Dirk Beutner

Calcium dependence of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse

Release of neurotransmitter at the inner hair cell (IHC) afferent synapse is a fundamental step in translating sound into auditory nerve excitation. To study the Ca2+ dependence of the underlying vesicle fusion and subsequent endocytosis, we combined Ca2+ uncaging with membrane capacitance measurements in mouse IHCs. Rapid elevations in [Ca2+]i above 8 microM caused a biphasic capacitance increase corresponding to the fusion of approximately 40,000 vesicles. The kinetics of exocytosis displayed a fifth-order Ca2+ dependence reaching maximal rates of >3 x 10(7) vesicle/s. Exocytosis was always followed by slow, compensatory endocytosis (tau congruent with 15 s). Higher [Ca2+]i increased the contribution of a faster mode of endocytosis with a Ca2+ independent time constant of approximately 300 ms. These properties provide for rapid and sustained transmitter release from this large presynaptic terminal.

Structure and Function of the Hair Cell Ribbon Synapse

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent synapse — the electron-dense synaptic ribbon or synaptic body — has been recognized for decades, dissection of the synapse’s molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years.

TORP-vibroplasty: a new alternative for the chronically disabled middle ear.

Objective: Surgery can often eradicate chronic middle ear disease in patients with recurrent cholesteatoma, tubal dysfunction, and others; however, in many cases, social hearing cannot be restored even after multiple revision tympanoplasties. A hearing aid is then recommended. Placement of an implantable hearing aid with its advantage of an unoccluded ear canal, irrespective of middle ear function, seems to be a promising alternative. Study Design: After establishing the biomechanics of the ear in our temporal bone laboratory, various locations and attachments of a Vibrant transducer were investigated. These experiments resulted in the development of a new titanium clip holder for a Vibrant integrated total ossicular replacement prosthesis assembly with placement on the footplate. Four patients with permanent severe combined hearing loss were implanted with this device after multiple revision tympanoplasties. The first case is described in detail. Results: Placing a transducer directly on the footplate via a rod transmission gave a better gain for the high frequencies than in the round window location. The acoustic results of the patients showed an improved gain in speech understanding, unobtainable by a conventional hearing aid. Conclusion: The concept of a total ossicular replacement prosthesis-vibroplasty establishes a straightforward procedure in the tympanic cavity similar to a normal tympanoplasty. The open ear canal and its superior acoustic performance offer a promising perspective for revision operations in cases of incurable middle ear dysfunction.

Gustatory Function in Chronic Inflammatory Middle Ear Diseases

Hypothesis: Changes of gustatory function after ear surgery have been studied extensively. However, little is known on the influence of repeated/chronic inflammation within the middle ear on taste.

Risk Factors for Auditory Neuropathy/Auditory Synaptopathy

Aims: It was the aim of this study to describe risk factors in auditory neuropathy/auditory synaptopathy (AN/AS). Methods: Between 1997 and 2005, we diagnosed 37 children with AN/AS. They underwent a critical chart review for risk factors and etiological coincidences in this idiosyncratic disorder. Results: Eighteen neonates had a history of prematurity and low birth weight. Hyperbilirubinaemia was present in 13 children. Three patients had evidence of infection during pregnancy, and AN/AS was associated with complex syndromal diseases in 2 cases. A congenital, familial pattern was seen in 2 siblings. Seven patients had idiopathic AN/AS. Conclusion: Rather than being a single etiological entity, AN/AS comprises a spectrum of risk factors and associated problems affecting the cochlea and the auditory pathway. This study shows that the majority of AN/AS in children is the result of perinatal problems and is not genetic in origin. Hyperbilirubinaemia is a common and etiologically significant finding in infants suffering from AN/AS. Thus, early hearing screening for AN/AS including transient evoked otoacoustic emissions and auditory brainstem response assessment among neonates with risk factors for AN/AS is crucial in order to better manage patients suffering from this disorder.

Vibroplasty for mixed and conductive hearing loss.

Objective To summarize new application methods of an active middle ear implant (Vibrant Soundbridge) in patients with conductive or mixed hearing loss. Data Sources Publications listed in the Medline/PubMed database. Study Selection All publications published in English language; search term Vibrant Soundbridge AND floating mass transducer in all fields. Data Extraction Structured analysis of all publications. Data Synthesis Extraction of significant findings and conclusions and audiometric data. Conclusion Modern application methods of an active middle ear implant (VSB) open new therapeutic options for patients with various outer and middle ear diseases resulting in conductive or mixed hearing loss. Titanium couplers can help to couple the active middle ear implant in a standardized way to remnants of the ossicular chain or to the round window. Thus, the active middle ear implant has been established as an alternative treatment option for patients with mixed and conductive hearing. However, the heterogeneity of the studies published so far complicates the analysis of the audiometric results, and thus, the functional hearing gain after VSB implantation varies a lot.

Experience with vibroplasty couplers at the stapes head and footplate.

Objective To report on experiences with implanting the Vibrant Soundbridge (VSB) coupled to the stapes head using a new Clip-Coupler or to the stapes footplate using a new OW-Coupler (CliP- or OW-Coupler Vibroplasty). Study Design Single subject, repeated measures. Setting Two university hospital ENT departments. Patients Fourteen German-speaking patients from 2 European study sites were implanted with either a CliP-Coupler or OW-Coupler attached to a VSB floating mass transducer (FMT). They were evaluated preoperatively and postoperatively for bone and air conduction thresholds with and without the implant, as well as speech perception tests. Main Outcome Measures Measuring the efficacy and safety of OW- and CliP-Coupler-Vibroplasty as a method to treat mixed hearing loss. Results Bone conduction thresholds remained stable preoperatively and postoperatively. The patients’ average speech perception performances at 65/80 dB (HL) increased from 0.8/13.8% to 63/82%. The pure tone audiograms showed an average improvement in air conduction thresholds after implantation with the VSB of 25 dB at 0.5 kHz to 50 dB at 4 kHz. Conclusion OW- or Clip-Coupler-Vibroplasty using couplers was found to be a straightforward procedure, which produced good results in this group of patients.

Sialoendoscopy: prognostic factors for endoscopic removal of salivary stones.

OBJECTIVE To detect prognostic factors for successful sialoendoscopic removal of salivary stones. DESIGN Retrospective case series. SETTING Tertiary referral hospital. PATIENTS Forty-nine consecutive patients who underwent sialoendoscopy for sialolithiasis between January 1, 2008, and January 1, 2010, at University Hospital of Cologne, Cologne, Germany. INTERVENTIONS Diagnostic and interventional sialoendoscopy using local anesthesia. MAIN OUTCOME MEASURES Stone removal rate, size, mobility, shape, and location, as well as clinical follow-up data. RESULTS Sixty-one percent (39 of 64) of all salivary stones were removed endoscopically. The cutoff point for endoscopic removal was between 5 and 6 mm in stone diameter. Small size, good mobility, round or oval, and distal location of a salivary stone were positive prognostic factors for sialoendoscopic removal, with sialolith mobility having the greatest effect in multivariate analysis. CONCLUSION Small size, good mobility, round or oval, and distal location of a salivary stone in the main duct predict significantly greater probability of endoscopic removal and consequently are positive prognostic factors.

Diagnostik und Therapie der auditorischen Synaptopathie/Neuropathie

ZusammenfassungDie audiologische Konstellation von pathologischen frühen akustisch evozierten Potenzialen (fehlend, erhöhte Schwelle und gestörte Kurvenform) trotz nachweisbarer otoakustischer Emissionen geht häufig mit einer von schlechtem Sprachverständnis geprägten Schwerhörigkeit bzw. mit Taubheit einher. Diese als auditorische Neuropathie erstbeschriebene, heterogene Erkrankungsgruppe beinhaltet peripher-auditorische Störungen der synaptischen Schallkodierung durch innere Haarzellen (Synaptopathie) und/oder der Erregungsbildung und -weiterleitung im Hörnerv (Neuropathie). Dieses Konsensuspapier gibt aktuelle Hintergrundinformationen sowie Empfehlungen zur Diagnostik und Therapie im deutschsprachigen Raum. Es nimmt dabei Bezug auf aktuelle internationale Statements.AbstractPathological auditory brainstem responses (lack of responses, elevated thresholds and perturbed waveforms) in combination with present otoacoustic emissions are typical audiometric findings in patients with a hearing impairment that particularly affects speech comprehension or complete deafness. This heterogenous group of disorders first described as “auditory neuropathy” includes dysfunction of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or of the generation and propagation of action potentials in the auditory nerve (neuropathy). This joint statement provides prevailing background information as well as recommendations on diagnosis and treatment. The statement focuses on the handling in the german language area but also refers to current international statements.

Impact of lateral parotidectomy for benign tumors on quality of life.

Conclusion. This study supports the use of lateral parotidectomy as a safe and standardized type of surgery for benign parotid gland disease. Objective. To assess quality of life in patients with benign salivary gland tumors who underwent lateral parotidectomy. Patients and methods. Fifty-one patients suffering from benign parotid gland disease were included in this prospective study. Using the EORTC QLQ-C30 and EORTC-QLQ-H&N35 questionnaire, surgery-affected changes in quality of life were assessed in 34 patients who completed this survey. Results. Overall results show no alterations in quality of life 1 year after lateral parotidectomy.