31 
manner from the same lot of leaves. The results indicated the prac- 
tical worthlessness of the method, as rabbits’ hearts evidently exhibit 
marked variations. 
Lutzkaja® published a critical study of the Focke method of 
standardization which he thinks is preferable to the one-hour method 
tvhich, according to his views, is too inexact. He carried out the 
experiments according to Focke’s directions with the exception that 
he used September and October frogs. 
In his first experiments, with 0.5 milligram doses of digitoxin 
injected into frogs of different weights, he obtained toxic values 
showing as great variations as from 1.9 to 8.3 with an average of 4.5. 
For his second experiments he estimated the doses so as to stop the 
heart in about ten minutes, and by this means the results were much 
more uniform, differing only 80 per cent. In a third experiment his 
results varied still less, only 65 per cent. His conclusion is that, in 
spite of some irritating individual variation, if a sufficient number 
of experiments are carried out useful results may be obtained. He 
urges as an objection to the “ short-time methods” that they might 
not give sufficient time for all the poison to be absorbed and by this 
means a very active preparation, absorbed with difficulty, would 
appear weaker than a weak preparation containing easily absorbable 
constituents. 
His results show that digitoxin and digitalinum verum do not give 
the same ratio on frogs as their relative doses appear to indicate that 
they possess in man; in some preparations of digitalis he suggests 
there might be a great deal of digitoxin, but in others not as much, 
and while they might show the same effect on frogs they would not 
on man. He therefore thinks such a condition would render the 
standardization of the leaves on frogs of little value. 
Practically every worker upon this subject has employed the frog 
in some way or other as a means of standardizing the preparations 
of the drugs under consideration and the results obtained upon this 
animal have been confirmed in some cases by control experiments 
carried out, usually upon the blood pressure, upon the higher animals. 
However, in 1908 Reed and Yanderkleed 5 introduced a method, using 
guinea pigs, as they object to the frog because the reaction of this 
animal is very irregular, being affected by the season of the year, 
the species, etc. They also point out that the action upon the heart 
is a toxic effect, a determination of the lethal dose, and therefore 
they substitute for the toxic dose in frogs the toxic dose in guinea 
pigs. To make the assay they prepare their tinctures by evapora- 
ting off the alcohol and diluting the residue with water. Progress- 
ively increasing doses are then injected subcutaneously into guinea 
a Lutzkaja, Arch, intemat. de Pharmacod, Gand et Par., 1908, XVIII, 77. 
&Reed and Vanderkleed, Am. J. of Pharm., 1908, LXX, 110. 
