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H Matzkin

Publications and source records attributed to H Matzkin.

At least 19 recordsLinked to original sources
PubMed1996

Functional melatonin receptors in human prostate epithelial cells.

Melatonin, secreted nocturnally by the pineal gland, affects gonadal growth and pubertal development in rodents and, presumably, in humans. Recently, we have found, using 125I-labeled melatonin as a probe, specific melatonin binding sites in the human benign prostate tissue; these sites were primarily associated with the microsomal fraction of the epithelial cells. In the present study, we have explored 125I-melatonin binding sites in human benign prostate epithelial cells in culture and investigated the effects of melatonin on growth and viability of these cells. 125I-melatonin bound to the prostate cells with high (K(d) = 68 pM) affinity. Competition experiments revealed that specific binding was inhibited by subnanomolar concentrations of melatonin and 2-iodomelatonin, whereas serotonin and 5-methoxytryptamine reduced the binding only partially. Melatonin (10 pM-10 nM) inhibited the incorporation of 3H-thymidine and 3H-uridine into the prostate epithelial cells in a dose-dependent manner. Inhibition was transient, and the incorporation recovered to control levels within less than 24 h. Protein synthesis as measured by the incorporation of 35S-methionine into cell proteins decayed to minimal levels about 2 h after addition of melatonin, and its recovery was slower compared with that of 3H-thymidine or 3H-uridine incorporation. Melatonin treatment (1 nM) for 2-7 days inhibited cell growth and markedly increased the percentage of non-viable cells in culture, measured by the trypan blue exclusion assay. The results demonstrate high affinity melatonin receptors in the human benign prostate epithelial cells, which may affect cell growth and viability.

Binding Sites↗
PubMed1996

Putative melatonin receptors in benign human prostate tissue.

Melatonin, secreted by the pineal gland at night, inhibits pubertal development of rats and presumably men. In addition, it may directly suppress prostate growth in the adult rat. To investigate the possibility for a causal relationship between the age-related decline in melatonin production and increase in prevalence of benign prostate hypertrophy (BPH) in man, the presence of melatonin binding sites in human BPH tissue was examined. In vitro autoradiography indicated specific 125I-labeled melatonin (125I-melatonin) binding in the prostate, localized to the glandular epithelium. Separation and subcellular fractionation indicated that these sites were associated with the microsomal fraction of the epithelial cells. Kinetic and equilibrium 125I-melatonin binding experiments revealed that the binding was time dependent and reversible, with an apparent half saturation at 140 pmol/L. Competition experiments indicated high and low affinity melatonin binding sites; binding was inhibited by melatonin (IC50 1 nmol/L and 1 micromol/L, respectively) and partially by the putative melatonin antagonist, N-(2,4 dinitrophenyl)-5-methoxytryptamine (ML-23; IC50 0.1 nmol/L). Serotonin and 6-hydroxymelatonin were less potent, whereas up to 0.1 mmol/Lol/L of 5-methoxytryptamine, 6-methoxymelatonin, and tryptamine caused only a partial reduction in specific binding. The guanine nucleotide analogs, guanosine 5'-O-[3-thiotriphosphate] and guanosine 5'-O-[2-thio-diphosphate, inhibited specific 125I-melatonin binding, whereas 5'-guanylyl imidodiphosphate was less potent. The results indicate putative melatonin receptors in the human prostate epithelium.

Aged↗
PubMed1996

Do reported micturition symptoms on the American Urological Association Questionnaire correlate with 24-hour home uroflowmetry recordings?

PURPOSE: Patient subjective descriptions of micturition habits using the American Urological Association (AUA) symptom index were compared with uroflowmetry recordings obtained during a 24-hour period. MATERIALS AND METHODS: In a prospective study, the AUA questionnaire was given twice to 42 men. All micturitions during a typical 24-hour period were continuously recorded by a home uroflowmetry system. Daytime frequency, strength and intermittency of the stream, and nocturia were calculated from the recorded data, which were correlated with the matching questionnaire answers. RESULTS: Except for nocturia, there was no correlation between the answers and recorded findings. CONCLUSIONS: Men are unable to quantify correctly their own clinical status. The study results cast doubt on the validity of the self-administered AUA survey to reflect clinical micturition.

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PubMed1994

Hyperthermia as a treatment modality in benign prostatic hyperplasia.

OBJECTIVE: To review the current status of hyperthermia (heating the prostate up to 45 degrees C) as a treatment modality for benign prostatic hyperplasia (BPH). METHODS: Hyperthermia versus thermotherapy is defined, the techniques and equipment are presented, and the current English literature regarding safety and efficacy is reviewed. RESULTS: Both transrectal and transurethral heat applications are very safe procedures. Most studies evaluating the efficacy have been nonrandomized and uncontrolled. The 50-70 percent symptom improvement rate should be compared with the natural history of the disease and the considerable placebo effect. The few controlled studies produced contradictory results. CONCLUSIONS: At the present time, hyperthermia has not been shown, in scientifically well-designed studies, to be a treatment modality with measurable and durable outcome in BPH.

Clinical Trials as Topic↗
PubMed1994

Stage T1A carcinoma of prostate.

When presented with a post-TURP patient with pathologically confirmed Stage T1a disease, several points should be considered (Fig. 1). Is the patient's anticipated longevity and quality-of-life likely to be affected by the confirmed diagnosis? From current knowledge, men over the age of seventy or with co-morbid risk factors probably will not be adversely affected, and no treatment is required apart from expectant follow-up with semiannual DRE and serum PSA determinations. The group at risk seems to be the young patient with a Stage T1a tumor who is likely to survive more than ten years after the diagnosis. Data showing progression rates without treatment as high as 16-25 percent at eight to ten years seem to indicate the need for additional therapy. If the patient belongs to this category and is ready to pursue more aggressive treatment, reestablishing the diagnosis might be suggested, as well as an evaluation of the pre- and post-TUR PSA levels. This can be done by TRUS-guided biopsies of the prostate (or repeat TURP, which we regard as less preferable). If residual tumor is not found, we would counsel a "wait and see" approach. If subsequent tissue sampling identifies other than well-differentiated cancer or indicates the likelihood of more extensive cancer than the T1a staging, treatment would be suggested. If the restaging reveals some residual well-differentiated disease that would not alter the initial staging of T1a, the patient should be offered the alternatives of close monitoring, radical prostatectomy, or radiation therapy. Until prognostic factors such as DNA ploidy and nuclear roundness are better studied, we are unable to counsel the patient on the biologic significance/aggressiveness of his Stage T1a disease.

Adenocarcinoma↗
PubMed1994

Effect of 5-alpha-reductase inhibition on sex-hormone-binding globulin in elderly men.

In this study we examined the possibility that chronic reduction in serum dihydrotestosterone (DHT) attained by pharmacologic inhibition of 5 alpha-reductase modulates serum sex-hormone-binding globulin (SHBG) levels in elderly men. Twenty-one men, ages 58-79 years (mean 66) with benign prostatic hypertrophy were treated with the 5 alpha-reductase inhibitor finasteride (5 mg daily) for 12 months. Serum DHT declined by 80% (p < 0.001) and total testosterone rose by 14% (p < 0.05). Serum SHBG concentration remained unchanged (44.1 +/- 4.5 vs 45.2 +/- 5.7 nmol/l for pre- and post-therapy levels, respectively). Thus, the conversion of testosterone to DHT is not required to maintain the androgenic effect on serum SHBG concentration in elderly men.

Aged↗
PubMed1993

Prognostic factors in metastatic prostate cancer.

Androgen deprivation therapy is the initial treatment choice for metastatic disease. When enrolling patients into androgen deprivation trials, it is important to consider stratification of enrollees based on prognostic factors that have been identified as important in determining the likelihood of response. Prognostic factors are also helpful in identifying which patients are less likely to respond to treatment; this information also would help to counsel patients. Performance status is an important prognostic factor; however, its impact is minimal because the great majority of men who receive treatment for advanced disease have a normal performance status. Hemoglobin, alkaline phosphatase, and a semiquantitative grading scale for the number of metastatic foci on the bone scan are useful prognostic factors. The pretreatment serum testosterone level is a powerful prognostic factor. Patients with a low serum testosterone level have a shorter progression-free survival than men whose pretreatment serum testosterone level is above normal. The prognostic importance of pretreatment serum testosterone level has been evaluated in studies using treatment methods that lower this level to castrate levels. Recently, we found that serum testosterone level was not a prognostic factor for men taking the nonsteroidal antiandrogen, Casodex (Zeneca, Wilmington, DE), which does not alter the serum testosterone level. The pretreatment serum prostatic-specific antigen also is a prognostic factor. This antigen may be the best single method for monitoring patients in regard to response to or progression following therapy. The return of the prostatic-specific antigen level to normal (< 4 ng/ml), or the decline in the prostatic-specific antigen level of > 90% indicates a prolonged progression-free survival. In the future, it will be interesting to incorporate both the initial prognostic factors as well as monitor the prostatic-specific antigen into a multivariate analysis, which will be highly predictive of a man's response to treatment.

Acid Phosphatase↗
PubMed1993

[Finasteride (Proscar) for benign prostatic hypertrophy].

Several alternatives to surgery for benign prostatic hypertrophy (BPH) were studied during the past few years. Finasteride (Proscar), a 4-azosteroid, is an inhibitor of the enzyme 5-alpha reductase, which is responsible for the conversion of testosterone to the biologically more active dihydrotestosterone (DHT). We report 3 years of experience with the drug in 23 men. Persistent significant decreases in serum DHT and prostate-specific antigen (PSA) were documented. Prostatic volume decreased by about 25% after 1 year, and remained fairly constant thereafter. Urination improved, as evidenced by increased maximal flow rate and decreased volume of residual urine. Symptoms were affected favorably, but only mildly. One of the main advantages of the drug is its lack of side-effects. More data on a larger number of patients with a longer follow-up are needed before finasteride can be established as having a role as an alternative treatment for BPH.

Aged↗
PubMed1993

Prognostic factors in stage D2 prostate cancer treated with a pure nonsteroidal antiandrogen.

BACKGROUND: Prognostic factors have been shown to be important when stratifying patients with prostate cancer into randomized trials and counseling the individual patient regarding his chances of response to treatment. However, there are no reports on prognostic factors in patients with Stage D2 prostate cancer treated with a pure antiandrogen as monotherapy. METHODS: The authors studied a variety of possible prognostic factors among 150 patients with metastatic prostate cancer treated with an antiandrogen (Casodex, Imperial Chemical Industries, Wilmington, DE). RESULTS: In a univariate analysis, performance status; extent of disease (EOD); pretreatment hemoglobin, alkaline phosphatase, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) levels; and extent of disease (EOD) on bone scan all were found to be significant prognostic factors (P < 0.05). Pretreatment serum testosterone levels, identified as one of the most important prognostic factors, was not identified as significant in the current study. CONCLUSIONS: Although the pretreatment testosterone level was shown to be an important prognostic factor in previous studies, using other modes of androgen ablation (reducing testosterone to below castrate levels), the current study suggest it may not be a helpful factor if the therapy used is antiandrogens as monotherapy. This may relate to the different mode of action of antiandrogens, which do not reduce serum testosterone levels.

Androgen Antagonists↗
PubMed1993

Antiandrogenic agents as monotherapy in advanced prostatic carcinoma.

Pure antiandrogens have a quality-of-life advantage over other androgen ablation methods in the treatment of patients with prostatic cancer because they do not reduce the serum testosterone and therefore do not have a marked inhibitory effect on libido and potency. The long half-life of two of the three currently studied pure antiandrogens permits once-a-day administration, which should enhance patient compliance. With continued administration, there is a gradual rise in serum testosterone, and the clinical impact of this requires additional study using randomized Phase III trials. Proper stratification of patients at entry into such studies with documentation of various prognostic factors will add statistical value and enable physicians to draw better conclusion on the relative efficacy of these agents.

Androgen Antagonists↗
PubMed1993

Cigarette smoking: a review of possible associations with benign prostatic hyperplasia and prostate cancer.

There are conflicting data on the effect of cigarette smoking on serum levels of the various sex hormones. Some studies suggest that cigarette smoke produces an antiestrogenic effect. Smoking may also affect the metabolism of other sex steroids such as testosterone and adrenal hormones, and thereby influence the incidence of benign and malignant growth of the prostate. Epidemiologic studies analyzing a possible association between cigarette smoking and prostate cancer are not conclusive, although some show a positive relationship. The etiology of BPH is undoubtedly multifactorial. Estrogens as well as androgens may be involved in the pathogenesis of BPH. There are several studies that indicate that cigarette smokers have a lower likelihood of requiring surgery for BPH. Growth of the prostate may not correlate with serum levels of androgens and estrogens. The local hormonal milieu of the target cells in the prostate are probably more critical than the more easily measured serum levels. This review examines the literature dealing with cigarette smoking and both BPH and prostate cancer. If there is an effect, then elucidation of the mechanism by which smoking affects the growth of the prostate may improve our understanding of BPH and prostate cancer, and may suggest preventive strategies for high risk groups.

Adenocarcinoma↗
PubMed1993

Relapse on endocrine treatment in patients with stage D2 prostate cancer. Does second-line hormonal therapy affect survival?

Patients with Stage D2 prostate cancer relapsing on endocrine treatment have a grim prognosis. The role of a second-line hormonal treatment is debatable. We analyzed retrospectively, response and survival among 119 men (57 black, 62 white) progressing on a variety of first-line hormonal therapy. Sixty-one received a second-line hormonal treatment. Fifty-eight received only supportive therapy after first line therapy was discontinued. Age and race were not a factor in survival. Based on this retrospective study the optimal management for progressive metastatic prostate cancer cannot be delineated. However, the best results were in patients treated with diethylstilbestrol (DES) as a single treatment or when employed as either first or second treatment in patients receiving two therapies. The other modalities, e.g., bilateral orchiectomy, LH-RH analogues, and anti-androgens resulted in comparable outcomes when used either as single treatment or in combinations. Further clarification of the trends shown in this report require randomized controlled studies.

Adenocarcinoma↗
PubMed1993

How reliable is a single measurement of urinary flow in the diagnosis of obstruction in benign prostatic hyperplasia?

Twenty-six elderly patients with obstructive symptomatology and an initial low peak urinary flow rate (< 15 ml/s) were observed for 6 to 12 months. Repeated assessments were made of flow rates and residual volumes. Within patients variation of the maximal urinary flow was significant; the standard deviation (SD) varied from 0.8 to 5.5 ml/s. The SD varied with the mean peak flow rates and this suggests that the precision of a single determination of a patient's peak flow is inversely related to the peak flow itself. In all, 333 determinations of peak flow were obtained. Only 80% were below 2 SD of the mean Siroky nomogram. Multiple determinations were used to estimate the sensitivity rate for each patient, i.e. the proportion of peak flows that were less than 2 SD below the mean of Siroky's nomogram. The average sensitivity for all of the flow values was 0.813 when applied to voided volumes and increased only slightly to 0.838 when applied to total bladder volume. Given a prevalence of 0.70 of obstruction ascribed to benign prostatic hyperplasia (BPH) among elderly men, the positive predictive value of an abnormally low peak flow was 0.97. A single low peak flow based on assessment of voided volume may serve as an almost sure indication of obstruction. If a patient has a single normal peak flow rate, he still has a 0.31 probability of having evidence of obstruction in his following uroflow determinations. Using total bladder volume does not make a difference in most patients and is not worth the effort and discomfort. The only patients who require accurate residual measurements are those with a normal uroflow but clear-cut obstructive symptomatology or with borderline peak flow. The results of this study are relevant to everyday clinical practice and to the evaluation of studies on alternatives to surgery in BPH.

Aged↗
PubMed1993

Posthernioplasty urinary retention: a noninvasive work-up for prediction.

The prognostic value of various subjective and objective noninvasive urological parameters was evaluated for their possible role in the prediction of post-hernioplasty urinary retention. In a prospective study, 35 patients aged 55-85 years without previous micturition complaints or urological surgery were evaluated 1 day prior to inguinal hernioplasty. This included medical history for modified Madsen subjective scoring profile, physical examination and uroflowmetry. Bladder capacity, residual urine and prostatic volume were measured by ultrasound. All patients underwent a similar method of hernioplasty, were closely followed 48 h postoperatively and any voiding difficulties or urinary retention were noted. Urinary retention occurred in 12 patients. None of the remaining 23 patients had urination difficulties. Comparing these two groups, we concluded that patient age, bladder capacity and prostatic volume have no prognostic value for potential postoperative urinary obstruction. On the other hand, obtaining a good anamnesis of obstructive and irritative symptoms for scoring, measuring maximal flow rate on urinary flowmetry and estimating residual urine volume may predict patients who are potentially at high risk for posthernioplasty urinary retention.

Aged↗
PubMed1993

Decreased bone density in elderly men treated with the gonadotropin-releasing hormone agonist decapeptyl (D-Trp6-GnRH).

Administration of GnRH agonist analogs to women may result in a hypoestrogenic state and bone mass reduction. In the present study we examined bone mineral density (BMD) and parameters of mineral metabolism in elderly men with benign prostatic hyperplasia before and during a hypoandrogenic state induced by the long-acting GnRH agonist D-Trp6-LHRH (decapeptyl). Our results showed that decapeptyl treatment caused a significant decrease in serum testosterone concentrations in all patients and resulted in a significant decrease in individual vertebral BMD in 10 of 17 patients. A significant decrease in BMD was observed in 5 patients after 6 months of treatment. Another 5 patients showed a decreased BMD only after 12 months. The mean serum concentrations of osteocalcin, phosphorus, and alkaline phosphatase activity increased after 6-12 months of treatment with decapeptyl. Serum calcium, vitamin D metabolites, and PTH concentrations remained unchanged during treatment. Urinary calcium excretion was slightly, but not significantly, increased after 6 months of treatment. These results demonstrate that long-acting GnRH agonist treatment may cause high turnover accelerated bone loss in some men during the first year of GnRH agonist treatment, as has been previously shown in women.

Aged↗
PubMed1992

Prognostic significance of changes in prostate-specific markers after endocrine treatment of stage D2 prostatic cancer.

BACKGROUND: The prognostic value was determined of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) measured before and after endocrine treatment in 57 patients with newly diagnosed Stage D2 prostatic cancer. METHODS: Therapy included orchiectomy or administration of luteinizing hormone releasing hormone analogues or an antiandrogen. RESULTS: The absolute pretreatment PSA (elevated in 100% of patients) but not PAP (abnormal in 93%) predicted disease progression (P < 0.0011), i.e., a poor response to therapy. Fifty-three patients responded to androgen deprivation with a decrease in PSA level. This declined to normal at 3 and 6 months in 25% of patients. Forty-nine percent had a greater than 90% decrease in their PSA level. By 1 year, 58% of patients had progressive disease. Both the nadir PSA level and the percent decline from the pretreatment level at 3 and 6 months predicted the progression-free interval (P < 0.001). Patients with a 90% or greater decline in PSA had a prolonged progression-free survival. Serial PAP levels were similarly prognostic. CONCLUSION: It was concluded that PSA was better than PAP in evaluating patients before and after androgen-deprivation therapy. The nadir level of both markers was an important tool to predict progression-free survival in patients with metastatic prostatic cancer.

Acid Phosphatase↗