Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the Guinea pig cochlea

Large-conductance calcium-activated potassium (BK) channels are known to play a prominent role in the hair cell function of lower vertebrates where these channels determine electrical tuning and regulation of neurotransmitter release. Very little is known, by contrast, about the role of BK channels in the mammalian cochlea. In the current study, we perfused specific toxins in the guinea pig cochlea to characterize the role of BK channels in cochlear neurotransmission. Intracochlear perfusion of charybdotoxin (ChTX) or iberiotoxin (IbTX) reversibly reduced the compound action potential (CAP) of the auditory nerve within minutes. The cochlear microphonics (CM at f1 = 8 kHz and f2 = 9.68 kHz) and their distortion product (DPCM at 2f1-f2) were essentially not affected, suggesting that the BK specific toxins do not alter the active cochlear amplification at the outer hair cells (OHCs). We also tested the effects of these toxins on the whole cell voltage-dependent membrane current of isolated guinea pig inner hair cells (IHCs). ChTX and IbTX reversibly reduced a fast outward current (activating above -40 mV, peaking at 0 mV with a mean activation time constant tau ranging between 0.5 and 1 ms). A similar block of a fast outward current was also observed with the extracellular application of barium ions, which we believe permeate through Ca2+ channels and block BK channels. In situ hybridization of Slo antisense riboprobes and immunocytochemistry demonstrated a strong expression of BK channels in IHCs and spiral ganglion and to a lesser extent in OHCs. Overall, our results clearly revealed the importance of BK channels in mammalian cochlear neurotransmission and demonstrated that at the presynaptic level, fast BK channels are a significant component of the repolarizing current of IHCs.     

A case of multiple schwannomas of the trigeminal nerves, acoustic nerves, lower cranial nerves, brachial plexuses and spinal canal: schwannomatosis or neurofibromatosis?

In most cases, while schwannoma is sporadically manifested as a single benign neoplasm, the presence of multiple schwannomas in one patient is usually indicative of neurofibromatosis 2. However, several recent reports have suggested that schwannomatosis itself may also be a distinct clinical entity. This study examines an extremely rare case of probable schwannomatosis associated with intracranial, intraspinal and peripheral involvements. A 63-year-old woman presented with a seven-year history of palpable lumps on both sides of the supraclavicular area and hearing impairment in both ears. On physical examination, no skin manifestations were evident. Facial sensory change, deafness in the left ear and decreased gag reflex were revealed by neurological examination. Magnetic resonance imaging revealed multiple lesions of the trigeminal nerves, acoustic nerves, lower cranial nerves, spinal accessory nerve, brachial plexuses, and spinal nerves. Pathological examination of tumors from the bilateral brachial plexuses, the spinal nerve in the T8 spinal position and the neck mass revealed benign schwannomas. Following is this patient case report of multiple schwannomas presenting with no skin manifestations of neurofibromatosis.     

The effect of beta adrenergic stimulation on QT and QTc interval in syncope children with or without coexisting ventricular arrhythmias

We investigated the effect of beta-adrenergic stimulation on the heart rate and QT interval in syncope children with or without coexisting ventricular arrhythmias (VA). Of the 24 children who presented with syncope or presyncope and showed negative tilt test, 13 were classified into a group with VA and the remaining 11 without VA. The provocative test was performed in bolus infusion and continuous infusion. RR, QT, and QTc intervals on routine 12-lead surface electrocardiogram were obtained during each stage of isoproterenol infusion. In all cases, malignant ventricular arrhythmia and syncope were not induced by isoproterenol provocative test. RR and QT intervals were shortened and QTc intervals were prolonged as the isoproterenol dose was increased in both groups and methods. The QTc interval reached its peak level after the bolus injection of 1.0 microgram and during the continuous infusion of 0.03 microgram/kg/min. The two groups showed no significant difference in the QTc interval change according to the infusion methods. This study indicates that changes in the heart rate and QT interval by beta-adrenergic stimulation were not different according to the coexisting ventricular arrhythmias in syncope children with negative head-up tilt test.     

Vergleichende Untersuchung von niedermolekularem Dextranoder Hydroxyäthylstärkelösungen als Volumenersatzmittel bei Hämodilutionstherapie

Summary Rheological therapy, as an immediate treatment in conjunction with physical therapy and the removal of risc factors, plays a significant role in the management of patients with peripheral vascular disease experiencing reduced walking tolerance. An essential element of rheological therapy is hemodilution. Currently, is still uncertain which plasma substitute solution would be the most appropriate in such cases. This study compared the effectiveness of low molecular hydroxyethyl starch to low molecular dextran during a 16-day hemodilution in combination to physical therapy. The clinical improvement observed with both plasma substitute solutions was comparable, yet in view of the cardiac volume overload, dextran demonstrates greater circulatory stress due to the transient pressure increase and more side effects. For this reason, we prefer to administer low or middle molecular hydroxyethyl starch in the dilution treatment of peripheral arterial occlusive disease as a chronic degenerative vascular disease.

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Abkürzungen A2M Alpha-2-Makroglobulin - D0 Meßzeitpunkt 0 der später mit Dextran behandelten Gruppe - D1 Meßzeitpunkt 1 der Dextran-Gruppe - D2 Meßzeitpunkt 2 der Dextran-Gruppe - Dextran 40 kleinmolekulares Dextran (mittleres Molekulargewicht 40000 Dalton) - ETA Plasmaviskosität - Fib Fibrinogen - Geh Gehstrecke - H0 Meßzeitpunkt 0 der später mit Hydroxyäthylstärke behandelten Gruppe - H1 Meßzeitpunkt 1 der HAES-Gruppe - H2 Meßzeitpunkt 2 der HAES-Gruppe - HAES 40 kleinmolekulare Hydroxyäthylstärke (mittleres Molekulargewicht 40000 Dalton) - Hkt Hämatokrit - LZ Leukozyten-Zahl - Pro Gesamteiweiß - SEA Erythrozyten-Aggregationsindex - SER Erythrozyten-Rigiditätsindex - TY Fließschubspannung - TZ Thrombozyten-Zahl     

Secondary amenorrhea caused by hydrocephalus due to aqueductal stenosis : report of two cases

Amenorrhea is rarely presented as a manifestation of endocrinological disturbances in patients of chronic hydrocephalus. We describe two cases of secondary amenorrhea caused by hydrocephalus due to aqueductal stenosis. Two female patients of age 30 and 20 yr presented with amenorrhea and increasing headache. Magnetic resonance images revealed marked, noncommunicating hydrocephalus without any tumorous lesion. In one patient, emergent extraventricular drainage was necessary because of progressive neurological deterioration. Each patient underwent surgical intervention for the hydrocephalus-ventriculoperitoneal shunt and endoscopic third ventriculostomy. Both resumed normal menstruation continuing so far with further normal menstrual bleeding. These two cases and others reported in the literature indicated that the surgical intervention for hydrocephalus resolves amenorrhea in all the cases of amenorrhea due to hydrocephalus. The suspected role of the surgery is the correction of increased intracranial pressure, which is an important pathogenetic factor in the development of amenorrhea.     

Multiple imputation technique applied to appropriateness ratings in cataract surgery

Missing data such as appropriateness ratings in clinical research are a common problem and this often yields a biased result. This paper aims to introduce the multiple imputation method to handle missing data in clinical research and to suggest that the multiple imputation technique can give more accurate estimates than those of a complete-case analysis. The idea of multiple imputation is that each missing value is replaced with more than one plausible value. The appropriateness method was developed as a pragmatic solution to problem of trying to assess "appropriate" surgical and medical procedures for patients. Cataract surgery was selected as one of four procedures that were evaluated as a part of the Clinical Appropriateness Initiative. We created mild to high missing rates of 10%, 30% and 50% and compared the performance of logistic regression in cataract surgery. We treated the coefficients in the original data as true parameters and compared them with the other results. In the mild missing rate (10%), the deviation from the true coefficients was quite small and ignorable. After removing the missing data, the complete-case analysis did not reveal any serious bias. However, as the missing rate increased, the bias was not ignorable and it distorted the result. This simulation study suggests that a multiple imputation technique can give more accurate estimates than those of a complete-case analysis, especially for moderate to high missing rates (30 - 50%). In addition, the multiple imputation technique yields better accuracy than a single imputation technique. Therefore, multiple imputation is useful and efficient for a situation in clinical research where there is large amounts of missing data.     

Cooperative transformation of murine fibroblast NIH3T3 cells by hepatitis C virus core protein and hepatitis B virus X protein

Co-infection with hepatitis B virus (HBV) and hepatitis C Virus (HCV) is associated with increased frequency in the development of hepatocellular carcinoma (HCC). Here, we demonstrated that HBV X protein (HBx) and HCV core cooperate to transform mouse fibroblast NIH3T3 cells. They additively stimulated cell growth, especially in the absence of serum growth factors. In addition, co-expression of HBx and HCV core had additive effects on the induction of anchorage-independent cell growth as well as on the secretion of matrix metalloproteases, which may contribute to increased metastatic potential. Furthermore, the cells expressing both viral proteins exhibited higher tumorigenicity, as demonstrated in athymic nude mice.     

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; {"type":"clinical-trial","attrs":{"text":"NCT04619277","term_id":"NCT04619277"}}NCT04619277).     

Estimation of theophylline clearance during intravenous aminophylline infusions

The utility of predicting theophylline clearance (CL) from two serum concentrations obtained during continuous intravenous aminophylline infusion was examined in 16 stable, adult patients. Blood for theophylline measurement was obtained 0, 6, and 12 h after starting infusions and, thereafter, at 12-h intervals. EMIT was used to assay samples in multiple runs as they were obtained. Later, each sample was reassayed by EMIT within a single run. Bayesian least-squares regression and the algebraic method of Chiou were used to predict CL using the 0,6 and 0,12 h concentrations. "Actual" CL was measured by nonlinear least-squares regression of all concentrations obtained during prolonged infusions. Prediction bias and precision were assessed by calculating mean percent error (PCE) and mean absolute percent error (APCE), respectively. A three-way repeated-measures ANOVA was used to examine the effect of the method of CL prediction, assay procedure, and time interval between samples on PCE and APCE. Bayesian predictions were less biased and slightly more precise than Chiou predictions. The assay procedure had no effect on bias but precision was improved using a single-assay run. Predictions were less biased and more precise with 0,12 h versus 0,6 h data. Serum samples for theophylline measurement should be obtained after initiating constant intravenous aminophylline and again 8-12 h later in stable, adult patients. Prediction of CL with either of the concentration-based methods studied will then allow safe and rapid adjustment of dosage to achieve therapeutic serum concentrations.     

Neonatal back-transport. Cost-effectiveness

This study examines the cost-effectiveness of returning previously ill neonates to community hospitals after treatment in a tertiary center, a concept known as "back-transport." The authors compared the charges for medical care during convalescence of a group of back-transported infants (BT infants; n = 20) with a similar group of infants who remained in a tertiary center for convalescence (NT infants; n = 20). The total charges for convalescent care (inpatient plus transport charges) for 20 representative BT infants was $61,840, compared with $68,240 for 20 matched NT infants, an average savings of $320 per BT infant. The average daily bed charge and charges for laboratory tests and medications were significantly less for BT infants compared with NT infants, and these reductions offset the transport charges for BT infants. The authors conclude that back transport decreases the charges for medical care for most infants. Therefore, the decision to back-transport an individual infant usually can be based on factors other than cost.