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Biomedical subjects

Ajay Nehra

Publications and source records attributed to Ajay Nehra.

At least 19 recordsLinked to original sources
PubMed2006

DHEA in elderly women and DHEA or testosterone in elderly men.

BACKGROUND: Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown. METHODS: We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life. RESULTS: As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects. CONCLUSIONS: Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].).

Adult↗
PubMed2006

Application of vacuum-assisted closure dressing in penile skin graft reconstruction.

INTRODUCTION: Skin grafting of penile defects is difficult because of the flexibility of the underlying recipient bed. This leads to disruption of the vascular ingrowth into the skin graft and compromises the results of the reconstruction. TECHNICAL CONSIDERATIONS: We successfully used a vacuum-assisted closure dressing with an incorporated wooden framework to secure penile skin grafts in place during the early postoperative period. CONCLUSIONS: A vacuum-assisted closure dressing can be used successfully to secure large and circumferential skin grafts, as well as skin grafts on concealed penises.

Adult↗
PubMed2006

Single-blind, multicenter, placebo controlled, parallel study to assess the safety and efficacy of intralesional interferon alpha-2B for minimally invasive treatment for Peyronie's disease.

PURPOSE: We investigated the efficacy and safety of intralesional interferon alpha-2b for the treatment of Peyronie's disease. MATERIALS AND METHODS: A total of 117 consecutive patients with a mean age of 55.1 years who had Peyronie's disease were enrolled in a single-blind, multicenter, placebo controlled, parallel study to determine the efficacy and safety of intralesional interferon alpha-2b therapy (Schering, Kenilworth, New Jersey), including 62 who received placebo and 55 who received interferon alpha-2b. Saline (10 ml) in controls and interferon alpha-2b (5 x 10(6) U) were administered biweekly for 12 weeks. Each patient was evaluated for penile curvature, plaque size and density, penile pain, erectile function and penile hemodynamics before and after study completion. Improvement in these parameters was statistically compared between the groups. RESULTS: A total of 53 patients in the control arm and 50 in the interferon alpha-2b arm completed the study. Improvement in penile curvature, plaque size and density, and pain resolution was significantly greater in patients treated with interferon alpha-2b vs placebo. The increase in mean International Index of Erectile Function scores was not significantly different between the groups. Penile blood flow improvement was observed in interferon alpha-2b treated patients but not in those who received placebo. The decrease in the number of penile vascular pathologies was significantly higher in interferon alpha-2b cases. Side effects, mostly flu-like symptoms, which were frequently noted in patients on interferon alpha-2b, were mild to moderate in degree and of short duration. CONCLUSIONS: This single-blind, multicenter, placebo controlled, parallel study demonstrates that intralesional interferon alpha-2b at a dose of 5 x 10(6) units biweekly for 12 weeks is effective and safe as minimally invasive therapy for Peyronie's disease.

Adult↗
PubMed2005

Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference).

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Cardiovascular Diseases↗
PubMed2005

Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference).

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Age Distribution↗
PubMed2005

Association between smoking and erectile dysfunction: a population-based study.

The association between smoking and erectile dysfunction was evaluated in a cohort of 2,115 Caucasian men, aged 40-79 years, randomly selected from Olmsted County, Minnesota. Smoking status was assessed by questionnaire; during the fourth biennial examination, erectile dysfunction was assessed with the Brief Male Sexual Function Inventory. Of the 1,329 men with a regular sexual partner, 173 were current smokers, 836 had previously smoked, and 203 reported erectile dysfunction. Compared with former and never smokers, current smokers in their forties had the greatest relative odds of erectile dysfunction, 2.74 (95% confidence interval (CI): 0.44, 16.89), compared with 1.38 (95% CI: 0.51, 3.74), 1.70 (95% CI: 0.82, 3.51), and 0.77 (95% CI: 0.27, 2.21) for men in their fifties, sixties, and seventies, respectively. Compared with men who never smoked, men who smoked at some time had a greater likelihood of erectile dysfunction (age-adjusted odds ratio = 1.42, 95% CI: 1.00, 2.02), and there was a dose response. Although the causal pathway underlying this association is not clear, this study contributes to the growing literature describing an association between smoking and erectile dysfunction.

Adult↗
PubMed2005

Clinical evaluation of erectile dysfunction in the era of PDE-5 inhibitors.

Erectile dysfunction (ED) is a common disorder that has gained attention since the introduction of relatively safe treatment with phosphodiesterase-5 inhibitors. ED is a multi-factorial disorder and a common presentation for several systemic illnesses,particularly vascular occlusive diseases. The clinical evaluation of ED should be thorough and systematic, with attention to the appropriate use of sexual symptom questionnaires and symptom scales, detailed medical and sexual history, physical examination,and basic screening laboratory tests. Patients should be referred for specialized evaluations when appropriate. The clinician must be familiar with the pathophysiologic mechanisms of ED, its associations with other systemic diseases, the indications for specialist referrals, and the role of specialized testing to diagnose and treat this disorder effectively.

3',5'-Cyclic-GMP Phosphodiesterases↗
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

Selecting therapy for maintaining sexual function in patients with benign prostatic hyperplasia.

In the first of these mini-reviews the selection of therapy for the maintenance of sexual function in patients with BPH is outlined, along with an explanation of how altered regulation of neurotransmitters, especially noradrenaline, may underlie the syndrome of LUTS and sexual dysfunction. Other mini-reviews outline the current status of robotic surgery to treat renal and adrenal disorders, and its future applications, and the potential use of the nitric oxide/cGMP pathway as a potential target to treat BOO associated with benign prostatic enlargement. Finally, the capacity to be creative in academic departments is extolled as a core property of academicians, and its surfacing described as having the potential to revitalize individuals and departments.

5-alpha Reductase Inhibitors↗
PubMed2004

Prognostic value of p53 and MIB-1 in transitional cell carcinoma of the urinary bladder with regional lymph node involvement.

BACKGROUND: The effect of p53 protein expression and MIB-1 proliferative activity on survival and chemotherapeutic response in patients with lymph node (LN)-positive transitional cell carcinoma (TCC) of the urinary bladder remains unclear. The objective of this study was to assess the ability of these markers to predict disease-associated outcomes and response to chemotherapy in a cohort of patients with LN-positive TCC. METHODS: The authors examined the expression of p53 and MIB-1 in the LN metastases from 139 patients who underwent cystectomy for TCC at their institution. P53 and MIB-1 nuclear staining were quantified using an image-analysis system. Cox proportional hazards regression models were used to test associations of these markers with death from TCC, distant metastases, and local recurrence for all patients and in the subset of patients who were treated with adjuvant chemotherapy. RESULTS: The median p53 and MIB-1 indices were 45.2% and 30.3%, respectively. The median follow-up was 4.5 years (range, 0.1-10 years). There were no statistically significant associations noted between the p53 and MIB-1 indices and the outcomes studied. When the analysis was limited to patients who were treated with adjuvant chemotherapy (n = 37 patients), the p53 index was found to have no prognostic value; however, there was a significant association between MIB-1 and distant metastases (P = 0.049). When disease-specific survival rates were stratified according to p53 index and chemotherapy, patients exhibited a response to chemotherapy regardless of p53 index. CONCLUSIONS: p53 and MIB-1 were not found to be associated significantly with disease-related outcomes in patients with LN-positive TCC. Adjuvant chemotherapy appeared to be effective regardless of p53 status. MIB-1 may prove useful in predicting response to chemotherapy.

Biomarkers, Tumor↗
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↗
PubMed2004

Lower urinary tract symptoms and sexual dysfunction in community-dwelling men.

OBJECTIVES: To evaluate the cross-sectional association between lower urinary tract symptoms (LUTS) severity and sexual function in a population-based sample of men and the extent to which this association might be explained by age. SUBJECTS AND METHODS: Subjects in The Olmsted County Study of Urinary Symptoms and Health Status Among Men (55% participation rate) included 2115 white men aged 40 to 79 years; subjects were recruited on January 1, 1990, from a random sample identified through the Rochester Epidemiology Project. At baseline in 1990 and biennially thereafter, these men completed a self-administered questionnaire that assessed LUTS severity with questions similar to those of the American Urological Association Symptom Index. At the 6-year follow-up, 11 previously validated questions about male sexual function from the Brief Sexual Function Inventory were added. RESULTS: Overall, each of the sexual function domains (sexual drive, erectile function, ejaculatory function, problem assessment, and overall sexual satisfaction) was inversely associated with the severity of LUTS, with Spearman correlation coefficients ranging from -0.21 to -0.31 (all P<.001). In age-adjusted analyses, the ejaculatory function and problem assessment domains were most strongly associated with overall LUTS severity, whereas the association with sexual drive was substantially diminished. Little difference was noted in the magnitude of association between sexual function and either obstructive or irritative symptoms. CONCLUSIONS: The cross-sectional data suggest that sexual function is inversely associated with LUTS severity and that this association is only partially attributable to the confounding effects of age.

Adult↗
PubMed2004

Erectile dysfunction and cardiovascular disease.

Cardiovascular disease and erectile dysfunction (ED) are closely interrelated disease processes. Erectile dysfunction reportedly affects 10 million to 20 million men in the United States and more than 100 million men worldwide. Each year, about 500,000 persons in the United States survive a myocardial infarction, and an estimated 11 million have existing cardiovascular disease, making the issue of sexual function and cardiac disease relevant to many patients. We explore the relationship between ED and the presence of cardiovascular disease in the general population. We also review the prevalence and pathophysiological associations of ED and cardiovascular disease. The risks of sexual activity for patients with cardiovascular disease are discussed, as are prevention and treatment strategies for ED in this patient population.

Cardiovascular Diseases↗
PubMed2003

Transitional cell carcinoma of the urinary bladder with regional lymph node involvement treated by cystectomy: clinicopathologic features associated with outcome.

BACKGROUND: Patients with transitional cell carcinoma (TCC) of the urinary bladder metastatic to regional lymph nodes (LN) typically have a poor prognosis. However, some patients are cured by radical cystectomy alone. The goal of this study was to identify predictors of survival in this cohort. METHODS: The authors identified 154 patients with TCC metastatic to regional LNs treated by cystectomy between 1970 and 1998. Clinical characteristics collected included age, gender, and preoperative computed tomographic or magnetic resonance image scan findings, as well as neoadjuvant and adjuvant therapy. Pathologic features evaluated included multifocality, size, pathologic stage, grade, and margin status of the primary tumor, as well as the number, location, and bilaterality of the positive LNs. Capsular penetration, greatest linear extent, and surface area of the largest metastatic LN deposit were also recorded. The Kaplan-Meier method was used to evaluate survival rates. Cox proportional hazards models were used to identify predictors of outcome. RESULTS: The mean follow-up was 4.5 years (range, 0.1-13.9 years). In a multivariate setting, only adjuvant chemotherapy and the number of positive LNs were associated significantly with death from TCC. Patients treated adjuvantly with chemotherapy were 2.1 times less likely to die of their disease (P = 0.005). Each increase in one positive LN increased the risk of death from TCC by 20% (P < 0.001). Recursive partitioning indicated that the optimal cutoff point to predict death from TCC was five or more positive LNs. CONCLUSIONS: Adjuvant chemotherapy and the number of positive LNs were associated significantly with death from TCC.

Adult↗
PubMed2003

The physiology of erectile dysfunction.

Male erectile dysfunction is a common urologic disorder which can have a profound detrimental impact on a patient's quality of life. Normal erectile function represents a complex physiologic process requiring integrated synchronized function of vascular, neurologic, and musculoskeletal body systems, with significant psychologic factors playing a role as well. A breakdown in any one of these body systems can contribute to the development of erectile dysfunction. As men age, many of the same risk factors for the development of cardiovascular disease also can have a detrimental effect on the organ systems needed for good erectile function. A solid grasp of the anatomy and physiology involved in normal erectile function is important in understanding the interactions between cardiovascular disease and erectile dysfunction, and in developing new ways to effectively treat and prevent both disease processes in the future.

Cardiovascular Diseases↗