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1.
BJU Int ; 134(2): 148-154, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38778743

ABSTRACT

OBJECTIVES: To provide guidance in the form of consensus statement in the management of ketamine uropathy. METHODS: A literature review of ketamine uropathy was performed. The consensus method was of a modified nominal group technique and has been use in the previous British Association of Urological Surgeons (BAUS) consensus documents and was led by the Female, Neurological and Urodynamic Urology Section of the BAUS. RESULTS: A number of consensus statements detailing the assessment and management of urological complications relate to the recreational use of ketamine (ketamine uropathy) in both elective and emergency urology settings. CONCLUSION: Comprehensive management pathway for ketamine-related urinary tract dysfunction and uropathy has been detailed.


Subject(s)
Ketamine , Female , Humans , Male , Anesthetics, Dissociative/adverse effects , Consensus , Ketamine/adverse effects , Substance-Related Disorders/complications , United Kingdom , Urologic Diseases/chemically induced , Urologic Diseases/therapy , Urology/standards
2.
BJU Int ; 129(2): 151-159, 2022 02.
Article in English | MEDLINE | ID: mdl-33772995

ABSTRACT

OBJECTIVES: To report the British Association of Urological Surgeon's (BAUS) guidance on the assessment and management of female voiding dysfunction. METHODS: A contemporary literature search was conducted to identify the evidence base. The BAUS Section of Female, Neurological and Urodynamic Urology (FNUU) Executive Committee formed a guideline development group to draw up and review the recommendations. Where there was no supporting evidence, expert opinion of the BAUS FNUU executive committee, FNUU Section and BAUS members, including urology consultants working in units throughout the UK, was used. RESULTS: Female patients with voiding dysfunction can present with mixed urinary symptoms or urinary retention in both elective and emergency settings. Voiding dysfunction is caused by a wide range of conditions which can be categorized into bladder outlet obstruction (attributable to functional or anatomical causes) or detrusor underactivity. Guidance on the assessment, investigation and treatment of women with voiding dysfunction and urinary retention, in the absence of a known underlying neurological condition, is provided. CONCLUSION: Wa have produced a BAUS approved consensus on the management pathway for female voiding dysfunction with the aim to optimize assessment and treatment pathways for patients.


Subject(s)
Surgeons , Urinary Bladder Neck Obstruction , Urinary Retention , Consensus , Female , Humans , Urinary Bladder Neck Obstruction/surgery , Urinary Retention/diagnosis , Urinary Retention/etiology , Urinary Retention/therapy , Urodynamics
3.
BJU Int ; 128(5): 539-547, 2021 11.
Article in English | MEDLINE | ID: mdl-33835614

ABSTRACT

Injuries to the bladder and ureter are uncommon but usually require prompt urological management. Due to their infrequent nature, Urologists maybe unfamiliar with managing these acute problems and may not work in specialist centres with readily available expertise in open and abdominal surgery. We aim to provide advice in the form of a consensus statement led by the Female, Neurological and Urodynamic Urology (FNUU) Section of the British Association of Urological Surgeons (BAUS), in consultation with BAUS members and consultants working in units throughout the UK, to create a comprehensive management pathway and a series of statements to aid clinicians.


Subject(s)
Hemorrhage/therapy , Ureter/injuries , Urinary Bladder/injuries , Wounds and Injuries/diagnostic imaging , Wounds and Injuries/therapy , Catheterization , Consensus , Foreign Bodies/surgery , Hemorrhage/etiology , Humans , Iatrogenic Disease/prevention & control , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/therapy , Plastic Surgery Procedures , United Kingdom , Urologic Surgical Procedures/adverse effects , Wounds and Injuries/complications
4.
BJU Int ; 128(6): 667-677, 2021 12.
Article in English | MEDLINE | ID: mdl-33811741

ABSTRACT

OBJECTIVE: To look at best evidence and expert opinion to provide advice in the form of a consensus statement lead by Female, Neurological and Urodynamic Urology (FNUU) section of the British Association of Urological Surgeons (BAUS) in conjunction with the British Association of Urological Nurses (BAUN). METHODS: Initially a literature search was performed with incorporation of aspects of the existing guidance and further informed by UK best practice by core members of the group. The document then underwent reviews by the FNUU Executive Committee members, the BAUN executive committee, a separate experienced urologist and presented at the BAUS annual meeting 2020 to ensure wider feedback was incorporated in the document. RESULTS: Complications of long-term indwelling catheters include catheter-associated urinary tract infections (CAUTI), purple urine bag syndrome, catheter blockages, bladder spasms (causing pain and urinary leakage), loss of bladder capacity, urethral erosion ("catheter hypospadias")/dilatation of bladder outlet and chronic inflammation (metaplasia and cancer risk). CONCLUSIONS: We have provided a list of recommendations and a troubleshooting table to help with the management of the complications of long term catheters.


Subject(s)
Catheter Obstruction/etiology , Catheter-Related Infections/therapy , Catheters, Indwelling/adverse effects , Urinary Bladder Diseases/therapy , Urinary Catheters/adverse effects , Urinary Tract Infections/therapy , Catheter-Related Infections/etiology , Consensus , Humans , Metaplasia/etiology , Necrosis/etiology , Necrosis/prevention & control , Spasm/etiology , Therapeutic Irrigation , Time Factors , Urethra/pathology , Urinary Bladder/pathology , Urinary Bladder Diseases/etiology , Urinary Tract Infections/etiology
5.
Neurourol Urodyn ; 39(4): 1170-1177, 2020 04.
Article in English | MEDLINE | ID: mdl-32187720

ABSTRACT

AIM: The International Continence Society (ICS) has standardized quality control and interpretation of uroflowmetry and urodynamics. We evaluated traces from two large studies of male lower urinary tract symptoms (UPSTREAM and UNBLOCS) against ICS standards of urodynamic equipment and practice. METHODS: Ten percent of uroflowmetry and urodynamics traces were selected at random from hospital sites. A data capture template was designed from the ICS Fundamentals of Urodynamic Practice checklist. Two pretrained blinded assessors extracted the data, with a third assessor to arbitrate. Departmental records of calibration checks and equipment maintenance were scrutinized. RESULTS: Seven out of twenty-five (28%) departments reported no calibration checks. Four sites (16%) could not provide annual service records. In 32 out of 296 (10.8%) uroflowmetry traces, findings were affected by artifact. One hundred ten urodynamic study traces were reviewed; in 11 records (10%), key pressure traces were incompletely displayed. In 30 (27.2%), reference zero was not set to atmospheric pressure. Resting pressures were outside the expected range for 36 (32.7%). Pressure drift was seen in 18 traces (16.4%). At pressure-flow study commencement, permission to void was omitted in 15 (13.6%). Cough testing after voiding was done in 71.2%, but the resulting cough spikes were significantly different in 16.5%. Erroneous diagnosis of bladder outlet obstruction (BOO) was identified in six cases (5.5%). CONCLUSIONS: Erroneous diagnosis of BOO is a serious error of interpretation, as it could lead to unnecessary surgery. Other errors of standardization, testing, and interpretation were identified with lower risk of adverse implications. Inconsistent documentation of service records mean equipment accuracy is uncertain.


Subject(s)
Lower Urinary Tract Symptoms/diagnosis , Urinary Bladder Neck Obstruction/diagnosis , Urination/physiology , Urodynamics/physiology , Diagnostic Errors , Humans , Lower Urinary Tract Symptoms/physiopathology , Male , Middle Aged , Quality Control , Societies , Urinary Bladder Neck Obstruction/physiopathology
6.
BMC Med Educ ; 20(1): 349, 2020 Oct 07.
Article in English | MEDLINE | ID: mdl-33028303

ABSTRACT

BACKGROUND: Whilst competence in the management of a wide range of urological emergencies is a requirement for certification in urology, many conditions are uncommon and exposure during training may be limited. This prospective observational study sought to evaluate the feasibility and effectiveness of a standardised cadaveric emergency urology simulation course aimed at improving operative confidence and competence prior to independent on-call practice in the United Kingdom. METHODS: A two-day cadaveric emergency urology simulation course supported by the British Association of Urological Surgeons (BAUS) was implemented at two pilot centres. All delegates that undertook one of the initial series of courses were invited to complete online pre- and post-course questionnaires relating to prior operative experience, documented competence and perceived confidence in being able to perform specific emergency procedures independently. Primary outcome was a self-reported 'confidence score' selected from a linear numeric scale ranging from 1 (not at all confident to perform a given procedure independently) to 10 (fully confident). Statistical analysis was undertaken using SPSS Statistics for Mac Version 25 and the paired student's t-test used to compare mean pre- and post-course scores. RESULTS: One hundred and four delegates undertook the course during the study period. Of these, 85 (81.7%) completed the pre-course survey and 67 (64.4%) completed the post-course survey, with 61 (58.7%) completing both. The greatest proportion of respondents were Speciality Trainees in Urology of ST5 level or higher (equivalent of Resident/Fellows with 4 or more years of surgical training; n = 31, 36.5%). Delegates reported variable pre-course exposure, with most experience reported in loin approach to the kidney (median 10) and least in exploration and packing of a transurethral resection cavity and emergency nephrectomy (median 0). Following course completion, a statistically significant increase in confidence score was observed for each procedure, with the greatest increases seen for shunt for priapism (4.87 to 8.80, p < 0.001), ureteric reimplantation (3.52 to 7.33, p < 0.001) and primary ureteric anastomosis (3.90 to 7.49, p < 0.001). CONCLUSIONS: A standardised high fidelity cadaveric simulation course is feasible and significantly improves the confidence of trainees in performing a wide range of emergency procedures to which exposure is currently limited.


Subject(s)
Urology , Cadaver , Clinical Competence , Emergencies , Humans , Male , United Kingdom , Urology/education
7.
BJU Int ; 123(1): 149-159, 2019 01.
Article in English | MEDLINE | ID: mdl-30222915

ABSTRACT

OBJECTIVES: To analyse the results of the stress urinary incontinence (SUI) audit conducted by the British Association of Urological Surgeons (BAUS), and to present UK urologists' contemporary management of SUI. PATIENTS AND METHODS: The BAUS audit tool is an online resource, to which all UK urologists performing procedures for SUI are invited to submit data. The data entries for procedures performed during 2014-2016 were collated and analysed. RESULTS: Over the 3-year period analysed, 2917 procedures were reported by 109 surgeons, with a median of 20 procedures reported per surgeon. A total of 2 366 procedures (81.1%) were recorded as a primary surgery, with 548 procedures (18.8%) performed for recurrent SUI. Within the time period analysed, changes were noted in the frequency of all procedures performed, with a trend towards a reduction in the use of synthetic mid-urethral tapes, and a commensurate increase in the use of urethral bulking agents and autologous fascial slings. A total of 107 (3.9% of patients) peri-operative complications were recorded, with no association identified with patient age, BMI or surgeon volume. Follow-up data were available on 1832 patients (62.8%) at a median of 100 days postoperatively. Reduced pad use was reported in 1311 of patients (84.5%) with follow-up data available and 86.3% reported a pad use of one or less per day. In all, 375 patients (85%) reported being satisfied or very satisfied with the outcome of their procedure at follow-up, although data entry for this domain was poor. De novo overactive bladder (OAB) symptoms were reported by 15.2% of patients (263/1727), and this was the most commonly reported postoperative complication. For those reporting pre-existing OAB prior to their SUI surgery, 28.7% (307/1069) of patients reported they got better after their procedure, whilst 61.9% (662/1069) of patients reported no change and 9.4% of patients (100/1 069) got worse. CONCLUSIONS: This review identified that, despite urological surgeons undertaking a relatively low volume of procedures per year, SUI surgery by UK urologists is associated with excellent short-term surgeon- and patient-reported outcomes and low numbers of low grade complications. Complications do not appear to be associated with surgeon volume, nor do they appear higher in those undergoing mesh surgery. Shortfalls in data collection have been identified, and a longer follow-up period is required to comment adequately on long-term complications, such as chronic pain and tape extrusion/erosion rates.


Subject(s)
Medical Audit , Practice Patterns, Physicians'/trends , Suburethral Slings/trends , Urinary Incontinence, Stress/surgery , Urology/statistics & numerical data , Absorbent Pads , Adolescent , Adult , Aged , Aged, 80 and over , Data Collection/standards , Fascia/transplantation , Female , Humans , Intraoperative Complications/etiology , Middle Aged , Pain, Postoperative/etiology , Patient Satisfaction , Reoperation , Suburethral Slings/adverse effects , Surgical Mesh/adverse effects , Treatment Outcome , United Kingdom , Urinary Bladder, Overactive/etiology , Urology/trends , Young Adult
8.
Curr Opin Urol ; 27(3): 307-313, 2017 May.
Article in English | MEDLINE | ID: mdl-28267055

ABSTRACT

PURPOSE OF REVIEW: To assess the contemporary literature on the prevalence, cause and management of lower urinary tract symptoms (LUTS) and bladder overactivity following treatment of prostate cancer with radical surgery, radiotherapy and minimally invasive therapies for localized prostate cancer, including cryotherapy and high-intensity focused ultrasound (HIFU). RECENT FINDINGS: Generally, the highest risk of urinary incontinence is after open radical prostatectomy (7-40%), although not all contemporary studies demonstrate a difference between open and laparoscopic techniques. An increased incidence of bladder overactivity is seen with radiotherapy (as compared to radical prostatectomy). Bladder outlet obstruction is most commonly encountered after radical prostatectomy and radiotherapy combination therapy (up to 26%). It manifests as voiding LUTS or urinary retention, and the risk can accumulate over time. Cryotherapy and HIFU provide effective cancer treatment with lower risks of urinary incontinence, but have fewer published studies and shorter follow-up. Medical treatment options for LUTS include alpha blockers, anticholinergics, and potentially intravesical glycosaminoglycan analogue instillations. Stress urinary incontinence requires surgical correction with artificial urinary sphincter or suburethral slings. SUMMARY: Patients who have undertaken successful prostate cancer treatment have a good prognosis, and commonly present for further interventions to optimise quality of life if bothersome urinary symptoms are experienced. It is important to be vigilant for and treat any adverse urinary consequences.


Subject(s)
Lower Urinary Tract Symptoms , Prostatectomy/adverse effects , Prostatic Neoplasms/surgery , Urinary Bladder, Overactive , Humans , Lower Urinary Tract Symptoms/epidemiology , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/therapy , Male , Prostatic Neoplasms/psychology , Quality of Life , Urinary Bladder, Overactive/epidemiology , Urinary Bladder, Overactive/etiology , Urinary Bladder, Overactive/therapy
9.
Neurourol Urodyn ; 35(3): 365-70, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25663151

ABSTRACT

AIMS: In this review, we focus on the current attempts of electrical nerve stimulation for micturition in spinal cord injury (SCI) patients. METHODS: A literature search was performed through PubMed using "spinal cord injury," "electrical nerve stimulation AND bladder," "sacral anterior root stimulation/stimulator" and "Brindley stimulator" from January 1975 to January 2014. RESULTS: Twenty studies were selected for this review. CONCLUSION: Electrical nerve stimulation is a clinical option for promoting micturition in SCI patients. Well-designed, randomized and controlled studies are essential for further investigation.


Subject(s)
Electric Stimulation Therapy/methods , Spinal Cord Injuries/therapy , Urinary Bladder, Neurogenic/therapy , Urinary Bladder/innervation , Urination , Electric Stimulation Therapy/instrumentation , Humans , Implantable Neurostimulators , Recovery of Function , Spinal Cord Injuries/complications , Spinal Cord Injuries/diagnosis , Spinal Cord Injuries/physiopathology , Treatment Outcome , Urinary Bladder, Neurogenic/diagnosis , Urinary Bladder, Neurogenic/etiology , Urinary Bladder, Neurogenic/physiopathology
10.
BJU Int ; 109(9): 1280-93, 2012 May.
Article in English | MEDLINE | ID: mdl-22117733

ABSTRACT

What's known on the subject? And what does the study add? There is a wealth of evidence on the development, indications, outcomes and complications of augmentation cystoplasty (AC). Over the last decade, new evidence has been emerging to influence our clinical practice and application of this technique. AC is indicated as part of the treatment pathway for both neurogenic and idiopathic detrusor overactivity, usually where other interventions have failed or are inappropriate. The most commonly used technique remains augmentation with a detubularised patch of ileum (ileocystoplasty). Controversy persists over the role of routine surveillance following ileocystoplasty for the detection of subsequent bladder carcinoma; however the indication for surveillance after gastrocystoplasty is clearer due to a rising incidence of malignancy in this group. Despite a reduction in the overall numbers of AC operations being performed, it clearly still has a role to play, which we re-examine with contemporary studies from the last decade.


Subject(s)
Urinary Bladder, Overactive/surgery , Urologic Surgical Procedures/methods , Humans , Postoperative Complications , Renal Insufficiency/complications , Urinary Bladder Diseases/etiology , Urinary Bladder, Overactive/complications , Urinary Calculi/etiology , Urologic Surgical Procedures/adverse effects
11.
BJU Int ; 103(4): 454-7, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18782304

ABSTRACT

OBJECTIVE: To assess the incidence and outcome of incidental prostate cancer detected at transurethral resection of the prostate (TURP), and to evaluate whether laser ablation prostatectomy would miss significant cancer by failing to provide tissue for histopathological analysis. PATIENTS AND METHODS: Information on TURP-detected prostate cancer was gathered from 1996 to 2006, from The South-west Cancer Intelligence Service, hospital-operating and coding records, histopathology databases and The British Association of Urological Surgeons Cancer Registry. We recorded the total number of prostate cancers diagnosed per year, number of TURPs performed, Gleason scores and patients outcomes. RESULTS: TURP-detected prostate cancer has declined since the relatively high rates (22%) recorded locally in 1996-97. Between 2001 and 2006, a mean (range) of 124 (111-135) prostate cancers were detected per year. Incidental cancers accounted for only 1.5-5.6% of all newly diagnosed prostate cancers per year. Incidental cancers had a mean (sem) Gleason score of 5.7 (0.3) compared to 8.0 (0.3) in known cancers (P < 0.01) undergoing TURP. Of newly diagnosed patients, 82% were allocated to active surveillance, whilst 18% were started on hormone therapy, with no prostate cancer-related deaths over a mean (sem, range) follow-up of 49.7 (2.4, 11-81) months. CONCLUSIONS: TURP mainly samples transitional-zone tissue where tumours are relatively uncommon, and have a good prognosis. Our series of incidental TURP-detected cancers showed an incidence in keeping with published data, and favourable histological and clinical outcomes. We suggest the lack of tissue should not discourage the use of laser prostatectomy surgery.


Subject(s)
Laser Therapy/standards , Prostatectomy/standards , Prostatic Hyperplasia/surgery , Prostatic Neoplasms/diagnosis , Transurethral Resection of Prostate/methods , Aged , Aged, 80 and over , Humans , Incidental Findings , Laser Therapy/adverse effects , Laser Therapy/methods , Male , Medical Audit , Middle Aged , Prognosis , Prostatectomy/adverse effects , Prostatectomy/methods , Prostatic Hyperplasia/pathology , Retrospective Studies , Treatment Outcome
12.
J Multidiscip Healthc ; 12: 205-210, 2019.
Article in English | MEDLINE | ID: mdl-30936714

ABSTRACT

PURPOSE: Pelvic floor dysfunction is a common and heterogenous condition with numerous clinical manifestations, making the optimal management challenging. The traditional single-specialty approach may fail to address its complex nature. Currently, there are no published data on the impact of joint pelvic floor multidisciplinary team (MDT) meetings on patient management. PATIENTS AND METHODS: This study represents a retrospective analysis of prospectively collected data on female patients discussed at a joint pelvic floor MDT over a 12-month period in a tertiary referral center. RESULTS: One hundred fifty-two cases were included with a median age of 55 years (range 18-83) and a BMI of 32 kg/m2 (range 17-58). Lower urinary tract dysfunction was the predominant symptom in 75% (114/152). The pelvic organ prolapse symptom of a vaginal bulge was present in 11% (17/152). All cases of vaginal prolapse were accompanied by either urinary incontinence, 59% (10/17), or obstructive defecation, 41% (7/17). Fecal incontinence was recorded in 10% (15/152). Mesh-related complications were reported in 3% (4/152). The MDT recommended a change in the initial management plan in 20% (31/152) of cases, of whom 80% (25/31) were patients with complex urinary incontinence. The MDT agreed a change in the primary care team in 16% (25/152) of cases. CONCLUSION: There is an increasing regulatory requirement for patients with pelvic floor dysfunction to be discussed in an MDT setting. Findings demonstrate that joint pelvic floor MDT meetings are feasible and contribute to a change in the management of complex patients.

13.
Int Urol Nephrol ; 39(4): 1039-41, 2007.
Article in English | MEDLINE | ID: mdl-17431810

ABSTRACT

We report the unusual case of a patient with G3 pT1 transitional cell carcinoma (TCC) of the bladder, which was treated with repeated transurethral resection and maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy. At 30 months follow-up, a symptomatic, solitary iliac lymph node mass was identified and biopsied. Histology demonstrated granulomatous tissue only, in the absence of any intravesical bladder tumour recurrence. Following 6 months of anti-tuberculous medication, the mass had progressed, and repeat biopsy revealed undifferentiated carcinoma (of a bladder primary). This is a rare case of metastatic superficial bladder cancer progression without local recurrence after BCG therapy. As such, it can be viewed as a diagnostic challenge.


Subject(s)
Adjuvants, Immunologic/therapeutic use , BCG Vaccine/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Iliac Vein , Lymphatic Diseases/chemically induced , Lymphatic Diseases/diagnosis , Urinary Bladder Neoplasms/drug therapy , Administration, Intravesical , Biopsy , Carcinoma, Transitional Cell/pathology , Diagnosis, Differential , Disease Progression , Humans , Male , Middle Aged , Tomography, X-Ray Computed , Urinary Bladder Neoplasms/pathology
14.
Auton Neurosci ; 115(1-2): 64-73, 2004 Sep 30.
Article in English | MEDLINE | ID: mdl-15507407

ABSTRACT

In order to assess the possible role of the c-kit positive cells in the bladder, the effects of c-kit tyrosine kinase inhibitor, Glivec, on spontaneous excitation and ion channel activity in detrusor smooth muscles of the guinea-pig bladder were investigated using intracellular microelectrodes, isometric muscle tension recordings and patch clamp techniques. Glivec (10 microM) converted action potential bursts into continuous firing without affecting their shape but at 50 microM abolished spontaneous action potentials. It had little effect on inward and outward currents at <10 microM, but inhibited them at >50 microM. Glivec decreased the amplitude of spontaneous contractions dose dependently. These results suggest that c-kit positive cells may play a role in modulating spontaneous electrical and mechanical activities. Drugs inhibiting the c-kit receptor may provide a new approach for treating the overactive bladder.


Subject(s)
Intracellular Signaling Peptides and Proteins/pharmacology , Piperazines/pharmacology , Proto-Oncogene Proteins c-kit/physiology , Pyrimidines/pharmacology , Urinary Bladder/drug effects , Urinary Bladder/physiology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Benzamides , Guinea Pigs , Imatinib Mesylate , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle Contraction/physiology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/physiology
15.
BJU Int ; 98(6): 1310-4, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17026593

ABSTRACT

OBJECTIVE: To examine the effects of a new selective beta3-adrenoceptor agonist, GW427353 on human detrusor function, as beta2- and beta3-adrenoceptors have been identified in the bladder, and can mediate detrusor relaxation, but beta3-adrenoceptors are less widely distributed and beta3-adrenoceptor agonists should have the therapeutic advantage of producing fewer treatment side-effects. PATIENTS AND METHODS: 'Normal' human detrusor was retrieved from 12 patients (mean age 56 years) at cystectomy and from organ donors. Detrusor strips (4 x 1 x 1 mm) were mounted in superfused organ baths. Tone was induced with carbachol (5 x 10(-7)m) before applying either a nonselective beta-adrenoceptor agonist (isoprenaline) or GW427353 (with or without the beta3-adrenoceptor antagonist, SR59230A). In addition, the effect of GW427353 was tested on intrinsic nerve-evoked smooth muscle contraction over time. Effects on spontaneous activity were also recorded. RESULTS: GW427353 produced significant relaxation at concentrations of >10(-7)m; isoprenaline produced a significant effect from 10(-6)m, but otherwise both agonists had similar effects. The addition of SR59230A (10(-7)m), produced partial inhibition of the GW427353 response. GW427353 at 10(-6)m significantly reduced spontaneous activity within 10 min of incubation, and at higher concentrations (>5 x 10(-6)m) inhibited detrusor contractions evoked by electrical field stimulation. CONCLUSION: Neuropathic bladder dysfunction is characterized by increased spontaneous activity and involuntary detrusor contractions, which can result in urinary frequency, urgency, nocturia and incontinence. The novel feature of GW427353 is the ability to suppress spontaneous activity and produce significant relaxation in human detrusor tissue at low concentrations, whilst also inhibiting evoked detrusor contractions at higher concentrations.


Subject(s)
Adrenergic beta-3 Receptor Agonists , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Urinary Bladder, Neurogenic/drug therapy , Adult , Aged , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , Middle Aged
16.
Neurourol Urodyn ; 25(3): 205-210, 2006.
Article in English | MEDLINE | ID: mdl-16425211

ABSTRACT

AIMS: In the gastrointestinal tract, slow wave activity in smooth muscle is generated by the interstitial cells of Cajal (ICC). Detrusor smooth muscle strips of most species show spontaneous contractions which are triggered by action potential bursts, however, the pacemaker mechanisms for the detrusor are still unknown. Recently, ICC-like cells have been found in guinea-pig bladder, using antibodies to the c-kit receptor. We have investigated the effects of Glivec, a c-kit tyrosine kinase inhibitor, on spontaneous action potentials in guinea-pig detrusor and intravesical pressure of isolated guinea-pig bladders. METHODS: Changes in the membrane potential were measured in guinea-pig detrusor smooth muscle using conventional microelectrode techniques. Pressure changes in the bladder were recorded using whole organ bath techniques. RESULTS: Smooth muscle cells in detrusor muscle bundles exhibited spontaneous action potentials, and spontaneous pressure rises occurred in isolated bladders. Glivec (10 microM) converted action potential bursts into continuous firing with no effects on the shape of individual action potentials. Glivec (>50 microM) reduced the amplitude of spontaneous pressure rises in the whole bladder in a dose dependent manner and abolished spontaneous action potentials in detrusor smooth muscle cells. CONCLUSIONS: The results suggest that ICC-like cells may be responsible for generating bursts of action potentials and contractions in detrusor smooth muscle. Drugs inhibiting the c-kit receptor may prove useful for treating the overactive bladder.


Subject(s)
Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-kit , Pyrimidines/pharmacology , Urinary Bladder/drug effects , Animals , Benzamides , Guinea Pigs , Imatinib Mesylate , In Vitro Techniques , Male
17.
BJU Int ; 97(3): 612-6, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16469036

ABSTRACT

OBJECTIVE: To describe the effect of a specific c-kit receptor inhibitor (imatinib mesylate) on human detrusor strips in vitro and guinea-pig cystometry in vivo, and to show histological data suggesting differences in the distribution of interstitial cells of Cajal (ICC)-like cells in 'normal' and overactive human detrusor, as these cells have been identified as possible mediators of spontaneous activity and excitability in bladder smooth muscle. MATERIALS AND METHODS: Specimens of human detrusor were stained immunohistochemically with a c-kit antibody. Human detrusor strips were mounted in a superfused organ-bath apparatus, and smooth muscle contraction was evoked with carbachol and electrical field stimulation in the presence and absence of imatinib mesylate. Also, guinea-pig urodynamic studies were conducted before and after i.v. administration of imatinib mesylate, and changes in bladder variables and spontaneous activity were recorded. RESULTS: Imatinib mesylate (10(-6)M) inhibited evoked smooth muscle contraction and spontaneous activity in overactive human detrusor, with less effect on normal human tissue. Imatinib mesylate (10(-5)M) improved bladder capacity, compliance, voided volumes, urinary frequency, and reduced contraction thresholds and spontaneous activity during guinea-pig cystometry. c-kit labelling showed significantly more ICC-like cells in overactive human detrusor than in normal specimens. CONCLUSION: c-kit receptor blockers have inhibitory effects on guinea-pig and overactive human detrusor, possibly via c-kit receptors on bladder ICC-like cells. This and the possibility that there are more ICC-like cells in overactive bladder suggest that the c-kit receptor may provide a novel target for treating detrusor overactivity.


Subject(s)
Muscle, Smooth/drug effects , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Urinary Bladder/drug effects , Urinary Incontinence/drug therapy , Animals , Benzamides , Guinea Pigs , Imatinib Mesylate , Immunohistochemistry , Male , Muscle, Smooth/pathology , Proto-Oncogene Proteins c-kit , Urinary Bladder/pathology , Urinary Incontinence/pathology , Urodynamics
18.
Curr Opin Urol ; 13(6): 495-500, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14560145

ABSTRACT

PURPOSE OF REVIEW: To assess the potential role of nerve regeneration in restoring urinary tract function, the rapidly developing and exciting area of central and peripheral nerve repair and regeneration is reviewed, with particular reference to papers in which animal models of nerve damage resulting in urogenital dysfunction have been used. The difficulties and potential of these techniques for therapeutic application to human subjects with functional problems of the urinary tract are discussed. RECENT FINDINGS: Methods for encouraging regeneration of cut axons and directed growth in the inhibitory environment of the central nervous system are being extensively explored. The recent discovery of the potential of olfactory ensheathing cells has proved a significant advance. Olfactory ensheathing cells are a type of glial cell which can be harvested from the olfactory mucosa. Transplantation of these cells, in conjunction with a biodegradable synthetic nerve guide or conduit, has been shown to restore urinary tract function after spinal cord injury. Artificial, biodegradable conduits have also restored bladder and spermatic duct function after sympathetic nerve damage. Other adjuvants facilitating the process of axonal recovery include the use of neurotrophins to accelerate and guide the formation of new nerve-fibre growth. SUMMARY: These revolutionary technologies may, in the future, provide a means of treating urinary tract dysfunction with some types of aetiology, including acute spinal cord injury, and injury to nerves following pelvic surgery. It is, however, less likely that these treatments will be used successfully in the near future in patients in which the neural damage is long term, or associated with death of post-ganglionic neurons.


Subject(s)
Female Urogenital Diseases/therapy , Male Urogenital Diseases , Nerve Regeneration , Animals , Autonomic Nervous System/physiology , Cell Transplantation , Disease Models, Animal , Humans , Nerve Growth Factors/pharmacology , Olfactory Mucosa/cytology , Radiculopathy/therapy , Spinal Cord Injuries/complications
19.
Urology ; 63(2): 380-2, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14972503

ABSTRACT

We report a case of acute renal failure in a man with medically treated advanced prostate carcinoma. Imaging suggested renal tract obstruction as the cause; however, the patient failed to respond to treatment with dialysis and bilateral nephrostomy insertion. Postmortem examination revealed the renal failure to have been due to severe thrombotic microangiopathy.


Subject(s)
Acute Kidney Injury/etiology , Adenocarcinoma/complications , Diagnostic Errors , Hemolytic-Uremic Syndrome/diagnosis , Prostatic Neoplasms/complications , Adenocarcinoma/pathology , Anemia/etiology , Fatal Outcome , Hemolytic-Uremic Syndrome/etiology , Humans , Hydronephrosis/etiology , Kidney Glomerulus/pathology , Male , Nephrostomy, Percutaneous , Prostatic Neoplasms/pathology , Renal Dialysis , Thrombocytopenia/etiology , Ureteral Obstruction/diagnosis
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