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201
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"Burnett, Arthur"
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Neuroprotective and Nerve Regenerative Approaches for Treatment of Erectile Dysfunction after Cavernous Nerve Injury
Erectile dysfunction (ED) is a significant cause of reduced quality of life in men and their partners. Cavernous nerve injury (CNI) during pelvic surgery results in ED in greater than 50% of patients, regardless of additional patient factors. ED related to CNI is difficult to treat and typically poorly responsive to first- and second-line therapeutic options. Recently, a significant amount of research has been devoted to exploring neuroprotective and neuroregenerative approaches to salvage erectile function in patients with CNI. In addition, therapeutic options such as neuregulins, immunophilin ligands, gene therapy, stem cell therapy and novel surgical strategies, have shown benefit in pre-clinical, and limited clinical studies. In the era of personalized medicine, these new therapeutic technologies will be the future of ED treatment and are described in this review.
Journal Article
Mirabegron improves erectile function in men with overactive bladder and erectile dysfunction: a 12-week pilot study
Phosphodiesterase type 5 inhibitors (PDE5i) is the only approved oral treatment for erectile dysfunction (ED) in the US, and alternative management remains necessary when this treatment fails or is contraindicated. Targeting other pathways than the NO-cGMP pathway and/or combining this approach with PDE5i may introduce new treatments for men who are unresponsive to PDE5i. This study aims to evaluate whether Mirabegron improves erectile function in men with concurrent overactive bladder and mild to moderate ED. Twenty subjects, 40–70 years old, registering International Index of Erectile Function (IIEF) score 11–25 and International Prostate Symptom Score 8–20, were treated with Mirabegron therapy for 12 weeks. Study participants were re-administered IIEF and OAB-q questionnaires on weeks 2, 4, 8, and 12 and assessed for adverse events. The primary and secondary endpoints were an increase in the IIEF-5 score of 4 units and a decrease in the Overactive Bladder questionnaire (OAB-q) symptom severity score of 10 units between study time points. Thirteen men completed the 12-week study. Mirabegron treatment improved the IIEF-5 scores in five patients (38.4%) by 4 points or more, whereas IIEF-5 scores were not affected by Mirabegron treatment in eight patients (61.5%). There were no clinically relevant decreases in the IIEF-5 score. Significant improvements were observed in intercourse satisfaction at week eight compared to baseline (p = 0.01). Orgasmic function and sexual desire were not affected by Mirabegron treatment. As expected, Mirabegron treatment reduced OAB symptoms based on OAB-q short form (p = 0.006) and OAB-q total health-related quality of life (HRQL) scores compared to baseline (p = 0.03). Residual bladder volumes were not affected by treatment. No serious side effects were reported during the study period. This study suggests that Mirabegron may improve both EF and OAB-related symptoms in some individuals without causing serious adverse events.
Journal Article
Penile preserving and reconstructive surgery in the management of penile cancer
A major paradigm shift has occurred in the clinical management of penile cancer: the adoption of alternative, less-invasive surgical strategies to address the primary tumour. Such penile-preserving approaches aim to retain aspects of penile function and improve quality of life outcomes by reducing penile alterations and sexual dysfunction incurred by historical surgical approaches without compromising oncological control. Novel options include wide local excision, glansectomy, and glans resurfacing, and these strategies are now included in the spectrum of interventions available to treat penile cancer. Surgical reconstructive techniques have also advanced to include primary closure, closure using skin flaps and grafts, penile lengthening and/or enhancement, and neophalloplasty. All of these options can be readily applied in the risk-informed patient after establishing disease-risk variables and instituting protocols for close surveillance and prompt action for possible disease recurrence.
Journal Article
External validation of the priapism impact profile in a Jamaican cohort of patients with sickle cell disease
Priapism impairs quality of life and has a predilection for males with sickle cell disease (SCD). The Priapism Impact Profile (PIP) is a novel 12-item instrument designed to measure general health-related impact of priapism. The aim of the study was to evaluate the validity and reliability of the PIP in a Jamaican cohort of SCD patients experiencing priapism.
One hundred SCD patients with a history of priapism were recruited from a sickle cell clinic in Kingston, Jamaica and administered the PIP questionnaire. Patients rated each item of the PIP for clarity and importance. Statistical testing was employed to evaluate the psychometric performance of the PIP. Content validation was assessed based on patient descriptive rating of the items based on clarity, and importance and criterion-oriented validity were assessed by evaluating the PIP's ability to distinguish between patient subgroups. Test-retest repeatability was assessed in 20 of the 100 patients.
Patients were stratified into active (54) and remission (46) priapism groups based on their experience of priapism within the past year. Patients in the active priapism group were younger (p = 0.011), had a shorter duration of disease (p = 0.023), and had more frequent priapism episodes (p = 0.036) than the remission group. PIP questionnaire scores differed significantly with respect to priapism activity (p < 0.001) and prevalence of erectile dysfunction (p < 0.05) but not by priapism severity (p = 0.62). The PIP questionnaire had good content validity, with questions rated as having medium or high clarity and importance by an average of 82.8% and 69.2% of patients, respectively.
The PIP questionnaire was successfully validated in a Jamaican cohort of SCD patients and adequately discriminated patients with active priapism from those in remission. The instrument may be utilized in routine clinical management of patients with SCD-associated priapism. Further clinical investigations are warranted in other populations.
Journal Article
Modified malleable prosthesis with a fixed mesh: case series for the Ghattas technique
Penile prosthetic implantation represents a cornerstone for patients with organic erectile dysfunction (ED) that is refractory, unsatisfactory, or contra-indicated for other approved medical or mechanical options. In this study, we introduce the \"Ghattas technique,\" wherein we constructed a polypropylene mesh sheath that surrounds and is fixed to a 13-mm malleable prosthesis cylinder, which can increase the cylinder diameter for cases that need a larger prosthesis. All patients underwent preoperative evaluation and completed the five-item International Index of Erectile Function questionnaire (IIEF-5). Postoperative outcomes were evaluated by IIEF-5 and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaires at final follow-up. The mean age of the 23 included patients was 57.9 (standard deviation [s.d.]: 11.4) years and the mean duration of ED was 8.5 (s.d.: 7.9) years. Erection improvement was determined by comparing mean preoperative and postoperative IIEF-5 scores (8.3 [s.d.: 3.9] vs 24.6 [s.d.: 0.6], P < 0.001). High treatment satisfaction was determined according to a mean EDITS score of 94.9 (s.d.: 9.9). The proposed Ghattas technique was safe and effective in our patients, and provides opportunity for cases that need a diameter larger than 13 mm. Further studies are needed to confirm these results.
Journal Article
Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse
Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis.
This study aimed to evaluate the effects of hybrid compound RVT-FxMe, derived from resveratrol bearing a NO-donor subunit, on two murine model that display priapism phenotype, SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice.
Wild-type, SCD, and eNOS-/- mice were treated with RVT-FxMe (25 mg/kg/d, 2 weeks).
Hematological parameters, concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as to electrical field stimulation (EFS), were obtained in mice corpus cavernosum strips.
Corpus cavernosum relaxations to SNP and EFS were increased in eNOS-/- group, which were normalized by RVT-FxMe treatment. SCD mice exhibited an excessive CC relaxant response induced by ACh, EFS and SNP RVT-FxMe treatment did not change the increased relaxant responses to ACh, EFS and SNP in corpus cavernosum from SCD group.
Excess of plasma hemoglobin in SCD may interfere in pharmacological activity of NO donors compounds.
While mechanistic data with promising potential is showed, the current study is not without limitations. RVT-FxMe effects in the mid- and long-term warrant complementary studies.
Treatment with RVT-FxMe reversed the enhanced NO-cGMP-mediated CC relaxations in eNOS-/- mice, but not in SCD mice; it is likely that excess of plasma hemoglobin in SCD mice act to inactivate NO before it reaches soluble guanylyl cyclase, avoiding restoration of NO bioavailability in penis.
Journal Article
The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease
Abstract The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.
Journal Article
Postphalloplasty urinary function test: an observational study of novel outcome instrument to capture urinary dysfunction and quality of life after phalloplasty
Due to growing social acceptance, there has been an increasing number of gender-affirmation surgeries performed in North America. Most research in this patient population focuses on surgical outcomes and advancing techniques. However, little work has been done to study functional outcomes. To better evaluate urinary dysfunction in the postphalloplasty trans men patient population, our group developed a novel patient-reported outcome instrument - the postphalloplasty urinary function test (PP UFT) and protocol to measure postvoid urethral volume (PVUR), and we present our preliminary results. We conducted a cross-sectional pilot study in a cohort of 15 adult trans men who had undergone phalloplasty with urethral lengthening surgery between 2018 and 2021. Patients had stable urinary function via the neophallus at the time of survey. Patients filled out the PP UFT and were asked to record their PVUR as per our protocol. The average PP UFT score was 8.9 out of 40 and the average quality-of-life (QOL) score was 2.6. Postvoid dribbling constituted the major complaint and on average comprised 63.2% of the reported PP UFT score. The average PVUR was 2.2 ml (range: 0.5-5.6 ml). There was a positive correlation between higher PP UFT and worse-reported quality of life (P < 0.01; R2 = 0.4). Current questionnaires accepted in cis-male urology have limitations for accurately capturing urinary dysfunction in this specific patient group. The combination of PP UFT and PVUR measurement offers potential for quantifying urinary function and quality of life in patients who undergo phalloplasty. Future studies will validate these instruments.
Journal Article
Proximal corporal reconstruction: adjunct of penile prosthesis revision surgery
Proximal corporal deformities may account for failed inflatable penile prosthesis (IPP) surgery. No contemporary series has focused solely on describing the natural history and management of isolated proximal corporal deformities in patients after IPP surgery. The aim of the current report is to present the clinical courses and surgical management with outcomes of proximal corporal deformities in the context of prior IPP implantation surgery. We conducted a retrospective analysis of the Johns Hopkins Hospital institutional database of IPP surgeries from May 2006 to March 2017 consisted of 198 patients who had undergone IPP revisions. All cases involving surgical revisions associated with isolated proximal corporal deformities (proximally from the penoscrotal junction) were identified. Data retrieved included clinical characteristics, operative findings, and surgical outcomes. Main outcome measures are the ability to achieve successful sexual intercourse after IPP revision. The findings of proximal corporal deformities were manifest in fifteen patients who had undergone previous IPP surgery. Deformities consisted of corporal dilatation (15 patients) and corporal rupture (8 patients). Associated prosthesis defects were mechanical failure (2 patients), aneurysmal dilatation (5 patients), and device breakage (4 patients). Median IPP treatment duration was 14 years. Mean number of prior IPP surgeries were 4.2 times. All patients underwent reduction corporoplasty with IPP device replacements consisting of controlled expansion devices. Mean age at revision was 59.7 years. All patients reported successful sexual intercourse and satisfaction within 6 months' follow-up after surgical revision. Proximal corporal deformities arising after IPP surgery are associated with dysfunctional device operation and as well as device defects. Proper recognition of this problem allows the opportunity for surgical correction with a definitive reduction corporoplasty. Failure to recognize these abnormalities timely may predispose to unsuccessful revisions and complicate future definitive surgical repair.
Journal Article