54 R. H. Chittenden — The Influence of TTrethan, Paraldehyde, 



determined each day by methods already indicated. After nitrogen- 

 ous equilibrium had been established, and the urine analyzed for ten 

 consecutive days, antifebrin was administered daily in divided doses, 

 at a time not to interfere with digestion, for a period of nine days. 

 The daily dose was gradually increased until at last there was a 

 slight approach to cyanosis. In all, ]3'3 grams or 205 grains of the 

 antipyretic were taken. No disagreeable symptoms were experienced, 

 but there was a very noticeable lividity of countenance with a de- 

 cided blueness of the lips, and a slight darkening of the skin near the 

 cheek bones. 



The initial daily dose was 0*4 of a gram or a little over 6 grains, 

 and was rapidly increased to 2*6 grams or 40 grains per day, given in 

 thi'ee doses. There are, to be sure, many cases recorded where 

 apparently smaller doses have led to serious results, but careful 

 watching failed to show any symptoms whatever even suggestive of 

 any disagreeable action on the digestive system, the circulation or 

 respiration. Weinstein, indeed, has said that persons not suf- 

 fering from fever may take antifebrin for weeks together without 

 any effect on the circulation, while according to Herczel the long- 

 continued administration of antifebrin, thirty to forty-five grains 

 daily for six weeks, may lead to what he terms aniline anaemia with 

 solution and decomposition of the haemoglobin of the blood. In 

 fact, the latter observer considers that aniline is set free from the 

 acetanilide and that the decomposition of the blood-coloring matter 

 is due to this cause. Whether this is the cause of the cyanosis so 

 often spoken of in connection Avith this drug is uncertain. 



In the second antifebrin period, 13*9 grams or 214 grains of the 

 drug were taken in seven days, accompanied at the close with the 

 same approach to cyanosis as before. 



Examination of the analytical results shows plainly that under 

 the conditions of this experiment the excretion of urea is not very 

 greatly affected. There is, however, in both antifebrin periods a 

 slight increase, indicating increased proteid metabolism under the 

 influence of the di'ug. This increased excretion of urea is more 

 apparent in the individual results than in the average of the series. 

 Thus, in the normal urine it is to be noticed that the daily excretion 

 of urea never exceeded 34'5 grams, while in the first antifebrin period, 

 on the days when the largest doses of acetanilide were taken, the 

 excretion of urea amounted to 35-37 grams, and in the after period 

 quickly fell to about 33 grams per day. The same peculiarity is 

 also noticeable, to a less extent, in the second antifebrin period. 



