Short-term pretreatment with a dual 5α-reductase inhibitor before bipolar transurethral resection of the prostate (b-turp): evaluation of prostate vascularity and decreased surgical blood loss in large prostates

Objective: To investigate if short-term treatment with dutasteride (8 weeks) before bipolar transurethral resection of the prostate (B-TURP) can reduce intraoperative bleeding, as dutasteride a dual 5α-reductase inhibitor (5-ARI) blocks the conversion of testosterone into its active form dihydrotestosterone (DHT), and reduces prostate volume and prostate-specific antigen (PSA) levels, while increasing urinary flow rate. Patients and Methods: In all, 259 patients were enrolled and randomised to two groups: Group A, receiving placebo and Group B, receiving dutasteride (0.5mg daily for 8 weeks). Blood samples were taken before and after B-TURP for serum chemistry evaluation. In particular we evaluated blood parameters associated with blood loss [haemoglobin (Hb) and haematocrit (Ht)] and prostate vascularity [vascular endothelial growth factor (VEGF) immunoreactivity and microvessel density (MVD) using cluster of differentiation 34 (CD34) immunoreactivity]. Results: Total testosterone, DHT, PSA level and prostate volume were evaluated and with the exception of DHT and PSA level there was no statistically significant differences between the groups. When comparing changes in Hb and Ht between Group A and Group B before and after B-TURP, there was a statistically significant difference only in patients with large prostates of ≥50mL (ΔHb 3.86 vs 2.05g/dL and ΔHt 4.98 vs 2.64%, in Groups A and B, respectively). There was no significant difference in MVD and VEGF index in prostates of <50mL, conversely in large prostates the difference become statistically significant. Conclusions: Dutasteride was able to reduce operative and perioperative bleeding only in patients with large prostates (≥50mL) that underwent B-TURP. Our findings are confirmed by Hb and Ht values reported before and after the B-TURP and reductions in the molecular markers for VEGF and CD34 in the dutasteride-treated specimens

Benign prostatic hyperplasia as a progressive disease: a guide to the risk factors and options for medical management

Benign prostatic hyperplasia (BPH) is a complex disease that is progressive in many men. BPH is commonly associated with bothersome lower urinary tract symptoms; progressive disease can also result in complications such as acute urinary retention (AUR) and BPH-related surgery. It is therefore important to identify men at increased risk of BPH progression to optimise therapy. Several factors are associated with progression, including age and prostate volume (PV). Serum prostate-specific antigen level is closely correlated with PV, making it useful for determining the risk of BPH progression. Medical therapy is the most frequently used treatment for BPH. 5-alpha-reductase inhibitors impact the underlying disease and decrease PV; this results in improved symptoms, urinary flow and quality of life, and a reduced risk of AUR and BPH-related surgery. Alpha-blockers achieve rapid symptom relief but do not reduce the overall risk of AUR or BPH-related surgery, presumably because they have no effect on PV. Combination therapy provides greater and more durable benefits than either monotherapy and is a recommended option in treatment guidelines. The Combination of Avodart® and Tamsulosin (CombAT) study is currently evaluating the combination of dutasteride with tamsulosin over 4 years in a population of men at increased risk of BPH progression. A preplanned 2-year analysis has shown sustained symptom improvement with combination therapy, significantly greater than with either monotherapy. CombAT is also the first study to show benefit in improving BPH symptoms for combination therapy over the alpha-blocker, tamsulosin, from 9 months of treatment

Baseline characteristics predict risk of progression and response to combined medical therapy for benign prostatic hyperplasia (BPH)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110594/1/bju12802.pd

Seasonal analysis of abiotic factors impacting phytoplankton assemblages in Offatts Bayou, Galveston, Texas

The aim of this investigation in Offatts Bayou was to quantify natural shifts in distributions and abundances of algal groups and to examine spatio-temporal patterns of abiotic and biotic characteristics in the water column over a one year period. To accomplish this, hydrological and meteorological parameters were collected and phytoplankton biomass, community composition and chlorophyll a data were examined for significant relationships. Seasonal variations in water temperature, salinity, dissolved oxygen concentrations and pH levels, as well as wind effects, zooplankton grazing, light availability and hydrodynamic restriction were considered as the key controlling factors in phytoplankton dynamics in Offatts Bayou. Surface water samples and water column hydrological data were collected at eleven stations in the Offatts Bayou embayment on a regular basis (2 to 4 times per month), along with phytoplankton tows on a monthly basis. Spatial patterns of phytoplankton abundance generally reflected the degree of circulation in Offatts Bayou with higher abundances observed in the restricted areas and lower abundances in the well mixed regions. Temporally, diatom blooms became more prominent during winter, spring and autumn, which were characterized by cooler temperatures, less light availability, increased dissolved oxygen concentrations and reduced salinities than observed in summer. The most dominant diatoms were Guinardia delicatula, Ditylum brightwelli, Rhizosolenia setigera, Dactyliosolen fragillissimus and numerous Chaetoceros species. During summer, the waters of Offatts Bayou were warmer and more saline, which lead to the haptophyte, Corymbellus aureus, becoming the dominant taxa, with highest standing crops at the circulation restricted stations in Lake Madeline. While the results of this study support the importance of temperature, dissolved oxygen and pH as the critical controlling factors (p < 0.05) of phytoplankton biomass and diversity, it is clear that phytoplankton dynamics in Offatts Bayou must be viewed within the broader context of additional parameters such as salinity, stratification and wind effects. The progressively degrading conditions within Offatts Bayou emphasize the significance of studying and understanding the interrelationships of factors and mechanisms that influence phytoplankton dynamics. Long term monitoring of Offatts Bayou is essential for tracking, recording and assessing various human impacts to phytoplankton distribution, abundance, and productivity as well as impacts to higher trophic levels such as fish and humans

The Benign Prostatic Hyperplasia Registry and Patient Survey: study design, methods and patient baseline characteristics

To describe the design and baseline cohort characteristics of the Benign Prostatic Hyperplasia (BPH) Registry and Patient Survey, an ongoing, prospective, observational, disease registry documenting management practices and patient outcomes in men in the USA with lower urinary tract symptoms associated with BPH (LUTS/BPH) in actual clinical practice settings. PATIENTS AND METHODS Men with LUTS/BPH who were either untreated or treated with Α 1 -adrenergic blockers (ABs), 5Α-reductase inhibitors (5ARIs), a combination of these medications, or anticholinergics, and who met selection criteria, were enrolled at sites throughout the USA. At each visit, standardized forms and validated questionnaires were completed to assess the physicians’ management practices and patients’ clinical characteristics, sexual function, and health-related quality of life. RESULTS At the close of recruitment (February 2005), 6909 men (mean age 66.0 years) were enrolled at 402 sites by urologists and primary-care physicians. Before enrolment, 49% of the men were managed with watchful waiting (WW), 21% with uroselective AB monotherapy, 11% with non-uroselective AB monotherapy, 6% with 5ARI monotherapy, 11% with AB + 5ARI, and 2% with anticholinergics. After enrolment, 42% were on WW and 26% were on selective AB monotherapy; changes in other management groups were minimal. Overall, 33% of the men had mild, 52% had moderate and 15% had severe LUTS. The most common comorbidities were hypertension (53%), high cholesterol (45%) and sexual dysfunction (36%). CONCLUSION The BPH Registry and Patient Survey will provide information on physician management practices and outcomes of men with LUTS/BPH, while examining the effects of demographics, socio-economics, comorbidities, and medical therapies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73286/1/j.1464-410X.2007.07061.x.pd

Current status of 5α-reductase inhibitors in the management of lower urinary tract symptoms and BPH

Benign prostatic hyperplasia (BPH) is a progressive disease that is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. Therefore, the goals of therapy for BPH are not only to improve LUTS in terms of symptoms and urinary flow, but also to identify those patients at a risk of unfavorable disease progression and to optimize their management. This article reviews the current status of therapy with 5 alpha-reductase inhibitors (5ARIs), namely fiasteride and dutasteride, for men with LUTS and BPH. Data from key randomized controlled trials (Oxford level 1b) on the use of 5ARIs are analyzed. The efficacy of 5ARIs either as monotherapy or in combination with alpha(1)-adrenoceptor antagonists in the management of LUTS and the impact of monotherapy and combined therapy on BPH progression are discussed. Further promises, including the withdrawal of the alpha-blocker from the combined medical treatment and the potential clinical implications from the use of 5ARIs for prostate cancer chemoprevention in patients receiving 5ARIs for symptomatic BPH are highlighted. Current evidence shows that 5ARIs are effective in treating LUTS and preventing disease progression and represent a recommended option in treatment guidelines for men who have moderate to severe LUTS and enlarged prostates

Impacts of the Quinazoline-Based Alpha1-Antagonist, Terazosin, and of the Sulfonamide Derivative, Tamsulosin, on Serum Prostate-Specific Antigen and Prostate Volume

The aim of this study was to compare the impacts of terazosin and tamsulosin, on prostate activity, i.e., serum prostate-specific antigen, total prostate volume (TPV), and transition zone volume (TZV). A total of 90 patients who presented with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), ranging in age from 52 to 83 yr (median 65 yr), were included in the study. Patients were given 0.2 mg tamsulosin, 2 mg terazosin, or 4 mg terazosin once daily for an average of 14 months (range, 6-56 months). Subjective (International Prostate Symptom Scores, I-PSS) and objective (maximal flow rate and post-void residual) parameters were assessed both at baseline and at treatment cessation. Serum prostate-specific antigen (PSA) levels were found to be unaffected by treatment (1.2 and 1.3 ng/mL). In total patients, multivariate analysis showed that baseline TPV was the only independent predictor of treatment-related TPV reduction. Moreover, baseline TPV ≥30 g was found to be associated with a higher likelihood of TPV reduction (odds ratio [OR], 3.939; 95% confidence interval [CI], 1.506-10.304; p=0.005), and a baseline TZV of ≥10 g was associated with a 7.1-times greater chance of TZV reduction (OR, 7.100; 95% CI, 2.428-20.763; p<0.001). The same model showed that patients on 2 mg terazosin had a 10.8-fold greater likelihood (OR, 10.770; 95% CI, 1.409-82.323; p=0.022) and that those on 4 mg terazosin had a 9.0-fold greater likelihood (OR, 9.001; 95% CI, 1.724-46.995; p=0.009) of a TZV reduction than those on 0.2 mg tamsulosin. In addition, symptoms improved regardless of prostate activity after taking alpha1-blockers. Our findings suggest that terazosin reduces TZV and demonstrate that the relief of symptoms associated with BPH may not be due to a prostate activity reduction induced by apoptosis in the prostate gland

Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base