Samuel B. Nadler

Peritoneal Lavage. Effective Elimination of Nitrogenous Wastes in the Absence of Kidney Function

The experiments of one of us have demonstrated that nephrectomized dogs eliminate considerable amounts of ammonia in vomiting. These results have been amply confirmed and extended by others. Martin has studied the elimination of ammonia, urea and other nitrogenous wastes lost in this manner. During a similar study on elimination of both urea and ammonia in the vomitus, we have demonstrated that really considerable quantities of urea and ammonia are thus eliminated. However, the prospect of this method of elimination serving as a therapeutic measure to tide patients over temporary periods of deficiency in kidney function is not bright. Elimination by way of the stomach becomes quantitatively important only when nitrogen retention has reached a very serious stage, and in our hands this mode of excretion has always failed to keep pace with nitrogen accumulation. During the course of these experiments we encountered edema of massive proportions. The ascitic fluid in these cases was found to be rich in urea and practically in equilibrium with the concentration of that substance in blood. We have been able to accomplish the elimination of nitrogen wastes by the introduction of a solution of balanced salts into the peritoneal cavity of a nephrectomized dog, allowing time (10 minutes) for diffusion of nitrogenous wastes into this fluid, and then drawing off the fluid through the trocar which remains in position throughout. We introduce on the average 750 cc. of solution, allow it to remain in the peritoneal cavity for 10 minutes and then allow it to flow out by gravity. Varying numbers of such washings are made at a single insertion of the trocar. Depending upon the severity of the retention at the time, we have done as few as 5 and as many as 20 washings at one sitting.

Chemical Interaction of S35-6-Mercaptopurine and Ribonucleic Acids.∗:

Summary These data indicate that 6-mercaptopurine can combine with ribonucleic acid both in vitro and in vivo. Binding is enhanced by added metals and the combination is stable to ribonucleic acid isolation procedures.

Recent Observations on Thyroxine and Allied Compounds

In an effort to determine whether the formation of the comparatively soluble disodium salt accounts for the well-marked increase in basal metabolism recently observed by Thompson et al 1 following the oral administration of thyroxine in alkaline solution, we have prepared a disodium salt of thyroxine according to the method of Kendall 2 and have determined its calorigenic action in patients with myxedema. In one patient a single oral dose in distilled water of 15.1 mg. of the product containing 6.5 mg. of iodine, produced an increase in basal metabolism only from —-29% to —21%, and in another patient the same dose produced an increase only from —26% to —20%. These increases are about the same as those produced by single doses of the monosodium salt containing the same amount of iodine and only about 1/3 as great as those produced by thyroxine in alkaline solution. This small effect may be explained in at least 2 ways: (1) The method as used by us may not actually yield the disodium salt. (2) A large part of the disodium salt may hydrolyze when treated with distilled water to form sodium hydroxide and thyroxine. Although the disodium salt is said to be soluble to the extent of 4% and the monosodium salt only slightly soluble, the well-marked effect of thyroxine in alkaline solution by mouth must not be attributed to the formation of the disodium salt without more evidence. N-acetyl thyroxine, prepared according to the method of Kendall and Osterberg, 3 has been given intravenously in alkaline solution to 3 patients with myxedema in doses of from 10.5 mg. to 31.5 mg., containing from 6.5 mg. to 19.5 mg. of iodine; subcutaneously, suspended in 10% glucose, to 2 patients with myxedema in doses of 10.5 and 21.0 mg. respectively; and orally to one patient with myxedema in a dose of 10.5 mg. The patient who received 31.5 mg. intravenously showed a slight but fairly prolonged increase in basal metabolism of from —41% to —35%. If this slight increase may be considered definite, then this compound when administered intravenously in alkaline solution produces only about 1/16 of the effect of thyroxine. When given subcutaneously in suspension, the effect was greater and amounted in one patient to about 1/4 and in another to about 1/6 of the effect of thyroxine given intravenously. These data suggest that the amino group is important for the calorigenic action of thyroxine.

A Technic for Measurement of Radioactive Iodine (I-131) Uptake by the Human Thyroid Gland

Summary It has been found that with the bismuth cathode tube, a 50 uC dose can be used efficiently, and that a tube-to-patient distance of 17 cm will cover a sufficiently large area to make variations in gland size unimportant to the accuracy of the test.

Enzymatic Digestion of Desiccated Thyroid

In the course of studies on the calorigenic activity of various fractions derived from the enzymatic digestion of desiccated thyroid, 1 we have observed that the organic iodine in the gland is rapidly split into acid soluble and acid insoluble iodine fractions. The 2 fractions are separated by adjusting the pH to 5.0. A single large lot of desiccated thyroid was used for these experiments (Lot No. 2∗). The desiccated thyroid was insoluble at pH 5 and contained 2% of the total iodine in the form of “preformed inorganic”iodine as determined by the method of Lawson. 2 When like volumes of enzyme digest were precipitated in dilutions of one, 2 and 4 volumes, the ratio of acid soluble iodine to total iodine was not increased, indicating that the acid insoluble iodine fraction has a negligible solubility at pH 5. The iodine soluble at pH 5 consisted of organic iodine digested off in the acid soluble form and a small amount of “preformed inorganic”iodine. It was thus possible to measure the rate of hydrolysis of desiccated thyroid into, acid soluble and acid insoluble iodine fractions, by measuring the ratio of acid soluble to total iodine in the digest. Incubation of the desiccated thyroid in one and 2% pepsin at pH 2 resulted in a liberation of 55% of the total iodine in an acid soluble form in 4 hours. (The acid soluble fraction is not increased after several months incubation in pepsin solutions.) In one and 2% trypsin at pH 8, 60% of the total iodine was rendered acid soluble in 4 hours. With each enzyme, about 70% of the total hydrolysis into acid soluble and acid insoluble iodine fractions occurred during the first 15 minutes of digestion.