Channel Interaction and Current Level Affect Across-Electrode Integration of Interaural Time Differences in Bilateral Cochlear-Implant Listeners

Sensitivity to interaural time differences (ITDs) is important for sound localization. Normal-hearing listeners benefit from across-frequency processing, as seen with improved ITD thresholds when consistent ITD cues are presented over a range of frequency channels compared with when ITD information is only presented in a single frequency channel. This study aimed to clarify whether cochlear-implant (CI) listeners can make use of similar processing when being stimulated with multiple interaural electrode pairs transmitting consistent ITD information. ITD thresholds for unmodulated, 100-pulse-per-second pulse trains were measured in seven bilateral CI listeners using research interfaces. Consistent ITDs were presented at either one or two electrode pairs at different current levels, allowing for comparisons at either constant level per component electrode or equal overall loudness. Different tonotopic distances between the pairs were tested in order to clarify the potential influence of channel interaction. Comparison of ITD thresholds between double pairs and the respective single pairs revealed systematic effects of tonotopic separation and current level. At constant levels, performance with double-pair stimulation improved compared with single-pair stimulation but only for large tonotopic separation. Comparisons at equal overall loudness revealed no benefit from presenting ITD information at two electrode pairs for any tonotopic spacing. Irrespective of electrode-pair configuration, ITD sensitivity improved with increasing current level. Hence, the improved ITD sensitivity for double pairs found for a large tonotopic separation and constant current levels seems to be due to increased loudness. The overall data suggest that CI listeners can benefit from combining consistent ITD information across multiple electrodes, provided sufficient stimulus levels and that stimulating electrode pairs are widely spaced.     

Resiniferatoxin and Tetrodotoxin Induced NPY and TH Immunoreactivity Changes Within the Paracervical Ganglion Neurons Supplying the Urinary Bladder

Both resiniferatoxin (RTX) and tetrodotoxin (TTX) have been reported to be effective in several urinary bladder dysfunction clinical trials. The aim of this study was to establish the effect of intravesical administration of RTX and TTX on neuropeptides Y (NPY) and tyrosine hydroxylase (TH) relationship in the paracervical ganglion (PCG) neurons supplying the urinary bladder in the pig. TH is an enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine (DOPA) and is used as a marker of catecholaminergic neurons. NPY augments the vasoconstrictor effects of noradrenergic neurons, and is involved in pathophysiological processes as a neuromodulator. To identify the PCG neurons supplying urinary bladder Fast Blue (FB) was injected into the bladder wall prior to intravesical RTX or TTX administration. Consequent application of immunocytochemical methods revealed that in control group 64.08 % of FB-positive PCG neurons contain NPY and 4.25 % TH. Intravesical infusion of RTX resulted upregulation of the NPY-IR neurons to 82.97 % and TH-IR to 43.78 %. Also administration of TTX induced further increase number of TH-IR neurons to 77.49 % but induced decrease number of NPY-IR neurons to 57.45 %. Both neurotoxins affect chemical coding of the PCG neural somata supplying urinary bladder, but the effects of their action are different. This results shed light on possible involvement of RTX and TTX on curing tissue, and potentially could help us to broaden our neurourological armamentarium.     

Clinical management of mantle cell lymphoma in the elderly

ABSTRACT

Introduction: Mantle cell lymphoma (MCL) is a disease with an indolent histology, but mostly aggressive clinical course. While treatment can yield more promising results in younger patients, the disease is most diagnosed at a median age of approximately 70 years, and treatment in this group still presents a major challenge for oncohematologists. Unfortunately, due to comorbidities and poorer general status, the implementation of intensive treatment approaches with the cytarabine-based regimens and autologous stem cell transplantation is generally not possible, and the disease remains incurable, especially in elderly patients.

Areas covered: In this paper, the authors discuss the therapeutic options available for older patients with MCL in the first line and relapsed/refractory settings, indicating new therapeutic options, which may achieve longer remissions and overall survival.

Expert opinion: Although great progress has been made in the treatment of MCL in recent years, there remains a need for new treatment lines which can allow improved patient outcomes. Novel agents targeting altered the signal transduction pathways in MCL cells may offer more promise than traditional chemotherapy or immunochemotherapy and are currently being tested in clinical trials.     

Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats

Naunyn-Schmiedeberg's Archives of Pharmacology - Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CYP). Studies have indicated that Rho kinase (ROCK) inhibitors...