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It has been shown from the apparent first-order urinary excretion studies of D-(-)-mandelic acid and certain of its homologs, DL-tropic acid, D-(-)-4-hydroxy-4-phenylbutanoic acid, DL-phenyllactic acid, and D-(-)-benzyllactic acid, that the biological half-lives of the homologs are significantly shorter than that of D-(-)-mandelic acid in rats. Since these compounds, which differ from each other in their content of methylene groups around the carboxyl group, exhibit negligible metabolism and protein binding, low pKa values (3.3-4.7), and low lipid solubility at the physiological pH, and are primarily recovered in the urine in the intact form, they are utilized in these studies as model compounds to study the effect of hydrophobic group(s) on the rate of secretion. These compounds are shown to exert a mutual inhibitory effect on their renal tubular secretion, indicating a common “carrier” mechanism for their secretion. The utilization of these compounds indicated that the addition of methylene group(s) in the vicinity of the carboxyl group of the mandelic acid molecule increased its affinity for the carrier molecules of the renal tubular secretion system in rats.

From the pseudo-first-order urinary excretion studies of D-(-)mandelic acid and DL-tropic acid in rats, data regarding the apparent initial secretion rate versusdose (i.v.) are obtained for these compounds and treated according to the Michaelis-Menten kinetics. While the values of maximum apparent initial secretion rate (Vm) determined for these compounds are similar, the value of the dose of the substrate required to produce one-half of the maximum apparent initial secretion rate (Km) determined for D-(-)-mandelic acid is found to be about twice that determined for DL-tropic acid. Data have been obtained to demonstrate that these compounds competitively inhibit the renal tubular secretion of each other, thereby strongly indicating that these compounds share a common carrier transport system for their secretion. Data obtained in the present studies and those described earlier are utilized to distinguish a certain structural characteristic around the cationic site of the “carrier” molecules of the renal tubular secretion system in rats.

Fifty‐one chemical substances, not heretofore employed as preservatives in ophthalmic solutions, were examined for their effectiveness as antibacterial agents against 13 different strains of Pseudomonas aeruginosa. In vitroand in vivomethods were employed. Eleven of these agents showed a satisfactory sterilizing time against these strains. Further study of the following is indicated to determine their practical use as effective preservatives in ophthalmic preparations: Intexsan LB, Intexsan MB, Dichloran, DMBC, Cetol, Arquad 16, Virac, Betadine, Biopal VRO, chlorhexidine, and colistin.

Seven chemical substances or combinations of these substances presently employed as preservatives in ophthalmic solutions were studied to note their effectiveness as antibacterial agents against 13 different strains of Pseudomonas aeruginosa.New in vitromethods were devised. Among the latter were techniques to (a) differentiate between bacteriostatic and bactericidal activities and (b) determine the sterilizing time for each antibacterial agent. The methods presented here have several advantages over those previously employed and those now in use. An in vivoprocedure was also employed in evaluating these chemical agents to note whether the findings were in agreement with the final results obtained in the in vitrostudies. The following chemicals were examined: chlorobutanol, benzal-konium chloride, thimerosol, combinations of methyl and propylparaben, phenyl-mercuric nitrate, phenylethyl alcohol, and polymyxin B sulfate.

Pseudo-first-order rate constants for the overall elimination of (−)-mandelic acid both in the absence (K) and in the presence (Kas) of sulfadiazine, sulfamethazine, or sulfamerazine were determined in three human subjects. Since the extent of metabolism of (−)-mandelic acid was not significantly altered in the presence of these sulfonamides, the ratio of the rate constants, K/Kas, has been calculated as a measure of the inhibitory effect of each sulfonamide on the urinary excretion of (−)-mandelic acid. For the dosage levels of the inhibitors employed, the range of such ratios found in all three subjects is 1.29—1.55 due to sulfadiazine, 1.33—1.62 due to sulfamethazine, and 1.33-1.76 due to sulfamerazine. Similar inhibitory effects were observed on the urinary excretion of sulfadiazine in the presence of (−)-mandelic acid in two subjects. Therefore, it is concluded that these compounds probably share the same renal tubular transport system(s) for their secretion in humans.

I count not the least valuable to myself of my former collaborations with the late Dr. Isaac Kerlin a study that we made together-with intent of reducing to tabulated form-of those diseases most common to the feeble-minded. This study involved the examination of medical records of 1400 cases, covering a period of twenty-five years, and I have since extended it so as to include some 3000 cases. Sifted out, we find the diseases, some eighty in number, distributed equally among the sexes, and in varying proportion in the different grades. Broadly considered, there are three conditions or classes which the feebleminded present to the eye of the medical observer, with modifications of course in different grades, causing the individual, therefore, to repel or to succumb to disease each in a different way. We have, first, a physical development according to age, susceptibilities to pain or pleasure being almost normal, and