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OBJECTIVES: To define the prevalence of cognitive impairment and sphincter misuse among men who had undergone AUS placement. METHODS: Men who had previously undergone AUS placement from 2004 to 2019 were assessed through comprehensive telephone surveys. The primary survey outcome was cognitive function, assessed via validated Telephone Mini-Mental State Examination. Secondary survey outcomes included rate of AUS misuse, surgical outcomes, and overall device satisfaction. Statistical analysis was performed to assess for differences between patients with and without cognitive impairment. RESULTS: A total of 74 patients participated, with a mean age and follow-up of 75 and 7.8 years, respectively. Telephone Mini-Mental State Examination assessment revealed cognitive impairment in 18 (24%) patients, 13 (18%) with mild-moderate and 5 (7%) with severe impairment. Overall, 23 (31%) and 11 (15%) patients reported inconsistent use (not cycling AUS with every void) and device neglect, respectively. Patients with impaired cognition were more likely to report difficulty with AUS use compared to those with normal cognition (39% vs 9%, P= .01). There was no difference seen in rates of revision, rates of retention, or urinary tract infections between cognitive groups. CONCLUSIONS: Our study revealed significant rates of cognitive impairment and sphincter misuse among men with AUS. These data suggest a role for long-term follow-up and monitoring for cognitive changes. Prospective study of cognitive decline and surgical outcomes in patients undergoing AUS is warranted.
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Disfunción Cognitiva/epidemiología , Esfínter Urinario Artificial/psicología , Anciano , Anciano de 80 o más Años , Falla de Equipo/estadística & datos numéricos , Humanos , Masculino , PrevalenciaRESUMEN
BACKGROUND: In May 2012, the US Preventive Services Task Force assigned prostate-specific antigen-based screening a grade D recommendation, advising against screening at any age. Our objective was to compare prostate cancer characteristics pre- and post-recommendation with an adjusted analysis of our data and a pooled analysis including other primary data sources. METHODS: We identified all incident prostate cancer diagnoses at our institution from 2007 to 2016. Multivariable log binomial regression was used to determine the relative risk (RR) of metastasis at diagnosis, ≥Gleason Group 4, and high D'Amico risk disease pre- versus post-recommendation. The meta-analysis included primary data studies evaluating these outcomes. RESULTS: At our institution, 287 (44.6%) and 224 (48.8%) patients were diagnosed in the pre- and post-cohorts. The RR of metastatic disease at diagnosis did not differ between groups (p = 0.224), nor did the risk of high D'Amico category disease (p = 0.089). The risk of ≥Gleason Group 4 was 1.58 times higher post-recommendation (p = 0.007). The pooled risk of ≥Gleason Group 4 disease was 1.5 (p < 0.001) post-recommendation and was 1.29 (p = 0.006) for high D'Amico risk disease. CONCLUSIONS: While the number of metastatic cases did not differ after the recommendation, the risk of high-grade cancers increased at both a local and aggregated level.
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Detección Precoz del Cáncer/métodos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/prevención & control , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Servicios Preventivos de Salud , Neoplasias de la Próstata/diagnóstico , Estados UnidosRESUMEN
PURPOSE: Clomiphene citrate may be used as an off label treatment of hypogonadism. There are few long-term data on clomiphene citrate efficacy and safety when administered for more than 3 years. We assessed improvements in testosterone and hypogonadal symptoms while on clomiphene citrate for extended periods. MATERIALS AND METHODS: We performed a retrospective review to identify patients treated with clomiphene citrate for hypogonadism (baseline testosterone less than 300 ng/dl) at a total of 2 institutions from 2010 to 2018. We assessed the duration of clomiphene citrate therapy, serum testosterone levels, symptom improvement and clomiphene citrate side effects. RESULTS: A total of 400 patients underwent clomiphene citrate treatment for a mean ± SD of 25.5 ± 20.48 months (range 0 to 84). Of the patients 280 received clomiphene citrate for 3 years or less (mean 12.75 ± 9.52 months) and 120 received it for more than 3 years (mean 51.93 ± 10.52 months). Of men on clomiphene citrate for more than 3 years 88% achieved eugonadism, 77% reported improved symptoms and 8% reported side effects. Estradiol was significantly increased following clomiphene citrate treatment. Results did not significantly differ between patients treated for more than 3, or 3 or fewer years. The most common side effects reported by patients treated more than 3 years included changes in mood in 5, blurred vision in 3 and breast tenderness in 2. There was no significant adverse event in any patient treated with clomiphene citrate. CONCLUSIONS: Clomiphene citrate is not typically offered as primary treatment of hypogonadism in men who do not desire fertility preservation. These data demonstrate that clomiphene citrate is safe and effective with few side effects when used as long-term treatment of hypogonadism.
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Clomifeno/administración & dosificación , Hipogonadismo/tratamiento farmacológico , Adulto , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Estudios de Seguimiento , Gonadotropinas/sangre , Humanos , Hipogonadismo/sangre , Masculino , Prolactina/sangre , Estudios Retrospectivos , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Testosterona/sangre , Factores de Tiempo , Resultado del TratamientoRESUMEN
Neuronal and endothelial nitric oxide synthases (nNOS and eNOS respectively) play major roles in generating the nitric oxide bioactivity necessary for erectile function. S-nitrosylation has been shown to regulate NOS activity. The presence of S-nitrosylated NOS in the penis and the impact of NOS S-nitrosylation/denitrosylation on erectile function were examined. S-nitrosylated forms of NOS were identified by biotin-switch assay followed by western blot analysis. Erectile function in S-nitrosoglutathione reductase deficient (GSNO+/-) and null (GSNO-/-) mice were assessed by continuous cavernous nerve electrical stimulation (CCNES). Glutathione ethyl ester (GSHee) was used to manipulate S-nitrosylated NOS levels. Immunohistological and immunofluorescence analyses were used to identify the location of eNOS and GSNO-R in corporal tissue. eNOS and nNOS were S-nitrosylated in unstimulated penises of the mice. CCNES resulted in a time-dependent increase in eNOS S-nitrosylation with peak eNOS S-nitrosylation observed during detumescence. S-nitrosylated nNOS levels were unchanged. Intracorporal injection of GSHee reduced S-nitrosylated eNOS levels, enhancing time to maximum intracorporal pressure (ICP). eNOS and GSNO-R co-localize to the endothelium of the corpus cavernosum in the mouse and the human. ICP measurements obtained during CCNES demonstrate GSNO-R+/- and GSNO-R-/- animals cannot maintain an elevated ICP. Results suggest eNOS S-nitrosylation/denitrosylation is an important mechanism regulating eNOS activity during erectile function. GSNO-R is a key enzyme involved in the eNOS denitrosylation. The increase in eNOS S-nitrosylation (inactivation) observed with tumescence may begin a cycle leading to detumescence. Clinically this may indicate that alterations in the balance of S-nitrosylation/denitrosylation either directly or indirectly contribute to erectile dysfunction.
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Aldehído Oxidorreductasas/metabolismo , Disfunción Eréctil/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Erección Peniana/fisiología , Aldehído Oxidorreductasas/genética , Animales , Endotelio Vascular/metabolismo , Disfunción Eréctil/genética , Masculino , Ratones , Ratones Noqueados , Pene/metabolismoRESUMEN
BACKGROUND: Limited investigation exists to understand whether obesity affects outcomes of urethral reconstruction. We sought to assess whether body mass index (BMI) is an independent predictor for stricture recurrence following urethroplasty. METHODS: We performed a retrospective review of patients undergoing urethroplasty between 2007-2014, identifying 137 patients for study inclusion. Data collected included BMI and patient demographic and surgical characteristics, including age, stricture length and location, etiology, and urethroplasty technique. Stricture-free survival analysis was performed using Kaplan-Meier method. Logistic regression was performed to assess predictors for stricture recurrence using both univariate and multivariate models. RESULTS: Mean patient age and follow-up was 46.7 (±16.4) years and 91.8 (±30.5) months, respectively. A recurrence rate of 17% was identified, with a mean time to recurrence of 29 months. There was no difference when comparing the mean BMI in patients with and without recurrence (28.9 vs. 30.4 kg/m2, respectively) (P=0.4). A higher rate of stricture recurrence was seen when comparing the cohort with a BMI <25 kg/m2 versus remaining cohorts (BMI: 25-30 kg/m2; BMI >30 kg/m2). However, in univariate and multivariate analysis, BMI failed to demonstrate statistical significance as a predictor for urethroplasty outcome. On multivariate analysis, fasciocutaneous repair type was predictive of stricture recurrence. No additional potential predictors assessed were found to be significant. CONCLUSIONS: In the present study, BMI did not independently predict for stricture recurrence following urethroplasty.
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Chronic idiopathic orchialgia is a urologic disease process that is as frustrating as it is common. While no consensus exists on management for otherwise-unexplained testicular pain, most providers would agree that once other treatable organic causes are ruled out, initial management should be symptom focused, and should be medical rather than surgical. This chapter presents a review of the evidence available for a variety of pharmacotherapies commonly employed in the treatment of idiopathic chronic orchialgia.
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PURPOSE: We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. MATERIALS AND METHODS: In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. RESULTS: Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. CONCLUSIONS: The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism.
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Andrógenos/efectos adversos , Clomifeno/efectos adversos , Terapia de Reemplazo de Hormonas/efectos adversos , Hipogonadismo/tratamiento farmacológico , Policitemia/inducido químicamente , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversos , Testosterona/efectos adversos , Adulto , Andrógenos/uso terapéutico , Clomifeno/uso terapéutico , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Testosterona/uso terapéuticoRESUMEN
INTRODUCTION: Pediatric patients with chronic urologic conditions frequently require lifelong evaluation and treatment. Transition to adult urologic care is critically important as these patients mature and the goals of care shift to include sexual function, fertility, and reconstruction. OBJECTIVE: Our objectives are to (1) quantify and describe the population of young adult patients with congenital or childhood-acquired urologic problems who continue to be followed in pediatric urology clinic, to (2) discuss the numerous obstacles to successful care transition, and to (3) outline the design features of the dedicated transition clinic we established in response to the identification of a sizeable population in need. STUDY DESIGN: We (1) performed a retrospective review of our electronic health record to identify young adult patients 19-35 years of age seen in pediatric urology clinic over a five year period. Patients without a chronic urologic diagnosis were excluded. We identified each patient's primary diagnosis and status with respect to transition of care. We then (2) established a dedicated transition clinic to facilitate progression to adult care services at our institution. RESULTS: Among 480 young adult patients seen in the pediatric clinic during the five-year period, 99 patients with an average age of 22.4 years were identified as having a chronic congenital or childhood-acquired diagnoses requiring urologic care. At the end of the five-year period, 40 of 99 patients (40.4%) had successfully transitioned to adult care while 59 patients (59.6%) continued care with pediatric urology. Among patients yet to transition, spinal dysraphism (30%) was the most common primary diagnosis. In this same group, discussion regarding transfer to adult care was documented during at least one visit in only 8 of the 59 patients (13.6%). All patients in this cohort had healthcare needs that included sexual function, fertility, or reconstruction. DISCUSSION: The present data confirm the presence of sizeable population of young adult patients with chronic urologic problems and maturing care needs who 1) continue to receive exclusively pediatric care, and 2) are rarely engaged in preparatory discussions regarding care transition. Obstacles to successful transition of care are numerous and include limited staff training, lack of identified staff member responsible for transition, financial and psychosocial barriers, and discomfort on the part of physicians, patients and families. We describe the additional challenges that are unique to transition of care in urology. We share a blueprint of our recently-established transition with the hope of prompting additional discussion and facilitating transitional urologic care elsewhere. CONCLUSION: Many young adult patients with chronic urologic conditions continue to receive care from pediatric urologists well into adulthood. We hope that our clinic might serve as a model for augmentation of urologic transition services at other institutions. We anticipate a future report evaluating our clinic's impact on long-term follow up, clinical outcomes, and patient satisfaction.
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Atención Ambulatoria/organización & administración , Transición a la Atención de Adultos/organización & administración , Anomalías Urogenitales/diagnóstico , Anomalías Urogenitales/terapia , Adolescente , Adulto , Factores de Edad , Niño , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Monitoreo Fisiológico/métodos , Satisfacción del Paciente/estadística & datos numéricos , Pediatría/métodos , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales , Resultado del Tratamiento , Estados Unidos , Urología/métodos , Adulto JovenRESUMEN
Penile masses are a concerning finding for both patient and clinician upon initial presentation. There is a wide differential for penile masses from the benign (fibrous plaques, cysts, ulcerative lesions, benign penile pearly papules, etc.) to more concerning malignant lesions. A proper history and physical is the first step to determining the etiology of the mass and any future clinical interventions. In this paper, we review a case of a 73-year-old male who is found to have an enlarging mass during work-up for possible placement of inflatable penile prosthesis. Fortunately, the mass was determined to be a benign epidermoid cyst presenting thirty years after reconstruction for Peyronie's disease using dermal penile skin graft. With this unique presentation we review the scant literature on penile mass formation following Peyronie's repair.
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INTRODUCTION: During female sexual arousal, clitoral blood flow is controlled by endothelial nitric oxide synthase (eNOS) and its product, nitric oxide (NO). The mechanisms regulating eNOS activity and NO bioavailability in the clitoris are largely unknown. AIM: To identify proteins involved in regulation of eNOS activity within the clitoris and to evaluate the effects of S-nitrosoglutathione reductase (GSNO-R) and eNOS nitrosylation/denitrosylation on clitoral blood flow. METHODS: Immunohistochemistry for eNOS, caveolin-1 (Cav1), heat shock protein-90 (Hsp90), phosphodiesterase type 5 (PDE5), GSNO-R, and soluble guanylate cyclase (sGC) was performed on human and murine clitoral tissue. Western blot analysis was performed for eNOS, phosphorylated eNOS (phospho-eNOS, Ser1177), Cav1, Hsp90, sGC, PDE5, phosphoinositide 3-kinase (PI3K), Akt (protein kinase B), and GSNO-R on protein from human clitoral tissue. A biotin switch assay was used to analyze the S-nitrosylation of eNOS, nNOS, and GSNO-R. Clitoral blood flow was measured in wild-type and GSNO-R(-/-) mice at baseline and during cavernous nerve electrical stimulation (CNES). MAIN OUTCOME MEASURES: Localization of eNOS regulatory proteins and clitoral blood flow. RESULTS: eNOS and GSNO-R co-localized to the vascular endothelium and sinusoids of human clitoral tissue. Immunohistochemistry also localized Cav1 and Hsp90 to the endothelium and PDE5 and sGC to the trabecular smooth muscle. Expression of S-nitrosylated (SNO)-eNOS and SNO-GSNO-R was detected by biotin switch assays. Wild-type control mice exhibited increased clitoral blood flow with CNES whereas GSNO-R(-/-) animals failed to show an increase in blood flow. CONCLUSIONS: Several key eNOS regulatory proteins are present in the clitoral tissue in a cellular specific pattern. S-nitrosylation of eNOS may also represent a key regulatory mechanism governing eNOS activation/deactivation since mice deficient in GSNO-R failed to increase clitoral blood flow. Additional studies are necessary to define the role of S-nitrosylation in the genital vascular response and its subsequent impact on female sexual function.
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Clítoris/enzimología , Óxido Nítrico Sintasa de Tipo III/fisiología , Óxido Nítrico/fisiología , Aldehído Oxidorreductasas/fisiología , Animales , Caveolina 1/metabolismo , Clítoris/irrigación sanguínea , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/metabolismo , Endotelio/metabolismo , Endotelio Vascular/metabolismo , Femenino , Guanilato Ciclasa/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Ratones Endogámicos C57BL , Músculo Liso/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/fisiología , Receptores Citoplasmáticos y Nucleares/metabolismo , Guanilil Ciclasa SolubleRESUMEN
INTRODUCTION: Calciphylaxis, a rare obliterative small vessel vasculopathy associated with diabetes mellitus (DM), end-stage renal disease (ESRD), portends a poor prognosis. Because penile involvement is rare, agreement on appropriate diagnosis and management is unclear. AIM: To determine the role and effect of penile biopsy for diagnosis and management of penile calciphylaxis. METHODS: Medical records of three penile calciphylaxis patients from our institution were evaluated. Data collected included age, history of DM, ESRD, and hemodialysis (HD) status, serum calcium (Ca), Ca × phosphorous product (C × P), parathyroid hormone (PTH), performance of biopsy, presence of non-penile cutaneous lesions, intervention, survival, and time from diagnosis to death. PubMed Search for relevant publications from 1995 to 2012 was performed to identify case reports of penile calciphylaxis that provided the same clinical data obtained from the 3 patients from our institution. MAIN OUTCOME MEASURES: Clinical evidence for outcomes in patients with penile calciphylaxis after biopsy of penile lesion compared to those without biopsy. RESULTS: A total of sixteen patients were identified in the literature and in our institution with clinical data of interest. Overall, 10/16 (62.5%) patients identified with penile calciphylaxis had a penile biopsy, and 7/10 (70%) experienced disease progression, while only 3/10 (30%) stabilized. Mean time to death in this patient population was short, approximately 6.5 months, regardless of type of intervention. CONCLUSION: Based on the results of our study, we argue that conservative measures should be employed as first line therapy for penile calciphylaxis. More importantly, secondary to likely resultant progression of necrosis, penile biopsy is not only unnecessary for diagnosis of penile calciphylaxis, but is also harmful and contraindicated.
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Biopsia , Calcifilaxia/diagnóstico , Pene/patología , Adulto , Calcifilaxia/patología , Contraindicaciones , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , NecrosisRESUMEN
INTRODUCTION AND OBJECTIVES: Evaluate the impact of scrotal color Doppler ultrasound (CDUS) on epididymitis treatment patterns in a university-based institution. MATERIALS AND METHODS: From 1 January 1999 to 30 July 2005, 870 patients from a single institution were diagnosed with epididymitis. A total of 480 men met the inclusion criteria for acute epididymitis. Scrotal ultrasound was included as a part of the diagnostic evaluation in 42.7% of men. Ultrasound reports were available for review in 187 cases. Information regarding patient demographics, diagnostic evaluation, and treatment was reviewed. RESULTS: Ultrasound findings consistent with epididymitis were identified in 69.3% of men. The four most commonly reported irregularities were scrotal wall thickening (84.2%), abnormal epididymal echotexture (74%), increased epididymal vascularity (72.9%), and an enlarged epididymis (71.5%). Scrotal ultrasound was performed in 67% men under age 20 compared to 36% men between ages 30 and 69. Patients presenting to the Emergency Department underwent sonographic evaluation 57% of the time versus 17.2% men presenting to primary care physicians (P < 0.001). Ninety-five per cent (194/204) of patients who underwent CDUS were treated with antibiotics compared to 96% (263/275) of those who did not receive an ultrasound (P = 0.78). CONCLUSIONS: CDUS can be helpful in patients with a potential diagnosis of testicular torsion, however, the use of CDUS as a diagnostic adjunct in the evaluation of epididymitis is of limited value. Treatment patterns and antibiotic usage were not significantly altered by ultrasound findings at this institution.
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This review paper highlights the important health issue of orchialgia and the chronic pelvic pain syndrome. There are a number of specific and non-specific etiologies and different treatment options based on the sub-categorization of orchialgia. The focus of this article is on the specific etiologies of chronic orchialgia as well as non-specific scrotal pain, and the diagnostic evaluation and optimal management of these men. The clinician must be cautious about assuming that orchialgia is constitutive in the chronic pelvic pain syndrome, and must be diligent in ruling out specific etiologies for scrotal pain prior to managing orchialgia as a non-specific chronic pain syndrome.
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Dolor Crónico/etiología , Prostatitis/diagnóstico , Enfermedades Testiculares/etiología , Algoritmos , Dolor Crónico/epidemiología , Comorbilidad , Manejo de la Enfermedad , Humanos , Masculino , Manejo del Dolor , Prostatitis/epidemiología , Prostatitis/etiología , Prostatitis/terapia , Enfermedades Testiculares/diagnóstico , Enfermedades Testiculares/epidemiología , Enfermedades Testiculares/terapiaRESUMEN
INTRODUCTION: Erectile dysfunction has been successfully treated with penile prosthesis implantation for over 50 years. Ferromagnetic implants or devices may create a potentially hazardous or painful situation during magnetic resonance imaging (MRI). A modern catalog of the MRI compatibility of penile prostheses is not available. AIM: Evaluate the safety profile of implanted, penile prostheses during MRI. MAIN OUTCOME MEASURE: Review available in vitro safety data and reported patient complications experienced during MRI with a penile prosthesis in place. METHODS: A search of PubMed™ for articles documenting a penile prosthesis present during MRI was performed. Radiology texts and product information from manufacturers' producing a penile prosthesis were reviewed. Direct discussion with product manufacturers was also performed to obtain additional safety and compatibility information. RESULTS: Nine clinical articles noted the presence of a penile prosthesis at the time of magnetic resonance imaging. No articles documented a complication from MRI of a man with a penile prosthesis. A single patient with an unnamed malleable prosthesis was noted to have twisting of the device during MRI which did not result in discomfort or malfunction of the device. In vitro studies support the safety of most prostheses during MRI. CONCLUSION: The available data suggests there is little risk for most patients with a penile prosthesis who undergo MRI. Notable exceptions include Dacomed's Omniphase and Duraphase device and the MRI-conditional Spectra device manufactured by AMS. Current manufacturers of penile implants provide wallet cards and medical letters to support safety when undergoing an MRI. Prior prosthesis implantation should not preclude patients from having an MRI.
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Imagen por Resonancia Magnética , Prótesis de Pene , Catálogos como Asunto , Contraindicaciones , Humanos , Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/normas , Masculino , Prótesis de Pene/efectos adversos , Prótesis de Pene/normasRESUMEN
PURPOSE: Microdissection testicular sperm extraction markedly improves the sperm retrieval rates in men with nonobstructive azoospermia. However, localizing sperm foci can be time-consuming and it is not always successful. Fiberoptic confocal fluorescent microscopy offers the advantage of rapid in vivo detection of fluorescently labeled sperm in the seminiferous tubules. MATERIALS AND METHODS: After establishing the feasibility of fiberoptic confocal fluorescent microscopy to identify antibody labeled sperm in vivo C57/B6 mice underwent intraperitoneal injection of busulfan to induce azoospermia. During spermatogenesis reestablishment at approximately 16 weeks the mice were anesthetized and the testes were delivered through a low midline incision. Fluorescein isothiocyanate labeled antibody to intra-acrosomal protein Hs-14 was injected retrograde into a single murine rete testis. The testes were imaged in vivo with fiberoptic confocal fluorescent microscopy and sperm foci were detected. The respective seminiferous tubules were excised and squash prepared for immunofluorescence microscopy. RESULTS: Sperm foci were identified in the testis injected with fluorescently tagged antibody by in vivo fiberoptic confocal fluorescence microscopy. The contralateral control testis of each mouse showed no specific signal. Immunofluorescence microscopy of the excised tubules provided morphological confirmation of the presence of labeled sperm with an absence in controls. Findings were consistent in the feasibility portion of the study and in the busulfan model of nonobstructive azoospermia. CONCLUSIONS: Fiberoptic confocal fluorescent microscopy was feasible during microdissection testicular sperm extraction in an azoospermic mouse model to identify fluorescently labeled sperm in vivo. Translation to the clinical setting could decrease operative time and improve the sperm harvest rate.
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Microdisección/métodos , Recuperación de la Esperma , Testículo/citología , Animales , Azoospermia/inducido químicamente , Busulfano/efectos adversos , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Microscopía Fluorescente , Túbulos Seminíferos/metabolismo , Recolección de Tejidos y Órganos/métodosRESUMEN
INTRODUCTION: To ensure public safety all Food and Drug Administration (FDA)-approved medications undergo postapproval safety analysis. Phosphodiesterase type-5 inhibitors (PDE5-i) are generally regarded as safe and effective. AIM: We performed a nonindustry-sponsored analysis of FDA reports for sildenafil, tadalafil, and vardenafil to evaluate the reported cardiovascular and mortality events over the past 10 years. METHODS: Summarized reports of adverse events (AEs) for each PDE5-i were requested from the Center for Drug Evaluation and Research within the FDA. These data are available under the Freedom of Information Act and document industry and nonindustry reports of AEs entered into the computerized system maintained by the Office of Surveillance and Epidemiology. MAIN OUTCOME MEASURE: The data were analyzed for the number of AE reports, number of objective cardiovascular events, and reported deaths. RESULTS: Overall, 14,818 AEs were reported for sildenafil. There were 1,824 (12.3%) reported deaths, and reports of cardiovascular AEs numbered 2,406 (16.2%). Tadalafil was associated with 5,548 AEs and 236 deaths were reported. Vardenafil was associated with 6,085 AEs and 121 reports of deaths. The percentage of reported severe cardiovascular disorders has stabilized at 10% to 15% of all AE reports for sildenafil and tadalafil and 5% to 10% for vardenafil. Only 10% of AE reports sent to the FDA for PDE5-i were from pharmaceutical manufacturers. CONCLUSION: Reports of deaths associated with PDE5-i remain around 5% of total reported events. Despite inherent limitations from evaluating FDA reports of AEs, it is important that these reports be reviewed outside pharmaceutical industry support in order to provide due diligence and transparency. Lowe G and Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012;9:265-270.
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Inhibidores de Fosfodiesterasa 5/efectos adversos , Carbolinas/efectos adversos , Carbolinas/uso terapéutico , Enfermedades Cardiovasculares/inducido químicamente , Disfunción Eréctil/tratamiento farmacológico , Humanos , Imidazoles/efectos adversos , Imidazoles/uso terapéutico , Masculino , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Piperazinas/efectos adversos , Piperazinas/uso terapéutico , Vigilancia de Productos Comercializados/estadística & datos numéricos , Purinas/efectos adversos , Purinas/uso terapéutico , Citrato de Sildenafil , Sulfonas/efectos adversos , Sulfonas/uso terapéutico , Tadalafilo , Triazinas/efectos adversos , Triazinas/uso terapéutico , Estados Unidos , United States Food and Drug Administration/estadística & datos numéricos , Diclorhidrato de VardenafilRESUMEN
OBJECTIVES: To determine cytokine responses in rat epididymal tissues after retrograde Escherichia coli inoculation of the cauda epididymidis via the intact and obstructed vas deferens. METHODS: Adult male Sprague-Dawley rats were divided into 3 groups: bilateral sham vasectomy followed by unilateral sham retrograde inoculation in the vas deferens (group A), bilateral sham vasectomy followed by unilateral retrograde inoculation of E. coli (group B), and bilateral vasectomy followed by left-sided inoculation of E. coli (group C). Three days later, the cauda epididymides and proximal vasa were subjected to histologic examination and assay for 9 cytokines. RESULTS: Groups A and C showed no histologic evidence of epididymal inflammation. Group B had leukocyte infiltrates in the inoculated tissue. Cytokine levels in the injected cauda epididymides were low in groups A and C; however, interleukin (IL)-1α, IL-1ß, and IL-4 were significantly increased in group B. The 6 other cytokines showed no significant change after E. coli infection though tumor necrosis factor-α, and IL-6 did show strong trends for increase. Contralateral epididymides never showed an inflammatory response. CONCLUSIONS: Experimental epididymitis induced by retrograde movement of bacteria in the vas deferens results in different responses by different cytokines. The cytokine responses and the histologically evident inflammation are prevented by vasectomy.
Asunto(s)
Citocinas/biosíntesis , Epididimitis/microbiología , Escherichia coli/metabolismo , Vasectomía/métodos , Animales , Citocinas/metabolismo , Epidídimo/microbiología , Regulación de la Expresión Génica , Humanos , Inflamación , Masculino , Ratas , Ratas Sprague-Dawley , Conducto Deferente/microbiologíaRESUMEN
PURPOSE: To review the evaluation and treatment of epididymitis in a contemporary population and evaluate adherence to Centers for Disease Control (CDC) guidelines. MATERIALS AND METHODS: From 1999 to 2005, 870 patients from a single institution were diagnosed with epididymitis. Information regarding patient demographics, diagnostic evaluation, and treatment was reviewed. Adherence to CDC guidelines for the treatment of acute epididymitis was evaluated. RESULTS: A total of 455 men between 3 and 88 years met inclusion requirements for acute epididymitis. Seven percent of pediatric patients (< 18 years) and 29.5% of adult patients (> or = 18 years) undergoing urine culture demonstrated bacterial growth. Twelve percent of adult patients with urethral swab PCR performed for Chlamydia trachomatis had positive results. A bacterial etiology for epididymitis was documented in 6.6% of pediatric patients and 28% of adult patients who were tested by urine culture and/or urethral swab for C. trachomatis. Less than 35% of adult men underwent the appropriate CDC work-up. Fifty percent of patients, 18-35 years and 85% of patients, > 35 years were prescribed an effective treatment according to CDC guidelines. Patients were less likely to be admitted to the hospital (100 vs. 2.3%) and more likely to be treated with antibiotics than in previously published series (97 vs. 75%). CONCLUSIONS: CDC guidelines for the evaluation and treatment of acute epididymitis were followed in less than 35% of patients seen in a university based health care system. Despite a paucity of documented urinary infection, 97% of adult men are treated empirically with antibiotics often not in accordance with CDC guidelines.