Search PubMed⌕ Search

Biomedical subjects

Wayne J G Hellstrom

Publications and source records attributed to Wayne J G Hellstrom.

At least 19 recordsLinked to original sources
PubMed2005

The impact of vascular risk factors on erectile function.

The main cause of erectile dysfunction is organic in nature, with vascular etiologies being the most common risk factors. The incidence of erectile dysfunction increases with the number of vascular comorbidities such as hypertension, diabetes, hyperlipidemia, smoking and atherosclerosis. The earliest signal of endothelial damage in men with vascular risk factors is the manifestation of erectile dysfunction. The penis is a barometer of the body's endothelial function, so it is reasonable then to correlate vascular pathologies as direct causes of erectile dysfunction. Moreover, erectile dysfunction may be the first clinical presentation of any of these comorbidities, with the vascular endothelium playing a pivotal role in regulating vascular homeostasis of the corpora cavernosa. This article addresses the impact of vascular risk factors on erectile function based on current evidence.

Diabetes Mellitus↗
PubMed2005

The impact of vascular risk factors on erectile function.

The main cause of erectile dysfunction is organic in nature, with vascular etiologies being the most common risk factors. The incidence of erectile dysfunction increases with the number of vascular comorbidities such as hypertension, diabetes, hyperlipidemia, smoking and atherosclerosis. The earliest signal of endothelial damage in men with vascular risk factors is the manifestation of erectile dysfunction. The penis is a barometer of the body's endothelial function, so it is reasonable then to correlate vascular pathologies as direct causes of erectile dysfunction. Moreover, erectile dysfunction may be the first clinical presentation of any of these comorbidities, with the vascular endothelium playing a pivotal role in regulating vascular homeostasis of the corpora cavernosa. This article addresses the impact of vascular risk factors on erectile function based on current evidence.

Arteriosclerosis↗
PubMed2004

RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction.

Significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. RhoA/Rho-kinase may suppress endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that RhoA/Rho-kinase contributes to diabetes-related erectile dysfunction and down-regulation of eNOS in the streptozotocin (STZ)-diabetic rat penis. Colocalization of Rho-kinase and eNOS protein was present in the endothelium of the corpus cavernosum. RhoA/Rho-kinase protein abundance and MYPT-1 phosphorylation at Thr-696 were elevated in the STZ-diabetic rat penis. In addition, eNOS protein expression, cavernosal constitutive NOS activity, and cGMP levels were reduced in the STZ-diabetic penis. To assess the functional role of RhoA/Rho-kinase in the penis, we evaluated the effects of an adeno-associated virus encoding the dominant-negative RhoA mutant (AAVTCMV19NRhoA) on RhoA/Rho-kinase and eNOS and erectile function in vivo in the STZ-diabetic rat. STZ-diabetic rats transfected with AAVCMVT19NRhoA had a reduction in RhoA/Rho-kinase and MYPT-1 phosphorylation at a time when cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were restored to levels found in the control rats. There was a significant decrease in erectile response to cavernosal nerve stimulation in the STZ-diabetic rat. AAVT19NRhoA gene transfer improved erectile responses in the STZ-diabetic rat to values similar to control. These data demonstrate a previously undescribed mechanism for the down-regulation of penile eNOS in diabetes mediated by activation of the RhoA/Rho-kinase pathway. Importantly, these data imply that inhibition of RhoA/Rho-kinase improves eNOS protein content and activity thus restoring erectile function in diabetes.

Adenoviridae↗
PubMed2004

Vardenafil provides reliable efficacy over time in men with erectile dysfunction.

OBJECTIVES: To evaluate the reliability of vardenafil efficacy and tolerability within 12 weeks in a broad population of men with erectile dysfunction (ED). METHODS: In a retrospective analysis of two pivotal, Phase III, randomized, double-blind, placebo-controlled trials conducted in 107 centers, 1650 men aged 18 years or older with ED received vardenafil 5 mg, 10 mg, or 20 mg on demand for 12 to 26 weeks. Outcome measures included the first-time and subsequent overall success rate until week 12 for diary entries regarding vaginal penetration (Sexual Encounter Profile [SEP]-2), erection maintenance (SEP-3), satisfaction with erection hardness, and overall satisfaction with the sexual experience. Mean efficacy was calculated for each patient during 12 weeks and then averaged for all patients within each treatment group. RESULTS: At baseline, the intention-to-treat population had moderate ED (International Index of Erectile Function-Erectile Function domain score of 13). For SEP-2 (penetration), the first-attempt and subsequent success rate was 44% and 74% for placebo, 71% and 81% for vardenafil 5 mg, 76% and 86% for vardenafil 10 mg, and 76% and 91% for vardenafil 20 mg, respectively. For SEP-3 (maintenance), first-attempt and subsequent success rate was 25% and 56% for placebo, 51% and 76% for vardenafil 5 mg, 65% and 76% for vardenafil 10 mg, and 59% and 84% for vardenafil 20 mg, respectively. For overall satisfaction with the sexual experience, the first-attempt and subsequent success rate was 19% and 48% for placebo, 48% and 68% for vardenafil 5 mg, 57% and 72% for vardenafil 10 mg, and 56% and 79% for vardenafil 20 mg, respectively. The reliability of vardenafil was similar or slightly greater in sildenafil-naive subjects compared with prior sildenafil responders. The most common adverse events were mild-to-moderate headache, flushing, and rhinitis. CONCLUSIONS: Vardenafil provides reliable efficacy for key erectile function parameters important to patients when continuing oral treatment for ED.

Clinical Trials, Phase III as Topic↗
PubMed2004

Critical analysis of surgery for Peyronie's disease.

PURPOSE OF REVIEW: This review focuses on the surgical management of Peyronie's disease in the light of recent published reports from 2003 and 2004. RECENT FINDINGS: Although there have been a number of non-surgical innovations in this field, the surgical treatment of Peyronie's disease still remains the only alternative for patients not responding to other therapies. Various surgical modalities have recently been promulgated, however the ideal surgical procedure is still not perfected, particularly in cases of severe and complex penile curvature. The recent results of various surgical approaches have engendered concern about their long term benefits. SUMMARY: The initial management of the acute presentation of Peyronie's disease is conservative and non-surgical. Surgery for Peyronie's disease is contemplated only after stabilization of the fibrotic process, and is generally reserved for men with severe penile deformities that impede satisfactory sexual intercourse. If there is ample penile length and the deformity is mild to moderate in severity, a variety of plication techniques may be considered to provide a straight and functional penis. In patients with larger plaques, severe curvature, complete or hourglass deformities, then incision or excision of the plaque and the placement of a graft are recommended. Most authorities currently favor non-synthetic graft materials whose properties resemble the anatomy and functionality of the tunica albuginea. The implantation of a penile prosthesis, with or without excision/incision of the diseased tunica albuginea, is reserved for patients with erectile dysfunction who have not responded to medical therapies. Manual modeling of the deformed penis over a penile prosthesis may prevent some patients from needing more complex surgical grafting procedures.

Humans↗
PubMed2004

Relationship between the severity of penile curvature and the presence of comorbidities in men with Peyronie's disease.

PURPOSE: We investigated the relationship between penile curvature severity and co-morbidities in men with Peyronie's disease (PD) and assessed whether the severity of curvature had an impact on penile vascular status and/or erectile function. MATERIALS AND METHODS: Based on a 10-year period 469 patients with PD were retrospectively evaluated in regard to age at diagnosis, type and degree of penile curvature, erectile dysfunction (ED) and other comorbidities, such as diabetes mellitus, hypertension, serum lipid abnormalities, smoking and ischemic heart disease. To assess penile vascular status all men with PD underwent penile duplex Doppler ultrasound evaluation. The severity of penile curvature was classified using the Kelami system, that is grade 1--curvature 30 degrees or less, grade 2--30 to 60 degrees and grade 3--greater than 60 degrees. RESULTS: Mean patient age was 54.8 +/- 4.3 years (range 18 to 79) and the mean duration of symptoms was 24.8 +/- 13.7 months (range 3 to 120). The most common penile abnormality was dorsal curvature in 47.1% of patients. The most frequently documented co-morbid conditions in association with PD were hypertension in 27.2% of cases, smoking in 25.5%, hypercholesterolemia in 18.3%, diabetes mellitus in 17.2%, hyperlipidemia in 15.7% and a history of penile trauma in 13.2%. There was no relationship between the number or severity of each of these co-morbid conditions and the severity of the penile abnormality. In addition, there was no relationship between the severity of penile curvature and penile vascular status in patients with PD. Moreover, the prevalence of these comorbidities, except smoking and penile trauma history, was significantly higher in patients with PD and concurrent ED than in patients with PD only. CONCLUSIONS: While co-morbid conditions, such as hypertension, smoking, hypercholesterolemia, diabetes mellitus and hyperlipidemia, are commonly seen in patients with PD and may seem to be risk factors for PD, there was no statistical relationship between penile curvature severity and any of these comorbidities. Similarly there was no statistically significant relationship between the severity of curvature and penile vascular status or ED. The fact that the prevalence of associated comorbidities is higher in patients with PD and ED than in patients with PD only indicates that these comorbidities are more likely related to ED than to the pathogenesis of PD.

Adolescent↗
PubMed2004

Stratification of penile vascular pathologies in patients with Peyronie's disease and in men with erectile dysfunction according to age: a comparative study.

PURPOSE: Erectile dysfunction (ED) occurs in 20% to 54% of men with Peyronie's disease (PD). We investigated the role of vascular status in the pathophysiology of ED in patients with PD. MATERIALS AND METHODS: A total of 509 consecutive men with PD (group 1--impotent 259, 1a, and potent 250, 1b, mean age +/- SD 54.6 +/- 4.4 years) and 507 consecutive men with ED only (group 2--mean age 49.4 +/- 12.4 years) underwent penile duplex ultrasonography (PDU). Detailed sexual and medical history, and focused physical examination were performed in all patients. Patients in the 2, groups were stratified according to age (18 to 80 years) and classified according to PDU results (normal vascular status, arterial insufficiency, veno-occlusive dysfunction [VOD] and mixed vascular pathology). RESULTS: VOD was observed in 23.1% and 42.8% of patients in groups 1 and 2, respectively (p <0.05). Although VOD was significantly more common in group 2 (ED alone) than in group 1a (PD plus ED) in the third decade (p <0.05), overall PDU results showed no statistical difference for VOD between these 2 groups (p >0.05). Of note, mixed vascular pathologies were significantly higher in group 1a than in group 2 in the third through fifth decades (p <0.05), while arterial insufficiency was more common in the seventh decade (p <0.05). CONCLUSIONS: While many groups have investigated the vascular causes of ED, the exact etiology of ED in men with PD remains controversial. A possible relationship between ED and VOD in patients with PD has been previously reported. The current PDU study demonstrates that for all ages except 30 to 39 years the prevalence of VOD in patients with PD plus ED is similar to that of patients with ED alone.

Adolescent↗
PubMed2004

Intralesional interferon-alpha-2B injections for the treatment of Peyronie's disease.

BACKGROUND: Intralesional therapies provide an alternative to surgical treatment of Peyronie's disease (PD). This study examines the efficacy of intraplaque injections of interferon-alpha-2B (IFN-alpha-2B) in the treatment of PD. METHODS: Twenty-five patients were enrolled in the study with 21 completing the study. The average age of the study participants was 55.8 years, with 10 of the 21 having diabetes, hypertension, or both. Seven patients received placebo injections using 10 ml saline biweekly for 6 weeks before interferon therapy, and all 21 patients received biweekly injections of 2 x 10(6) U IFN-alpha-2B for 6 weeks before reevaluation. Patients were evaluated with duplex Doppler ultrasonography to assess penile curvature and blood flow. RESULTS: The International Index of Erectile Function questionnaire was completed by 14 of 21 men to assess severity of erectile dysfunction (ED) before and after treatment. Improvements of 20% or more in penile curvature occurred in 14 (67%) of 21 men. Penile pain decreased in eight (80%) of 10, and plaque size decreased subjectively in 15 (71%) of 21 participants. The International Index of Erectile Function questionnaire showed significant improvement of ED in five (71%) of seven men with baseline moderate to severe ED. Peak systolic blood flow improved in three (43%) of seven men with baseline hemodynamic impairment, and veno-occlusive disease resolved in three (18%) of 17 individuals. IFN-alpha-2B injections led to significant improvements in penile pain and curvature caused by PD. CONCLUSION: Results of intralesional IFN-alpha-2B injections in improving ED are encouraging. The study findings warrant further investigation of the effectiveness of IFN-alpha-2B injections for treatment of PD.

Adult↗
PubMed2004

The protective effect of aminoguanidine on erectile function in diabetic rats is not related to the timing of treatment.

OBJECTIVE: To assess the accumulation of advanced glycation end products (AGEs) in streptozotocin (STZ)-induced diabetic rat cavernosal tissue, and to determine whether the protective effect of aminoguanidine (AG) on erectile function is related to the timing of treatment, as the accumulation of AGEs in the penis may be important in the pathogenesis of diabetes mellitus-induced erectile dysfunction, and prolonged treatment with AG (a selective AGE inhibitor), prevents erectile dysfunction in this situation. MATERIALS AND METHODS: Harlan Sprague-Dawley rats were divided into groups 1-4, i.e. age-matched controls; STZ diabetic rats (60 mg/kg intraperitoneal) given free access to water; STZ diabetic rats treated with AG (1 g/L per day in the drinking water) immediately after inducing diabetes; and STZ-diabetic rats treated with AG 1 month after inducing diabetes, respectively. Two months after inducing diabetes the intracavernosal pressure was measured after cavernosal nerve stimulation, and cavernosal AGE (5-hydroxy methyl furfural, 5-HMF) levels assessed. RESULTS: Cavernosal tissue 5-HMF levels from groups 2 and 4 were significantly higher than in group 1 (control). The expression of 5-HMF in group 3 was similar to that in group 1. Diabetic rats had significantly lower erectile function than controls, while groups 3 and 4 (treated with AG) had normal erectile function, as measured by cavernosal nerve stimulation. CONCLUSIONS: The effect of AG on AGE levels seems to be time-dependent; that the 1-month treatment with AG improved erectile function with no change in AGEs suggests that AG has protective effects on the penile vasculature through alternative pathways.

Animals↗
PubMed2004

Gene therapy techniques for the delivery of endothelial nitric oxide synthase to the corpora cavernosa for erectile dysfunction.

Erectile dysfunction (ED) is defined as the consistent inability to obtain or maintain an erection for satisfactory sexual intercourse. In the last decade, significant advancements in the pathophysiology of male ED have occurred. Basic science research on erectile physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin. Nitric oxide (NO) is the principal mediator of penile erection. NO is synthesized by endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) in the penis. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the occurrence of ED. This chapter reviews the use of two gene transfer techniques: adenoviral gene transfer of eNOS and eNOS gene-modified rat marrow stromal cells (rMSCs) to the penis of aged rats for the potential application of gene therapy for the treatment of ED.

Adenoviridae↗
PubMed2004

Vardenafil: a novel type 5 phosphodiesterase inhibitor for the treatment of erectile dysfunction.

Orally administered phosphodiesterase type 5 (PDE5) inhibitors have become the first-line treatment option for erectile dysfunction (ED). Vardenafil is a potent and highly selective PDE5 inhibitor developed as an oral therapy for ED. Two pivotal, randomised, double-blind, multi-centre studies have evaluated the use of vardenafil in men with ED. Vardenafil improved the rate of achieving and maintaining an erection during sexual intercourse. Improvement was also noted in other aspects of sexual function, including confidence, orgasmic function and overall satisfaction. Vardenafil produces clinically and statistically significant improvements in erectile function regardless of age, baseline severity and aetiology and is efficacious for the treatment of ED in diabetic and postradical prostatectomy patients. Vardenafil has a rapid onset of action, in which erections sufficiently rigid for eventual intercourse completion can be achieved as early as 16 min after ingestion. Vardenafil 20 mg has sustained long-term efficacy by providing up to 92% of patients with improved erections during > 2 years of treatment. Vardenafil is well-tolerated, with an adverse event profile typical of this class of PDE5 inhibitors. The most common adverse events were headache, flushing, rhinitis and dyspepsia, which were mild-to-moderate in severity and they generally attenuated with continued use. Vardenafil may be associated with transient reductions in blood pressure and commensurate increases in heart rate, with the overall incidence of cardiovascular-related adverse events similar to that of placebo. Although claims can be made about potential features of benefit for each of the currently marketed PDE5 inhibitors, there are at present, no non-pharmaceutical company sponsored, peer-reviewed, head-to-head trials that have been published.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Current concepts in the management of erectile dysfunction in men with prostate cancer.

Development in the management of prostate cancer has placed increased attention on patient quality of life after treatment, particularly sexual function. The incidence of erectile dysfunction (ED) in men following radical prostatectomy has been estimated to range from 16% to 82%. Several factors determine the postoperative incidence of erectile difficulties; these include patient age, degree of cavernosal nerve sparing during surgery, cancer stage, and associated comorbidities. Early initiation of available treatments after radical prostatectomy, such as phosphodiesterase-5 (PDE-5) inhibitors and intracavernosal alprostadil, may improve the speed and degree of recovery of erectile function. Oral PDE-5 inhibitors are recognized as the first line of therapy for men with ED after radical prostatectomy, with reasonable success rates reported for all commercially available PDE-5 inhibitors. In recognition of the neurogenic basis for erectile dysfunction after radical prostatectomy, new strategies have been devised, such as cavernous nerve graft interposition procedures, perioperative neuroprotection measures, and postoperative neurotrophic treatments. Hopefully, these efforts will improve quality of life for patients with prostate cancer. The aim of this article is to review the current modalities of ED management for men with prostate cancer.

Adult↗
PubMed2004

Benign prostatic hyperplasia, sexual function, and overall evaluation of the male patient.

Erectile dysfunction (ED) and benign prostatic hyperplasia (BPH) are a significant problem for a large proportion of men in the United States. Lower urinary tract symptoms (LUTS), which are often caused by BPH, and ED are common in the aging male population. From numerous epidemiologic studies, it is well known that the prevalence of BPH and the loss of erectile function increase with advancing age. Men with LUTS have sexual dysfunction, including ejaculatory loss, painful ejaculation, and ED. Even though the pathogenic relationship between BPH and ED is not completely understood, a direct association between these two symptom complexes in aging men is now becoming evident. This presentation reviews the role of LUTS and ED in aging men and noninvasive and invasive treatment modalities for BPH.

Age Factors↗
PubMed2003

Vardenafil: a new approach to the treatment of erectile dysfunction.

Vardenafil is a phosphodiesterase type-5 (PDE-5) inhibitor developed as an oral therapy for erectile dysfunction (ED). Multiple phase 3 clinical trials have been completed and vardenafil is expected to launch worldwide in 2003. Two pivotal, randomized, double-blind, multicenter studies have evaluated the use of vardenafil in men with ED. Vardenafil improved the rate of achieving and maintaining an erection during sexual intercourse. Improvement also was noted in other aspects of sexual function, including confidence, orgasmic function, and overall satisfaction. Vardenafil produces clinically and statistically significant improvements in erectile function regardless of age, baseline severity, and etiology and is efficacious for the treatment of ED in diabetic and postprostatectomy patients. Vardenafil has a rapid onset of action and completion of successful sexual intercourse is possible for some patients 16 minutes after its administration. Twenty milligrams of vardenafil has sustained long-term efficacy by providing up to 92% of patients with improved erections during more than 2 years of treatment. Vardenafil is well tolerated, with an adverse event profile typical of the class of PDE-5 inhibitors. The most common adverse events were headache, flushing, rhinitis, and dyspepsia, which were mild or moderate and generally decreased with continued treatment. Vardenafil may be associated with transient reductions in blood pressure and commensurate increases in heart rate, with the overall incidence of cardiovascular-related adverse events similar to that of placebo.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial.

The durability of key efficacy response parameters and safety of vardenafil was evaluated in a pivotal trial conducted in a broad population of men with erectile dysfunction (ED) in North America. In this randomized, double-blind, placebo-controlled, multicenter, fixed-dose, parallel-group, 6-month comparison study, men >18 years of age with ED for >6 months received 5-mg, 10-mg, and 20-mg doses of vardenafil as needed for up to 26 weeks. The primary efficacy variables were the International Index of Erectile Function (IIEF)-Erectile Function (EF) domain scores, and the Sexual Encounter Profile (SEP) mean per-patient success rates for penetration (SEP question 2) and maintenance of erections (SEP question 3). Safety data were also collected over time. Improvement in all primary efficacy variables was observed in all vardenafil groups versus placebo. These improvements occurred early and were either sustained or increased through week 26. Vardenafil in 10-mg and 20-mg doses was significantly superior to placebo at all time points for all efficacy variables (P <0.01), and all doses were superior to placebo at endpoint (P <0.001). Most treatment-emergent adverse events (headache, flushing, dyspepsia, and rhinitis) were mild or moderate in intensity, and incidence generally decreased over time. All 3 doses of vardenafil were superior to placebo across all primary efficacy variables and all study time points in a broad range of patients with ED, regardless of etiology or severity. Vardenafil was well tolerated. These results demonstrate that vardenafil provides sustained efficacy with reduced incidence of nuisance side effects over time. High resolution video, medium resolution video, low resolution video.

Aged↗