Patients with uncontrolled hypertension or concomitant hypertension and benign prostatic hyperplasia

At optimal doses, individual antihypertensive agents lower blood pressure (BP) by an average of 10 mmHg. Many patients with hypertension, including those with stage 3 hypertension, target organ damage, or those at high risk for cardiovascular events and/or adverse effects of high-dose monotherapy, are likely to require combination antihypertensive drug treatment to achieve the recommended systolic/diastolic BP (< 140/90 mmHg). Two studies, a placebo-controlled, double-blind trial (n = 70) and a community-based, open-label trial (n = 491) investigated the antihypertensive efficacy of doxazosin, a long-acting selective alpha1-adrenoceptor blocker, as add-on therapy for uncontrolled hypertension with other antihypertensive medications and in patients with concomitant benign prostatic hyperplasia (BPH) and treated but inadequately controlled hypertension, respectively. The addition of doxazosin to baseline antihypertensive medication(s) significantly lowered BP and had a significantly positive effect on the serum lipid profile. In patients with concomitant BPH, doxazosin significantly improved all BPH symptom scores, regardless of initial symptom severity. Add-on doxazosin sufficiently reduced systolic/diastolic BP such that many patients whose hypertension was previously uncontrolled by other antihypertensive medications were able to reach goal BP (< 140/90 mmHg). Doxazosin as add-on therapy was well tolerated. In conclusion, doxazosin as add-on therapy improves BP control in hypertensive patients not at goal BP and improves lower urinary tract symptoms in patients with concomitant BPH.     

Long-term treatment with doxazosin in men with benign prostatic hyperplasia: 10-year follow-up

INTRODUCTION AND OBJECTIVES: Benign prostatic hyperplasia (BPH) is a progressive condition that is characterized by an increased risk of acute urinary retention and BPH-related surgery. This study evaluates the safety and efficacy of doxazosin over 10 years in men with BPH. MATERIAL AND METHODS: The trial enrolled men (aged 49-83 years--mean 64.0) with symptomatic BPH (clinical stage II according to Alken) and no evidence of prostate cancer. The trial involved a 1.5 year controlled efficacy study with doxazosin (4 mg/day) 64 ambulatory patients with BPH, followed by a 5-year extension. During the study after 1 year 11 pts discontinued it (expense given as reason) and 6 pts underwent surgery. Then 47 pts (100%) receiving doxazosin continued therapy. After 5 years 32 pts (60%) aged 54-92 years--mean 69.4 years continued to be followed for further 5 years, giving a total follow-up of 10 years (next 8 pts underwent surgery; total 14 (26%) pts; and 14 (26%) pts died. RESULTS: Twenty (38%) of the 47 pts (100%) enrolled into doxazosin were judged as being successfully treated during the 10-year follow-up. In further 5 years only 2 pts underwent surgery and 7 pts (13%) died for reasons unrelated to doxazosin treatment. Three pts after 6 years therapy left study. Excluding 14 pts who died plus 14 pts who left the trial it means that after 10 years 20 pts remained successfully treated and 16 pts who had to be surgically treated. Assuming that all group make 36 pts (100%) than long term follow-up showed effective results in doxazosin treated 20 pts (56%) and thus can obviate surgery. Adverse events associated with doxazosin therapy were insignificant. 10 years therapy proved effective in increasing urina flow rates and decreasing residual urine volume--respectively 14.6 ml/s and 57.0 ml (mean value). CONCLUSIONS: 1. Long-term 10 years doxazosin (4 mg/daily) therapy has demonstrated that appropriately selected BPH patients are likely to have an excellent response. 2. The a/m trial indicates that surgery can be obviated in up to half of BPH treated patients. 3. The results of the trial demonstrate that doxazosin is safe, efficacious and well-tolerated.     

Focal nodular hyperplasia in normal and fatty liver: a qualitative and quantitative evaluation with contrast-enhanced ultrasound

The aim of this study was to describe gray-scale appearance of liver parenchyma and focal nodular hyperplasia (FNH) by pulse inversion (PI) ultrasound (US) at baseline and after contrast agent administration in patients with normal and fatty liver. Sixteen consecutive patients (12 women, 4 men) with 29 previously diagnosed FNHs (15 of 29 located in normal liver and 14 of 29 in fatty liver) underwent PI US before and after SH U 508A (Levovist) injection. Signal intensity values were measured within the FNHs and the adjacent liver parenchyma in selected images. Baseline echogenicity of fatty liver was higher (15.19±2.90 dB±SD) than normal liver (10.91±3.15 dB±SD; p<0.001). After Levovist administration, normal livers (7 of 16) showed a statistically significant increase of echogenicity (16.59±3.81 dB±SD; p<0.001) in comparison with fatty livers (9 of 16; 15.75±3.12 dB±SD). The FNHs located in normal liver showed baseline echogenicity higher (12.29±3.22 dB±SD) than that of FNHs arising in fatty liver (7.06±2.43 dB±SD; p<0.001). After Levovist administration, FNHs located in normal liver showed a statistically significant increase of echogenicity (25.30±4.62 dB±SD) in comparison with FNHs located in fatty liver (13.58±3.54 dB±SD; p<0.001); the latter always showed mean values of echogenicity lower than surrounding liver parenchyma. In our series decreased contrast-enhancement pattern of both fatty liver and FNHs located in fatty liver was the most prominent finding when Levovist is administered. Contrast washout was a distinctive feature of FNH arising from the fatty liver.This paper has been accepted for presentation as a scientific paper at the Scientific Assembly and Annual Meeting of the ECR 2003.     

Labioscrotal island flap in feminizing genitoplasty

Background/Purpose

Stenosis of the vaginal introitus is the most frequent complication after genital reconstruction for ambiguous genitalia associated with congenital adrenal hyperplasia (CAH). With the aim of enlarging the vaginal introitus, the authors present a technical modification of the introitoplasty that uses a bilateral cutaneous island flap based on the perineal superficial branches of the internal pudendal artery.

Methods

Eleven girls with CAH and Prader III to V genital ambiguity were included. Feminizing genitoplasty was performed in 1 stage. Bilateral cutaneous labioescrotal island flaps, based on the posterior labial artery, were included in the introitoplasty. The cosmetic results of the genitoplasty were evaluated by photographic analysis of the external genitalia.

Results

Integrity of the vaginal introitus as well as excellent integration of the flap and absence of additional scars in the donor area were assessed in all girls.

Conclusions

This modified island flap is technically feasible and reproducible producing no additional sequels in the donor area. It uses perineal skin that is usually excised in other techniques avoiding the use of harvesting skin from adjacent areas. Thus, it can be a useful additional procedure in the introitoplasty in association with the currently used techniques.     

Temporal gene expression following prosthetic arterial grafting

BACKGROUND: Following prosthetic arterial grafting, cytokines and growth factors released within the perianastomotic tissues stimulate smooth muscle cell proliferation and matrix production. While much in vitro work has characterized this response, little understanding exists regarding the sequential up- and down-regulation of genes following prosthetic arterial grafting. This study evaluates temporal gene expression at the distal anastomosis of prosthetic arterial grafts using microarray analysis. METHODS: Expanded polytetrafluoroethylene (ePTFE) carotid interposition grafts (n = 12) were surgically implanted into mongrel dogs. Distal anastomotic segments were harvested at 7, 14, 30, or 60 days. Contralateral carotid artery served as control. Total RNA was isolated from the anastomotic tissue and paired controls. Samples were probed with oligonucleotide microarrays consisting of approximately 10000 human genes to analyze differential gene expression at each time point. RESULTS: Forty-nine genes were found to be up-regulated and 37 genes were found to be down-regulated at various time points. Six genes were found to be consistently up-regulated at all time intervals, including collagen type 1 alpha-1 and alpha-2, 80K-L protein (MARCKS), and osteopontin. Six genes were found to be consistently down-regulated, including smoothelin and tropomyosin 2. RT-PCR and immunohistochemistry confirmed the microarray data. CONCLUSIONS: This study uses microarray analysis to identify genes that were temporally up- and down-regulated after prosthetic arterial grafting. Genes with similar patterns of expression have been identified, providing insights into related cellular pathways that may result in the formation of anastomotic intimal hyperplasia.     

Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement

PURPOSE: Nocturia is a common condition often attributed in aging men to benign prostatic enlargement. Older adults are prone to nocturnal sleep disturbance, of which disturbed circadian rhythm may be a component since it improves with nighttime administration of melatonin. This study was designed to investigate melatonin as a potential treatment for nocturia associated with bladder outflow obstruction in older men. MATERIALS AND METHODS: A total of 20 men with urodynamically confirmed bladder outflow obstruction and nocturia were entered into a randomized, double blind, placebo controlled crossover study assessing the effect of 2 mg controlled release melatonin at night on nocturia. Symptoms were assessed at baseline and after each 4-week treatment period using a frequency volume chart, the International Prostate Symptom Score and symptom problem index. Maximum urinary flow rate and post-void residual urine volume were also assessed. RESULTS: Baseline frequency of nocturia was 3.1 episodes per night. There were 7 men (35%) with detrusor overactivity and 10 (50%) had nocturnal polyuria. Melatonin and placebo caused a decrease in nocturia of 0.32 and 0.05 episodes per night (p = 0.07) and a decrease in the nocturia bother score of 0.51 and 0.05, respectively (p = 0.008). Nocturia responder rates (a reduction from baseline of at least -0.5 episodes per night) differed between the active medication and placebo groups (p = 0.04). Daytime urinary frequency, International Prostate Symptom Score, relative nocturnal urine volume, maximum urinary flow rate and post-void residual were unaffected by melatonin treatment. CONCLUSIONS: Melatonin treatment is associated with a significant nocturia response rate, improvement in nocturia related bother and a good adverse effect profile. However, it is uncertain whether the observed changes in this study are clinically significant.     

Holmium laser enucleation versus transurethral resection of the prostate. Are histological findings comparable?

PURPOSE: We investigated if an adequate histological diagnosis can be made from tissue after holmium laser enucleation of the prostate (HoLEP) and whether it is comparable to transurethral prostate resection (TURP) tissue findings in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: We analyzed 40 HoLEP and 40 age matched TURP tissue specimens from patients who underwent 1 of the 2 procedures between January 2001 and August 2002. Each histological specimen was reviewed by a single pathologist. Preoperative prostate ultrasound volume, total serum prostatic specific antigen and postoperative tissue weight were evaluated. Microscopic histological diagnosis was assessed by standard histological techniques and immunohistochemical evaluation. RESULTS: Patients were comparable in terms of age and preoperative total serum prostate specific antigen. Tissue remaining following the procedure was estimated to be 36.3% of preoperative ultrasound volume after HoLEP and 52.8% after TURP (p <0.001). Incidental adenocarcinoma and high grade PIN of the prostate were diagnosed in a comparable percent of specimens in the 2 groups. Tissue thermal artifacts induced by the laser were mostly due to coagulation. Thus, the alterations were similar to those after TURP. CONCLUSIONS: Tissue quality is altered after HoLEP and TURP. General prostatic architecture was maintained in the majority of HoLEP histological specimens. A moderately higher percent of prostatic tissue obtained by the Ho laser is lost by vaporization and coagulation. Nevertheless, these differences do not seem to alter pathologist ability to detect incidental prostate cancer and PIN.     

Prostatic tissue ablation by injection: a literature review

PURPOSE: Most men 50 to 80 years old will have development of some degree of benign prostatic hyperplasia (BPH). Many who experience lower urinary tract symptoms (LUTS) will be treated medically. However, significant numbers will have more severe and progressive disease requiring surgery. Transurethral resection of the prostate is the current gold standard of treatment for BPH. Minimally invasive therapies for symptomatic BPH emerge and fade continuously. However, intraprostatic injection for BPH has been used for more than 100 years and may be on the verge of a rebirth. The goal of this review is to familiarize the reader with the origins and history of intraprostatic injection, and its evolution using transperineal, transrectal and transurethral routes with multiple injectants. Initially used to treat urinary retention in men with BPH, its primary indication is now for LUTS. MATERIALS AND METHODS: We performed a structured MEDLINE review of the literature on intraprostatic injections from 1966 to 2003, augmented with relevant articles from select journals and documents dating to 1832. RESULTS: In patients with BPH transperineal and transurethral injections have the most systematic evaluation. Most injectants will cause localized prostatic necrosis and gland volume reduction with varying degrees of LUTS relief. Anhydrous ethanol is the most widely studied injectable to date. There are advantages and disadvantages associated with each route of injection. CONCLUSIONS: Examined for more than a century, the potential for using injectables for prostatic tissue ablation remains significant. More systematic laboratory research and clinical trials, currently ongoing, need to be completed.     

Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia

PURPOSE: We provide a comprehensive overview of the role of alpha1-adrenergic receptors (alpha1ARs) as critical mediators of lower urinary tract symptoms (LUTS) and pathophysiology in benign prostatic hyperplasia (BPH), and we review the pharmacological antagonists of alpha1ARs. MATERIALS AND METHODS: A review was performed of pertinent studies in the literature relating to the pathophysiology of LUTS and BPH, focusing on the role of alpha1ARs, and of clinical trial and practice data evaluating the different agents that inhibit these receptors. RESULTS: Further characterization of the alpha1AR gene family indicates that 3 receptor subtypes exist in humans. Their different distribution between urinary tract and cardiovascular tissues has provided a strategy for the development of improved therapeutic agents. Since excessive activity of the alpha1aAR and alpha1dAR subtypes appears to be a common feature in symptomatic BPH and alpha1aARs are enriched in prostatic tissue, drugs that demonstrate high alpha1aAR selectivity have attracted attention. Tamsulosin, which has high affinity for alpha1aAR and alpha1dAR subtypes but not for alpha1bAR, shows efficacy similar to the nonsubtype selective agents terazosin and doxazosin. It is associated with fewer cardiovascular side effects, although it has some ejaculatory side effects. The nonsubtype selective agent alfuzosin also demonstrates efficacy and offers an enhanced side effect profile, particularly minimizing hypotension. Other agents with super selective specificity for the alpha1aAR subtype are under investigation. CONCLUSIONS: Further advances in the treatment of LUTS associated with BPH may depend not only on receptor subtype selectivity, but also on other pharmacokinetic and pharmacodynamic factors.