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Biomedical subjects

Gerald Brock

Publications and source records attributed to Gerald Brock.

12 recordsLinked to original sources
PubMed2006

Sexual disorders and associated help-seeking behaviors in Canada.

OBJECTIVES: To study sexual activity, the prevalence of sexual difficulties and related help-seeking behaviors, among mature adults in Canada. MATERIALS AND METHODS: A telephone survey (random digit dialed) was conducted in Canada in 2001 to 2002. Interviews were based on a standardized questionnaire, including demographics, general health, relationships, and sexual behaviors, attitudes and beliefs. The survey was completed by a total of 1007 individuals (500 men and 507 women) aged 40 to 80 years in Canada. RESULTS: Overall, 83% of men and 71% of women had engaged in sexual intercourse during the 12 months preceding the interview, and 42% of men and 36% of women engaged in sexual intercourse more than once a week. Early ejaculation (23%) and erectile difficulties (16%) were the sexual problems most frequently reported by men. The sexual problems most frequently reported by women were a lack of sexual interest (30%) and lubrication difficulties (24%). Older age (60 to 80 years compared with 40 to 49 years) and diagnoses of depression and diabetes were all significant predictors of erectile difficulties in men. More than 75% of men and women had sought no help for their sexual problem(s) from a health professional. CONCLUSIONS: Many middle aged and older adults in Canada report continued sexual interest and activity. Although a number of sexual problems are highly prevalent in this population, few individuals seek medical help for these problems. This may be partly because they are not sufficiently bothered by the problem or do not think that it is serious.

Adult↗
PubMed2005

Vardenafil improved patient satisfaction with erectile hardness, orgasmic function and sexual experience in men with erectile dysfunction following nerve sparing radical prostatectomy.

PURPOSE: Nerve sparing radical retropubic prostatectomy (NS-RRP) results in erectile dysfunction in a significant number of patients. Vardenafil, a potent and selective phosphodiesterase type 5 inhibitor, is generally safe. It improves International Index of Erectile Function erectile function domain scores, and penetration and erection maintenance success rates in patients who have undergone NS-RRP. We report additional parameters important to patient perceptions regarding erection quality and satisfaction with sexual experience following NS-RRP. MATERIALS AND METHODS: A total of 440 men at 58 centers throughout the United States and Canada participated in this randomized, placebo controlled, double-blind trial with 3 phases, namely baseline (4-week untreated period), treatment (12 weeks) and followup (7 days). Participants received placebo (145), 10 mg vardenafil (146) or 20 mg vardenafil (149) at home on demand but no more than once per calendar day. Efficacy and satisfaction with erection quality and sexual experience were determined during the trial. RESULTS: The 10 and 20 mg vardenafil doses were significantly superior to placebo for the International Index of Erectile Function domains for intercourse satisfaction, orgasmic function and overall satisfaction with sexual experience (vs placebo p <0.0009). Significant improvement in the satisfaction rate with erection hardness were demonstrated for each vardenafil dose compared with placebo (p <0.0001). Vardenafil was generally well tolerated. Common adverse events were headache, vasodilatation and rhinitis. CONCLUSIONS: In this difficult to treat population of men with erectile dysfunction subsequent to NS-RRP on demand treatment with vardenafil during a 3-month period significantly improved key aspects of the sexual experience important to patient quality of life.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Improving the sexual quality of life of couples affected by erectile dysfunction: a double-blind, randomized, placebo-controlled trial of vardenafil.

INTRODUCTION: Erectile dysfunction (ED) has a dual negative impact on men and their female partners; both are likely to face a drop in sexual quality of life and challenges to their intimate relationship as couples' sexual activities are curtailed by the loss of erectile function. AIM: The primary objective of this study was to compare the efficacy of vardenafil vs. placebo in terms of success of maintenance of erection in men with ED and improvement of their female partner's sexual quality of life. METHODS: This was a randomized, double-blind, multicenter, flexible-dose, parallel-group comparison of vardenafil vs. placebo for 12 weeks in men (> or =18 years) with ED of > or = 6 months duration, and their female partners. MAIN OUTCOME MEASURES: Changes in patient's overall response rate to Sexual Encounter Profile question 3 (SEP3) "Did your erection last long enough for you to have sexual intercourse?" and female partner's response to the quality of life domain of the modified Sexual Life Quality Questionnaire (mSLQQ-QOL) at last observation carried forward (LOCF) were considered the primary efficacy measures. In addition, patient's response to SEP2 "Were you able to insert your penis into your partner's vagina?," the erectile function domain of the International Index of Erectile Function (IIEF-EF) and patient's mSLQQ-QOL score were also assessed. RESULTS: Compared with placebo, vardenafil significantly improved overall least square (LS) mean per-patient SEP3 success rate (28% vs. 68%; P < 0.0001) and partner's LS mean (standard error [SE]) mSLQQ-QOL score at LOCF (32.14 [3.24] vs. 65.80 [3.10]; P < 0.0001). In addition, compared with placebo, vardenafil also improved overall LS mean per-patient SEP2 success rate (47% vs. 80%; P < 0.0001), LS mean (SE) IIEF-EF scores at LOCF (12.7 [0.8] vs. 22.8 [0.8]; P < 0.0001) and patient's LS mean (SE) mSLQQ-QOL (28.37 [3.46] vs. 63.85 [3.28]; P < 0.0001) at LOCF. CONCLUSIONS: Vardenafil improved erectile function in men with ED and improved the sexual quality of life of the couple.

Double-Blind Method↗
PubMed2005

Women's sexual function improves when partners are administered vardenafil for erectile dysfunction: a prospective, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: There are limited data concerning the sexual function of women whose male partners receive pharmacological treatment for erectile dysfunction (ED). AIM: One objective of this research was to prospectively compare the efficacy of vardenafil vs. placebo administered to men with ED in improving men's and women partners' sexual function and satisfaction. Another goal was to assess the relationship of erectile function changes in men with ED receiving treatment with sexual function changes in women partners not directly receiving treatment. METHODS: A randomized, double-blind, placebo-controlled, multi-institutional comparison of vardenafil vs. placebo was performed in 229 couples (treated man with ED>6 months and untreated woman partner). Co-primary outcomes for which this research was statistically powered were Sexual Encounter Profile (SEP3) (treated man with ED) and Sexual Life Quality Questionnaire (mSLQQ-QOL) (untreated woman partner). MAIN OUTCOME MEASURES: Erectile function changes in men with ED receiving vardenafil vs. placebo were compared at last observation carried forward (LOCF) in SEP3, International Index of Erectile Function (IIEF-EF) and Erection Quality Scale (EQS). Sexual function at LOCF in women partners was determined by mSLQQ-QOL and Female Sexual Function Index (FSFI). RESULTS: Compared with placebo at LOCF, vardenafil significantly increased least square (LS) mean scores in: (i) overall per-treated male SEP3 success rate, IIEF-EF, and EQS; and (ii) mSLQQ-QOL, total FSFI and sexual desire, subjective arousal, lubrication, orgasm and satisfaction FSFI domains in untreated women partners. Treatment-related improvement in erectile function as assessed by IIEF-EF and EQS was correlated reliably with improvement in women partners' FSFI total and individual domain scores. CONCLUSIONS: Vardenafil is an effective ED treatment in men that also significantly improves sexual function/satisfaction in untreated women partners. Women partners' sexual function improvements relate significantly and consistently to treatment-related improvements in men's erectile function. ED management should emphasize both members of the couple.

Adult↗
PubMed2005

Arteriogenic erectile dysfunction alters protein expression within the cavernosal tissue in an animal model.

INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent and often untreated condition. It may be a marker of underlying chronic illness and negatively impacts quality of life. Penile arterial insufficiency, frequently found in association with hypertension, dyslipidemia, diabetes mellitus, pelvic irradiation, trauma, and smoking, is the most common cause of ED. AIM: This study was designed to measure the effect of penile hypoperfusion-induced alteration and injury on erectile tissue at the cellular and protein level. METHODS: Eighteen 4-month-old male Sprague Dawley rats were placed into three groups (n = 6): sham surgery, unilateral internal iliac artery ligation (UIIAL), and bilateral internal iliac artery ligation (BIIAL). MAIN OUTCOME MEASURE: Erectile function was assessed 4 weeks following arterial ligation surgery as measured by a rise in intracavernosal pressure induced by cavernosal nerve stimulation. Penile tissue alterations were characterized by immunohistochemistry, protein content measured by western blot, and "global" protein expression profile carried out by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip technology. RESULTS: Significantly lower intracavernous pressures were demonstrated in animals subjected to UIIAL surgery, which correlated to the extent of artery ligation. The intensity and quantity of immunohistochemical staining for neuronal nitric oxide synthase, endothelial cell integrity, smooth muscle cell alpha-actin, and vascular endothelial growth factor (VEGF) receptor flk1 were decreased in the BIIAL group compared to sham controls. SELDI-TOF-MS analysis revealed changes in molecular expression of a approximately 6,560 Da protein relative to a 7,720 Da protein (peak ratio = 1.34 +/- 0.3, BIIAL; 0.36 +/- 0.1 controls, P < 0.05). CONCLUSIONS: In this report, an animal model of vascular penile insufficiency demonstrates altered protein expression associated with cavernosal tissue injury and reduced erectile function. Although the clinical significance of these observations is currently undefined, this model may allow greater insight into the complex biologic changes associated with arteriogenic ED in man.

Actins↗
PubMed2004

Erectile dysfunction: management update.

Dramatic advances in the management of erectile dysfunction have occurred over the past decade. Oral therapy with vasoactive agents has emerged as first-line treatment and has transformed both the manner in which the public views erectile dysfunction and the way health care providers deliver care. Whereas an extensive investigation was previously common in the management of erectile dysfunction, recent treatment guidelines promote a more minimalist, goal-oriented approach. In this article, we review the physiology of erection, and the pathophysiology, diagnosis and clinical management of erectile dysfunction. We also present the existing evidence for the efficacy of 3 phosphodiesterase inhibitors, the most widely used class of agents for erectile dysfunction.

Erectile Dysfunction↗
PubMed2004

Pharmacotherapy for erectile dysfunction.

INTRODUCTION: Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction. AIM: To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction. METHODS: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation. CONCLUSIONS: There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.

Apomorphine↗
PubMed2003

Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial.

OBJECTIVES: To perform a Canadian multicenter randomized placebo-controlled trial to evaluate the safety and efficacy of 6 weeks of levofloxacin therapy compared with placebo in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Uncontrolled studies have supported the use of antibiotics in CP/CPPS. METHODS: Men with a National Institutes of Health (NIH) diagnosis of CP/CPPS (specifically, no infection localized to the prostate) were randomized to levofloxacin (500 mg/day) or placebo for 6 weeks in 11 Canadian centers. Patients were assessed at baseline and at 3, 6, and 12 weeks with the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and global patient assessments (subjective global assessment and patient assessment questionnaire). RESULTS: Eighty men (average age 56.0 years, range 36 to 78; duration of symptoms 6.5 years, range 0.6 to 32) were randomized to receive levofloxacin (n = 45) or placebo (n = 35). All were evaluated in an intent-to-treat analysis. Both groups experienced progressive improvement in symptoms as measured by the NIH-CPSI. However, the difference in response was not statistically or clinically significant at end of treatment (6 weeks) or at the end of the follow-up visits (12 weeks). No patients withdrew because of adverse events. One patient withdrew before the 6-week assessment. Adverse events (all mild) were reported in 20% of the levofloxacin group and 17% of the placebo group. CONCLUSIONS: This pilot placebo-controlled study showed that 6 weeks of levofloxacin therapy in men diagnosed with CP/CPPS resulted in symptom improvement that was not significantly different from that with placebo at end of treatment or follow-up. The clinical ramifications of these findings need to be addressed.

Adult↗
PubMed2003

Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy.

PURPOSE: More than one-third of men may experience erectile dysfunction (ED) after nerve sparing radical retropubic prostatectomy. The efficacy and safety of vardenafil, a potent, selective, phosphodiesterase 5 inhibitor, was assessed for the treatment of ED after radical prostatectomy. MATERIALS AND METHODS: In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were randomized to take placebo, or 10 or 20 mg vardenafil. Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function, diary questions measuring vaginal penetration and intercourse success rates, and a global assessment question (GAQ) on erection. RESULTS: Of the intent to treat population 70% had severe ED (erectile function less than 11) at baseline. After 12 weeks both vardenafil doses were significantly superior to placebo (p <0.0001) for all efficacy variables. Improved erections (based on GAQ) were reported by 65.2% and 59.4% of patients on 20 and 10 mg vardenafil, respectively, and by only 12.5% of patients on placebo (p <0.0001). Among men with bilateral neurovascular bundle sparing, positive GAQ responses were reported by 71.1% and 59.7% of patients on 20 and 10 mg vardenafil, respectively, versus 11.5% of those on placebo (p <0.0001). The average intercourse success rate per patient receiving 20 mg vardenafil was 74% in men with mild to moderate ED and 28% in men with severe ED, compared to 49% and 4% for placebo, respectively. Few adverse events were observed. They were generally mild to moderate headache, flushing and rhinitis. CONCLUSIONS: In men with severe ED after nerve sparing radical retropubic prostatectomy, vardenafil significantly improved key indices of erectile function.

Double-Blind Method↗
PubMed2002

Selective phosphodiesterase type 5 inhibition using tadalafil for the treatment of erectile dysfunction.

Erectile dysfunction (ED) pharmacotherapy has undergone dramatic advances over the past decade, since the introduction of phosphodiesterase type 5 inhibitors (PDE5). The availability of an oral agent, sildenafil, able to restore erectile function in the majority of men with an organic basis to their dysfunction, transformed the management. The numbers of men seeking medical attention for ED, along with the increased comfort of physicians treating it, has resulted in enhanced management of this condition. In spite of these advances, there exist a significant number of men who remain unsuccessfully treated with sildenafil. Development of new PDE5 inhibitors, with the promise of enhanced selectivity, longer duration of action, increased potency and greater ease of use are currently in the final stages of regulatory review in many countries. Tadalafil is the first such agent to gain preliminary EU approval and is reviewed in detail in this report. Focusing on its phase II/III trial results, tadalafil appears to have an enhanced period of responsiveness extending out to 36 hours in 60% of men using the 20 mg dose. Efficacy across a large population of men with ED of various causes (n = 1112) is in accordance with the other PDE5 inhibitors at 81%. Side effects are generally mild-to-moderate with study drop-out rate at 1.7% in the active arm compared to 1.1% among those receiving placebo. In summary, this agent will likely play an important role in the management of ED across a broad spectrum of aetiologies, once past the ongoing regulatory review process.

3',5'-Cyclic-GMP Phosphodiesterases↗