Publications (6)39.91 Total impact
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Article: Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration.
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ABSTRACT: To investigate the possible associations of urothelial and suburothelial muscarinic receptors with human bladder pathophysiology we examined the immunohistochemical expression of muscarinic receptors types 1, 2 and 3 in the bladder urothelium and suburothelium of patients with neurogenic or idiopathic detrusor overactivity compared with that in controls. We also examined associations with patient quantified symptoms and the effect of intradetrusor botulinum neurotoxin type A treatment. We obtained bladder biopsies from 36 patients with detrusor overactivity before, and 4 and 16 weeks after treatment with intradetrusor botulinum neurotoxin type A via flexible cystoscopy. Patients with neurogenic detrusor overactivity were injected with 300 U botulinum neurotoxin type A and those with idiopathic detrusor overactivity received 200 U. Control biopsies were taken from 7 patients during investigation for asymptomatic microscopic hematuria. We studied muscarinic receptor immunohistochemical expression using commercial antibodies to muscarinic receptors 1, 2 and 3 with results quantified by image analysis. We noted decreased suburothelial muscarinic receptor immunoreactivity in detrusor overactivity biopsies vs controls, which were significant for muscarinic receptors 1 and 3. After successful botulinum neurotoxin treatment we noted only increased muscarinic receptor 1 and 2 immunoreactivity. Urothelial muscarinic receptor 1 and 3 immunoreactivity was increased after treatment. We identified no substantial urothelial muscarinic receptor 2 immunoreactivity. Receptor levels showed inverse correlations with patient urgency and frequency. Decreased muscarinic receptor levels in the urothelium and suburothelium of patients with detrusor overactivity were largely restored to control levels after successful treatment with botulinum neurotoxin type A. Correlations of receptor levels with patient symptoms further support a role for urothelial and suburothelial muscarinic receptors in detrusor overactivity in humans.The Journal of urology 10/2010; 184(6):2578-85. · 4.02 Impact Factor -
Article: Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity.
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ABSTRACT: We examined, for the first time in a prospective study, the histological changes in the urothelium and suburothelium of patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO) after one or repeat treatments with intradetrusor BoNTA. Flexible cystoscopic bladder biopsies were obtained from patients with urodynamically proven intractable spinal NDO or IDO before and 4 and 16 wk after one or repeat treatments with intradetrusor injections of BOTOX1 (NDO 300 U, IDO 200 U). Specimens were stained for haematoxylin-eosin and analysed blindly for inflammatory changes, fibrosis, hyperplasia, and dysplasia in the urothelium and suburothelium. Statistical comparisons were significant at p values less than 0.05. Signs of chronic inflammation were found in 59.1% of baseline biopsies (65.6% of NDO vs. 50% of IDO, p=0.049), 67.6% of post-first biopsies and 86.4% after repeat injections. The two groups were comparable for degree of baseline inflammation, which did not change significantly after first injection and up to 16 wk after a third injection. Mild fibrosis was found in 2.2% of biopsies examined, equally before and after treatment, but not after repeat injections. No dysplasia or hyperplasia was identified. Eosinophils were identified more frequently in biopsies taken after repeat injections compared with the post-first injection and baseline biopsies (chi2=8.23, p=0.018). No difference existed between NDO and IDO bladders. BoNTA injections do not appear to be producing significant inflammatory changes, fibrosis, or dysplastic changes in human bladder urothelium/suburothelium after a single injection and in a limited number of repeat treatment biopsies. The presence of eosinophils might be treatment-related, because they were mostly found in post-treatment biopsies.European Urology 07/2008; 53(6):1245-53. · 8.49 Impact Factor -
Article: Botulinum injections for the treatment of bladder symptoms of multiple sclerosis.
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ABSTRACT: Our objective was to demonstrate the efficacy and impact on quality of life of detrusor injections of botulinum neurotoxin type A in the treatment of bladder dysfunction in patients with multiple sclerosis. Forty-three patients with multiple sclerosis suffering from severe urgency incontinence were treated with detrusor injections of botulinum neurotoxin type A. Data from cystometric assessment of the bladder, voiding diaries, quality-of-life questionnaires, and procontinence medication usage were collected before treatment and 4 and 16 weeks after injection. The same data were also collected after repeat treatments. Highly significant improvements (p < 0.0001) in incontinence episodes and urinary urgency, daytime frequency and nocturia, were the symptomatic reflection of the significant improvements in urodynamically demonstrated bladder function. Although 98% of patients had to perform self-catheterization after treatment, there were sustained improvements in all quality-of-life scores. The mean duration of effect was 9.7 months. Similar results were seen with repeat treatments. Minimally invasive injections of botulinum neurotoxin type A have been shown to be exceptionally effective in producing a prolonged improvement in urinary continence in patients with multiple sclerosis. This treatment is likely to have a major impact on future management.Annals of Neurology 11/2007; 62(5):452-7. · 11.09 Impact Factor -
Article: Successful treatment with botulinum toxin A after failed augmentation ileocystoplasty.
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ABSTRACT: A 49-year old man initially underwent clam ileocystoplasty 14 years ago. A revision of this original procedure was required 11 years ago for intractable detrusor overactivity secondary to transverse myelitis; he experienced only temporary symptomatic improvement that lasted 6 months after each procedure. Despite the use of oral anticholinergic drugs, the patient subsequently needed to perform clean intermittent self-catheterization approximately 10 times every 24 h, and when he presented to our department, he still suffered from occasional episodes of urgency incontinence that required the regular use of a penile sheath. Symptom severity was assessed using a 4-day bladder diary. Cystometry confirmed the presence of terminal detrusor overactivity. After the patient provided his informed consent, he was treated as an outpatient with intradetrusor injections of botulinum toxin A, delivered under local anesthesia by a minimally invasive technique that used a flexible cystoscope. A significant improvement was noted in the patient's lower urinary tract symptoms, urodynamic parameters and quality of life, measured at 4 and 16 weeks after treatment. The patient was completely dry at both follow-up visits and was able to discontinue the use of anticholinergic drugs and the penile sheath for a total of 11 months.Nature Clinical Practice Urology 06/2007; 4(5):280-4. · 4.07 Impact Factor -
Article: Quality of life changes in patients with neurogenic versus idiopathic detrusor overactivity after intradetrusor injections of botulinum neurotoxin type A and correlations with lower urinary tract symptoms and urodynamic changes.
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ABSTRACT: Little published data exist on the effect of intradetrusor botulinum neurotoxin type A (BoNT/A) on the quality of life (QOL) of patients with overactive bladder. We examined post-BoNT/A QOL changes of patients with neurogenic detrusor overactivity (NDO) in comparison to those with idiopathic detrusor overactivity (IDO), and their correlations with respective changes in lower urinary tract symptoms (LUTS) and urodynamic parameters. Patients with urodynamically proven intractable DO were assessed for changes in QOL 4 and 16 wk after treatment with intradetrusor BOTOX injections (NDO 300U; IDO 200U) using the short forms of the Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7). Percent changes in total QOL score were correlated to respective changes in clinical parameters recorded by bladder diaries and voiding cystometry. Forty-eight treated patients (32 NDO, 16 IDO) had QOL data in at least one follow-up. Highly significant decreases (p < 0.0001) in mean +/- standard error QOL score at 4 wk were maintained at 16 wk for both the NDO and IDO subgroups. Percent improvement in QOL score was similar for NDO versus IDO at 4 (67.6 +/- 4.5 versus 70.3 +/- 7.7, p = 0.74) and 16 wk (65.2 +/- 5.5 versus 71.9 +/- 8.8, p = 0.51). Percent changes in QOL score of the whole patient group correlated with changes in 24-h micturition frequency, number of voids associated with urgency, and number of urge incontinence episodes, but not with urodynamic parameters. Intradetrusor BoNT/A produces comparable, significant improvements in the QOL of patients with either NDO or IDO at least up to 16 wk after treatment. In contrast to urodynamic parameters, changes in LUTS appear to be the major determinants of improvements in the patients' QOL.European Urology 04/2006; 49(3):528-35. · 8.49 Impact Factor -
Article: A comparison between the response of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botulinum-A toxin.
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ABSTRACT: Several studies have shown that intradetrusor injections of botulinum neurotoxin type A (BoNT/A) may effectively treat intractable spinal neurogenic detrusor overactivity (NDO), but fewer reports exist on the use of BoNT/A in patients with idiopathic detrusor overactivity (IDO). The purpose of this study was to investigate whether comparable efficacy could be displayed in the response of patients with IDO to those with NDO. In a prospective, open label study, patients with urgency, and/or urgency incontinence due to urodynamically proven intractable detrusor overactivity received 300 units (NDO) or 200 units (IDO) of Botox injected into the bladder with a minimally invasive outpatient technique. Urodynamic maximum cystometric capacity and maximum detrusor pressure during filling, frequency of voids (frequency), number of incontinence episodes (leak) and number of voids associated with urgency per 24 hours (urgency) from 4-day voiding diaries were compared between the 2 groups at baseline and for changes at 4 and 16 weeks after treatment. A total of 44 patients with spinal NDO and 31 with IDO were treated. At 16 weeks, mean +/- standard error maximum cystometric capacity increased from 229.1 +/- 24.8 to 427.0 +/- 26.9 ml, p <0.0001 in NDO and from 193.6 +/- 24.0 to 327.1 +/- 36.1 ml, p=0.0008 in IDO. Maximum detrusor pressure during filling decreased from 60.7 +/- 6.8 to 26.1 +/- 3.7 cm H2O, p <0.0001 in NDO and from 62.1 +/- 10.8 to 45.1 +/- 8.1 cm H2O, p=0.027 in IDO. Frequency decreased from 12.3 +/- 0.7 to 6.6 +/- 0.6 voids per 24 hours, p <0.0001 in NDO and from 13.6 +/- 1.1 to 8.3 +/- 0.7, p=0.0002 in IDO. Leak decreased from 3.9 +/- 0.5 to 0.7 +/- 0.2 incontinence episodes per 24 hours, p <0.0001 in NDO and from 3.2 +/- 0.8 to 0.6 +/- 0.3, p=0.0017 in IDO, and urgency decreased from 7.5 +/- 0.6 to 1.44 +/- 0.3 episodes per 24 hours, p <0.0001 in NDO and from 10.9 +/- 1.7 to 4.9 +/- 1.1, p <0.0001 in IDO. The 2 groups were comparable for baseline data, but percent improvement in urgency was greater in patients with NDO at 4 weeks (78.2% vs 56.3%, p=0.019) and 16 weeks (78.3% vs 50.7%, p=0.013). Of patients with NDO 69% required self-catheterization de novo posttreatment compared with 19.3% of those with IDO. Patients with intractable IDO respond to intradetrusor BoNT/A with equally significant improvements in urodynamic and lower urinary tract symptom parameters as those with spinal NDO, despite the lower dose of toxin used.The Journal of Urology 10/2005; 174(3):984-9. · 3.75 Impact Factor
Top Journals
Institutions
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2007
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University College London
- Institute of Neurology
London, ENG, United Kingdom
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2005
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University College London Hospitals
London, ENG, United Kingdom
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