Technical aspects of botulinum toxin type A injection in the bladder to treat urinary incontinence: reviewing the procedure.

AIMS: Standardise the injection technique with botulinum toxin type A (BoNT A) in the bladder of patients with overactive bladder (OAB) [idiopathic overactive bladder (iOAB) or neurogenic overactive bladder (nOAB) with urinary incontinence], using a literature review and a survey of an International expert panel. METHODS: PubMed literature searches of BoNT A in adults with iOAB/nOAB together with a survey of 13 experts from 10 countries. RESULTS: Data from 21 articles and completed questionnaires were collated. The procedure can be carried out in an out-/inpatient setting. Dose used in clinical studies vs. clinical practice was 300 and 200 U for nOAB and 200 and 100 U for iOAB. Recent studies have also demonstrated that there are no clinically relevant benefits between 100 and 150 U in iOAB or between 300 and 200 U in nOAB, though adverse effects are increased with higher doses. Usually, 30 sites for nOAB (range: 6.7-10 U/ml) and 20-30 sites for iOAB (range: 5-10 U/ml) are injected in clinical studies vs. 20-30 sites of 1 ml/injection for 200 U in nOAB and 10-20 sites of 0.5-1 ml/injection for 100 U in iOAB in clinical practice. BoNT A is usually injected directly into the detrusor, sparing the trigone. Flexible or rigid cystoscopes are used. The needle should be typically 22-27 gauge and 4 mm in length and should have a stopper to avoid any leakage or perforation of the bladder wall while ensuring a targeted injection. CONCLUSION: Based on the literature and survey analysis, recommendations are proposed for the standardisation of the injection procedure.

Metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin by human hepatic CYP isoforms: evidence for selectivity towards CYP3A4.

1. The metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin (BFBFC) to 7-hydroxy-4-trifluoromethylcoumarin (HFC) was studied in human liver microsomes and in cDNA-expressed human liver CYP isoforms. For purposes of comparison, some limited studies were also performed with 7-benzyloxyquinoline (7BQ). 2. Initial interactive docking studies with a homology model of human CYP3A4 indicated that BFBFC was likely to be a selective substrate for CYP3A4 with a relatively high binding affinity, due to the presence of several key hydrogen bonds with active site amino acid residues. 3. Kinetic analysis of NADPH-dependent BFBFC metabolism to HFC in three preparations of pooled human liver microsomes revealed mean (+/- TSEM) Km and Vmax = 4.6 +/- 0.3 microM and 20.0 +/- 3.8 pmol/min/mg protein, respectively. 4. The metabolism of BFBFC to HFC was determined in a characterized bank of 24 individual human liver microsomal preparations employing a BFBFC substrate concentration of lO microM (i.e. around twice Km). Good correlations (r2 = 0.736-0.904) were observed between BFBFC metabolism and markers of CYP3A isoforms. 5. While 10O microM BFBFC was metabolized to HFC by cDNA-expressed CYP3A4, little or no metabolism was observed with cDNA-expressed CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. 6. The metabolism of 10 microM BFBFC in human liver microsomes was markedly inhibited by 5-50 microM troleandomycin and 0.2-5 microM ketoconazole, but stimulated by 0.2-10 microM alpha-naphthoflavone. The metabolism of 10 microM BFBFC in human liver microsomes was also markedly inhibited by an antibody to CYP3A4. 7. Kinetic analysis of NADPH-dependent 7BQ metabolism to 7-hydroxyquinoline (7HQ) in human liver microsomes revealed Km and Vmax = 70 microM and 3.39 nmol/min/mg protein, respectively. 8. While 80 microM 7BQ was metabolized to 7HQ by cDNA-expressed CYP3A4, only low rates of metabolism were observed with cDNA-expressed CYPIA2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. 9. In summary, by correlation analysis, the use of cDNA-expressed CYP isoforms, chemical inhibition and inhibitory antibodies, BFBFC metabolism in human liver microsomes appears to be primarily catalysed by CYP3A4. BFBFC may be a useful fluorescent probe substrate for human hepatic CYP3A4, but compared with 7BQ has only a low rate of metabolism in human liver microsomes.

An assessment of the surgical outcome and urodynamic effects of the pubovaginal sling for stress incontinence and the associated urge syndrome.

PURPOSE: We assessed the urodynamic changes after pubovaginal sling procedure for stress incontinence, particularly in regard to the associated symptoms of urgency, frequency, nocturia and urge incontinence, known as the urge syndrome. MATERIALS AND METHODS: A total of 85 women with proved stress incontinence underwent a pubovaginal sling procedure using rectus fascia between 1992 and August 1996. Of the women 41 (48%) had undergone previous anti-incontinence surgery and 59 (69%) had the associated urge syndrome. There was at least some degree of hypermobility in 51 cases and type III stress incontinence was diagnosed in 34. Patients were assessed with a questionnaire and video urodynamics preoperatively and 3 months postoperatively. Preoperative and postoperative ambulatory studies were performed in 25 cases. RESULTS: Of the 85 patients 83 (97%) were symptomatically cured of stress incontinence. The urge syndrome resolved in 32 patients (69%), almost all of whom had a closed bladder neck at rest. Overall bladder neck incompetence at rest decreased from 57 to 18% (p<0.001). Of 27 patients with the persistent urge syndrome postoperatively 9 (41%) had an open bladder neck at rest compared to 4 of 50 (8%) without urge incontinence (p<0.01). Despite symptomatic control of stress incontinence in 83 patients (97%), only 66 were satisfied with the surgical result, mainly because of the persistent urge syndrome in 27. Despite care to avoid obstruction overall, there were statistically significant obstructive changes in detrusor pressure at maximum flow rate, maximum flow rate and residual urine volumes. CONCLUSIONS: The pubovaginal sling is effective in curing genuine stress incontinence and, when correctly placed at the right tension, the associated urge syndrome also can be managed, usually by achieving bladder neck closure at rest. However, despite careful maneuvers, obstruction occasionally persists.

The modified rectus fascial sling for the treatment of genuine stress incontinence.

We aimed to assess the results of the modified rectus fascial sling for the treatment of genuine stress incontinence (GSI), using an observational study of patients at a South Wales Teaching Hospital. Seventy-three patients with proven GSI underwent a modified rectus fascial sling. Thirty-seven also had a significant urge component to their symptoms though only two had demonstrable detrusor instability. Fifty-one had undergone previous incontinence surgery. All had pre-operative videourodynamics and 50 agreed to follow up urodynamics. Of these who had undergone previous surgery 48 (94%) were subjectively dry, though four (8%) still demonstrated GSI on videourodynamics. There were no failures in the previously unoperated group. Three require long-term intermittent self-catheterisation and three others catheterise occasionally. Overall, 29 patients (78%) were improved or cured of their urge component but three were worse, with urge incontinence. From our data, it seems that the modified rectus fascial sling is superior to standard techniques for GSI especially in patients who have undergone previous surgery. However loosely the sling is placed, a small but significant group are obstructed by the procedure, and may require self-catheterisation.

The fate of the 'modern' artificial urinary sphincter with a follow-up of more than 10 years.

OBJECTIVE: To assess the long-term outcome of patients who had an artificial urinary sphincter (AUS) implanted between 10 and 15 years ago. PATIENTS AND METHODS: Of 68 patients who had an AUS implanted more than 10 years ago, 61 were followed with sufficient detail for analysis. Thirty-four had a neuropathic bladder with sphincter dysfunction, 15 had post-prostatectomy sphincter weakness incontinence and 12 further patients had a variety of indications. RESULTS: The 61 patients experienced a total of 58 major complications and 49 have required at least one revision procedure. Currently eight (13%) patients are satisfactorily continent with their original AUS in situ and 29 others have a satisfactory revised AUS. Thus 37 of 61 (61%) are continent using an AUS at least 10 years after first implantation. Eleven patients died and of these two had a satisfactory original AUS in situ and seven had successful revisions. In two patients the AUS failed but they were considered unfit for revision. Four female patients were continent and used intermittent catheterization after the explantation of eroded AUS cuffs. In seven patients the AUS was abandoned; two of these patients reverted to condom drainage and five had continent or incontinent urinary diversions fashioned. Thus, if those who died with a functioning AUS are included, 46 of 61 (75%) achieved long-term continence with the AUS. CONCLUSIONS: Despite the high complication and revision rate, these results show that acceptable continence rates can be achieved in the long-term, particularly in the male neuropathic bladder and in those with post-prostatectomy sphincter weakness. Many of the complications encountered may be less common with the current re-designed models of the AUS. However, it is essential that both surgeon and patient recognize and accept the likelihood of complications and revisions before using the AUS. The continued use of the AUS where simpler methods of obtaining continence are inappropriate remains justified.

Tumors in bladder remnant after augmentation enterocystoplasty.

PURPOSE: We attempted to determine the tissue of origin of tumors after augmentation enterocystoplasty. MATERIALS AND METHODS: We retrospectively reviewed the histological findings of 4 tumors that developed after clam ileocystoplasty. RESULTS: Tumors were primarily adenocarcinoma that originated on the bladder side of the anastomosis. The urothelium showed glandular metaplasia and dysplasia with intestinalization overlying normal detrusor muscle. These changes were also present in the renal pelvis in 1 patient with ureteral reflux. Bowel mucosa was normal except for inflammation. CONCLUSIONS: These tumors are derived from urothelium, which may be due to elevated urinary nitrosamines in this group of patients.

Reduction of urinary basic fibroblast growth factor using pentosan polysulphate sodium.

OBJECTIVE: To evaluate the use of pentosan polysulphate sodium (PPS) to reduce the level of urinary basic fibroblast growth factor (bFGF). PATIENTS AND METHODS: Forty-one patients with a clam enterocystoplasty were randomized to receive either 200 mg three times daily of oral PPS (n = 21) or placebo (n = 20) for 6 weeks. Three patients acted as a cross-over study. Urinary bFGF was measured before and after treatment and the degree of symptomatic benefit assessed using a questionnaire. RESULTS: There was no reduction in bFGF in the patients receiving placebo (P = 0.235) but there was a statistically significant reduction in bFGF (P = 0.0251) in the patients receiving PPS, most of whom were symptomatically improved, especially with regard to mucus production. CONCLUSION: PPS may have a role in reducing urinary bFGF in patients with bladder tumours or following an enterocystoplasty and also in improving the quality of life of patients with a clam enterocystoplasty.

Use of calcium alginate to pack abscess cavities: a controlled clinical trial.

Many conventional dressings are painful when removed, and may be detrimental to healing. In a pilot study ten consecutive abscesses, requiring incision and drainage, were packed with a calcium alginate dressing: this was well tolerated, its removal causing minimal pain. No adverse effects were attributable to its use. A controlled trial was therefore carried out to compare calcium alginate with the more traditional saline-soaked gauze for packing abscess cavities, following incision and drainage. Patients were randomized to receive either calcium alginate (16 patients) or gauze dressing (18 patients). At the first dressing change the patient marked on a linear analogue scale the pain experienced; the nurse noted similarly the ease of removal of the dressing. Calcium alginate was significantly less painful to remove after operation (P less than 0.01), and also easier to remove (P less than 0.01) than gauze dressings. If abscess cavities are packed after incision and drainage, calcium alginate appears to be an improvement on conventional dressings.

Effects of rotational atherectomy in normal canine coronary and diseased human cadaveric arteries: potential for plaque removal from distal, tortuous, and diffusely diseased vessels.

To test the hypothesis that tortuous, diseased vessels could be successfully treated with a flexible rotational atherectomy device we evaluated the BARD atherectomy device with quantitative angiography and histology in normal canine coronary arteries and diseased human below-knee amputation specimens. The mid left anterior descending and the circumflex vessels were treated in 4 dogs serially with 1 wk separating treatments. The acute and follow-up anterior descending artery size was unchanged (1.41 mm before, 1.39 mm after, and 1.59 mm at 1 week). Similar findings were obtained in the circumflex vessels. In 4 adult human amputated legs, diseased peroneal or tibial arteries were treated with a significant reduction in the percent luminal diameter stenosis from 62.75 prior to intervention to 36.5 following intervention (p = 0.021). The luminal diameter increased from 0.81 to 1.54 mm (p = 0.06). In 2 canine arteries there was histologic evidence of localized perforation of the arterial wall, but there was no angiographic evidence of perforation or dissection and no significant myocardial necrosis in the distribution of the treated vessels at 1 wk. The majority of the diseased human vessels demonstrated smoothly cut atheromas with sparing of the media. The rotational atherectomy catheter system holds promise for removal of plaque in relatively small, diffusely diseased, tortuous vessels.