Cochrane[268] cited three cases where caffein was hypodermically administered in cases of acute indigestion, etc., and concluded that the cases prove that caffein, or a compound containing it as a synergist, does indirectly make the injection of morphia a safe proceeding, and directly increases the force of the heart and arterial tension. However, Wood[269] found that medium doses of caffein do not produce any marked rise in blood pressure, and cause a reduction in pulse rate. He attributes the contradictory results which prior investigations gave, to employment of unusually large doses and to inaccurate experimental methods. Caffein was found by Nonnenbruch and Szyszka[270] to have a slight action toward accelerating the coagulation time of the blood, being active over several hours. It inhibits coagulation _in vitrio_. Its action in the body apparently rests on an increase of the fibrin ferment. There is no reason to believe that the behavior is dependent on a toxic action, but there is probably an action on the spleen; for in several rabbits from which the spleen was removed, no action was observed. Experiments conducted by Levinthal[271] gave no positive information as to the formation of uric acid from caffein in the human organism. The elimination of caffein has also been studied by Salant and Reiger[272], who found that larger amounts of caffein are demethylated in carnivora than in herbivora, and resistance to caffein is inversely as demethylation, caffein being much more toxic in the former class. In a similar investigation, Zenetz[273] observed that caffein is very slightly eliminated from the system by the kidneys, and that its action on the heart is cumulative; therefore he concludes that it is contra-indicated in all renal diseases, in arterio-sclerosis, and in cardiac affections secondary to them. The inaccuracy of these conclusions regarding the non-elimination of caffein and those of Albanese,[274] Bondzynski and Gottlieb[275], Leven[276], Schurtzkwer[277], and Minkowski[278], has been shown by Mendel and Wardell[279], who point out that many of these experimenters worked with dogs, in which the chief end-product of purin metabolism is not uric acid, but allantoin. They observe that the increase in excretion of uric acid after the addition of caffein to the diet seems to be proportional to the quantity of caffein taken, and equivalent to from 10 to 15 percent of the ingested caffein. The remainder of the caffein is probably eliminated as mono-methylpurins. Regarding the alleged cumulative action of caffein, Pletzer[280], Liebreich,[281] Szekacs[282], Pawinski,[283] and Seifert[284] all concluded from their investigations that the action of caffein is usually of brief duration, and does not have a cumulative effect, because of its rapid elimination; so that there is no danger of intoxication. Dr. Oswald Schmiedeberg says: