Serena Preyer

Randomized, double blind, placebo controlled trial on the safety and efficacy of continuous intratympanic dexamethasone delivered via a round window catheter for severe to profound sudden idiopathic sensorineural hearing loss after failure of systemic therapy.

To study the safety and efficacy of continuous intratympanic dexamethasone‐phosphate (Dex‐P) for severe to profound sudden idiopathic sensorineural hearing (ISSHL) or sudden idiopathic anacusis after failure of systemic therapy.

Outcomes research analysis of continuous intratympanic glucocorticoid delivery in patients with acute severe to profound hearing loss: Basis for planning randomized controlled trials

Conclusions. The data presented herein form the basis for conducting randomized placebo-controlled clinical trials evaluating the safety and efficacy of salvage treatment in patients with idiopathic sudden severe sensorineural hearing loss (but not anacusis) refractory to initial systemic therapy. Comparison of different application protocols and drug delivery systems will allow assessment of the value of continuous versus intermittent intratympanic glucocorticoid drug delivery. Objectives. To describe and critically evaluate the results of continuous intratympanic glucocorticoid delivery in patients with acute unilateral severe and profound sensorineural hearing loss refractory to initial systemic therapy and to compare the outcome with a historical control group. Material and methods. In a retrospective chart review, treatment results were analyzed in 23 patients with acute severe and profound hearing loss and failure of systemic standard therapy who received a continuous intratympanic delivery of glucocorticoids as a salvage treatment. Audiological results were compared within the local therapy group and with the results of an historical control group who did not receive salvage treatment. The study and control groups were matched with respect to hearing loss after initial systemic treatment failure. Results. The average pure-tone threshold after intratympanic salvage treatment showed a statistically significant improvement of 15 dB (95% CI 7–24 dB; p<0.001). After exclusion of patients with complete anacusis, i.e. a non-measurable hearing threshold, the local therapy group showed a significantly better improvement (mean 19 dB; 95% CI 6–32 dB) than the historical control group (mean 5 dB; 95% CI  − 2–11 dB; p<0.05).

Distortion product otoacoustic emissions in human hypercholesterolemia.

Epidemiological and experimental studies suggest that hypercholesterolemia promotes the development of sensorineural hearing loss; however, the underlying cellular pathomechanism remains obscure. In the present study, 20 healthy subjects and 20 patients with familial hypercholesterolemia were compared with respect to their hearing function. None of the 40 persons reported any history of hearing disorder. In accordance with this subjective impression, mean hearing thresholds were within the normal, age-dependent ranges in both groups. In contrast, the single-generator distortion product otoacoustic emissions (sgDPOAE) were reduced at and above 4 kHz. Input-output functions of DPOAE could be subdivided into three groups: (i) normal, with unity slope at low intensities and slope less than unity (0.24+/-0.07 dB/dB at higher intensities; (ii) pathologic, described by a single straight line; (iii) ill-defined, with data usually indistinguishable from the background noise level. The ill-defined DPOAE behavior was only found in patients with hypercholesterolemia; namely, for 25% of patients at f(2)=1.5 kHz and for 50% at f(2)=4 kHz. Patients belonging to the pathologic and ill-defined DPOAE groups had significantly (P<0.05) higher total serum cholesterol and LDL-cholesterol levels compared with subjects from the normal DPOAE group. While hearing thresholds of patients with ill-defined growth functions were not statistically different from those of normal subjects, speech scores were significantly reduced in these cases. The data imply that nonlinear mechanical processes in the cochlea are compromised in hypercholesterolemic patients.

Nonlinearity of mechanoelectrical transduction of outer hair cells as the source of nonlinear basilar-membrane motion and loudness recruitment.

The sound-induced travelling wave in the mammalian cochlea is believed to be enhanced and sharpened by a positive-feedback mechanism, causing the passive, linear growth function of the basilar membrane (BM) to become nonlinear. Based on direct measurements of the receptor potential of isolated outer hair cells, it is shown here how nonlinear BM motion might be due predominantly to the nonlinear growth function of the receptor potential. Since intensity coding in the inner ear is supposed to depend on an interaction of nonlinear BM motion with afferent fibres of different synaptic thresholds, intensity coding is expected to be directly dependent on the mechanoelectrical transduction of outer hair cells (OHC). According to the present experimental data and the feedback concept of outer hair cell action, disruption of the mechanoelectrical transduction of OHC leads to both a reduction of gain and linearizing of the response; that is, to both hearing loss and loudness recruitment.

Acoustomechanical properties of open TTP® titanium middle ear prostheses

OBJECTIVE The purpose of the study was to identify acoustcomechanical properties of various biostable and biocompatible materials to create a middle ear prosthesis with the following properties: (i) improved handling including a good view of the head of the stapes or footplate and adjustable length, (ii) improved acoustical characteristics that are adequate for ossiculoplastic. The identified material should serve to build CE and FDA approved prostheses for clinical use in patients. METHODS Test models made of Teflon, polyetheretherketone, polyethylenterephtalate, polysulfone, gold, Al2O3 ceramics, carbon and titanium were investigated for their potential to fulfill the requirements. Acoustical properties were investigated by laser Doppler velocimetry (LDV) in mechanical middle ear models (MMM). Measured data were fed in to a recently created computer model of the middle ear (multibody systems approach, MBS). Using computer-aided design (CAD) measured and computed data allowed creation and fine precision of titanium prostheses (Tübingen Titanium Protheses, TTP). Their handling was tested in temporal bones. Acoustomechanical properties were investigated using the MBS and mechanical middle ear models. MAIN OUTCOME MEASURES Input impedance, mass, stiffness, and geometry of test models and prostheses were determined. Furthermore, their influence on the intraprosthetic transfer functions and on coupling to either tympanic membrane or stapes was investigated. RESULTS Final results were FDA- and CE-approved filigreed titanium prostheses with an open head that fulfilled the four requirements detailed above. The prostheses (TTP) were developed in defined lengths of between 1.75 and 3.5 mm (partial) and 3.0 and 6.5 mm (total) as well as in adjustable lengths (TTP-Vario). CONCLUSIONS The results suggest acoustomechanical advantages of TTPs because they combine a significantly low mass with high stiffness. In contrast to closed prostheses, the open head and filigreed design allow an excellent view of the prosthesis foot during coupling to the head or footplate of stapes, contributing to an improved intraoperative reliability of prosthesis coupling.

Abolition of the receptor potential response of isolated mammalian outer hair cells by hair-bundle treatment with elastase : a test of the tip-link hypothesis

To test the hypothesis that the tip-links of hair-cell stereocilia are essential for mechanoelectrical transduction, tip-links of isolated outer hair cells (OHCs) of the guinea-pig cochlea were eliminated with a proteolytic enzyme, elastase, and the influence on the receptor potential measured with the whole-cell patch-clamp technique. Within 45 s of immersion of the hair bundle in 20 IU/ml elastase, the receptor potential in response to direct deflection of the hair bundle was irreversibly abolished. The electrical input impedance of the cell remained unchanged, implying that the channels of the basolateral membrane were not affected by elastase. The effect of elastase on the receptor potential was comparable to changes seen after mechanically induced hair-bundle damage. As a further control, a putative transduction-channel blocker, dihydrostreptomycin (68 microM), which does not affect tip-links, was applied to the hair bundle. Although the receptor potential was also blocked by dihydrostreptomycin, the effect was reversible. The results suggest that tip-links are required for mechanoelectrical transduction of mammalian OHCs.

Mechanical Transduction in Outer Hair Cells

The outer hair cells are responsible for the exquisite sensitivity, frequency selectivity and dynamic range of the cochlea. These cells are part of a mechanical feedback system involving the basilar membrane and tectorial membrane. Transverse displacement of the basilar membrane results in relative motion between the tectorial membrane and the reticular lamina, causing deflection of the stereocilia and modulation of the open probability of their transduction channels. The resulting current causes a change of membrane potential, which in turn produces mechanical force, that is fed back into the motion of the basilar membrane. Experiments were conducted to address mechanical transduction mechanisms in both the stereocilia and the basolateral cell membrane, as well as modes of coupling of the outer hair cell force to the organ of Corti.

Frequency response of mature guinea-pig outer hair cells to stereociliary displacement

Outer hair cells (OHC) were isolated from the apical two turns of the guinea-pig cochlea and their hair-bundle stimulated mechanically by a glass probe. In accordance with in vivo data (Dallos, 1985), the resting membrane potential was typically -64 mV (N = 200). The maximum amplitudes of the receptor potentials were between 0.4 and 5.2 mV peak-to-peak, with mean of 1.5 mV +/- 0.9 mV (N = 81). The sensitivity was 0.015 mV/nm or 2 mV/deg. The frequency response of the receptor potential followed a first order low-pass filter characteristic with a corner frequency of about 63 Hz. For frequencies up to at least 1.6 kHz, the frequency response of mechanoelectrical transduction was dominated by the electrical input impedance of the cell. The presence of a single time constant in the voltage response to stereociliary deflection implies that the frequency response of mechanoelectrical transduction far exceeds that of the electrical input impedance of the cell; its time constant must be faster than 100 microseconds. Under in vivo conditions, OHC should be capable of providing a sufficiently large receptor potential to supply enough energy for electromechanical feedback.

Tonic mechanosensitivity of outer hair cells after loss of tip links

Tip links - the extracellular connectors between the distal ends of adjacent stereocilia - are essential for the fast mechanical gating of hair-cell transducer channels. Transduction in the absence of tip links was investigated for outer hair cells of the adult guinea-pig cochlea by patch-clamp recordings of the whole-cell current during mechanical stimulation of the hair bundle. Loss of tip links induced by application of BAPTA led to permanently opened transducer channels, as evidenced by a constant inward current, loss of response to sinusoidal mechanical deflection of the hair bundle and block by the open-channel blocker dihydrostreptomycin (100 microM). Step deflection of the hair bundle (200-500 nm) in the inhibitory direction exponentially reduced this current to a constant value with time constant, tau(on), of the order of seconds. The current returned exponentially to the pre-stimulus level with time-constant, tau(off), also of the order of seconds. tau(on) was dependent on the inter-stimulus interval, Deltat, such that reducing this interval below about 40 s resulted in an exponentially faster response. tau(off) was independent of Deltat. Application of the calcium ionophore, ionomycin (10 microM), showed that tau(on) became independent of Deltat after saturating elevation of the intracellular Ca(2+) concentration. Flash-photolytic release of intracellular caged calcium (25-microM NP-EGTA/AM) showed that tau(on) is dependent on intracellular Ca(2+) concentration. These experiments imply an intracellular, calcium-dependent gating mechanism for hair-cell transducer channels.

Glial lesion of the infratemporal fossa presenting as a soft tissue middle ear mass — rudimentary encephalocele or neural crest remnant?

We report about ectopic glial tissue of the skull base and the parapharyngeal space presenting as a soft tissue mass in the middle ear. An 11-year-old boy presented with bilateral conductive hearing loss since early childhood. The history included previously removed lesions consistent with ectopic neuroglial tissue of the tongue and the parapharyngeal space soon after birth, as well as surgery for cleft palate. High resolution computed tomography of the petrous bone and magnetic resonance imaging were useful in identifying the skull base defect and in characterizing the lesions relation to the brain. There was no clinical, radiological or surgical evidence of any associated dural defect. The lesion was removed via a modified infratemporal approach. Histology revealed neuroglial tissue with calcifications without any signs of mesodermal or entodermal origin. On the basis of this case the pathogenesis and diagnosis of ectopic brain tissue and its relation to the more commonly encountered meningoencephalic herniations are reviewed. Furthermore therapeutical implications are discussed.