating nuclein caused a hyperforma- 

 tion of leucocytes on the part of the lymph organs. On these 

 facts he based the theory that nuclein is derived from the 

 leucocytes, that uric acid is formed from the nuclein, and that all 

 the means which increase the leucocytes determine a simultaneous 

 increase in the formation and elimination of uric acid. 



Clinical and experimental investigation of this theory, however, 

 militate against the supposed parallelism between the increase in 

 the number of leucocytes of the blood and the uric acid content of 

 the urine, although they confirm the fact that there is a relation 

 between the nuclein introduced and the uric acid excreted. 



Kriiger and Wulff (1894) invented a method for estimating 

 the total nitrogen of the purines, and endeavoured by its means 

 to establish the "ratio between the nitrogen of the uric acid and 

 that of the purines. They saw that this ratio varies considerably 

 in normal individuals, but that the nitrogen of the uric acid 

 always exceeds that of the purines, on an average by 4 : 1. 



Weintraud (1895) studied the effect of feeding substances rich 

 in nuclein on the elimination of uric acid, by substituting thymus 

 which is an organ very rich in nuclein for alimentary protein, 

 in an adult man. He found a relative increase in the elimina- 

 tion of uric acid without any constant augmentation in the 

 number of leucocytes in the blood. From this he concluded that 

 the purine bases are formed in the alimentary canal, independent 

 of leucocy tosis, and that on absorption they determine an incre- 

 ment of uric acid. 



Zagari, in collaboration with Pace (1897), experimented on 

 six normal and two leucaeinic subjects and one nephritic, and 

 observed that when thymus and nuclein were added to the usual 

 diet of these individuals, there was no constant hyper-production 

 of leucocytes, but there hardly ever failed to be a considerable 

 increase of uric acid, both in healthy subjects and in invalids : 

 that in leucocytosis of varying degree the value of the uric acid 

 excretion was not parallel with the fluctuations of the leucocytosis ; 

 that in the rare cases in which there was no increase of uric acid the 

 total nitrogen of the urea did increase. We are not at present 

 able to account for these differences of result, which are certainly 

 due to special conditions of metabolism in different individuals. 



Laquer (1896) studied the influence of water and milk on the 



