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H Lepor

Publications and source records attributed to H Lepor.

At least 55 records · Page 3Linked to original sources
PubMed1999

Radical retropubic prostatectomy reduces symptom scores and improves quality of life in men with moderate and severe lower urinary tract symptoms.

PURPOSE: We determine the impact of radical retropubic prostatectomy on lower urinary tract symptoms and quality of life due to urinary problems in men with clinically localized prostate cancer. MATERIALS AND METHODS: The American Urological Association (AUA) symptom index, a symptom problem index and a quality of life due to urinary problems question were administered to 104 men before and 12 months after radical prostatectomy. Urinary continence and satisfaction with the decision to undergo radical prostatectomy were also examined. RESULTS: In men with moderate or severe baseline urinary symptoms (AUA score 8 or greater) the total AUA symptom, symptom problem and quality of life question scores decreased by 51 (-6.39), 57 (-4.22) and 25% (-0.65), respectively, after radical prostatectomy. Except for nocturia statistically significant improvements were observed for all questions captured by the AUA symptom index. Radical prostatectomy did not significantly change mean AUA symptom score or symptom problem index in men with mild urinary symptoms (AUA score less than 8). In men with moderate or severe urinary symptoms radical prostatectomy significantly improved quality of life due to urinary problems. Although 10% of men exhibited some degree of clinically relevant stress incontinence, 98% were very satisfied or satisfied with the decision to undergo radical prostatectomy. CONCLUSIONS: In men with moderate or severe urinary symptoms radical prostatectomy improves lower urinary tract symptoms and quality of life due to urinary problems. The overall beneficial impact on voiding makes radical prostatectomy an attractive treatment option for clinically localized prostate cancer.

Adult↗
PubMed1999

Does site specific labeling of sextant biopsy cores predict the site of extracapsular extension in radical prostatectomy surgical specimen.

PURPOSE: We determine whether site specific labeling of sextant prostate biopsy cores predicts the site of extracapsular extension in a radical prostatectomy specimen, thereby justifying increased cost of pathological evaluation. MATERIALS AND METHODS: Between January 1994 and December 1997, 407 radical prostatectomies were performed at our institution by a single surgeon (H. L.). Surgical specimens showing extracapsular extension were examined by a single pathologist (J. M.) to identify the site of extension. Several different methods of submitting transrectal ultrasound guided biopsy cores were used since the majority of cases did not undergo biopsy at our institution. In 243 cases sextant biopsies were labeled right versus left. Of these cases 103 specimen cores were individually labeled. The ability of the positive biopsy core location to predict the location of extracapsular extension in the surgical specimen was determined. Univariate and multivariate logistic regression analyses were performed to assess the ability of biopsy core characteristics, including Gleason score, percentage of cancer in the core, core location and number of positive cores in the specimen, to predict the site of extracapsular extension. A similar analysis was performed for the 243 cases with right versus left core labeling. RESULTS: The positive predictive value was 8.9+/-2.2% for a single positive core to identify the location of extracapsular extension correctly in the individually labeled core cases. The absence of cancer in a sextant biopsy had a negative predictive value of 96.9+/-1.4%. The overall sensitivity was 59.4+/-3.8% for a positive biopsy core. In the right versus left core cases the positive predictive value was 12.9+/-3.0% with a sensitivity of 85.1+/-3.2%. In an individual core Gleason score 8 or greater and/or cancer in more than 50% of tissue enhanced the positive predictive value but not to a clinically useful level. Multivariate logistic regression identified Gleason score, number of positive ipsilateral cores and base position of the positive biopsy as the most predictive variables for the site of extracapsular extension. CONCLUSIONS: When submitting biopsy specimens by individually labeled core or right versus left core, the positive predictive value of an individual positive core for the location of extracapsular extension is not sufficient to guide the surgical decision to spare or excise a neurovascular bundle. Therefore, the clinical information provided by individually labeled or right versus left core labeling does not justify the increased associated costs.

Biopsy↗
PubMed1999

Changes in Penile Morphometrics in Men with Erectile Dysfunction after Nerve-Sparing Radical Retropubic Prostatectomy.

There have been anecdotal reports of a decrease in penile size in men with erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (NSRRP). Penile circumference and length measurements are obtained by one physician from 100 men, age 47 to 74, who presented at various intervals (1.7&endash;27.6 months) for the treatment of ED after NSRRP from 1994 through 1997. All patients were asked to complete a brief male sexual function inventory at their initial visit. Penile measurements were obtained both in the flaccid and erect states, with erections being induced with intracorporal injections of Trimix. The sexual inventory scores were compared with those of an age-matched control cohort of 130 men presenting for evaluation of ED during the same time period and 132 age-matched men who completed the inventory at the time of a prostate screening. By self-report, men experiencing ED after NSRRP had better libido but more severe ED than men presenting with ED of other causes. There was a decrease in all penile dimensions after NSRRP. The flaccid and erect measurements of length and circumference decreased 8% and 9%, respectively after surgery (p > 0.05). The most substantial change occurred between the first 4 and 8 months postoperatively. The average change in volume between the first 4 and 8 months was 19% to 22% in the flaccid and erect state, respectively. There is a significant decrease in penile size in men with ED after NSRRP. The etiology may be denervation smooth muscle atrophy, apoptosis, or hypoxia-induced damage to the corpora. Further research is needed to elucidate the nature of these postoperative changes.

Journal Article↗
PubMed1999

Localization and expression of the alpha1A-1, alpha1B and alpha1D-adrenoceptors in hyperplastic and non-hyperplastic human prostate.

PURPOSE: To determine the expression and localization of the alpha1A-1, alpha1B and alpha1D-adrenoceptor (AR) subtypes in hyperplastic and non-hyperplastic human prostate tissue. MATERIALS AND METHODS: The expression of the alpha1-AR subtypes was examined at the mRNA level by quantitative solution hybridization, and at the protein level by immunohistochemistry using subtype selective antibodies. RESULTS: While the overall level of alpha1-AR mRNA was not significantly different between hyperplastic and non-hyperplastic tissue, there were significant differences in the ratio of the alpha1-AR subtypes expressed in the two tissue types. The most significant finding from these studies was the reduced expression of the alpha1b-AR mRNA in both glandular and stromal hyperplasia. By immunohistochemistry, the alpha1A-1-AR was detected in the stroma and not in the glandular epithelium. The alpha1B-AR was localized predominantly in the epithelium and was weakly present in the stroma. Lower levels of the alpha1B-AR were detected in the hyperplastic prostatic epithelium. The alpha1D-AR was detected in areas of stroma and was abundantly present in blood vessels. CONCLUSIONS: The alpha1A-1-, alpha1B- and alpha1D-AR subtypes are differentially localized in human prostate, and the expression levels of all three subtypes are altered in BPH. Alterations in a1-AR subtype expression (particularly the alpha1B-AR) in BPH cannot be solely attributed to changes in tissue morphometry resulting from hyperplasia and may be of significance in the pathogenesis of BPH.

Humans↗
PubMed1998

Identification of genes associated with stromal hyperplasia and glandular atrophy of the prostate by mRNA differential display.

Despite the well-characterized histology associated with benign prostatic hyperplasia, very little is known about the underlying etiology of the disease on a molecular basis. The objective of this study was to use the technique of mRNA differential display in order to identify genes differentially expressed in human transition zone prostate tissue with high stromal density, with high epithelial density, and with nonhyperplastic histology. The extracellular matrix chondroitin/dermatan sulfate proteoglycan (CDSP) mRNA was more abundantly expressed in tissue with high stromal density, consistent with earlier findings that dermatan and chondroitin 6-sulfate glycosaminoglycans are increased in hyperplastic prostates. Messenger RNA encoding the negative regulator of cell cycle progression, BTG2, was more abundantly expressed in tissue with high epithelial densities. CDSP mRNA was abundantly expressed in primary cultures of stromal cells but was undetectable in epithelial cells. BTG2 mRNA was expressed in primary cultures of both cell types, but more abundantly in epithelial cells. BTG2 mRNA, but not CDSP mRNA, was subject to significant growth cycle regulation in cultured stromal and epithelial cells, with maximum expression occurring in quiescent cells. Generation of specific antibodies to BTG2 revealed that this protein was expressed at low levels in stroma, nonhyperplastic glands, and in hyperplastic glands. Consistent with a role in cell-cycle regulation, BTG2 protein was abundantly expressed in atrophic glands and preatrophic glands.

Atrophy↗
PubMed1998

Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate.

A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3-(methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned human alpha adrenoceptors as well as the rat L-type calcium channel. Within this compound series, 5-(aminocarbonyl)-1,4-dihydro-2, 6-dimethyl-4-(4-nitrophenyl)-3-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed good binding affinity and selectivity for the alpha1a adrenoceptor (pKi = 8.73) and potently inhibited (pA2 = 9.23) phenylephrine-induced contraction of the human prostate.

Adrenergic alpha-Agonists↗
PubMed1998

Endothelin-1 production and agonist activities in cultured prostate-derived cells: implications for regulation of endothelin bioactivity and bioavailability in prostatic hyperplasia.

BACKGROUND: Endothelin-1 (ET-1) interacts with specific G-protein-coupled receptors to initiate short-term (contraction) and long-term (mitogenesis) events in target cells. ET-1 is an abundant prostate secretory protein that, in its biologically active form, elicits prostatic smooth muscle contraction. The present study was designed to determine the effects of ET-1 on prostate cell growth and to examine the regulation of endogenous ET-1 activity and bioavailability. METHODS: Primary cultures of prostate secretory epithelial (PE) and prostate fibromuscular stromal (PS) cells were established from benign human prostate tissue. RESULTS: In culture, PE cells secrete immunoreactive ET-1 (38.5 +/- 1.6 pg/ml/10(6) cells/24 hr) into the conditioned medium. Levels of immunoreactive ET-1 produced by PS cells were more than 10-fold lower. Endothelin-converting enzyme-1 (ECE-1) mRNA was detected in PE cells and not in PS cells; however, big ET-1 was the predominant immunoreactive ET-1 secretory product of PE cells. The ET(B) endothelin receptor was the predominant subtype in both PE and PS cells. In PS cells, but not PE cells, ET-1 induced significant inositol phosphate accumulation and [3H]-thymidine uptake. Agonist activity was inhibited by the ET(B) receptor selective antagonist, BQ 788. Intact PE cell monolayers secrete ET-1 through the apical surface, consistent with secretion of ET-1 into the glandular lumen in vivo. CONCLUSIONS: On the basis of these findings, regulation of ET-1 activity and bioavailability appears to be tightly regulated. Such findings have important implications in the pathophysiology of prostate disease.

Apoptosis↗
PubMed1998

Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate for the detection of prostate cancer.

PURPOSE: We investigated the role of performing 2 consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate in a single office visit as the protocol for detecting prostate cancer in men presenting for the first time with an abnormal digital rectal examination and/or elevated serum prostate specific antigen (PSA). MATERIALS AND METHODS: A total of 137 consecutive men presenting for the first time with a clinically localized prostate nodule on digital rectal examination and/or elevated serum PSA based upon age specific reference ranges underwent 2 consecutive sets of sextant prostate biopsies under transrectal ultrasound guidance in a single office visit. The 2 sets of biopsies were processed and analyzed separately by pathologists. RESULTS: Adenocarcinoma of the prostate was diagnosed in 43 of the patients (31%) undergoing biopsy. Adenocarcinoma of the prostate was diagnosed in only the second set of biopsies in 13 cases (10%). High grade prostatic intraepithelial neoplasia without adenocarcinoma of the prostate was observed in 18 of the first set of biopsies (15%). High grade intraepithelial neoplasia without adenocarcinoma of the prostate was the only pathological diagnosis in the second set of biopsies in 3 cases. The second set of biopsies provided important new clinical information related to prostate cancer in 20 cases (28%) and increased the number of cancers detected by 30%. In addition, 14 patients with high grade intraepithelial neoplasia who would have required a second set of biopsies were found not to have adenocarcinoma of the prostate. Prostate cancer was detected in 43, 27 and 24% of men with prostate volumes less than 30, 30 to 50 and greater than 50 cc, respectively. The percentage of prostate cancers detected only in the second set of biopsies was not significantly related to prostate size. CONCLUSIONS: Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate performed in a single office visit represent a cost-effective biopsy strategy for men presenting with an abnormal digital rectal examination and/or elevated serum PSA. The benefits include increasing the detection of adenocarcinoma of the prostate and providing the recommended second set of biopsies for high grade intraepithelial neoplasia without increased morbidity or cost.

Adenocarcinoma↗
PubMed1998

Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Tamsulosin Investigator Group.

OBJECTIVES: To evaluate the efficacy and safety of two once-daily doses of tamsulosin, the first selective alpha1A-antagonist studied in clinical trials. METHODS: Patients with benign prostatic hyperplasia (BPH) were randomized to receive either tamsulosin (0.4 and 0.8 mg/day) or placebo (n = 756). Primary efficacy parameters were improvement in the total American Urological Association (AUA) symptom score and peak urinary flow (Qmax). Secondary efficacy parameters were improvement in measurements at individual double-blind visits corresponding to the primary efficacy parameters; percentage of patients with a 3-mL/s increase in Qmax; total AUA irritative, obstructive, and bother scores; individual AUA symptom scores; total, irritative, obstructive, and individual Boyarsky symptom scores; average urinary flow rate and other uroflowmetric parameters; and investigator's global assessment. RESULTS: Statistically significant improvements in all efficacy parameters were observed in tamsulosin-treated compared with placebo-treated patients. Additionally, the 0.4-mg/day dose demonstrated a rapid onset of action (4 to 8 hours) based on Qmax after the first dose of double-blind medication. A review of the safety parameters demonstrated excellent tolerance at 1 week after the initial 0.4-mg/day dose and continued tolerance during the additional 12 weeks of 0.4- and 0.8-mg/day dosing. The incidence of positive orthostatic test results in the tamsulosin groups was comparable to that observed in the placebo group. Adverse events were comparable in the 0.4-mg/day tamsulosin and placebo groups and were somewhat higher in the 0.8-mg/day tamsulosin group. CONCLUSIONS: Tamsulosin was effective, safe, and well tolerated in the target BPH population at both the 0.4- and 0.8-mg/day dose levels, without the blood pressure-lowering effects typical of nonselective alpha-adrenergic antagonists.

Adrenergic alpha-Antagonists↗
PubMed1998

Long-term evaluation of tamsulosin in benign prostatic hyperplasia: placebo-controlled, double-blind extension of phase III trial. Tamsulosin Investigator Group.

OBJECTIVES: To evaluate the long-term efficacy and safety of once-daily tamsulosin (0.4 and 0.8 mg), a unique selective alpha1A-adrenoceptor antagonist in patients with benign prostatic hyperplasia (BPH). METHODS: This trial extended a 13-week, Phase III multicenter placebo-controlled, double-blind outpatient trial for an additional 40 weeks. Of 618 patients, 418 (68%) continued into the extension phase on the same double-blind medication and dose. The primary efficacy parameters were total American Urological Association (AUA) symptom score and maximum urinary flow (Qmax). RESULTS: The mean changes in AUA symptom score from baseline to end point were statistically significant in all groups (P <0.001). Significant improvements were observed in Qmax for both tamsulosin groups but not for the placebo group. The statistically significant improvements from baseline in efficacy parameters observed for each tamsulosin group at the end of the 13-week Phase III trial were maintained during the long-term extension phase. Tamsulosin at both dosages was well tolerated as maintenance therapy. Clinically significant orthostatic hypotension was not observed. Vital sign changes in either hypertensive or normotensive patients were not clinically significantly different across the three groups. CONCLUSIONS: Tamsulosin once-daily at 0.4 or 0.8 mg was shown to be effective, safe, and well tolerated in the target BPH population during long-term use.

Adrenergic alpha-Antagonists↗
PubMed1998

Altered smooth muscle development and innervation in the lower genitourinary and gastrointestinal tract of the male human fetus with myelomeningocele.

PURPOSE: We determine whether smooth and skeletal muscle or nerve density is altered in the lower genitourinary or gastrointestinal tract of male human fetuses with myelomeningocele at 20 weeks of gestation. MATERIALS AND METHODS: We serially cross sectioned the lower genitourinary and gastrointestinal tracts in 7 male fetuses (mean age 20 weeks of gestation) with myelomeningocele and 4 age matched controls. Immunohistochemical staining was performed using Masson's trichrome stain and antibodies to smooth and skeletal muscle actin. S-100 protein staining for Schwann cell localization and neurofilament protein was also done. Fluorescein and rhodamine double immunolabeling was used to demonstrate the co-expression of smooth and skeletal muscle. RESULTS: Peripheral neural innervation of the bladder, prostate and rectum was markedly decreased in myelomeningocele. Masson's trichrome and smooth muscle actin staining also demonstrated that smooth muscle was less well differentiated in myelomeningocele specimens. Scant smooth muscle was present in the myelomeningocele bladder and bladder neck with an excess of collagen in an interfascicular and intrafascicular distribution. Double immunofluorescence staining revealed persistent co-expression of smooth and skeletal muscle actin by myocytes in the myelomeningocele detrusor, while in the control bladder there was only smooth muscle expression. The skeletal muscle component of structures in fetuses with myelomeningocele, including the external sphincter, was similar to that in controls. Prostatic size, ductal morphogenesis and smooth muscle were decreased compared to those in controls. CONCLUSIONS: A global defect exists in the development of smooth muscle in myelomeningocele in the lower genitourinary and gastrointestinal tracts by 20 weeks of gestation. Peripheral nerve density is decreased in smooth muscle in myelomeningocele, suggesting that an intact nervous system is important for the development of normal smooth muscle. Fetal surgery with coverage of the spinal cord in select cases may prevent progressive environmental injury to the somatic nervous system during the second half of gestation. However, achieving normal autonomic function is unlikely due to the extent of early global organ maldevelopment.

Digestive System↗
PubMed1998

The role of bladder neck biopsy in men undergoing radical retropubic prostatectomy with preservation of the bladder neck.

PURPOSE: Radical retropubic prostatectomy is often performed with preservation of the bladder neck. We examine the incidence of benign and malignant prostatic tissue at the bladder neck margin in men undergoing radical retropubic prostatectomy with preservation of the bladder neck for clinically localized prostate cancer. MATERIALS AND METHODS: The study included 100 cases of radical retropubic prostatectomy with preservation of the bladder neck performed by a single surgeon (H. L.). A 2 mm. thick circumferential specimen was excised from the bladder neck, divided into 4 quadrants (anterior, posterior, right and left) and submitted for frozen section examination. The permanent sections from these bladder neck biopsies and the entire surgical specimens were analyzed by a single pathologist (J. M.). RESULTS: The frozen section diagnosis from the bladder neck biopsies were adenocarcinoma, benign prostatic tissue and no prostatic tissue in 3, 38 and 59 cases, respectively. The permanent section diagnosis of the bladder neck biopsies was adenocarcinoma, benign prostatic tissue and no prostatic tissue in 4, 57 and 39 cases, respectively. The sensitivity specificity, and positive and negative predictive values for examination of the surgical specimen to identify benign prostatic tissue was 67, 90, 90 and 65%, respectively. The bladder neck was re-biopsied because of the findings of adenocarcinoma and benign prostatic tissue in 3 and 8 cases, respectively. The initial bladder neck biopsy resulted in pathological down staging to pT2c in only 1 case. Repeat resection of the bladder neck in all cases with 10% or less benign prostatic tissue showed no prostatic tissue, whereas 50% of the cases with more than 10% benign prostatic tissue demonstrated residual benign prostatic tissue. Serum prostate specific antigen was undetectable immediately after radical retropubic prostatectomy in all cases with benign prostatic tissue only. CONCLUSIONS: Preservation of the bladder neck during radical retropubic prostatectomy does not significantly compromise total extirpation of the malignant process. Benign prostatic tissue at the bladder neck margin is relatively common. Examination of the surgical specimen has limited sensitivity, and negative and positive predictive values for the presence of benign prostatic tissue at the bladder neck margin. The impact of benign prostatic tissue as it relates to future malignant transformation is unknown. Submitting frozen section specimens from the bladder neck is reasonable for the younger man who may be at risk from benign prostatic tissue at the bladder neck margin.

Adenocarcinoma↗
PubMed1998

Localization of P2Y1 purinoceptor transcripts in the rat penis and urinary bladder.

PURPOSE: The aim of this study was to determine the expression and localization of the P2Y1 purinoceptor mRNA in rat penis and urinary bladder using reverse transcription polymerase chain reaction (RT-PCR), northern blotting and in situ hybridization (ISH). MATERIALS AND METHODS: RT-PCR: First strand cDNA was prepared from rat penis and urinary bladder dome total RNA and used for PCR with primers designed to amplify fragments of the P2Y1 purinoceptor cDNA sequence. Northern blotting: PCR products were subcloned into the pGEM-5Zf(+) plasmid vector, sequenced and random primer labeled using 32p. Labeled probe was hybridized. ISH: Digoxigenin labeled cRNA probes were synthesized by in vitro transcription. RESULTS: P2Y1 purinoceptor mRNA was detected by RT-PCR analysis in both rat penis and urinary bladder. RNA blotting using a P2Y1 purinoceptor cDNA probe revealed a single transcript of 4.2kb in both tissues. This band was the same size as that expressed by the heart, which contains high levels of P2Y1 purinoceptor (Burnstock, G.: Physiological and pathological roles of purines: an update. Drug. Dev. Res., 28: 195, 1993). By ISH, P2Y1 purinoceptor mRNA was localized in detrusor smooth muscle cells and blood vessels in urinary bladder. In penis, positive signals were detected in endothelial cells which line the lacunar space and blood vessels. No hybridization was seen in corpus cavernosum smooth muscle cells and urethra. CONCLUSION: These results indicate that mRNAs for P2Y1 purinoceptor are expressed in detrusor smooth muscle cells and blood vessels of rat urinary bladder. However, in penis, this receptor is expressed in endothelial cells which lines the lacunar space and blood vessels, but not expressed in corpus cavernosum smooth muscle cells and urethra.

Animals↗
PubMed1998

The impact of medical therapy on bother due to symptoms, quality of life and global outcome, and factors predicting response. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.

PURPOSE: We determine the effect of placebo, finasteride, terazosin and a combination of drugs on bother due to symptoms, quality of life and patient perception of improvement, and identify baseline clinical factors that predict clinical response to medical therapy. MATERIALS AND METHODS: A total of 1,229 subjects with clinical benign prostatic hyperplasia (BPH) were randomized to 1 year of placebo, finasteride, terazosin or drug combination. The primary outcome measures were American Urological Association (AUA) symptom score and peak flow rate. Relevant secondary outcome measures were symptom problem score, BPH impact score and global rating of improvement. RESULTS: Group mean differences in symptom problem and BPH impact scores between the finasteride versus placebo, and terazosin versus combination groups were not statistically or clinically significant. Group mean differences in all outcome measures were highly statistically significant between the terazosin and finasteride, and combination and finasteride groups. The percentage of subjects who rated improvement as marked or moderate with placebo, finasteride, terazosin and combination was 39, 44, 61 and 65%, respectively. In the subsets of men in the placebo, finasteride, terazosin and combination groups with prostates greater than 50 cm.3 group mean decrease from baseline in AUA symptom score was -2.5, -3.6, -6 and -7, group mean increase in peak flow rate was 0.6, 2.7, 3.6 and 3.7 ml. per second, group mean decrease in symptom problem score was -2.2, - 1.9, -3.1 and -4.5, and group mean decrease in BPH impact score was -0.6, -0.3, -1.1 and -1.5, respectively. A correlational analysis failed to show a significant relationship between baseline prostate volume and treatment response to finasteride. There was a significant but weak relationship between change in AUA symptom score and peak flow rate in the finasteride and combination groups. The symptom responses with terazosin were independent of baseline peak flow rate. CONCLUSIONS: In men with clinical BPH finasteride and placebo are equally effective, while terazosin and combination are significantly more effective. In men with clinical BPH and large prostates the advantage of finasteride over placebo in terms of symptom reduction, impact on bother due to symptoms and quality of life is small at best, while the advantage of terazosin and combination over finasteride and placebo is highly significant. Baseline prostate volume was not a predictor of response to finasteride in the overall study population. On the basis of our results alpha1 blockers, such as terazosin, should be first line medical treatment for BPH.

Adrenergic alpha-Antagonists↗
PubMed1997

Morphometric analysis of pediatric and nonhyperplastic prostate glands: evidence that BPH is not a unique stromal process.

BACKGROUND: Although quantitative morphometry of benign prostatic hyperplasia (BPH) has been described, there is a paucity of information on the morphometry of the nonhyperplastic prostate. This study determines the histologic composition of prostates obtained from males, ages 2 days to 40 years, in order to provide insights into the morphometry of the "normal" gland. METHODS: The histologic composition of 45 prostates was obtained from autopsies of males with age groups stratified to reflect the neonatal, childhood, peripubertal, adolescent, and young adult periods. Double immunoenzymatic staining and computer image analysis were used to determine the mean area densities of the smooth muscle (SM), connective tissue (CT), glandular epithelium (E), and lumen (L). RESULTS: A progressive decrease in SM area density throughout childhood, prepuberty, and puberty was seen. The density of SM significantly increased following puberty and throughout adolescence and early adulthood. There was a concomitant increase in CT from the neonatal period throughout childhood, prepuberty, and puberty, and a decrease after puberty and throughout adolescence and early adulthood. Since the changes in SM and CT were inversely related, the percent contribution of the stromal compartment to the total gland remained constant. CONCLUSIONS: The stromal to epithelial ratio remains constant from birth to age 40 in nonhyperplastic glands and is similar to the ratios in asymptomatic and symptomatic BPH tissues.

Adolescent↗
PubMed1997

Prostatic alpha 1-adrenoceptors and uroselectivity.

BACKGROUND: alpha 1-adrenoceptor antagonists (blockers) are now commonly used in the treatment of the symptoms of lower urinary tract obstruction. Originally phenoxybenzamine, a non-selective antagonist at both alpha 1- and alpha 2-adrenoceptors, was used by Marco Caine. In an attempt to minimize side effects, selective alpha 1-antagonists, e.g. prazosin, were subsequently developed. More recently, agents such as alfuzosin, doxazosin, terazosin, and tamsulosin have been introduced and claims of "uroselectivity" and "prostate" selectivity have emerged. METHODS: This review attempts to put these claims into perspective and represents a comprehensive analysis of all pre-clinical and clinical data including several papers from the Japanese literature. An attempt is made to define what is meant by selectivity at various levels including the test tube, in the laboratory animal and, most importantly, in the clinical context of the whole patient. CONCLUSIONS: The conclusions are interpreted within the context of the subdivision of the alpha 1-adrenoceptor into alpha 1A, alpha 1B, and alpha 1D subtypes.

Adrenergic alpha-Antagonists↗