INTRODUCTION 31 



gland extracts is that a sort of immunity is developed. As long ago as 

 1898 Howell observed this in connection with studies on the vasomotor 

 effects of pituitary extracts. He observed that although an augmentation 

 of blood pressure resulted from the first injection, a second shortly there- 

 after might give rise even to a depression. This observation was confirmed 

 a year later by Schafer and Vincent. Etienne and Parisot (1908) have 

 observed that repeated injections of pituitary extracts fail to provoke an 

 increase in cardiac discharge such as is observed after the first injection. 

 This observation was confirmed by Salvioli and Carraro. Similarly, 

 although a first injection of pituitary extract may cause marked contrac- 

 tion of the bladder, this becomes less and less extensive with succeeding 

 injections. Schafer and Herring, in their classic observations on the 

 diuretic effect of pituitary extracts, noted that a second injection is likely 

 to cause much less vasodilatation in the kidney and correspondingly less 

 diuresis. That repeated injections of epinephrin may produce successively 

 decreasing effects is well known. Roger and Josue have observed that a 

 first injection of extract of intestinal mucosa causes a marked fall of blood 

 pressure, but that such a result is not obtained from a second injection. 

 Gley and Champy have made a similar observation as regards extract of 

 corpus luteum (Grley, 1917). That such effects are not due merely to 

 the introduction of foreign proteins is shown by the fact, observed in 

 the writer's laboratory, that marked fall in blood pressure may result 

 from the injection of freshly prepared extracts of the experimental ani- 

 mal's own pancreas or salivary glands. 



In the investigations of the physiology of the endocrin glands by injec- 

 tion experiments due regard should be paid to the quantitative aspects 

 of the research. When, at a single dose, as much material is administered 

 as a normal animal could be expected to secrete in several hours, no 

 conclusions can be drawn as to the physiological aspects of the hormone in 

 question. At best such a research can afford data of pharmacological 

 value. As a case in point, the greatest amount of epinephrin that can be 

 obtained from the suprarenal glands by stimulation of the splanchnic 

 nerve is, according to Osgood, but one two-hundredth of the quantity neces- 

 sary to provoke glycosuria. Yet the glycosuric effect of epinephrin has 

 been made the basis of much theorizing as to the physiology of the supra- 

 renal glands. A theory of carbohydrate metabolism, prominent a few 

 years since, had no more secure foundation than the fact that it is 

 possible, by the use of large doses, to produce epinephrin glycosuria. In 

 classroom demonstrations from which students are supposed to make de- 

 ductions regarding suprarenal physiology, it is the custom to inject from a 

 half to one milligram of epinephrin at a single dose. Yet the researches 

 of Stewart and Rogoff, Hoskins and McClure, and others, indicate that 

 the output from these glands does not transcend two ten-thousandth of a 

 milligram per kilogram per minute. Neither by direct massage of the 



