OnabotulinumtoxinA and multiple sclerosis.

Lower urinary tract dysfunction is present in two of three patients with multiple sclerosis five years after the diagnosis. Most frequent symptoms are related to neurogenic detrusor overactivity, often associated with detrusor-sphincter dyssynergia. From the end of the 1990s, there is growing evidence that neurogenic detrusor overactivity can be effectively managed by intradetrusorial injections of botulinum toxin type A. This treatment has shown, in different randomised placebo-controlled trials, to be safe and effective on clinical and urodynamic parameters with significant improvement in quality of life. The median duration of effect is in mean nine months. The vast majority of studies have been conducted with onabotulinumtoxinA. The dose of onabotulinumtoxinA commonly used to treat neurogenic detrusor overactivity in patients with multiple sclerosis is 200 UI, even if in selected patients lower doses can be preferred. To be considered eligible for treatment, all patients should accept and be instructed to perform clean intermittent self-catheterisation, since the risk of increased post-void residual volume and/or urinary retention after injection is high, especially with 200 UI of onabotulinumtoxinA. However, quality of life and patient satisfaction seem not to be affected by the need of intermittent catheterisation. The risk of urinary infection after the procedure is to be kept in mind, mainly in patients with multiple sclerosis, so that adequate antibiotic prophylaxis is highly recommended

The facilitatory effect of duloxetine combined with pelvic floor muscle training on the excitability of urethral sphincter motor neurons

INTRODUCTION AND HYPOTHESIS: Aim of this study was to investigate the excitability of sphincter motor neurons under the influence of pelvic floor muscle training (PFMT) and duloxetine. Due to their mechanisms of action, there might be a synergistic effect of duloxetine and PFMT in regard to the facilitation of spinal reflexes controlling urethral sphincter contractions and hence continence. METHODS: In ten healthy female subjects, clitoral electric stimulation (CES) and transcranial magnetic stimulation (TMS) were used to determine individual motor thresholds for external urethral sphincter (EUS) contractions before and after PFMT, duloxetine, and PFMT + duloxetine. RESULTS: PFMT and duloxetine alone significantly decreased the motor thresholds for EUS contractions during CES and TMS. However, the combined treatment reduced the motor threshold for EUS contractions significantly stronger compared to PFMT or duloxetine alone. CONCLUSIONS: The results are suggestive for a synergistic facilitatory effect of PFMT and duloxetine on sphincter motor neuron activation

Relativistic iron K X-ray Reverberation in NGC 4151

Recent X-ray observations have enabled the study of reverberation delays in AGN for the first time. All the detections so far are in sources with a strong soft excess, and the measured delay is between the hard (1-3 keV) direct continuum and the soft excess (0.5-1 keV), interpreted as the reflection continuum smeared by relativistic effects. There is however an inherent ambiguity in identifying and studying the details of the lines in the soft excess. Here we report the first detection of reverberation in the iron K band in any AGN. Using XMM-Newton observations of NGC 4151, we find delays of order 2000 s on time-scales of 10e5 s between the 5-6 keV band and 2-3 and 7-8 keV bands, with a broad lag profile resembling a relativistically-broadened iron line. The peak of the lag spectra shifts to lower energies at higher frequencies, consistent with the red wing of the line being emitted at smaller radii, as expected from reflection off the inner accretion disk. This is a first detection of a broad iron line using timing studies.Comment: final version, corrected small typo

Cortical substrate of bladder control in SCI and the effect of peripheral pudendal stimulation

We investigate (i) the central representation of lower urinary tract (LUT) control and (ii–iii) the acute and 23 short-term central neuromodulatory effect of peripheral pudendal nerve stimulation in incomplete spinal 24 cord injured (SCI) patients using functional magnetic resonance imaging (fMRI). The urinary bladder of eight 25 SCI patients has been passively filled and emptied using a catheter, to identify the neural substrate of bladder 26 control (i), and with simultaneous peripheral pudendal nerve stimulation to investigate its acute central 27 neuromodulatory effect (ii). To identify the potential effects of pudendal nerve stimulation treatment (iii), 28 six patients underwent a 2-week training using pudendal nerve stimulation followed by another fMRI 29 session of bladder filling. The pre- and post-training fMRI results have been compared and correlated with 30 the patient's pre- and post-training urological status. Our results suggest that the central representation of 31 bladder filling sensation is preserved in the subacute stage of incomplete SCI. However, compared to earlier 32 data from healthy subjects, it shows decreased neural response in right prefrontal areas and increased in left 33 prefrontal regions, indicating diminished inhibitory micturition control as well as, compensatory or de- 34 compensatory reorganization of bladder control. We also provide evidence for a neuromodulatory effect of 35 acute pudendal nerve stimulation, which was most prominent in the right posterior insula, a brain region 36 implicated in homeostatic interoception in human. Pudendal stimulation training also induced significant 37 neuromodulation, predominantly signal increases, in the normal cortical network of bladder control. 38 Correlations with the patient's urological status indicate that this neuromodulatory effect may reflect the 39 clinical improvement following training

The messy environment of Mrk 6

In recent years it has become clear that understanding the absorption present in AGN is essential given its bearing on unification models. We present the most recent XMM-Newton observation of Mrk 6, with the goal of understanding the nature and origin of the complex absorption intrinsic to this source. X-ray spectral fitting shows that a simple warm absorption model provides an equally good statistical representation of the CCD data as a partial covering model. Furthermore, once the RGS data are included in the spectral fitting, the simple warm absorber model provides a very good fit to the data, without increasing the complexity of the model, in contrast with the partial covering model which requires the addition of either a low metalicity (<0.03 solar) thermal plasma or low temperature blackbody emission in order to provide a similar quality fit. The warm absorber is also a considerably more natural way to explain the variability observed in the X-ray absorbing column density between the previous XMM-Newton observation and this one, requiring only a second, higher column density, higher ionisation, absorber to be present during the previous XMM-Newton observation. In comparison, the partial covering models which requires moving, clumpy, material relatively close to the source that result in two distinct lines of sight, with separate absorbing columns that each vary considerably without any associated change in their covering fractions, in order to explain the observed variability. We associate the warm absorber either with an accretion disk wind with densities of ~10^9 /cm^3, or with an ionised `skin' or atmosphere of the molecular torus with densities of ~10^3 - 10^5 /cm^3.Comment: 11 pages, 8 figures. Accepted for publication by MNRAS 05/200

Multi-dimensional modelling of X-ray spectra for AGN accretion-disk outflows III: application to a hydrodynamical simulation

We perform multi-dimensional radiative transfer simulations to compute spectra for a hydrodynamical simulation of a line-driven accretion disk wind from an active galactic nucleus. The synthetic spectra confirm expectations from parameterized models that a disk wind can imprint a wide variety of spectroscopic signatures including narrow absorption lines, broad emission lines and a Compton hump. The formation of these features is complex with contributions originating from many of the different structures present in the hydrodynamical simulation. In particular, spectral features are shaped both by gas in a successfully launched outflow and in complex flows where material is lifted out of the disk plane but ultimately falls back. We also confirm that the strong Fe Kalpha line can develop a weak, red-skewed line wing as a result of Compton scattering in the outflow. In addition, we demonstrate that X-ray radiation scattered and reprocessed in the flow has a pivotal part in both the spectrum formation and determining the ionization conditions in the wind. We find that scattered radiation is rather effective in ionizing gas which is shielded from direct irradiation from the central source. This effect likely makes the successful launching of a massive disk wind somewhat more challenging and should be considered in future wind simulations.Comment: 14 pages, 8 figures. Accepted for publication by MNRA

The reprocessing features in the X-ray spectrum of the NELG MCG-5-23-16

We present results from the spectral analysis of the Seyfert 1.9 galaxy MCG-5-23-16, based on ASCA, BeppoSAX, Chandra and XMM-Newton observations. The spectrum of this object shows a complex iron Kalpha emission line, which is best modeled by a superposition of a narrow and a broad (possibly relativistic) iron line, together with a Compton reflection component. Comparing results from all (six) available observations, we do not find any significant variation in the flux of both line components. The moderate flux continuum variability (about 25% difference between the brightest and faintest states), however, does not permit us to infer much about the location of the line-emitting material. The amount of Compton reflection is lower than expected from the total iron line EW, implying either an iron overabundance or that one of the two line components (most likely the narrow one) originates in Compton-thin matter.Comment: Accepted for publication in A&