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.

Comparison of acute responses to isotonic or isokinetic eccentric muscle action: differential outcomes in skeletal muscle damage and implications for rehabilitation.

Both isotonic and isokinetic eccentric muscle contractions are commonly used in muscle research laboratories to induce muscle damage, yet, the muscle damage outcomes between these 2 modes of eccentric contraction have not been compared. The purpose of this study was to compare modes of contraction for differences in muscle damage. 16 men were placed in the isotonic (IT: 110% of maximal isometric torque) or the isokinetic (IK: 120°/s) group, with each group performing 200 eccentric muscle actions of the knee extensors. Isometric peak torque, perceived soreness and CK activity were measured immediately pre and post exercise, and 48-h post exercise. Mean total work (~1700 J) and peak torque per set (~265 Nm) decreased over the 200 repetitions (p<0.01), and was not different between groups. Damage markers changed 48-h post exercise (p<0.05): peak isometric torque (-13%), creatine kinase activity (+200%) and self-perceived muscular soreness (+4 unit change). Significant group×time interactions (p<0.01) indicated that peak isometric torque was 22% lower, and creatine kinase and self-perceived muscular soreness were 330% and 3 unit difference higher in the IT as compared to the IK groups, 48-h post exercise. When equating for total work, skeletal muscle damage markers are higher during IT vs. IK modes. This reflects differences inherent in contraction type and suggests that this should be taken into account during physical rehabilitation.

Overactive Bladder and Continence Guidelines: implementation, inaction or frustration?

Guidelines for the management of continence and overactive bladder are generally available across Europe. For a majority of countries, these have been adopted by professional societies in either urology or gynaecology for local use. There has, however, been little monitoring of formal implementation of these guidelines and seldom any attempt to audit their operation. The state of continence care therefore remains largely unknown. This article reviews current guidelines and their status across Europe and examines what might be relevant from other disease areas to promote successful implementation.

Overactive bladder: The importance of new guidance.

Overactive bladder (OAB) affects an estimated 49 million people in Europe, but only a minority receive appropriate treatment. Others are bothered by unacceptable levels of symptoms that severely impair their quality of life and represent a significant financial burden to themselves and to their healthcare providers. Recently updated guidelines from the International Consultation on Incontinence (ICI) and the European Association of Urology (EAU) take account of important new developments in the management of bladder problems in both primary and secondary care. However, local implementation of previous guidance has been variable, with many patients with OAB and other bladder problems failing to gain full benefit from current clinical and scientific understanding of these conditions. The recent expansion of the range of treatments available for OAB and stress urinary incontinence makes it especially important that physicians become aware of the differential diagnosis of these conditions - the questions they need to ask, and the investigations which will help determine the most appropriate course of action.

Chronotoxicology of florfenicol.

Sixty 3-month-old homozygote male mice were studied for circadian rhythmicity in the toxicity of florfenicol overdose. Animals were kept under a regimen of 12h light, 12h darkness (12:12 LD) with food and water available ad libitum. The LD50 (median lethal) dose was determined in a preliminary experiment and was administered to groups of 10 mice at six different clock times (hours) after light onset (HALO): 0, 4, 8, 12, 16, and 20 HALO. Cosinor analysis verified a statistically significant (P < .04) circadian rhythm in the toxic effect (mortality) of florfenicol. Mortality was greatest when the drug was injected 4h after the commencement of the activity span (16 HALO) and least when injected 4h after the start of the diurnal rest span (4 HALO). Mortality was 2.5 times greater when drug injection was given at 16 HALO than at 4 HALO.

Pharmacokinetics of miocamycin following intravenous administration to cattle.

The plasma pharmacokinetics for a single intravenous dose (10 mg/kg body weight) of miocamycin (a 16-membered macrolide drug) was investigated in Holando Argentino cattle (n = 5). Blood drug concentrations were determined by a microbiological method and data were best-fitted to a two-compartment open model. The pharmacokinetic profile consisted of a short distribution phase (t1/2 alpha = 7.41 +/- 0.53 min), followed by an extended terminal elimination phase (t1/2 beta = 2.49 +/- 0.23 h). The volume of distribution at steady-state was large (2.13 +/- 0.17 l/kg), suggesting extensive tissue distribution, the clearance value was 0.60 +/- 0.03 l/h.

Characteristics of crystallographic gratings.

We report the observation and characterization of a resonance effect in gratings fabricated on GaAs substrates by use of a crystallographically preferential wet chemical etch that terminates at the (111) family of planes. Also, we demonstrate an in situ etch-monitoring study of the diffraction characteristics of these gratings. The light intensity in the first order of diffraction was monitored in Littrow reflection during etching at 632.8- and 543.5-mm wavelengths. Scanning-electron microscopy was performed on several samples to correlate the etch depth with diffraction efficiency. The variation of diffraction intensity with depth showed a narrow peak at a shallower grating depth and a broader peak at a larger grating depth. These diffraction characteristics are explained on the basis of a competitive interaction between the resonance effect of the incident optical mode and the magnitude of the first Fourier component of the grating profile that primarily couples the incident and diffracted optical modes.

Crystallographically limited submicrometer gratings in (100) and (211) silicon.

We demonstrate the fabrication of submicrometer gratings in (100) and (211) Si with periodicities that are appropriate for normal-incidence coupling into Ge-Si waveguides. Gratings of periodicities in the 0.25-0.75microm range were fabricated by a standard holographic lithography technique. Crystallographically preferential wet etching that effectively terminates at the {111} family of planes facilitates the fabrication of symmetric gratings in (100) Si and of blazed gratings in (211) Si. The gratings used in this study are appropriate for the fabrication of integrated first- and second-order, normal-incidence grating couplers at a 1.30-microm wavelength. The blazed gratings show a preferential coupling of more than 80% of the total diffraction into the (+1) diffraction order at normal incidence. The maximum first-order diffraction efficiency obtained with these gratings was approximately 28% in (100) Si and 23% in (211) Si.

The development of tumors in experimental gastroenterocystoplasty.

Bladder augmentation with segments of the gastrointestinal tract is commonly used to treat patients with small or noncompliant bladders. Reliable data on the incidence of tumors in patients with enterocystoplasty are not available. In the small number of cases reported in the literature the mean latency period is approximately 18 years. We designed a study in Sprague Dawley rats to try to determine the risk of carcinogenesis in different types of augmentation cystoplasty and its possible relationship with infected urine, and to investigate the possibility of detecting the tumors by cytological analysis. We performed 30 gastrocystoplasties, 35 sigmoid cystoplasties, 30 ileocystoplasties and 10 sham operations, and used 10 nonoperated animals as controls. The animals were sacrificed upon completing 1 year of followup and bladder urine samples were collected at the time of sacrifice. Of 115 animals 86 were available for histological evaluation (26 gastrocystoplasty, 22 sigmoid cystoplasty, 18 ileocystoplasty, and all sham and control animals). Mean followup was 11.2 months in the gastrocystoplasty, 11.8 months in the sigmoid cystoplasty, and 12 months in the ileocystoplasty, sham and control groups. Multifocal or superficial transitional metaplasia was found in 65.4% of the gastrocystoplasty, 50% of the sigmoid cystoplasty and 55.5% of the ileocystoplasty animals. Proliferations that we classified as papillary hyperplasia were present in 53.8% of the gastrocystoplasty, 40.9% of the sigmoid cystoplasty and none of the ileocystoplasty rats. The proliferations occurred either at or close to the anastomosis between the bladder and the gastric or colonic patch, or in areas of transitional metaplasia. Cytological urinalysis was negative for neoplastic cells in all cases. No correlation was found between the occurrence of papillary hyperplasia and urinary infection. These data indicate that in rats transitional metaplasia is common in gastrocystoplasty, sigmoid cystoplasty and ileocystoplasty, and that papillary hyperplasia may occur near or at the anastomosis, or in areas of transitional metaplasia in either gastrocytoplasty or sigmoid cystoplasty. In contrast to other studies, we observed no examples of papillary hyperplasia in the ileocystoplasty group in this series. No transitional cell carcinomas or adenocarcinomas were identified in this study. It is not known if these papillary lesions have an increased malignant potential, thus further studies with longer followup are warranted.