Control of conception by hormonal steroids.

Experience with the use of progestinestrogen preparations as oral contraceptives indicates that they inhibit fertility by preventing ovulation and that their action is clearly a physiological process. Their efficiency as antifertility agents is extraordinary. An examination of their physiological effects over many years of use indicates that actions to be expected from the hormonal properties of the steroidal components occur but that none of these constitute pathological phenomena. Rather, we observe a state conditioned by the rather constant hormonal milieu resulting from the particular dosages and regimes of use. Thus far, despite use by millions of women, none of the alleged pathological adverse reactions (such as thromboembolism) to the drugs have been established as more than coincidental. Clearly beneficial effects are inherent not only in the avoidance of risks attendant upon pregnancy but also in improvements in menstrual function (regularity, reduction of hypermenorrhea and dysmenorrhea) and perhaps in a prophylactic effect upon certain abnormalities of the reproductive tract (cervical anaplasia, endometrial cystic and adenomatous hyperplasia). Psychogenic phenomena due to use of oral contraceptives are difficult to measure, but beneficial effects would seem to outweigh adverse ones.

A comparison of the metabolism of radioactive 17-isoaldosterone and aldosterone administered intravenously and orally to normal human subjects.

After intravenous and oral administration of radioactive aldosterone to normal subjects, 7.3 +/- 0.4 (SE) and 5.4 +/- 0.5 (SE)%, respectively, of the dose was recovered from a 48-hour collection of urine as aldosterone released by mild acid hydrolysis (from aldosterone 18-glucuronide), and 35 +/- 5 (SE) and 39 +/- 4 (SE)%, respectively, was recovered as tetrahydroaldosterone after incubation with beta-glucuronidase.After intravenous and oral administration of 17-isoaldosterone-4-(14)C to a similar group of subjects, 35 +/- 3 (SE) and 53 +/- 4 (SE)%, respectively, of the dose was recovered as 17-isoaldosterone released by acid and less than 5% as total metabolites after incubation with beta-glucuronidase. No detectable radioactivity (< 0.5%) could be recovered as tetrahydroaldosterone or as a compound with the expected chromatographic properties of tetrahydro-17-isoaldosterone. The total radioactivity in the neutral extracts was also relatively small (< 2%) after administration of either labeled aldosterone or 17-isoaldosterone. The radioactivity as aldosterone in the neutral extract was much lower after oral [0.017 +/- 0.003 (SE)%] than after intravenous [0.21 +/- 0.04 (SE)%] administration of labeled aldosterone. The radioactivity as 17-isoaldosterone in the neutral extract was similar after intravenous [0.20 +/- 0.02 (SE)%] and after oral [0.38 +/- 0.18 (SE)%] administration of 17-isoaldosterone. These results indicated that, due to lack of A-ring reduction of the molecule and the consequent slowing of hepatic clearance, 17-isoaldosterone is converted to an acid-labile conjugate (presumably 17-isoaldosterone 18-glucuronide) as the major metabolite. 17-Isoaldosterone was not secreted or converted to aldosterone to any significant extent in the normal subjects investigated.

The metabolism and secretion of aldosterone in elderly subjects.

The secretion rates [34 +/- 6 (SE) mug per day, 9 subjects] and metabolic clearance rates (MCR) [1,288 +/- 120 (SE) L of plasma per day, 9 subjects] of aldosterone in elderly subjects are significantly lower than those of young subjects [77 +/- 7 (SE) mug per day and 1,631 +/- 106 (SE) L per day, respectively]. There is a correlation of the MCR and secretion rate values (p = 0.02), but the calculated plasma concentrations (secretion rate/MCR) are also significantly low in the elderly subjects [2.6 +/- 0.3 (SE) compared with concentrations in the plasma from young subjects of 4.7 +/- 0.6 (SE) mug per 100 ml plasma]. The urinary excretion of radioactivity from oral and intravenously administered labeled aldosterone as aldosterone in the neutral extract, as aldosterone released by acid hydrolysis, and as tetrahydroaldosterone released by incubation with beta-glucuronidase is generally similar for young and elderly subjects except that a larger portion of the oral compared with the intravenous dose is excreted as free aldosterone in the elderly subjects, indicating that the splanchnic extraction is reduced. The calculated splanchnic blood flow (assuming no alteration in extrasplanchnic metabolism) is also slightly lowered. Therefore, as in patients with mild cardiac dysfunction, the lowered MCR of subjects is due to both reduced splanchnic extraction and blood flow. However, unlike the heart failure patients, in the elderly subjects the plasma concentration of aldosterone is also reduced.

Dynamic evaluation of the viscoelastic properties of a biomedical polymer (biomer).

This paper deals with the experimental determination of the dynamic constants, storage and loss moduli of a viscoelastic material currently used as membranes in the artificial heart or other types of cardiac bypass pumps. A brief discussion of the viscoelastic theory is given, starting with the relaxation and creep function leading to the determination of the stress-strain relationship in integral equation form. It is shown that when dealing with periodical strain histories, the integral equation form may be reduced to a complex form. The complex moduli are used to describe the stress-strain relationship. The "Hysteresis Loop" method was used in this investigation to experimentally determine the material constants. This method was found to be convenient and direct for the experimental evaluation of the constants. These dynamic constants may then be used in a computer analysis, i.e., finite elements analysis, to determine the stress distribution in the membrane when subjected to loads or deformations.