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Biomedical subjects

Ajay Nehra

Publications and source records attributed to Ajay Nehra.

29 records · Page 2Linked to original sources
PubMed2003

Sleep apnea and cardiovascular disease. Implications for understanding erectile dysfunction.

BACKGROUND AND PURPOSE: There is increasing recognition of the high and rising prevalence of obstructive sleep apnea (OSA). It has been suggested that OSA may contribute to erectile dysfunction. This review will examine the evidence and potential mechanisms, including abnormalities of neural, endothelial and hormonal function, linking OSA to erectile dysfunction. CONCLUSION: Available data suggest, but do not prove, a higher prevalence of erectile dysfunction in OSA. Certainly, the pathologic processes activated by OSA are also those that may predispose to impaired erectile function. Further well-designed and controlled studies are needed to show conclusively that any increased prevalence of erectile dysfunction in OSA is secondary to the OSA per se and not a consequence of the frequently associated comorbidities, such as obesity and vascular disease, that characterize this patient population.

Cardiovascular Diseases↗
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

Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease: a randomized crossover trial.

CONTEXT: The relationship between sildenafil citrate use and reported adverse cardiovascular events in men with coronary artery disease (CAD) is unclear. OBJECTIVE: To evaluate the cardiovascular effects of sildenafil during exercise in men with CAD. DESIGN, SETTING, AND SUBJECTS: Randomized, double-blind, placebo-controlled crossover trial conducted March to October 2000 at a US ambulatory-care referral center among 105 men with a mean (SD) age of 66 (9) years who had erectile dysfunction and known or highly suspected CAD. INTERVENTIONS: All patients underwent 2 symptom-limited supine bicycle echocardiograms separated by an interval of 1 to 3 days after receiving a single dose of sildenafil (50 or 100 mg) or placebo 1 hour before each exercise test. MAIN OUTCOME MEASURES: Hemodynamic effects of sildenafil during exercise (onset, extent, and severity of ischemia) assessed by exercise echocardiography. RESULTS: Mean (SD) resting ejection fraction was 56% (7%) (range, 39%-68%). After sildenafil use, resting systolic blood pressure was reduced from 135 (19) mm Hg to 128 (17) mm Hg, for a mean change of -7 mm Hg (95% confidence interval [CI], -9 to -4 mm Hg; P<.001). After placebo use, the mean (SD) change was from 135 (20) mm Hg to 133 (19) mm Hg, a difference of -2 mm Hg (95% CI, -6 to 0.3 mm Hg; P =.08). The difference between mean change after sildenafil and placebo use was 4.3 (95% CI, 0.9-7.7; P =.01). Resting heart rate, diastolic blood pressure, and wall motion score index (a measure of the extent and severity of wall motion abnormalities) did not change significantly in either group. Exercise capacity was similar with sildenafil use (mean [SD], 4.5 [1.0] metabolic equivalents) and placebo use (mean [SD], 4.6 [1.0] metabolic equivalents; mean difference, 0.07; 95% CI, -.06 to 0.19; P =.29). Exercise blood pressure and heart rate increments were similar. Dyspnea or angina developed in 69 patients who took sildenafil and 70 patients who took placebo (P =.89); exercise electrocardiography was positive in 12 patients (11%) who took sildenafil and 17 patients (16%) who took placebo (P =.09). Exercise-induced wall motion abnormalities developed in similar numbers of patients after sildenafil and placebo use (84 and 86 patients, respectively; P =.53). Wall motion score index at peak exercise was similar after sildenafil and placebo use (mean [SD], 1.4 [0.4] vs 1.4 [0.4]; mean difference, 0.01; 95% CI, -0.01 to 0.03; P =.40). CONCLUSION: In men with stable CAD, sildenafil had no effect on symptoms, exercise duration, or presence or extent of exercise-induced ischemia, as assessed by exercise echocardiography.

Adult↗
PubMed2002

Combination therapy for erectile dysfunction: where we are and what's in the future.

Penile erection occurs in response to visual, olfactory, imaginative, and tactile stimuli initiated within the brain and/or on the periphery. Responses to these stimuli are mediated by efferent autonomic outflow originating in the sacral spinal cord and transmitted by the cavernosal and penile nerves. A number of neurotransmitters can play an integral role in corpus cavernosum smooth muscle relaxation, in part regulating penile erection through increased smooth muscle synthesis of the secondary messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). In addition to direct-acting agents, there are indirect-acting smooth muscle-relaxing agents. Phosphodiesterase (PDE) inhibitors such as sildenafil act indirectly and require sexual stimulation and endogenous nitric oxide production to activate the cGMP pathway effectively. In contrast, agents such as prostaglandin E(1) (PGE(1)) act directly on the trabecular smooth muscle, binding to specific e-prostanoid receptors and increasing cAMP synthesis. For this reason the direct-acting agents do not require sexual stimulation for efficacy. Combination pharmacotherapy has been used experimentally to treat erectile dysfunction for 25 years, using combinations of cAMP synthesis augmentors, smooth muscle relaxants and PDE inhibitors, and alpha-blockers administered via intracavernosal injection. The present era of oral pharmacotherapy treatment has resulted in significant awareness in the field of sexual dysfunction; however, a single agent may not be ideal to sustain penile rigidity, especially if comorbidities and severity of erectile dysfunction are accounted for. The rationale for and recent reports on combination therapy are presented in this review.

Alprostadil↗
PubMed2002

The efficacy of sildenafil citrate (Viagra) in clinical populations: an update.

Although certain risk factors are known to be associated with erectile dysfunction (ED), the demographic and ED characteristics of the population of men with ED are quite diverse. We examined results from randomized trials of sildenafil citrate (Viagra) to ascertain if efficacy differed across various subgroups of men with ED. In addition, we reviewed findings from long-term extension studies and published accounts of sildenafil use in clinical practice to determine if effectiveness is maintained with long-term sildenafil treatment and to determine if effectiveness in the clinic practice setting is consistent with that reported in clinical trials. Data were pooled from 11 double-blind, placebo-controlled, flexible-dose (taken as needed) studies to assess efficacy (N = 2667) of sildenafil in men (aged 23 to 89 years) with ED of broad-spectrum etiology who were not receiving concomitant nitrate therapy. Efficacy evaluations included the International Index of Erectile Function, a global efficacy question ("Did treatment improve your erections?"), and a patient-recorded event log of sexual activity. Significantly improved erectile function was demonstrated for sildenafil compared with placebo for all efficacy parameters analyzed (P <0.02 to 0.0001), regardless of patient age, race, body mass index, ED etiology, ED severity, ED duration, or the presence of various comorbidities. Long-term effectiveness was assessed in 3 open-label extension studies. Of those who continued long-term therapy (1 to 3 years) with sildenafil, >95% of patients reported that they were satisfied with the effect of treatment on their erections, and that treatment had improved their ability to engage in sexual activity. Findings from published accounts of sildenafil use in the clinical practice setting further demonstrated that sildenafil is an effective treatment for a wide range of patients with ED.

Adult↗
PubMed2002

Global perspectives and controversies in the epidemiology of male erectile dysfunction.

PURPOSE OF REVIEW: Erectile dysfunction is a neurovascular phenomenon that requires an intact psychological, neural, and vascular component. The advent of Food and Drug Administration approval of sildenafil citrate (Viagra) in 1998 has resulted in increased awareness and a large population of patients seeking treatment. Unfortunately, the estimated number of patients seeking medical therapy still persists at approximately 10%. The predominant reasons suggested here are the complexity of sexuality, taboos, cultural restrictions, lack of satisfactory treatment, and acceptance of the situation as a normal sequence of aging. This perspective discusses the global prevalence and the differences in prevalence on a worldwide basis. RECENT FINDINGS: Recent epidemiologic studies from Spain and Germany have suggested lower rates of erectile dysfunction. This, however, may actually reflect population or cultural differences in the perceptions and attitudes towards the condition. Aging, diabetes, coronary artery disease, and cigarette smoking as epidemiologic factors are reviewed extensively, including some of the controversies with the prevalence rates on a global scale. Chronic renal failure, pelvic surgery, and lifestyle determinants similarly suggest there may be subtle differences, requiring further education from the medical care provider in order to have patient acceptance on a relatively earlier scale. SUMMARY: Erectile dysfunction is a worldwide health issue that affects nearly half the men over the age of 40. As the world population ages, the number of patients affected by this disorder will certainly be increased. With the identification of risk factors, it may be possible to identify patients at risk of erectile dysfunction.

Adult↗
PubMedDate not supplied

The Kv2.2 alpha subunit contributes to delayed rectifier K(+) currents in myocytes from rabbit corpus cavernosum.

K(+) currents are known to regulate the excitability of corpus cavernosum myocytes and therefore to play a role in the control of penile erection and detumescence. We used electrophysiology and molecular cloning techniques to identify ion channel proteins that contribute to K(+) currents in rabbit cavernosal myocytes. Currents were recorded from freshly isolated myocytes using whole-cell patch clamp techniques. Cavernosal myocytes expressed a delayed rectifier voltage-gated K(+) current that appeared to contribute to the resting membrane potential. This voltage-gated K(+) (K(v)) current was inhibited by the nonselective compounds 4-aminopyridine (1-10 mM), (+)-fenfluramine (10 micro M-1 mM), and Grammostola spatulata venom (1:100) in a dose-dependent and reversible fashion. Hanatoxin-1 (1 micro M), a selective Kv2 channel inhibitor, partially inhibited the current, but alpha-dendrotoxin (200 nM), a Kv1 channel blocker, had no effect. The nucleotide sequence of K(+) channel subunits was determined by polymerase chain reaction-based cloning techniques using RNA derived from cavernosal muscle strips and single identified myocytes. Molecular cloning techniques identified the full-length sequence of the rabbit ortholog of the Kv2.2 alpha subunit. This sequence contains 911 amino acid residues and is 92% identical to the recently revised human Kv2.2 sequence. Identified cavernosal myocytes of the type used in physiological recordings expressed Kv2.2 messenger RNA. We conclude that Kv2.2 alpha subunits contribute to whole-cell currents in rabbit canvernosal myocytes. Further, K(v) currents play a role in regulating membrane potential and hence excitability in rabbit cavernosal myocytes.

Amino Acid Sequence↗