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Biomedical subjects

J Geller

Publications and source records attributed to J Geller.

At least 55 records · Page 3Linked to original sources
PubMed1995

Proscar: five-year experience.

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.

Aged↗
PubMed1995

Five-year follow-up of patients with benign prostatic hyperplasia treated with finasteride.

In 18 of 55 original patients who completed 5 years of treatment with finasteride, significant reductions in prostate size were noted at 1 year and sustained thereafter. Symptom scores in these same patients were significantly improved or stable over the 5 years while maximal urinary flow rates were unchanged. Data from 15 of 18 other patients who dropped out of the study before 5 years showed changes in prostate size, symptom score and flow rates that were similar to those noted in patients treated for 5 years. No side effects were noted in this study except for sexual dysfunction, which occurred in less than 5% of the patients. With few exceptions, finasteride appears to arrest the process of BPH over a 5 year period as indicated by sustained reductions in prostate size accompanied by either symptomatic improvement or stability in all other patients.

Adult↗
PubMed1994

In vivo and in vitro effects of androgen on fibroblast growth factor-2 concentrations in the human prostate.

Prostatic growth is primarily regulated by dihydrotestosterone (DHT). Recent studies have demonstrated that a large number of growth factors are present in the human benign prostatic hyperplasia (BPH) prostate, including epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), transforming growth factor beta (TGF-beta), insulin-like growth factor (IGF), and basic fibroblast growth factor (bFGF) (FGF-2). DHT may mediate its mitogenic effects in the prostate by regulating growth factors. To test this hypothesis, we have utilized a histoculture androgen sensitivity assay (HASA) in which 3H-thymidine incorporation is measured in aliquots of BPH tissue in histoculture with either added DHT or hydroxyflutamide (HF). The resulting DHT/HF ratio is an expression of the androgen sensitivity of the tissue. In this study, we have compared the DHT/HF ratio for 3H-thymidine incorporation to the DHT/HF ratio for FGF-2 measured in the histocultured prostates. The DHT/HF ratio for the HASA studies of 3H-thymidine incorporation averaged 2.68 compared to the DHT/HF ratio for FGF-2 in the same specimens of 1.01. These values were significantly different, therefore indicating no relationship between DHT stimulation and FGF-2 levels. In addition, FGF-2 levels were measured in human BPH prostates from patients medically castrated with megesterol acetate and estradiol 17-beta prior to surgery. These values were not significantly different, and therefore do not suggest any effect of DHT on the concentration of prostatic FGF-2. Although these studies did not show any effect of DHT on the regulation of prostatic FGF-2, they do indicate that the HASA assay is feasible and appropriate to use in the study of relationships between DHT and various growth factors.

Androgen Antagonists↗
PubMed1993

Basis for hormonal management of advanced prostate cancer.

BACKGROUND: In the early 1940s, when it was established that most prostatic cancers were androgen dependent and could be controlled by androgen withdrawal, little was known about the mechanism of androgen action. Measurements of hormones, both in the circulation and in the tissue, were not available, nor were measurements of androgen receptors known at that time. METHODS: Since that time, a large body of information has been published regarding the mechanism of androgen-mediated action. With the understanding of androgen-mediated action has come the opportunity to develop drugs targeted to block specific steps in the sequence of androgen action, beginning in the hypothalamus-pituitary area and extending down to the intracellular processes of enzymatic reduction, receptor binding, and nuclear translocation of the hormone receptor complexes. The major focus in prostate cancer therapy currently is the role of the adrenal androgens. RESULTS: It was established in the 1970s that, after castration, there was a 75% reduction in the dihydrotestosterone (DHT) present in prostate tissue. This observation contrasted with the finding that there was a greater than 90% reduction in circulating testosterone levels in the plasma after castration. Based on this important observation regarding tissue DHT concentrations after castration, attempts were made in the 1980s to block androgen totally using simultaneous gonadal and adrenal suppression. Dramatic results were reported after this type of therapy in the early uncontrolled studies. A luteinizing hormone-releasing hormone agonist plus flutamide was used for total androgen blockade. Other techniques for such blockade were available using megestrol acetate in combination with 17-beta-estradiol. One of the key issues has been whether the 25% residual DHT after castration provides a sufficient stimulus to growth of residual prostate tumor cells. The best evidence for the importance of the role of adrenal androgens came from clinical studies in which objective clinical responses were found in patients treated with various inhibitors of androgen action after relapse and castration. If "objectively stable" is included as a category after treatment, then approximately 33% of patients who have relapses after castration can be shown to have an additional response, albeit short, to adrenal androgen withdrawal. CONCLUSIONS: Thus, the control of the relatively small amounts of DHT remaining after castration became a major focus for therapy in metastatic prostate cancer.

Androstenedione↗
PubMed1993

Job satisfaction of rural public and home health nurses.

Based on Vroom's expectancy theory, this study was conducted to identify differences in job satisfaction between nurses working in public health settings, and staff nurses and administrators working in both settings. Questionnaires containing an adaptation of a job satisfaction scale were mailed to all 258 registered nurses practicing in public health and home health settings (response rate 57%) in a rural midwestern state. Respondents were asked to rate their satisfaction with various dimensions of their jobs, as well as how important each aspect was to them. Although both groups of nurses reported low satisfaction with salary, public health nurses were significantly less satisfied with their salaries than were home health nurses (F = 32.96, P < or = 0.001); home health nurses, however, were significantly less satisfied with benefits/rewards (F = 11.85, P < or = 0.001), task requirements (F = 8.37, P < or = 0.05), and professional status (F = 5.30, P < or = 0.05). Although administrators did not differ significantly from staff nurses on job satisfaction, they did perceive organizational climate (F = 4.50, P < or = 0.05) to be an important feature of satisfaction. These differences may be partially explained by divergent salaries, roles, and responsibilities between public health and home health nurses.

Adult↗
PubMed1992

The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.

BACKGROUND: Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. METHODS: In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. RESULTS: As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. CONCLUSIONS: The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

5-alpha Reductase Inhibitors↗
PubMed1992

Nonsurgical treatment of prostatic hyperplasia.

BACKGROUND: Epidemiologic studies in castrates strongly support the key role of the testis in the pathogenesis of benign prostatic hyperplasia (BPH). Since the testis secretes both androgen and estrogen, both of these hormones have been implicated in BPH. Many data support the important role of dihydrotestosterone (DHT) in BPH. It is now possible to quantify prostate size and function with reliable new techniques and to utilize androgen withdrawal studies to test the validity of the DHT theory. METHODS: A variety of androgen-blocking drugs have been demonstrated to decrease prostate size by approximately 30% by either blocking secretion of circulating testosterone and adrenal androgen, inhibiting 5 alpha-reductase to prevent DHT formation, or blocking DHT binding to androgen receptors. RESULTS: Accompanying these changes in size have been significant improvement in clinical symptoms of prostatism in approximately 50% of patients when double-blind, large multicenter studies were conducted with one of these drugs. Although these results suggest a very important role for androgen, particularly dihydrotestosterone, in the pathogenesis of BPH, other abnormalities besides those of androgen metabolism may coexist since significant numbers of patients do not show a total reversal of disease. There is strong indirect evidence for a possible role for estrogen in the pathogenesis of BPH and studies are under way to test the effects of estrogen withdrawal on prostate size and symptoms. Similarly, dynamic aspects of prostatic obstruction, which are under alpha adrenergic regulation, may also be a component of this disease and amenable to therapy with alpha-adrenergic blockers. CONCLUSIONS: Therefore it would seem that BPH may be multifactorial and require combined therapy. Androgen would certainly appear to be necessary, but perhaps not sufficient, for the pathogenesis of this disorder.

5-alpha Reductase Inhibitors↗
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↗
PubMed1992

Job satisfaction and retention of rural community health nurses in North Dakota.

A correlation between job satisfaction and employment longevity has been demonstrated by a number of researchers. However, the measurable aspects of job satisfaction only partially explain an individual's tenure at a particular job. Information about the relationship between job satisfaction and retention of community health nurses in a rural state was provided by 258 community health nurses in North Dakota who responded to a mailed questionnaire. Job satisfaction assessment included measures of autonomy, task requirements, salary, benefits, rewards, professional status, organizational climate, and interpersonal interactions. Job satisfaction was analyzed by taking into account the individual importance of each component. While the majority (61%) of the responding nurses indicated that they expected to stay in their current jobs for a period of five years or more, they were dissatisfied with various aspects of their jobs. The greatest factor influencing the nurses' choice of current position was job availability, followed by preferences for the particular health care agencies or communities. These findings indicate that retention of rural nurses should focus on strategies that go beyond improving job satisfaction.

Analysis of Variance↗