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INTRODUCTION: There is an average of 25 cases of penile cancer in the Republic of Ireland each year. Due to the low volume of cases, the National Institute for Clinical Excellence recommends that treatment is centralised to allow the best standardised treatment for primary tumours and nodal disease. OBJECTIVES: To determine whether outcomes for patients with penile cancer differed significantly between secondary and tertiary referral centres in the Republic of Ireland. METHODS: Between 2001 and 2014, 36 patients were treated in the Mercy University Hospital (MUH) with penile cancer. Twenty patients were treated primarily in MUH and 16 patients underwent initial management in a secondary referral centre (SRC) with subsequent referral to the MUH. A retrospective matched case-control study was performed on this patient cohort. RESULTS: There were no significant differences in length of follow-up or risk factors for the development of penile cancer between both groups (p = 0.6 and p = 0.5 respectively) Ultimately, the incidence of high risk disease, nodal metasases, high grade disease and pelvic lymph node dissection were significantly greater in patients that were initially managed in a SRC (p = 0.02, p = 0.03, p = 0.004 and p = 0.028 respectively). Patients undergoing initial treatment in a SRC had a non-significantly reduced rate of cancer specific survival (88 Vs 66%, MUH Vs SRCs, p = 0.495) and recurrence free survival (85 Vs 46%, MUH Vs SRCs, p = 0.24). CONCLUSION: Our findings suggest that managing penile cancer in special interest centres may improve oncological outcome.
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Manejo de la Enfermedad , Estadificación de Neoplasias , Neoplasias del Pene/terapia , Anciano , Estudios de Seguimiento , Humanos , Incidencia , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias del Pene/epidemiología , Estudios RetrospectivosRESUMEN
OBJECTIVES: To describe our experience of all patients presenting to a tertiary referral centre over a 3 year time period with blunt scrotal trauma and to describe a methodical approach for managing this group of patients. METHODS: A retrospective analysis was performed on all patients presenting to the Emergency Department (ED) of a level 1 trauma centre with blunt scrotal trauma from 2010 to 2013 inclusive. Inclusion criteria included a recent history of blunt scrotal trauma with associated pain and/or swelling of the affected testis on clinical examination. RESULTS: Twenty-seven male patients with a median age of 19 (range 8-65) years were included and all but 1 patient underwent scrotal ultrasonography upon presentation. Sixteen patients (59%) presented with scrotal trauma secondary to a sports related injury. Fifteen patients were managed conservatively and of the 12 who underwent urgent exploration 9 had a testicular rupture, including 1 who had an emergency orchidectomy due to a completely shattered testis. Four patients had >30% of the testis replaced by necrotic tissue/haematoma; of which 2 ultimately underwent orchidectomy and insertion of testicular prosthesis. CONCLUSION: Our findings demonstrate that the necessity for scrotal protection in sports that predispose to scrotal trauma should be reviewed. We also demonstrate the importance of scrotal ultrasonography for determining an appropriate management strategy (i.e., conservative versus surgical treatment) in this young patient cohort.
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Diagnóstico por Imagen/métodos , Manejo de la Enfermedad , Servicio de Urgencia en Hospital , Guías de Práctica Clínica como Asunto , Escroto/lesiones , Heridas no Penetrantes , Adolescente , Adulto , Anciano , Niño , Humanos , Islandia/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Heridas no Penetrantes/epidemiología , Heridas no Penetrantes/etiología , Heridas no Penetrantes/terapia , Adulto JovenRESUMEN
INTRODUCTION AND HYPOTHESIS: Botulinum toxin-A (BoNT-A) is a potent neurotoxin that is an effective treatment for patients with pharmacologically refractory detrusor overactivity (DO). Data assessing the effectiveness of trigonal BoNT-A are limited. This study evaluates adverse events (AEs) and short-term efficacy associated with trigonal and extratrigonal BoNT-A. METHODS: Electronic databases (PubMed, EMBASE, and the Cochrane database) were searched for studies comparing trigonal and extratrigonal BoNT-A for DO. Meta-analyses were performed using the random effects model. Outcome measures included incidence of AEs and short-term efficacy. RESULTS: Six studies describing 258 patients met the inclusion criteria. The meta-analysis did not show significant differences between trigonal and extratrigonal BoNT-A for acute urinary retention (AUR; 4.2 vs 3.7 %; odds ratio [OR]: 1.068, 95 % confidence interval [CI]: 0.239-4.773; P = 0.931) or high post-void residual (PVR; 25.8 vs 22.2 %; OR: 0.979; 95 % CI: 0.459-2.088; P = 0.956). The incidence of urinary tract infection (UTI; 7.5 vs 21.0 %; OR: 0.670; 95 % CI: 0.312-1.439; P = 0.305), haematuria (15.8 vs 25.9 %; OR: 0.547; 95 % CI: 0.264-1.134; P = 0.105) and post-operative muscle weakness (9.2 vs 11.3 %; OR: 0.587; 95 % CI: 0.205-1.680, P = 0.320) was similar in both groups. Finally, differences in short-term cure rates between two study arms were not statistically significant (52.9 vs 56.9 %; OR: 1.438; 95 % CI: 0.448-4.610; P = 0.542). CONCLUSIONS: Although data are limited, no significant differences between trigonal and extratrigonal BoNT-A in terms of AEs and short-term efficacy were observed. Additional randomised controlled trials are required to define optimal injection techniques and sites for administering intra-vesical BoNT-A.
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Inhibidores de la Liberación de Acetilcolina/administración & dosificación , Inhibidores de la Liberación de Acetilcolina/efectos adversos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/efectos adversos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Administración Intravesical , HumanosRESUMEN
Since the National Treatment Purchase Fund (NTPF) scheme was introduced in 2002, public patients waiting longer than three months for investigations and treatment are offered care in the private medical sector. Our aim was to assess the impact of the NTPF scheme on the number of training cases performed at University Hospital Galway (UHG). The number and type of urological procedures performed in the private medical sector under the NTFP scheme in 2008 were obtained from the UHG waiting list office. The number of these procedures performed on public patients by trainees at UHG in 2008 was determined retrospectively by reviewing theatre records. A significant number of core urology procedures were performed in the private sector via the NTPF scheme. Cancer centre designation and implementation of the EWTD will also place further pressures on urological training opportunities in Ireland.
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Enfermedades Urológicas/cirugía , Procedimientos Quirúrgicos Urológicos/educación , Listas de Espera , Competencia Clínica , Educación de Postgrado en Medicina , Hospitales Universitarios , Humanos , Internado y Residencia , Irlanda , Sector Privado , Estudios RetrospectivosRESUMEN
AIMS: To compare sextant and 12 core transrectal ultrasound-guided (TRUS) prostate biopsies for detecting prostate cancer (PCa) and to determine whether 12-core prostate biopsies are associated with a higher incidence of insignificant prostate cancer and complications. METHODS: A retrospective study was performed on all patients with a positive TRUS biopsy for prostate cancer between January 2011 and December 2013. Group A underwent a sextant core prostate biopsy and group B underwent a 12-core prostate biopsy. Outcome variables were cancer detection rates, oncological outcomes, incidence of clinically insignificant PCa and incidence of biopsy associated complications. Exclusion criteria included a negative TRUS biopsy and metastatic prostate cancer. RESULT: In total 718 prostate biopsies were performed and 286 patients met inclusion criteria (143 patients in each group). The overall cancer detection rate was 43 % in group A compared to 53 % in group B (p = 0.03). In group A, 31 (21.7 %) patients proceeded to open retropubic radical prostatectomy (RRP) compared to 36 (25.2 %) in group B (p = 0.7). Sextant biopsies were associated with a significantly higher rate of upgrading compared to 12-core biopsies in RRP specimens (51.6 versus 25 % respectively, p < 0.01). The incidence of clinically insignificant PCa was 10.5 % in group A versus 14.7 % in group B (p = 0.2). The incidence of urosepsis post biopsy was 0.7 % in both groups (n = 1). CONCLUSION: Twelve-core biopsies were associated with higher PCa cancer detection rates, greater accuracy for Gleason grading and no differences for detecting clinically insignificant PCa or urosepsis compared to sextant biopsies.
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Prostatectomía/estadística & datos numéricos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Anciano de 80 o más Años , Biopsia con Aguja/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Próstata/patología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Estudios RetrospectivosRESUMEN
BACKGROUND: Our institution has recently developed a rapid access outpatient clinic to investigate men with testicular lumps and/or pain suspicious for testicular cancer (TCa). AIMS: To present our experience after 12 months. METHODS: All referrals to the rapid access testicular clinic (RATC) clinic were prospectively analysed from 01/01/2013 to 01/01/2014. The primary outcome variable was incidence of TCa in the referred patient cohort. Secondary outcome variables were waiting times prior to clinical review and waiting times prior to radical orchidectomy in patients diagnosed with TCa. RESULTS: Seventy-four new patients were referred to the RATC during the 1-year period and the mean age was 34 (range 15-81 years). TCa was the most common diagnosis and was found in 18 (25 %) patients. Patients diagnosed with TCa underwent radical orchidectomy, a median of 3 (range 1-5) days after their initial GP referral. Patients requiring surgical intervention for benign scrotal pathology underwent their procedure a median of 32 (range 3-61) days after their initial referral. Of the 18 patients diagnosed with TCa, 9 (50 %) were diagnosed with a seminomatous germ cell tumour on histopathology. CONCLUSION: The RATC is a new initiative in Ireland that provides expedient and definitive treatment of patients with newly diagnosed TCa. Early treatment will ultimately improve long-term prognosis in this patient cohort.
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Atención Ambulatoria/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Neoplasias de Células Germinales y Embrionarias/terapia , Derivación y Consulta/estadística & datos numéricos , Neoplasias Testiculares/terapia , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Incidencia , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/epidemiología , Orquiectomía/estadística & datos numéricos , Estudios Prospectivos , Neoplasias Testiculares/epidemiología , Factores de Tiempo , Servicio de Urología en Hospital/estadística & datos numéricos , Adulto JovenRESUMEN
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic debilitating condition that can have a severely negative impact on a patient's quality of life. Its prevalence ranges from 52 to 500/100,000 in females compared to 8-41/100,000 in males, and its incidence is increasing globally. Treatment algorithms are sub-classified into behavioural, pharmacological, intravesical, interventional and surgical therapies. Short-term (i.e. <1 year) cure rates range from 50% to 75% for non-/minimally-invasive therapies, but repeat administration of a therapeutic agent is required. Although definitive surgical intervention is associated with greater long-term cure rates (≥80%); significant short- and long-term adverse effects occur more frequently. Clinicians are likely to experience increasing numbers of patients with IC/PBS as more is understood about its pathophysiology and evolving epidemiology. Therefore urogynaecologists should familiarise themselves with appropriate diagnostic criteria and evidence based therapies to optimise clinical outcomes in this patient cohort.
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Cistitis Intersticial/terapia , Cistitis Intersticial/diagnóstico , Cistitis Intersticial/epidemiología , Cistitis Intersticial/fisiopatología , Medicina Basada en la Evidencia , HumanosRESUMEN
BACKGROUND: Paediatric circumcision is one of the oldest surgical procedures performed worldwide. Traditionally performed by general surgeons, paediatric surgeons and urologists, there is a falling trend in the rate of paediatric circumcision being performed by adult and paediatric general surgeons. There is currently no corresponding contemporary data pertaining to trends and attitudes of general surgeons to paediatric circumcision in Ireland. AIM: The aim of this study was to assess the trends and attitudes of consultant general surgeons, and to assess its potential impact on the specialist delivery of paediatric urological care. METHODS: A questionnaire was mailed to all practicing general surgeons in whom we identified as having a potential role in the management of paediatric circumcision. Data pertaining to population demographics within the south of Ireland were accessed through the Central Statistics Office. RESULTS: There was an 89 % response rate to the questionnaire survey. Seventy-seven percent of those under 50 were trained in adult circumcision compared with 100 % of those respondents over 50 years. There was a significant difference in paediatric circumcision with only 24 % those under 50 performing this procedure compared with 68 % above 50 years. Eighty-six percent respondents under 45 years (35 % over 45 years) felt that this procedure should be carried out by urology. CONCLUSION: In a region with an expanding paediatric population, it is crucial to maintain paediatric urological services. Given present trends and attitudes of newer appointed general surgeons, it is essential that further specialist appointments are made, and funding directed towards demand in order to keep pace.
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Actitud del Personal de Salud , Circuncisión Masculina/tendencias , Cirugía General/tendencias , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Irlanda , Masculino , Persona de Mediana Edad , Rol del Médico , Encuestas y CuestionariosRESUMEN
Methylphenidate is a medication used routinely in the management of attention deficit hyperactivity disorder. We report a case of a prepubertal child who developed unwanted erections after commencing a response-adjusted dosing regimen of sustained release methylphenidate. Despite priapism being a rare adverse reaction associated with methylphenidate, physicians and parents need to be aware as it can have significant long-term complications.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/efectos adversos , Metilfenidato/efectos adversos , Priapismo/inducido químicamente , Factores de Edad , Estimulantes del Sistema Nervioso Central/administración & dosificación , Niño , Humanos , Masculino , Metilfenidato/administración & dosificaciónRESUMEN
PURPOSE: The pubovaginal sling has been criticized as having a higher incidence of postoperative voiding dysfunction than other surgical approaches for the management of stress urinary incontinence. In 2 similar patient groups we prospectively compared the rates of early postoperative voiding dysfunction after the pubovaginal sling or Stamey procedure. MATERIALS AND METHODS: Between June 1995 and January 1997, 50 consecutive patients underwent the pubovaginal sling or Stamey procedure. Emptying efficiency was measured 48 hours postoperatively by suprapubic catheter in the Stamey group and intermittent catheterization in the pubovaginal sling group. When emptying efficiency was greater than 75%, intermittent catheterization was stopped or the suprapubic catheter was removed. RESULTS: There was no statistically significant difference in emptying efficiency for the first 3 voids using the Dunn multiple comparison method. Median voiding efficiencies were 37%, 43% and 61% with the Stamey procedure in group 1 (mean 43%, 45% and 54%), and 60%, 75% and 75% with the pubovaginal sling in group 2 (mean 49%, 68% and 69%), respectively. The mean number of intermittent catheterizations performed in patients with the pubovaginal sling was 5.7 in less than 1 day. In the Stamey group the suprapubic catheter was removed an average of 6 days postoperatively. The mean duration of hospital stay was similar for the sling and Stamey groups (5.4 versus 6 days, respectively). There were 2 patients in each group who were voiding inefficiently after day 7. Voiding efficiency was restored at 53 and 86 days in the 2 patients with slings and at 18 days in 1 of the 2 who underwent the Stamey procedure, respectively. The second patient who underwent the Stamey procedure was able to void without using the catheter at all, and it was removed 30 days postoperatively when emptying efficiency was confirmed greater than 75%. CONCLUSIONS: These data show that early postoperative voiding dysfunction, measured using bladder emptying efficiency, after the pubovaginal sling is no more common than after the Stamey procedure and help justify the broadened indications for pubovaginal sling for treatment of stress urinary incontinence.
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Vejiga Urinaria/fisiopatología , Incontinencia Urinaria de Esfuerzo/cirugía , Femenino , Humanos , Tiempo de Internación , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Cateterismo Urinario , Incontinencia Urinaria de Esfuerzo/fisiopatología , Micción , Trastornos Urinarios/diagnóstico , Trastornos Urinarios/etiología , Urodinámica , Procedimientos Quirúrgicos Urológicos/métodosRESUMEN
OBJECTIVES: To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy. METHODS: Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital. RESULTS: Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication. CONCLUSIONS: Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.
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Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/etiología , Hipotensión Ortostática/inducido químicamente , Atrofia de Múltiples Sistemas/complicaciones , Enfermedad de Parkinson/complicaciones , Inhibidores de Fosfodiesterasa/uso terapéutico , Piperazinas/uso terapéutico , Anciano , Presión Sanguínea/efectos de los fármacos , Estudios Cruzados , Diástole , Método Doble Ciego , Efedrina/uso terapéutico , Disfunción Eréctil/clasificación , Disfunción Eréctil/psicología , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Midodrina/uso terapéutico , Purinas , Calidad de Vida , Índice de Severidad de la Enfermedad , Citrato de Sildenafil , Sulfonas , Encuestas y Cuestionarios , Sístole , Factores de Tiempo , Resultado del Tratamiento , Vasoconstrictores/uso terapéuticoRESUMEN
The majority of patients with multiple sclerosis (MS) develop troublesome lower urinary tract symptoms (LUTS). Anecdotal reports suggest that cannabis may alleviate LUTS, and cannabinoid receptors in the bladder and nervous system are potential pharmacological targets. In an open trial we evaluated the safety, tolerability, dose range, and efficacy of two whole-plant extracts of Cannabis sativa in patients with advanced MS and refractory LUTS. Patients took extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD; 2.5 mg of each per spray) for eight weeks followed by THC-only (2.5 mg THC per spray) for a further eight weeks, and then into a long-term extension. Assessments included urinary frequency and volume charts, incontinence pad weights, cystometry and visual analogue scales for secondary troublesome symptoms. Twenty-one patients were recruited and data from 15 were evaluated. Urinary urgency, the number and volume of incontinence episodes, frequency and nocturia all decreased significantly following treatment (P <0.05, Wilcoxon's signed rank test). However, daily total voided, catheterized and urinary incontinence pad weights also decreased significantly on both extracts. Patient self-assessment of pain, spasticity and quality of sleep improved significantly (P <0.05, Wilcoxon's signed rank test) with pain improvement continuing up to median of 35 weeks. There were few troublesome side effects, suggesting that cannabis-based medicinal extracts are a safe and effective treatment for urinary and other problems in patients with advanced MS.
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Cannabis/química , Esclerosis Múltiple/complicaciones , Extractos Vegetales/uso terapéutico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Neurogénica/etiología , Adulto , Cannabidiol/administración & dosificación , Cannabidiol/efectos adversos , Cannabidiol/uso terapéutico , Relación Dosis-Respuesta a Droga , Dronabinol/administración & dosificación , Dronabinol/efectos adversos , Dronabinol/uso terapéutico , Esquema de Medicación , Estudios de Seguimiento , Humanos , Registros Médicos , Persona de Mediana Edad , Proyectos Piloto , Extractos Vegetales/administración & dosificación , Extractos Vegetales/efectos adversos , Sensación , Encuestas y Cuestionarios , Resultado del Tratamiento , Vejiga Urinaria/fisiopatología , Vejiga Urinaria Neurogénica/fisiopatología , Incontinencia Urinaria/fisiopatología , Micción , UrodinámicaRESUMEN
OBJECTIVE: To investigate endothelial nitric oxide synthase (eNOS) immunoreactivity in bladder biopsies from patients with neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, and compare this with control material; the distribution of two other vascular markers, von Willebrand Factor (vWF) and the vascular endothelial growth factor (VEGF), was also studied. PATIENTS AND METHODS: Flexible cystoscopic bladder biopsies from eight controls investigated for asymptomatic microhaematuria and 19 patients with refractory spinal NDO enrolled in a clinical trial of intravesical treatment with escalating doses of resiniferatoxin were immunostained with polyclonal rabbit antibodies for eNOS, vWF and VEGF. Fewer baseline NDO specimens (eight) were available for vWF and VEGF staining. Computerized image analysis was used to quantify immunoreactivity, and the Mann-Whitney test for statistical analysis. RESULTS: eNOS immunoreactivity was found in the suburothelium and less often in the urothelium, with a distribution indicating a location in small blood vessels at the urothelium-suburothelium junction. Immunostaining for vWF showed a similar location. There was a trend to higher eNOS values before treatment in those responding than in those not responding to resiniferatoxin (P = 0.059), and a significant reduction in eNOS immunoreactivity after successful treatment (P = 0.016). VEGF staining was weaker but there was a significant increase in pretreatment biopsies of responders to resiniferatoxin (P = 0.048). Clinical and histopathology features were similar in both groups. CONCLUSIONS: The trend for higher eNOS expression in patients with NDO who responded to resiniferatoxin suggests that increased vasculature or vasodilatation in the suburothelium may be necessary for successful intravesical treatment. Further studies with more patients are required to confirm this relationship and to examine the mechanisms underlying changes in vasculature with levels of bladder overactivity.
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Diterpenos/administración & dosificación , Neurotoxinas/administración & dosificación , Óxido Nítrico Sintasa/metabolismo , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria/enzimología , Administración Intravesical , Biopsia/métodos , Método Doble Ciego , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III , Estudios Prospectivos , Vejiga Urinaria/patología , Vejiga Urinaria Neurogénica/enzimología , Vejiga Urinaria Neurogénica/patología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To compare PGP9.5 and transient receptor potential vanilloid receptor (TRPV1) suburothelial immunoreactivity between controls and patients with spinal neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, as suburothelial PGP9.5-staining nerve fibres decrease in patients with spinal NDO who respond to intravesical capsaicin, and TRPV1 is present on these suburothelial nerve fibres in normal and overactive human urinary bladder. PATIENTS AND METHODS: Patients with refractory NDO were enrolled in a prospective, randomized, parallel-group, double-blind, placebo-controlled trial using escalating doses of resiniferatoxin to a maximum of 1 micro mol/L. Flexible cystoscopic bladder biopsies obtained at baseline, 4 weeks after each instillation and at the time of maximum clinical response were compared with biopsies taken from control subjects. Frozen sections were incubated with rabbit antibodies to TRPV1 and PGP9.5, and assessed using standard immunohistochemical methods. PGP9.5 nerve density was analysed using a nerve-counting graticule by an observer unaware of sample origin. Another two independent observers unaware of each other's results used a random grading scale to evaluate TRPV1 nerve fibre density and intensity. The immunohistochemistry results were compared with histology findings (haematoxylin-eosin), and the Mann-Whitney test used to assess any differences (P < 0.05 significant) and the Pearson test for correlation. RESULTS: There were eight controls and 20 patients with spinal NDO, 14 (five clinical responders and nine not) who received the maximum dose of resiniferatoxin. There were more PGP9.5 and TRPV1 nerve fibres in patients with NDO than in controls (P = 0.007 and 0.002, respectively). Immunoreactivity before resiniferatoxin was similar in both groups for both PGP9.5 and TRPV1. In responders there were fewer PGP9.5 and TRPV1-positive fibres after treatment (P = 0.008 for each) but no change in those not responding. Changes after treatment for TRPV1 correlated well with those for PGP9.5 (r = 0.88, P < 0.001). CONCLUSIONS: The decrease of PGP9.5 and TRPV1 immunoreactive nerve fibres in responders to resiniferatoxin (to levels in control tissues) suggests that the increased numbers of nerve fibres in patients with NDO are mainly of sensory origin and express TRPV1. As baseline nerve fibre values were similar in responders and nonresponders, an additional factor may account for the difference in treatment outcome.