41 
ried out at the same temperature. That a given preparation should 
show a worth of 5 at one time and only 3 at another seems of very 
little importance if its keeping qualities are known to be good. All 
that is necessary is to keep such a preparation in stock and, at any 
time when an assay is to be made, to redetermine its activity and then 
make the unknown conform to the value found. The only essential 
is that the known and the unknown digitalis preparation be tested at 
the same temperature. 
Focke° carried out a series of experiments especially designed to 
show the effect of season. (The temperature factor probably played 
some part in the results.) He employed a digitalis powder which had 
been very thoroughly dried and carefully preserved. During April, 
May, and the early part of June the average of all experiments gave 
the powder a worth of 2.66. From the last of June to the end of Sep- 
tember a V of 4.36; during October, a Y of 5, and on November 20 a 
V of 3.3. These variations he ascribes to the nutrition of the frogs 
which is lowest in the spring and gradually improves during the 
summer, reaching its highest point just before the winter sets in, when 
it falls off sharply until it reaches the low point in the spring. He 
also says in a later paper that in the spring the frogs react weakly, 
and this is supported by the results of experiments in which he 
shows that the temperature must be increased in order to obtain the 
same values for the same preparation as at other seasons. His tables 
show that reacting weakly the frogs require a larger dose of the drug 
or an increase in the temperature of the operating room to produce 
the same effect and therefore give a lower V to the specimen of leaves 
examined. 
The effect of a lowered nutrition in increasing the resistance to the 
drug is rather surprising, especially as our experiments, while not as 
complete as Focke’s, show exactly the opposite effect, viz, that in the 
summer when the animals are most vigorous they require a larger 
dose to produce systolic standstill of the heart. We worked with a 
different variety of frogs from those Focke employed, but it would 
hardly be expected that this factor should make such a fundamental 
difference. Our experience may be summarized as follows: 
The U. S. Pharmacopoeia tincture examined by Edmunds * 6 in 1907 
required a dose of from 0.16 to 0.20 c. c. to produce systolic stand- 
still in one hour. In experiments carried out in August, 1908, frogs 
belonging to the same species (R. pipiens) and of the same size 
required 0.40 to 0.50 c. c. to produce the same effect. 
To be still more exact, in April, 1907, a Parke, Davis and Co. tinc- 
ture required 0,15 c. c. to produce the end reaction described above; 
in 1908 one of their fluid extracts made to correspond to tincture 
a Focke, Arch. d. Pharm., 1903, CCXLI, 678. Ther. d. Gegenw., 1904, XLV, 251. 
6 Edmunds, J. Am. Med. Ass., Chicago, 1907, XLVIII, 1744. 
