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Biomedical subjects

Hunter Wessells

Publications and source records attributed to Hunter Wessells.

At least 19 recordsLinked to original sources

Predictors and prevalence of erectile dysfunction in a racially diverse population.

BACKGROUND: To our knowledge, the burden of disease attributed to erectile dysfunction (ED) has not been adequately quantified across a complete spectrum of age and race using a global disease definition, as recommended by the National Institutes of Health consensus statement. To obtain a better understanding of the national estimates of prevalence and risk factors for ED, we analyzed data from the 2001-2002 National Health and Nutrition Examination Survey. METHODS: The National Health and Nutrition Examination Survey collects data by household interview. The sample design is a stratified, multistage, probability sample of clusters of persons representing the civilian noninstitutionalized population. Data include medical histories in which specific queries are made regarding urological symptoms (including ED). These items were selected for analysis in 3566 men, 20 years and older. RESULTS: In men 20 years and older, ED affected almost 1 in 5 respondents. Hispanic men were more likely to report ED (odds ratio [OR], 1.89), after controlling for other factors. The prevalence of ED increased dramatically with advanced age; 77.5% of men 75 years and older were affected. In addition, there were several modifiable risk factors that were independently associated with ED, including diabetes mellitus (OR, 2.69), obesity (OR, 1.60), current smoking (OR, 1.74), and hypertension (OR, 1.56). CONCLUSIONS: The burden of ED on the US population is significant. Hispanic men had an elevated risk for ED, a finding that requires confirmation in prospective studies. Obesity, hypertension, smoking, and diabetes mellitus are significantly associated with ED risk. Mitigation of these risk factors may ameliorate the burden of ED.

Adult↗

Radiographic and clinical predictors of bladder rupture in blunt trauma patients with pelvic fracture.

RATIONALE AND OBJECTIVES: Bladder rupture is a potentially serious injury in blunt trauma patients. We determined whether location and displacement of pelvic fractures and the degree of hematuria can accurately predict bladder injury. MATERIALS AND METHODS: A retrospective database of 721 blunt trauma pelvic fractures that presented to a single large regional level 1 trauma center between January 1, 1997, and July 15, 2003, was expanded to include data on bladder injury and the initial urinalysis. Multiple logistic regression was performed to determine if an association exists between pelvic fracture pattern, degree of hematuria, and bladder injury. A potential clinical prediction rule was then derived using a point system for four independent, significant risk factors identified from the logistic regression results. RESULTS: There were 37 bladder ruptures (5.0%), all of which presented with hematuria >30 red blood cells per high-powered field (RBC/HPF). Pelvic injuries that were independently associated with bladder injury included diastasis of the pubic symphysis >1 cm, RR = 9.8 (95% CI 4.6-20.9), and fracture of the obturator ring with displacement >1 cm RR = 3.2 (95% CI 1.6-6.5). No patient with isolated acetabular fractures sustained bladder injury. A clinical prediction rule was derived, consisting of a single point for each of the significant pelvic injury sites in patients with hematuria >30 RBC/HPF. Patients with a prediction score of 0 had a 2.3% probability of bladder injury, whereas patients with scores of 1 and 2 had probabilities of bladder injury of 9.2% and 43.7%, respectively. CONCLUSIONS: Patients with isolated acetabular fractures and patients with <30 RBC/HPF did not sustain bladder injury. In addition to hematuria, specific pelvic injury patterns are associated with bladder rupture. If validated, a clinical prediction rule derived from this data has the potential to guide the care of the blunt trauma patient.

Adult↗

Penile and genital injuries.

Genital injuries are significant because of their association with injuries to major pelvic and vascular organs that result from both blunt and penetrating mechanisms, and the chronic disability resulting from penile, scrotal, and vaginal trauma. Because trauma is predominantly a disease of young persons, genital injuries may profoundly affect health-related quality of life and contribute to the burden of disease related to trauma. This article reviews the mechanism, initial evaluation, and operative management of injuries to the male and female external genitalia including the penis, scrotal skin, and vaginal structures.

Female↗

What is the most cost-effective treatment for 1 to 2-cm bulbar urethral strictures: societal approach using decision analysis.

OBJECTIVES: Direct vision internal urethrotomy (DVIU) and urethroplasty are the primary methods of managing urethral stricture disease. Using decision analysis, we determine the cost-effectiveness of different management strategies for short, bulbar urethral strictures 1 to 2 cm in length. METHODS: A decision tree was constructed, with the number of planned possible DVIUs before attempting urethroplasty defined for each primary branch point. Success rates were obtained from published reports. Costs were estimated from a societal perspective and included the costs of the procedures and office visits and lost wages from convalescence. Sensitivity analyses were conducted, varying the success rates of the procedures and cost estimates. RESULTS: The most cost-effective approach was one DVIU before urethroplasty. The incremental cost of performing a second DVIU before attempting urethroplasty was $141,962 for each additional successfully voiding patient. In the sensitivity analysis, urethroplasty as the primary therapy was cost-effective only when the expected success rate of the first DVIU was less than 35%. CONCLUSIONS: The most cost-effective strategy for the management of short, bulbar urethral strictures is to reserve urethroplasty for patients in whom a single endoscopic attempt fails. For longer strictures for which the success rate of DVIU is expected to be less than 35%, urethroplasty as primary therapy is cost-effective. Future prospective, multicenter studies of DVIU and urethroplasty outcomes would help enhance the accuracy of our model.

Cost-Benefit Analysis↗

Renal and extrarenal predictors of nephrectomy from the national trauma data bank.

PURPOSE: The kidney is injured in 1.4% to 3.0% of all trauma cases. The management of renal injuries is controversial, as reflected in regional and institutional variations in treatment preferences. Using a national trauma database we identified independent risk factors for nephrectomy. MATERIALS AND METHODS: The population was selected from the National Trauma Data Bank, a voluntary data repository containing all trauma admissions to 268 participating trauma centers. Patients with renal injuries were identified by Abbreviated Injury Scale codes. Patient demographic, associated injuries and facility characteristics were recorded. Univariate and Poisson regression analysis with clustering by facility was performed. RESULTS: Renal injury was present in 8,465 patients. Nephrectomy was performed in 4% of all blunt and 21% of all cases of penetrating renal injuries. Only 0.5% of blunt renal injury cases underwent repair compared with 15% of those of penetrating injuries. On multivariate analysis renal injury severity was the strongest predictor of nephrectomy. The relative risk of nephrectomy for grade V renal injuries was 146 (95% CI 74 to 289) and 33 (95% CI 13 to 89) in the blunt and penetrating models, respectively. The need for laparotomy and surgery on other intra-abdominal organs predicted nephrectomy in patients with blunt and penetrating injuries. Hospital trauma designation did not statistically impact nephrectomy rates. CONCLUSIONS: The severity of renal injury based on the AAST organ injury scale for Renal Trauma is the strongest risk factor for nephrectomy. The need for surgery on other intra-abdominal injuries increases the risk of nephrectomy to a lesser extent. In cases of blunt trauma severe renal injury usually necessitates nephrectomy.

Adult↗

Urethral and bladder neck injury associated with pelvic fracture in 25 female patients.

PURPOSE: We describe the presentation, diagnostic evaluation, management and outcome of female urethral trauma. MATERIALS AND METHODS: All female patients treated at Harborview Medical Center between 1985 and 2001 with urethral injury were identified by International Classification of Diseases 9th revision code. Approval of the Human Subject Division was obtained and patient charts were reviewed. The Urogenital Distress Inventory Short Form, the Incontinence Impact Questionnaire Short Form and the Female Sexual Function Index were sent to the patients. RESULTS: A total of 25 patients (13 adults, 12 children) with a mean age of 22 years (range 4 to 67) met inclusion criteria. All had pelvic fracture related to blunt trauma. They represented 6% of all female patients treated in the same review period with pelvic fracture. Blood was seen at the introitus in 15 patients and 19 had gross hematuria. Of the injuries 9 were avulsions, 15 were longitudinal lacerations and 1 was not further specified. Primary repair was performed in 21 patients and 4 were treated nonoperatively. There were 5 patients who required secondary procedures including fistula repair in 4 and continent urinary diversion in 1. At a mean followup of 7.3 years (range 1.6 to 14.4) 9 of 21 patients (43%) had moderate or severe lower urinary tract symptoms and 8 of 13 (38%) had sexual dysfunction (FSFI score less than 26.55). CONCLUSIONS: Female urethral and bladder neck injury occurs with pelvic fracture, presents with gross hematuria and/or blood at the introitus, and requires operative repair for avulsions and longitudinal lacerations. These patients are at risk for significant sexual and lower urinary tract dysfunction.

Adolescent↗

American Association for the Surgery of Trauma Organ Injury Scale for kidney injuries predicts nephrectomy, dialysis, and death in patients with blunt injury and nephrectomy for penetrating injuries.

BACKGROUND: Despite broad clinical use of the American Association of the Surgery of Trauma (AAST) injury scale for kidney, it has only been found to predict the need for renal surgery in single institution series. We sought to validate this scheme for morbidity and mortality in a national cohort of patients with renal injury. METHODS: A retrospective cohort design was used to determine the association between increasing AAST scores and nephrectomy, dialysis, and mortality. The cohort included all patients with a renal injury in the National Trauma Data Bank (NTDB) from 1994 and 2003. Univariate and multivariate prediction models were used for analysis of data. RESULTS: At the time of review, a total of 742,774 patient records were registered in the NTDB. Renal injury occurred in 8465 patients (1.2%). Increasing injury grade was associated with a greater nephrectomy (RR 12-127), dialysis (RR 1.3-4.7), and mortality (RR 1.3-1.9) rate for blunt kidney injury. For penetrating injury, nephrectomy was the only outcome that was associated with higher grades of renal injury with a RR of 7.7 to 31 for grades III to V injuries. CONCLUSION: The AAST injury scale for kidney predicts for morbidity in blunt and penetrating renal injury and for mortality in blunt injury. Thus, we continue to support its use as a clinical and research tool.

Abbreviated Injury Scale↗

Fluid shear stress-induced nitric oxide production in human cavernosal endothelial cells: inhibition by hyperglycaemia.

OBJECTIVE: To investigate whether fluid shear stress (FSS) induces endothelial nitric oxide synthase (eNOS) activity and NO production in isolated human corpus cavernosal endothelial cells (HCCECs), and whether this response is altered during hyperglycaemia in vitro, as haemodynamic signalling during penile erection induces eNOS-mediated NO production in vivo. MATERIALS AND METHODS: ECs were cultured from HCC and characterized by the uptake of acetylated low-density lipoprotein and the expression of von Willebrand factor, VE-cadherin, CD31 and eNOS. HCCECs were exposed to FSS (1.2 Pa (12 dynes/cm2), 5 min) using a cone-and-plate viscometer in the presence or absence of high glucose (30 mm, 48 h). The phosphorylation of ser1177 on eNOS and total eNOS protein expression after FSS was examined by Western blot. NO in the conditioned media was assessed by measuring nitrate and nitrite levels. RESULTS: Compared to static conditions, FSS induced a significant increase in the phosphorylation of eNOS on ser1177 in HCCECs, and the release of NO to the conditioned media. Treatment of HCCECs with high glucose levels did not alter the ratio FSS-induced phosphorylated eNOS/total eNOS, but did result in the down-regulation of total eNOS and significantly attenuated FSS-induced NO release. CONCLUSION: These in vitro data suggest that FSS contributes to eNOS activation and NO release in HCCECs, and supports in vivo reports suggesting a role for haemodynamic signalling in the erectile response. Treatment with high glucose levels prevented FSS-induced NO release, suggesting a mechanism that may contribute to decreased erectile function associated with diabetes.

Down-Regulation↗

Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats.

To investigate the full range of molecular changes associated with erectile dysfunction (ED) in Type 1 diabetes, we examined alterations in penile gene expression in streptozotocin-induced diabetic rats and littermate controls. With the use of Affymetrix GeneChip arrays and statistical filtering, 529 genes/transcripts were considered to be differentially expressed in the diabetic rat cavernosum compared with control. Gene Ontology (GO) classification indicated that there was a decrease in numerous extracellular matrix genes (e.g., collagen and elastin related) and an increase in oxidative stress-associated genes in the diabetic rat cavernosum. In addition, PubMatrix literature mining identified differentially expressed genes previously shown to mediate vascular dysfunction [e.g., ceruloplasmin (Cp), lipoprotein lipase, and Cd36] as well as genes involved in the modulation of the smooth muscle phenotype (e.g., Kruppel-like factor 5 and chemokine C-X3-C motif ligand 1). Real-time PCR was used to confirm changes in expression for 23 relevant genes. Further validation of Cp expression in the diabetic rat cavernosum demonstrated increased mRNA levels of the secreted and anchored splice variants of Cp. CP protein levels showed a 1.9-fold increase in tissues from diabetic rats versus controls. Immunohistochemistry demonstrated localization of CP protein in cavernosal sinusoids of control and diabetic animals, including endothelial and smooth muscle layers. Overall, this study broadens the scope of candidate genes and pathways that may be relevant to the pathophysiology of diabetes-induced ED as well as highlights the potential complexity of this disorder.

Animals↗

Tadalafil-associated priapism.

A healthy 46-year-old man presented to the Emergency Department with a 36-hour history of persistent, painful erection after taking the cyclic guanylyl monophosphate-specific phosphodiesterase 5 inhibitor tadalafil. He had no other identified contributing factors for priapism. After confirmation of ischemic priapism and failure of bedside management in the Emergency Department, the patient underwent operative caverno-spongiosal shunting. Postoperatively, the erection initially rebounded but gradually receded with manual compression over 48 hours. At outpatient follow-up, the patient remained flaccid without erections. To our knowledge, this is the first report of tadalafil-associated priapism.

Adult↗

The relationship among lower urinary tract symptoms, prostate specific antigen and erectile dysfunction in men with benign prostatic hyperplasia: results from the proscar long-term efficacy and safety study.

PURPOSE: We evaluated the associations among lower urinary tract symptoms, prostate specific antigen (PSA) and erectile dysfunction (ED) in men with benign prostatic enlargement enrolled in the Proscar (Merck, Whitehouse Station, New Jersey) Long-Term Efficacy and Safety Study. MATERIALS AND METHODS: The Proscar Long-Term Efficacy and Safety Study was a 4-year, randomized, double-blind, placebo controlled study that enrolled 3,040 men with moderate to severe lower urinary tract symptoms and an enlarged prostate gland. Two questions assessed ED. A logistic regression model, including the effect of patient age, was used to examine the relationships among quasi-American Urological Association Symptom Score (AUASS), PSA, and ED at baseline. Changes in ED scores from baseline to study closeout were analyzed with ANOVA. RESULTS: A total of 2,981 patients had baseline data available for analysis. Mean age was 64 years, mean quasi-AUASS was 15, mean PSA was 2.8 ng/ml and mean prostate volume was 55 cm. At baseline every 1 point increase in quasi-AUASS was associated with a 2% increased risk of ED even after controlling for age (p <0.001). At 48 months in placebo but not in finasteride treated men a 1-unit decrease in quasi-AUASS was associated with a slight but statistically significant decrease in ED. No association existed between increasing PSA and ED on baseline or longitudinal analysis. CONCLUSIONS: We found a moderately strong association between baseline quasi-AUASS and the ED rate in men with an enlarged prostate, a finding that was supported by longitudinal data in the placebo arm. The absence of a relationship between PSA and ED highlights the need for further investigation into the mechanisms of benign prostatic hyperplasia related sexual dysfunction.

Aged↗

Immunohistochemical comparison of vascular and sinusoidal adherens junctions in cavernosal endothelium.

OBJECTIVES: To characterize endothelial cell-to-cell junctions in the sinusoids and microvasculature of the corpus cavernosum. METHODS: Corporal tissue was obtained from 6 potent human subjects, cut into 5-microm cryosections, and double-labeled with consecutive applications of primary and secondary antibodies. Laser scanning confocal microscopy identified subcellular localization of endothelial anchoring and adhesion molecules. Fluorescence intensity was rated as strong, weak, or absent by two observers. RESULTS: The cavernosal endothelial adherens junction was composed of vascular endothelial cadherin, alpha-catenin, plakoglobin, vinculin, and the regulatory proteins beta-catenin and ZO-1. Adherens junctions in sinusoids were elongated, redundant, and narrow versus short, dense, linear cell-to-cell contacts in small arterioles and venules. Vinculin expression along the basal interface of the endothelium and stroma was weak in the sinusoids and strong in the arterioles. Definite sinusoidal expression of CD31 and CD34 was noted. P-selectin was only expressed within the cavernosal microvessels. CONCLUSIONS: The regulatory and structural proteins extending from vascular endothelial cadherin provide immunohistochemical evidence of a role for adherens junctions in cavernosal endothelial barrier function and cellular homeostasis. The sinusoidal endothelium has a unique junctional phenotype consistent with its blood trapping function. Differential expression of functional proteins in sinusoidal and microvascular endothelium may reflect segmental variation in hemodynamic exposure to pressure, stretch, or flow.

Adherens Junctions↗

Meshed unexpanded split-thickness skin grafting for reconstruction of penile skin loss.

PURPOSE: Sheets of unmeshed, split-thickness skin grafts (STSGs) have been advocated in potent men with penile skin deficiency. Since the survival of sheet grafts is rarely 100% and the appearance of unexpanded 1:1 mesh grafts is quite good, we used this technique. We report our experience with meshed, unexpanded STSGs for all penile resurfacing regardless of erectile function. MATERIALS AND METHODS: Nine consecutive patients with penile skin loss were prospectively treated between March 2001 and January 2003 with meshed STSGs to the penis. The underlying condition was Fournier's gangrene in 4 cases, chronic lymphedema in 2, skin deficiency from prior surgeries in 2 and Crohn's disease in 1. Graft thickness was 0.012 or 0.016 inches and meshing was performed in a 1:1 ratio. Meshed slits were oriented transversely without expansion and the graft juncture was located on the ventral surface in zigzag fashion. Graft take, appearance, and sexual and voiding function were assessed postoperatively. RESULTS: All 9 patients had 100% graft take. At a mean followup of 6 months a satisfactory cosmetic outcome was documented photographically in all except 1 case involving chronic penile manipulation. Erectile function and ejaculation were preserved in potent patients. CONCLUSIONS: Unexpanded meshed STSGs of penile skin loss yielded satisfactory functional and cosmetic outcomes.

Adult↗

The penile implant for erectile dysfunction.

INTRODUCTION: Penile prostheses, introduced as the first effective organic treatment for erectile dysfunction over three decades ago, have an important role in the treatment of erectile dysfunction when other nonprosthetic treatment options have proven unsatisfactory. Although they are the least chosen and most invasive treatment option, they have the highest satisfaction rate of all available ED options and provide a predictable and reliable result. AIM: To provide recommendations/guidelines concerning state-of-the-art knowledge for utilization of the penile prosthesis in the management of men with erectile dysfunction. METHODS: An International Consultation in collaboration with the major sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various 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 2-year period. There were 10 experts from seven countries concerning the Penile Implant for Erectile Dysfunction. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Recommendations/guidelines for penile prosthesis (hydraulic, semi-rigid and soft silicone) insertion for management of men with erectile dysfunction were updated. Consensed issues included: criteria for patient selection, informed consent procedures, strategies for preoperative preparation, operative incisions/technical considerations and outcome results in terms of patient satisfaction and device survival. Updated information was reviewed concerning therapies for device failures, device insertion in scarred corporal bodies and strategies for managing implant infections. CONCLUSIONS: There is a need for more research in developing management strategies for insertion of penile prostheses in men with ED.

Consensus↗

A national survey of urinary and health related quality of life outcomes in men with an artificial urinary sphincter for post-radical prostatectomy incontinence.

PURPOSE: We determine health related quality of life and urinary outcomes of men undergoing implantation of an artificial urinary sphincter for post-radical prostatectomy incontinence. MATERIALS AND METHODS: Through a data base provided by American Medical Systems, we mailed the UCLA Prostate Cancer Index to men who underwent artificial urinary sphincter implantation during 6-month intervals in 1995 in 1999, providing 5 and 2-year followup data, respectively. RESULTS: Of the anonymous questionnaires 36% were returned from the 1995 cohort and 45% from the 1999 cohort. Age adjusted mean scores for the 8 health related quality of life domains were comparable in both groups. Urinary function and bother scores were worse in the 1995 cohort compared to the 1999 group (40 and 48 versus 53 and 58, respectively, p <0.001), with pad use of 97% and 83% respectively. Revision rates were 16% at 2 years and 28% at 5 years after implantation. CONCLUSIONS: Our national survey revealed that despite significant differences in urinary function and bother, men 2 and 5 years after artificial urinary sphincter implantation had similar general health related quality of life. The continence outcomes differed from most single institution studies in that men after sphincter implantation reported a high degree of urinary dysfunction and bother. Artificial urinary sphincter implantation may significantly improve scores in urinary function but continued pad use is to be expected.

Aged↗

Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the incidence and resolution of sexual adverse experiences (AEs) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo. METHODS: The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45 to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates, and no evidence of prostate cancer. Patients completed a questionnaire at screening regarding their history of sexual dysfunction. During treatment, spontaneously self-reported sexual AEs were recorded. RESULTS: At screening, 46% of patients in each treatment group reported some history of sexual dysfunction. During year 1 of the study, 15% of finasteride-treated patients and 7% of placebo-treated patients had sexual AEs that were considered drug related by the investigator (P <0.001). During years 2 to 4, no between-group difference was noted in the incidence of new sexual AEs (7% in each group). The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively. CONCLUSIONS: Compared with placebo, men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy.

Aged↗