Hearing rehabilitation for unilateral deafness using a cochlear implant: the influence of the subjective duration of deafness on speech intelligibility.

BACKGROUND: For patients with single sided deafness (SSD) or severe asymmetric sensorineural hearing loss (ASHL), cochlear implantation remains the only solution to restore bilateral hearing capacity. Prognostically, the duration of hearing loss in terms of audiological outcome is not yet clear. Therefore, the aim of this study was to retrospectively investigate the influence of subjective deafness duration on postoperative speech perception after cochlear implantation for SSD as well as its impact on quality of life. MATERIALS AND METHODS: The present study included a total of 36 adults aged 50.2 ± 15.5 years who underwent CI for SSD/ASHL at our clinic between 2010 and 2015. Patients were audiometrically assessed at 3 and 12-36 months postoperatively. Test results were correlated with self-reported duration of deafness. Quality of life was assessed by questionnaire. RESULTS: Mean duration of deafness was 193.9 ± 185.7 months. The side-separated hearing threshold showed an averaged target range between 30 and 40 dB HL. Freiburg monosyllable test increased from 0% pre-operatively to 20% after 3 months (p = 0.001) and to 50% after 12-36 months (p = 0.002). There was a significant correlation between audiometric outcome and subjective deafness duration at 12-36 months postoperatively (r = - 0.564; p = 0.02) with a cutoff for open-set monosyllable recognition at a duration of deafness of greater than 408 months. Quality of life was significantly improved by CI. CONCLUSIONS: CI implantation in unilaterally deafened patients provides objective and subjective benefits. Duration of deafness is unlikely to be an independent negative predictive factor and thus should not generally be considered as contraindication.

RREB1-MKL2 fusion in a spindle cell sinonasal sarcoma: biphenotypic sinonasal sarcoma or ectomesenchymal chondromyxoid tumor in an unusual site?

Biphenotypic sinonasal sarcoma (BSNS) is a rare, low grade spindle cell sarcoma, recently recognized in the WHO classification of head and neck tumors, which is characterized by a dual myogenic and neural differentiation and recurrent gene fusions, often involving PAX3-MAML3, and less commonly PAX3 fusions with other partners such as NCOA1, NCOA2, or WWTR1. Yet, in about 4% of tumors no gene rearrangements are identified. Herein, we describe a RREB1-MKL2 fusion in a BSNS lesion occurring in a 73-year-old female patient with a right maxillo-ethmoidal angle lesion. The polypoid, moderately cellular tumor with infiltrative submucosal growth was composed of fascicles of relatively bland spindle cells embedded in a loose collagenous matrix. The tumor cells showed moderate amounts of eosinophilic cytoplasm with indistinct borders and uniform, pale, ovoid to slender nuclei. The slowly proliferating neoplastic cells co-expressed smooth muscle actin and S100, and showed focal nuclear positivity for ß-catenin, while lacking staining for cytokeratins, desmin, myogenin, caldesmon, glial fibrillary acid protein, and SOX-10. Molecular analysis by targeted RNA-based next-generation sequencing identified an in-frame fusion between exon 8 of RREB1 and exon 11 of MKL2, a genetic event that was reported to be a molecular hallmark of ectomesenchymal chondromyxoid tumor. Gene rearrangements in both genes were independently verified by fluorescence in situ hybridization (FISH). To evaluate its recurrent potential an additional group of 15 fusion negative BSNS were tested for abnormalities in RREB1 and MKL2 genes by FISH, but no additional positive cases were identified.

Etiology, Management, and Outcome of Pediatric Epistaxis.

OBJECTIVE: Epistaxis in children is one of the most common causes for seeking professional medical help. Patients may be treated by several disciplines with various approaches to pediatric epistaxis. We reviewed cases of pediatric epistaxis from an otorhinolaryngologist's point of view. METHODS: A retrospective chart review was performed on all patients younger than 18 years presenting with epistaxis to the Department of Otorhinolaryngology at the University of Bonn, Germany. RESULTS: Sixty episodes of epistaxis in 58 patients were included in the study. Mean age was 10.1 ± 4.5 years. In terms of risk factors, 3 patients had a hemorrhagic diathesis, 3 had taken medication that interfered with hemostasis, and 8 had a history of previous trauma, most of which was digital manipulation. Twenty-six patients did not need invasive therapy. Twenty-six patients received cauterization to control the bleeding, and 4 patients needed surgery. The necessity for surgery was mainly noncooperation. CONCLUSIONS: Epistaxis in children is seldom serious. However, hemorrhagic diathesis needs to be kept in mind as a potential cause of epistaxis. In most cases, careful instruction of the patients and the relatives concerning nasal mucosal care is sufficient. If cauterization is necessary, silver nitrate coagulation should be preferred over electrocoagulation.

Hyaluronic Acid-based Filler Injection: Late-onset Thrombosis of the Frontal Vein.

Thrombosis is a serious complication of a hyaluronic acid-based filler injection. Little is known about the late-onset complications of fillers; therefore, an optimal complication management is necessary. In this case report, we describe a rare complication of thrombosis after a filler injection. A 35-year old woman was admitted to the emergency department, with swelling on her forehead in association with recurrent pain and light flashes in her right eye. Sonographic examination showed a thrombosis of the right frontal vein. The patient reported that a hyaluronic acid filler injection had been administered on the forehead 3 months ago. After several weeks of anticoagulation with heparin and apixaban, the symptoms persisted. The vein with thrombosis was ultimately resected under local anesthesia. Histological findings showed a chronic inflammatory reaction of the tissue to hyaluronic acid. Vascular complications may appear as late-onset complications even several months after the filler injection. Subcutaneous application of low molecular weight heparins is the therapy of first choice. If this treatment is not effective, resection of the thrombosis may be performed.

Robot-assisted endoscope guidance versus manual endoscope guidance in functional endonasal sinus surgery (FESS).

BACKGROUND: Having one hand occupied with the endoscope is the major disadvantage for the surgeon when it comes to functional endoscopic sinus surgery (FESS). Only the other hand is free to use the surgical instruments. Tiredness or frequent instrument changes can thus lead to shaky endoscopic images. METHODS: We collected the pose data (position and orientation) of the rigid 0° endoscope and all the instruments used in 16 FESS procedures with manual endoscope guidance as well as robot-assisted endoscope guidance. In combination with the DICOM CT data, we tracked the endoscope poses and workspaces using self-developed tracking markers. RESULTS: All surgeries were performed once with the robot and once with the surgeon holding the endoscope. Looking at the durations required, we observed a decrease in the operating time because one surgeon doing all the procedures and so a learning curve occurred what we expected. The visual inspection of the specimens showed no damages to any of the structures outside the paranasal sinuses. CONCLUSION: Robot-assisted endoscope guidance in sinus surgery is possible. Further CT data, however, are desirable for the surgical analysis of a tracker-based navigation within the anatomic borders. Our marker-based tracking of the endoscope as well as the instruments makes an automated endoscope guidance feasible. On the subjective side, we see that RASS brings a relief for the surgeon.

Workspace and pivot point for robot-assisted endoscope guidance in functional endonasal sinus surgery (FESS).

BACKGROUND: For the further development of robot-assisted endoscope guidance in functional endoscopic sinus surgery (FESS), ground data about the workspaces and endoscope movements in conventional FESS are needed. METHODS: Applying a self-developed marker-based tracking system, we collected the pose data (position and orientation) of the endoscope and all other instruments used in five real sinus surgeries. RESULTS: The automated segmentation of the endoscope poses shows the shape of a hourglass, with a pivot region or pivot point at the 'waistline' of the hourglass, close to the nasal entrance in the nasal dome. CONCLUSION: We were able to identify a pivot point at the waistline of the segmented endoscope poses. The size of the pivot point corresponds with the diameter of the 4 mm endoscope. Because of the reduction to four degrees of freedom for endoscope motions (three rotations and one translation), easier and safer robot-assisted endoscope guidance becomes feasible.

Factors predicting survival after diagnosis of laryngeal cancer.

Survival in patients with laryngeal cancer has not increased remarkably within the last years. It is presumed that a variety of factors act jointly in predicting survival after diagnosis: tumour stage, tumour site, treatment approaches, age and comorbidities. The aim of this German clinical multi-centre study is to present results from multivariate analysis. A retrospective cohort study was conducted in four hospitals in South-West Germany. Incident cases with laryngeal squamous cell carcinoma were included for the years 1998 to 2004, resulting in a population sample of 594 patients. Multivariate regression analysis was performed using the Cox proportional hazards model. Patients were followed up for 64.1months on average. Overall 5-year survival was 66% (95% confidence interval (CI): 62-70%). The strongest risk factors in multivariate analysis were age at first diagnosis (hazard ratio (HR): 1.5; 95% CI: 1.5-1.7 per each additional 10years), tumour stage, and the development of recurrences (HR 3.1; 95% CI: 2.3-4.2) or second primary carcinomas (HR 2.1; 95% CI: 1.4-3.1). A somewhat weaker effect was shown for patients with comorbidities (using Charlson's comorbidity index). The choice of treatment did not strongly affect survival when adjusting for other factors, possibly because the optimal treatment approach was applied for the specific constitution and requirements of each patient. For future research it would be desirable to study the effect of treatment on quality of life in multivariate analysis as well as other modifiable risk factors as smoking and drinking reduction or cessation after diagnosis.

Different antioxidative potencies of dihydropyridine calcium channel modulators in various models.

There is evidence that dihydropyridine calcium antagonists (DHP) play a beneficial role during the development of atherosclerosis. Since antioxidative properties of this substance class may be important, we investigated the antioxidative potency of the DHP prototype calcium channel antagonist nifedipine, the long acting calcium channel antagonist lacidipine, the DHP calcium channel agonist Bay K 8644 and the bulky DHP derivate Bay O 5572 (negligible effects on L-type calcium channels) in three different models. Additionally, we examined the potential correlation between lipophilic and antioxidative properties. In an in vitro model, Bay K 8644 was significantly more effective in scavenging superoxide anions (hypoxanthine/xanthine-oxidase-assay) than lacidipine, Bay O 5572 or nifedipine (micro- to millimolar concentration range). Addition of artificial membrane preparations (dimyristoylphosphatidylcholine) to mimic a physiological environment resulted in an enhanced antioxidative effect, with lacidipine being the most effective DHP to quench radicals (low micromolar concentration range). Thirdly, in a more physiological model of hyperglycemia (30 mmol/l) induced release of reactive oxygen species (ROS) from native endothelial cells of porcine coronary arteries, we showed that nifedipine was a significantly more potent antioxidant (therapeutical nanomolar concentration range) than the other DHP. Calculation of the lipophilicity of the four substances (lacidipine>Bay O 5572>Bay K 8644>nifedipine) showed a positive correlation between the antioxidative potency and the lipophilicity in the model with the artificial membranes but not in the other models. We conclude that it seems necessary to access antioxidative properties of substances in physiological models in which we could demonstrate that nifedipine exhibits ROS-quenching properties in a therapeutic concentration range.

Amlodipine increases endothelial nitric oxide by dual mechanisms.

Several experimental and clinical studies have demonstrated the antiatherogenic profile of the long-acting calcium antagonist amlodipine. Given the pivotal role of endothelial (dys)function during atherogenesis, we investigated the influence of amlodipine on endothelial nitric oxide (NO) bioavailability. Acute addition of amlodipine to segments of porcine coronary arteries resulted in a significant increase in NO release which could be blocked by the NO synthase inhibitor L-NMMA (N-monomethylarginine). This effect was mirrored by a rise in intracellular cGMP levels in porcine endothelial cell cultures. Long-term (24 h) treatment of porcine endothelial cell cultures with amlodipine (0.1-10 micromol/l) significantly enhanced the basal NO formation in a concentration-dependent manner which was abrogated in the presence of L-NMMA (0.1 mmol/l). In EA.hy 926 endothelial cells, amlodipine treatment for 24 h significantly increased the endothelial NO synthase protein expression. To evaluate whether the observed increase in NO was additionally due to an antioxidative protection of NO, we examined the influence of amlodipine in different in vitro models. In a cell-free system, amlodipine quenched superoxide anions (hypoxanthine/xanthine oxidase assay) at high concentrations (150 micromol/l). Addition of artificial membrane preparations (dimyristoylphosphatidylcholine) to mimic a physiological environment significantly enhanced this antioxidative effect. In a more physiological model of hyperglycemia (30 mmol/l, 20 min) induced formation of reactive oxygen species from native endothelial cells of porcine coronary arteries, amlodipine concentration dependently attenuated the reactive oxygen species release (>60%; 10 micromol/l). We conclude, that amlodipine increases the endothelial NO bioavailability, firstly via enhanced NO formation and secondly by prolonging the half-life of NO through antioxidative properties. This may result in an improved endothelial function.

Reaction rate constants of superoxide scavenging by plant antioxidants.

Plant phenols may exert protective effects by scavenging superoxide, which is implicated in tissue damage and accelerated inactivation of vasorelaxing nitric oxide. Preventing the interaction of superoxide with tissue biomolecules depends not only on the extent of superoxide scavenging but also on scavenging velocity. However, information on superoxide scavenging kinetics of plant phenols is scarce. We describe an improved lucigenin-based chemiluminescence assay for kinetic analysis. The use of potassium superoxide (KO2) as a nonenzymatic superoxide source allowed simple and reliable determination of the second-order reaction rate constants between superoxide and plant antioxidants at physiologically relevant conditions, avoiding unspecific effects of other reactive oxygen species or superoxide-generating enzymes. We calculated the rate constants for phenols of different structures, ranging from 2.9 x 10(3) mol(-1) l s(-1) for morin to 2.9 x 10(7) mol(-1) l s(-1) for proanthocyanidins. Compounds with pyrogallol or catechol moieties were revealed as the most rapid superoxide scavengers, and the gallate moiety was found to be the minimal essential structure for maximal reaction rate constants with superoxide.

Modification of Ti6AL4V surfaces using collagen I, III, and fibronectin. II. Influence on osteoblast responses.

Responses of osteoblastic cells are influenced by morphology and composition of the extracellular matrix, and this fact has been used to improve the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM). In this study, the effect of the collagen types I and III on adhesion, proliferation, and differentiation was studied, using primary osteoblastic cells from rat calvariae. Differences in alkaline phosphatase activity (ALP) and collagen synthesis were observed between differently composed collagen coatings. An increase in collagen type III resulted in an increase in collagen synthesis and a concomitant decrease in ALP activity and Ca deposition. Initial adhesion mechanism of the cells depended on the substrate (titanium, collagen, fibronectin).

The HMG-CoA reductase inhibitor cerivastatin enhances the nitric oxide bioavailability of the endothelium.

The aim of this study was to investigate whether the HMG-CoA reductase inhibitor cerivastatin alters the nitric oxide (NO) bioavailability of porcine aortic endothelial cell cultures and of native porcine coronary endothelium, after short-term (minutes) and long-term (24-hour) treatment with cerivastatin (electrochemical NO sensor). NO-synthase expression (Western blot, ELISA) and activity (3H-arginine assay) after cerivastatin treatment were determined. Furthermore, the authors investigated whether cerivastatin modulates an angiotensin II (10 micromol/L; 4 hours) induced reactive oxygen species (ROS) release from intact vessels (lucigenin-enhanced chemiluminescence-assay). Acute addition of cerivastatin induced a concentration-dependent NO release from endothelial cell cultures that could be blocked by the NO-synthase inhibitor N-monomethyl-arginine. A long-term incubation with cerivastatin also resulted in a concentration-dependent, significantly enhanced basal NO bioavailability (approximately 3-fold increase at 10 nmol/L cerivastatin) that could be partly reversed by a coincubation with mevalonate. No enhanced endothelial NO-synthase expression or increased NO-synthase activity was detected after long-term treatment with cerivastatin (24 hours). However, cerivastatin induced a significant concentration-dependent inhibition of the angiotensin II-induced ROS release from native endothelial cells of porcine coronary arteries. Therefore, there seems to be an acute and a long-term effect of cerivastatin that results in enhanced endothelial NO bioavailability.

Nitric oxide formation and corresponding relaxation of porcine coronary arteries induced by plant phenols: essential structural features.

The high intake of polyphenols is thought to contribute to the beneficial cardiovascular effects of plant-centered diets. A putative mechanism underlying the cardioprotective activity is thought to be a plant phenol-induced increase of nitric oxide formation by the constitutive endothelial nitric oxide synthase. Twenty-eight phenols of different classes commonly occurring in plant foods were examined for their capability of enhancing the endothelial nitric oxide release of isolated porcine coronary arteries by direct real-time measurement of the luminal surface nitric oxide concentration with an amperometric microsensor. Additionally, the relaxing activity of the phenols was measured on porcine coronary rings. Quercetin, myricetin, leucocyanidol, and oligomeric proanthocyanidins induced the highest increases in nitric oxide release (delta[NO] > 8.5 nM ); caffeic acid, fisetin, hyperosid, and isoquercitrin were moderately active (5 nM < delta[NO] < 8.5 nM ); the other phenolic compounds caused only marginal increases of the nitric oxide levels (delta[NO] < 5 nM). The nitric oxide-stimulating activity of the phenols was uniformly positively correlated with their vasorelaxing activity. However, endothelium-dependent vasorelaxations were limited to phenols inducing nitric oxide elevations > 5 nM (= Km value of the soluble guanylate cyclase). Analysis of structure-activity relations revealed that a high nitric oxide activity was confined to a flavan-moiety with free hydroxyl-residues at C3, C3', C4', C5, and C7 and a hydroxyl-, oxo-, or phenolic substituent at C4, whereas the caffeic acid scaffolding emerged as the minimally essential motif for the nitric oxide-dependent vasorelaxation.

Studies on the cardiotoxicity of noradrenaline in isolated rabbit hearts.

UNLABELLED: The concentration-dependent toxic effects of exogenous noradrenaline (NA, CAS 51-41-2) on acute regional myocardial ischemia (MI) was investigated with and without alpha- and beta-adrenoceptor blockade. Electrically-driven rabbit Langendorff-hearts with depleted catecholamine stores were used (reserpin 7.0 mg/kg i.p. 16-24 h before preparation, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). Repetitive MI, separated by a reperfusion period of 50 min, was induced by coronary artery branch ligature, and quantitated from epicardial NADH-fluorescence photography. Starting after a reperfusion period of 20 min, hearts were treated with exogenous NA (10(-7), 10(-6) or 10(-5) mol/l). Adrenoceptors were blocked by propranolol (10(-6) mol/l) and phentolamine (10(-6) mol/l). Without adrenoceptor blockers, NA 10(-6) mol/l induced an increase in left ventricular pressure and a reduction in the relative coronary flow. Concomitantly, MI was enhanced. After adrenoceptor blockade, NA 10(-7) or 10(-6) mol/l had no influence on functional parameters. MI was not affected by NA 10(-7) mol/l, but MI was significantly enhanced by NA 10(-6) mol/l. MI enhancement by NA 10(-6) mol/l was completely prevented by superoxide dismutase (30 U/ml). Functional effects of NA 10(-5) mol/l were not completely inhibited by adrenoceptor blockers at the concentrations used, and arrythmias were observed. MI was also enhanced by NA 10(-5) mol/l. CONCLUSION: Deleterious effects on MI, that are independent on functional effects, are induced by NA in a micromolar concentration. These direct toxic effects are mediated by superoxide anion radicals. In lower concentrations (10(-7) mol/l), there is no evidence for direct toxic actions of NA independent of functional effects. MI enhancement by NA 10(-5), or 10(-6) mol/l without adrenoceptor blockers may have been caused in part by functional and arrythmogenic effects and/or through the generation of oxygen free radicals.