The effects of chronic high dose androgen or estrogen treatment on the human prostate [corrected

Prostate development and disease are androgen dependent. However, the nature of hormonal effects on the prostate of healthy young men is not clear. We, therefore, measured prostate size in males chronically exposed to high doses of androgens (AS; habitual anabolic steroid abusers; n = 15) or estrogens (E; male to female transsexuals; n = 11) and compared the results with those in age-matched healthy eugonadal men without known prostate disorders. Prostate size was measured by planimetric ultrasound as cross-sectional areas and maximal dimensions in three orthogonal dimensions with a 7.5-megahertz B-mode sector scanner biplane in a transrectal transducer at 2.5 mm steps from the base to the apex of prostate. Total prostate volume (TPV) was reconstructed from planimetric sections, central prostate volume (CPV) was calculated by the ellipsoidal formula from the appropriate three maximum dimensions, and peripheral prostate volume was determined by the difference between TPV and CPV. Compared with age-matched controls, TPV was normal (-2%) in AS (P = 0.752) and reduced by 31% in E (P = 0.002), whereas CPV was increased by 20% in AS (P = 0.002) and reduced by 46% in E (P = 0.002), and the ratio of CPV/peripheral prostate volume was increased by 77% in AS (P < 0.001) and decreased by 33% in E (P = 0.047). Blood sex hormone-binding globulin was elevated by nearly 500% in E (P < 0.001), but was reduced by 47% in AS (P = 0.003). Prostate-specific antigen was normal (-6%) in AS (P = 0.799) and decreased by 86% in E (P = 0.002). Prostatic acid phosphatase was increased by 26% in AS (P = 0.007), but was unchanged (-28%) in E (P = 0.106). Total and free testosterone levels were reduced to castrate levels in E, whereas LH, FSH, and total testosterone levels were significantly reduced in AS. We conclude that in the human prostate of young men, CPV is more hormonally sensitive than TPV, and during high dose treatment, CPV is preferentially increased by chronic androgen treatment and decreased by chronic estrogen treatment. The reduction of TPV by estrogens was less than expected if solely attributable to inhibition of endogenous gonadotropin and testosterone secretion, suggesting that estrogens also have a positive effect on the normal human prostate. The reversibility and long term significance of androgen-induced stimulation of CPV and, in particular, its relationship to the onset and severity of benign prostatic hyperplasia remain to be clarified.     

Occlusion of large atrial septal defects with a centering buttoned device: early clinical experience

A feasibility clinical study was conducted for the transcatheter occlusion of large ostium secundum atrial septal defects with the centering buttoned device. The centering buttoned device is a modification of the regular buttoned device in which a centering counter-occluder is sutured at the central 40% portion of the occluder. During centering it is stretched, forming a parachute-shaped structure and pulling the occluder over the center of the defect. During buttoning, the counter-occluder forms a double figure eight, opposing the right atrial side of the atrial septum. Occlusion was performed in 12 patients aged 6 to 56 years. All had been rejected for transcatheter occlusion by the regular buttoned device, because of either their defect size or the lack of adequate septal rim. The defect size varied between 23 and 31 mm, and the device size varied between 45 and 60 mm. Nine had immediate effective occlusions of their defects and three residual shunts. One patient with unbuttoning had hemolysis at 2 weeks and underwent surgery. Early results of the transcatheter occlusion of large atrial septal defects are promising, and larger clinical trials are justified.     

Children's understanding of equality--inequality relationships for liquid quantities: the role of minimal-difference concept examples

When one of two same-amount liquid quantities was actually, or proposed to be, altered by a very tiny (smidgen) amount, kindergartners and 2nd graders failed to recognize the resulting inequality, whereas 3rd and 4th graders were increasingly successful. Alterations larger than a smidgen, but still small, improved the judgments of 2nd, 3rd, and 4th graders but left kindergartners still thinking that equality was unchanged. Alterations in larger amounts that provided noticeable perceptual discrepancies led to nearly perfect inequality judgement across all grade levels. A rigorous evaluation of children's understanding of equality-to-inequality changes must include minimal-amount differences in a quantity along with the solicitation of verbal reports.     

Antimicrobial and immunological activity of ethanol extracts and fractions from Isopyrum thalictroides

The antimicrobial and immunological properties of ethanol extracts, non-alkaloid, tertiary alkaloid and quaternary alkaloid fractions, obtained from roots and aerial parts of Isopyrum thalictroides were examined. The non-alkaloid fraction from aerial parts inhibited the growth of seven test microorganisms and was the most effective suppressor of classical pathway (CP) complement activity in normal human serum (NHS) and guinea pig serum (GPS). The alkaloid fractions, containing quaternary alkaloids expressed suppressive effect on mitogen-induced splenocyte proliferation. The in vitro antibody response against sheep red blood cells (anti-SRBC) was inhibited by ethanol extracts and quaternary alkaloid fraction. The intraperitoneal (i.p.) application of ethanol extract and tertiary alkaloid fraction from aerial parts showed that they possess in vivo effect on alternative pathway (AP) complement activity, anti-SRBC response and delayed type hypersensitivity (DTH).     

Embryotoxic doses of vitamin A to rabbits result in low plasma but high embryonic concentrations of all-trans-retinoic acid: risk of vitamin A exposure in humans

Retinoid pharmacokinetics were examined in plasma, placenta and embryos of gestational d 12 rabbits following application of an embryotoxic dosing regimen (10 mg retinyl palmitate/kg body wt per day from gestational d 7 to 12). Vehicle-treated or untreated rabbits served as controls. Physiological concentrations of all-trans-retinoic acid (all-trans-RA) and 13-cis-RA in rabbit plasma (5-8.33 nmol/L) were very close to the endogenous levels in human plasma. In addition, we identified endogenous all-trans-RA, 3,4-didehydroretinol and 3,4-didehydroretinoic acid in rabbit embryo. Following the last retinyl palmitate administration, apparent steady-state concentrations of all retinoids were reached in the examined compartments of rabbits. The major polar retinoid in plasma was 9, 13-di-cis-RA, but its embryonic concentrations were only about 6% of those in plasma. In the embryo, retinol and its esters were found at high concentrations; lower amounts of all-trans-4-oxo-RA and the newly identified 14-hydroxy-4, 14-retro-retinol could also be measured. Embryonic concentrations of all-trans-RA were about 100% higher than endogenous levels. The overall exposure of the embryo to this retinoid was, however, substantial. Embryonic area under the concentration time curve values strongly suggest that the embryotoxicity of the applied dosing regimen is mainly due to the action of all-trans-RA. A very remarkable finding of this study is the marginal increase of plasma concentrations of all-trans-RA over their endogenous levels, which is comparable to the human situation after vitamin A intake. This analogy indicates that high vitamin A intake may be associated with a higher risk for teratogenic effects in humans even in the absence of high elevation of plasma all-trans-RA levels.     

Analytical evaluation technique of self-phase-modulation effect onthe performance of cascaded optical amplifier systems

We propose an approximate analytical evaluation technique of self-phase-modulation (SPM) in cascaded optical amplifier systems. The effect of SPM on optical pulse distortion is represented by the increase in the α-parameter of the transmitter. The waveform distortion is approximated by assuming that the pulse is transmitted over a dispersive fiber without nonlinearity. This technique greatly reduces the calculation time, and is especially useful in designing cascaded amplifier systems, evaluating theoretical maximum transmission distance