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Biomedical subjects

J Geller

Publications and source records attributed to J Geller.

At least 19 recordsLinked to original sources
PubMed1992

Castration-like effects on the human prostate of a 5 alpha-reductase inhibitor, finasteride.

Epidemiological studies strongly support the contention that surgical castration prior to age forty prevents both benign prostatic hypertrophy (BPH) and prostate cancer. 5 alpha-Reductase deficiency in humans, an experiment of nature, is an uncommon genetically transmitted disorder in which prostate size remains very small throughout adult life. A 5 alpha-reductase inhibitor, finasteride, has recently been shown in double-blind, placebo-controlled trials in patients with BPH to statistically decrease prostate size and improve clinical symptoms in comparison to placebo controls. In the untreated BPH prostate, tissue levels of dihydrotestosterone (DHT) and testosterone (T) averaged 4.2 and 0.2 ng/g, respectively. Following one week of finasteride therapy, T levels rose to a mean of 1.32 ng/g while DHT levels decreased to 0.62 ng/g. These values contrast with values in prostate tissue from surgical castrates in which DHT and T values average 1.14 ng/g and 0.1 ng/g, respectively. If we use the relative binding affinity of T and DHT to the androgen receptor as a criterion of biological androgen potency, T would appear to be one-fourth as potent as DHT. Using this 1:4 ratio to convert prostatic T to a biologically equivalent amount of prostatic DHT, the total biologically active DHT equivalent in the prostate following one week of finasteride averages 0.95 ng/g compared to a mean of 1.14 ng/g in surgical castrates.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1992

Measurement of androgen sensitivity in the human prostate in in vitro three-dimensional histoculture.

We have adopted an in vitro three-dimensional histoculture technique for assay of androgen sensitivity in explants of human benign prostatic tissue. The assay is based on the uptake of 3H-thymidine/micrograms protein in explants of prostate incubated in parallel with dihydrotestosterone (DHT) and hydroxyflutamide (HF) controls. The ratio of 3H-thymidine/micrograms protein in DHT treated samples per 3H-thymidine/micrograms protein in HF treated samples provides an index of androgen sensitivity. The DHT/HF index measured in 24 BPH specimens averaged 3.6. To determine the specificity of the HF effect, we measured the DHT/HF index in a single prostate at different concentrations of HF in the presence of fixed concentrations of DHT (2 x 10(-8) M) and noted a dose-response relationship. In addition we noted no effects of HF on 3H-thymidine incorporation over a range of 2 x 10(-4)M compared to 2 x 10(-7)M, except at the highest concentration. Of surprise was the finding of an average DHT/HF index in 5 different nonprostate tissues, including breast, uterus, colon, kidney, and thyroid, that was similar to the index found in prostates. We plan to adapt this androgen sensitivity assay to measure the DHT/HF index in biopsy-size samples of prostate, since such an assay could then be utilized to determine androgen sensitivity in individual patients with prostate cancer.

Androgen Antagonists↗
PubMed1979

Effect of megestrol acetate on uroflow rates in patients with benign prostatic hypertrophy: double-blind study.

Sixty-one patients with benign prostatic hypertrophy (BPH) and decreased maximum and mean urine flow rates were randomly assigned to megestrol (Megace, 120 mg./day) or placebo therapy. The patients were studied over a five-month period with maximal and mean urine flow rates every two weeks. The patients on megestrol demonstrated significant increases in maximum and mean urine flow rates from the sixth through the twentieth weeks compared with their own control baseline values; the placebo-treated patients showed no significant changes in mean flow rates at any time point over the twenty weeks in comparison with their own baseline control values; maximum flow rates in placebo-treated patients did demonstrate statistically significant increases above their own control baseline values at eight, twelve, eighteen, and twenty weeks. Megestrol-treated patients, in comparison with the placebo group, showed statistically significant increases in maximum flow rate at fourteen, sixteen, and twenty weeks after therapy, and statistically significant increases in mean flow rate over the placebo patients at ten, twelve, fourteen, and twenty weeks. Clinical symptoms improved in 78 per cent of the megestrol-treated patients and 57 per cent of the placebo-treated patients. The side effects of megestrol were minimal except for loss of libido in 70 per cent of patients.

Aged↗
PubMed1978

Dihydrotestosterone concentration in prostate cancer tissue as a predictor of tumor differentiation and hormonal dependency.

Tissue dihydrotestosterone and 5alpha-reductase (delta4-3-ketosteroid-5alpha-oxidoreductase) levels have been measured in prostates of patients with cancer and benign prostatic hypertrophy; significant decreases in average values for both of these biochemical parameters were noted in prostate cancer compared to benign prostatic hypertrophy, although individual values overlapped in both groups. Prostate cancer tissue dihydrotestosterone levels appeared to correlate better than did either histological tumor grading or 5alpha-reductase with the ultimate clinical response to antiandrogen therapy. These results suggest that assay of tissue dihydrotestosterone levels in prostate cancer should be further explored as a possible marker for tumor differentiation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1977

Utilization review of the late adolescent patient in a mental health center: steps toward the development of criteria for the adequacy of assessment and treatment.

This study is concerned with an attempt to determine whether meaningful utilization review criteria could be productively generated by viewing a patient population from a developmental perspecitve. During a 2-year period, a multidisciplinary panel at Yale University sought to identify the sociodemographic, clinical, and administrative issues posed by late adolescents seeking treatment at the Connecticut Mental Health Center, New Haven. We sought to address the following questions: a) From what segment of the population were we drawing our adolescent patients? b) Who referred them for help? c) What kinds of problems led to referral? d) What were the diagnostic characteristics of the adolescent's evaluation? e) Under what conditions do adolescents terminate treatment? The charts of over 1222 adolescent patients were studied to help us answer these questions. Our investigation revealed that the adolescent patients seen at the Mental Health Center were sociodemographically and diagnostically heterogeneous. An increasingly large number of adolescents are referring themselves for evaluation and treatment, rather than being sent by schools, physicians, or social welfare agencies. The majority of patients seeking help come from blue collar or working class backgrounds mainly because of intrapsychic complaints of anxiety and depression. Upwardly mobile, they constitute a group who have completed their high school education, often live away from home, and are struggling with problems of defining an identity different from that of their family. Review of their charts indicated that significant sholastic, medical, and developmental information was frequently lacking or vaguely recorded. Our chart review also indicated that many clinicians did not ask their patients about symptoms relating to body functioning such as difficulties with sleeping, eating, or psychosomatic complaints. The study also discovered that it was difficult in the great majority of the charts reviewed to specify the adolescent's own perception of the difficulties which led them to seek help. Suggestions are then outlined for developing review criteria dealing with the emancipated adolescent, parental involvement in the treatment of the adolescent, treatment plans, and the termination of treatment. The comparative advantages of combining utilization review criteria from both a traditional "disease model" and a "developmental model" are discussed. The panel concluded that input from both perspectives is necessary in understanding the impact of a mental health delivery system upon adolescent patients, their family, and the community.

Adolescent↗
PubMed1976

A method for tissue extraction and determination of prostate concentrations of endogenous androgens by radioimmunoassay.

A method for simultaneously determining concentrations of major androgens in prostate has been developed. Extraction techniques used to isolate the androgens from minced tissue include homogenization with high-speed blades in Delsal's solvent mixture, adsorption to silica gel, followed by column and one thin-layer chromatography (TLC). Radioimmunoassays (RIA) of small aliquots of TLC eluates are used to quantitate picogram amounts of 5alpha-dihydrotestosterone (DHT) and 5alpha-androstanediols (Diol) and to estimate testosterone (T) and androstenedione (Ad). Contamination of blanks was reduced to RIA sensitivity limits primarily by treatment of glassware in a self-cleaning oven. The specificity of the method for each androgen was established by TLC separations of known prostate metabolites, antisera specificities, and parallelism of sample aliquots to androgen RIA standards. The overall precision, in terms of coefficients of variation, was 21% for DHT and 24% for Diol. T and Ad could not be measured with acceptable precision because their very low concentrations in prostate (less than or equal 0.5 ng/g tissue) were less than RIA sensitivity limits. Accuracy studies indicated recoveries ranging from 96% for Diol to 121% for DHT. In human benign hypertrophic prostate tissue, DHT averaged 153 ng/g soluble protein (5.8 ng/g tissue) which was 17 times higher than values obtained in human spleen and kidney; Diol in prostate showed no consistent differences from values noted in kidney or spleen.

Androgens↗
PubMed1976

Comparison of androgen metabolites in benign prostatic hypertrophy (BPH) and normal prostate.

5 alpha-Dihydrotestosterone (DHT) and androstanediols (diols) have been measured in human prostate tissue. DHT levels in surgical specimens of prostate from 8 patients with BPH averaged 5.6 +/- 0.93 S.E. ng/g and were significantly greater than (P less than 0.01) values of 2.1 +/- 0.32 S.E. ng/g in 6 normal prostates obtained post-mortem from males less than 50 yrs old. Androstanediols averaged 2.3 +/- 0.35 S.E. ng/g in the BPH specimens compared to values of 10.2 +/- 2.4 S.E. ng/g in the normal prostates (P less than 0.01). This significantly higher (P less than 0.001) ratio of diols/DHT in the normal (5.1 +/- 0.93 S.E.) compared to the BPH prostate (0.45 +/- 0.08 S.E.) suggests that a decrease in 3-hydroxysteroid oxido-reductase, which converts DHT to diol, may be an important clue to the pathogenesis of BPH.

Androstane-3,17-diol↗
PubMed1976

Effect of megestrol acetate (Megace) on steroid metabolism and steroid-protein binding in the human prostate.

Megestrol acetate (Megace), an antiandrogen, was administered in a dosage of 80 mg daily to 6 patients with benign prostatic hypertrophy (BPH) for 4 to 25 days prior to transurethral resection of the prostate (TURP). Surgical tissue from drug-treated patients was compared to untreated controls in regard to: 1) the enzymatic reduction of testosterone (T) and dihydrotestosterone (DHT); 2) DHT binding to a cytosol receptor protein; 3) tissue levels of endogenous dihydrotestosterone and androstanediols (diols). When minced prostate was incubated with 3H-T and 14C-androstenedione for 1 h at 37 C, prostate 5alpha-reductase activity, measured as reduced products formed from substrate, decreased to 31% and 39%, respectively, of the control values. Prostate 3-oxido-reductase enzyme activity, measured as diols formed from 3H-DHT, was decreased to neglible values in Megace-treated patients compared to an 8.7% conversion to diols in controls. No 3H-DHT binding to a cytosol receptor protein could be demonstrated in 4 out of 5 prostates from Megace-treated patients, whereas the presence of such a receptor was noted in 14 out of 17 untreated controls. Endogenous DHT levels in Megace-treated patients averaged 1.1 ng/g (SE = 0.26), significantly less than the average of 3.9 ng/g (SE = 0.49) found in controls (P less than 0.001). No significant difference was noted in endogenous diols. In addition to these effects on tissue, Megace significantly decreased plasma levels of T, LH, and FSH at the end of the 4- to 25-day period; plasma prolactin levels did not change. Continued studies of Megace for the possible treatment of benign prostatic hypertrophy may be warranted since the drug appears to block several important biochemical steps which mediate the effects of androgen on the human prostate.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗