Clinical study of Widex Senso on first-time hearing aid users.

Using psychoacoustic tests and questionnaires, the aim of this study was to clinically test Widex Senso (WS) versus analogue hearing aids on 200 first-time wearers. Half of the participants were selected at random for fitting with the behind-the-ear model (WS C8) or the in-the-canal model (WS CX). On a group basis, WS was found to provide more benefit than a palette of 29 analogue, modern hearing aid models from 10 manufacturers. Only 3 of 100 subjects changed from WS to another hearing aid. On average, the abbreviated profile of hearing aid benefit (APHAB) (Cox & Alexander, 1995) demonstrated superior performance for WS, i.e. no conflict existed between high comfort and high speech recognition. Median aided frequency-modulated tone thresholds in the sound field were better than 25 dB HL at frequencies up to 4 kHz inclusive. A distinct mean aided improvement of speech threshold in competing speech of 2.5 dB was found in both groups.

Quinine reduces the dynamic range of the human auditory system.

The aim of the study was to evaluate and quantify quinine-induced changes in the human auditory dynamic range, as a model for cochlear hearing loss. Six otologically normal volunteers (21-40 years old) received quinine hydrochloride (15 mg/kg body weight) in two identical oral doses and one intravenous infusion. Refined hearing tests were performed monaurally at threshold, at moderate hearing levels and at high hearing levels. Quinine induced a maximal pure-tone threshold shift of 23 dB (1000-2000 Hz). The increase in the psychoacoustical click threshold agreed with an increase in the detection threshold of click-evoked otoacoustic emissions. The change in the stimulus-response relationship of the emissions reflected recruitment. The self-attained most comfortable speech level and the acoustic stapedius reflex thresholds were not affected by quinine administration. Quinine is a useful model substance for reversibly inducing complete loudness recruitment in humans as it acts specifically on some parts of the hearing function. Its mechanism of action on the molecular level is likely to reveal further information on the physiology of hearing.

Description and primary results from an audiometric study of male twins.

OBJECTIVE: The purpose of this study is to present descriptive results from an audiometric examination of a male twin sample, compare the values with normative databases, and explore whether there are age differences in genetic and environmental contributions to variation in hearing. DESIGN: Audiometric and questionnaire data were collected on a subsample of male twins who were identified through the population-based Swedish Twin Registry. Hearing examinations were completed for a total of 557 intact pairs, comprised of 250 identical (monozygotic [MZ] pairs and 307 fraternal (dizygotic [DZ] pairs aged 36 to 80 yr. A scale measuring hearing in the high-tone ranges was constructed by calculating the mean for the hearing threshold values obtained for both ears combined at 3000, 4000, 6000, and 8000 Hz for air conduction. RESULTS: To assess whether the twin values are representative of genera hearing function, the hearing thresholds were compared with values from two normative databases. Results suggest that these twin data provide a valid representation of hearing function in a cross-section of the Swedish male population, aged 35 and older. The mean values for hearing ability decreased across age, and variation increased. Twin similarity, estimated across four age groups using intraclass correlations, decreased from 0.716 to 0.516 for the MZ pairs and increased from 0.131 to 0.279 for the DZ pairs. These results suggest that variation in hearing ability in the high ranges is due to genetic and environmental factors and that environmental effects become more important with age. CONCLUSIONS: These data reflect typical age-related deterioration in hearing ability accompanied by greater individual differences in hearing function with age. Across all ages, genetic and environmental effects are important sources of variation in hearing. However, preliminary analyses suggest that the relative influence of environment increases with age. These environmental effects are of the nonshared type that are not associated with shared family environments but rather are explained by unique exposures.

Quinine-induced hearing loss in the guinea pig is not affected by the Ca2+ channel antagonist verapamil.

It is well documented that quinine induces reversible hearing loss and tinnitus. The purpose in this study was to induce a quinine hearing loss and to investigate if verapamil, a Ca2+ channel antagonist of L-type might affect the response. Pigmented guinea pigs (n = 24) were anaesthetized by atropine. Hypnorm and midazolam but permitting spontaneous respiration. An electrode of platinum was placed on the round window and short (10 msec) tone pulses at 8 kHz were presented to the external ear. A typical deflection of the N1-wave was determined as the hearing threshold. Quinine hydrochloride 40 mg/kg and verapamil 1 mg/kg were given intravenously. Quinine induced a significant and reversible hearing loss (mean 16 dB). This hearing loss was not at all affected by verapamil given before or after quinine. Verapamil often caused acute cardiac arrest and particularly the combination verapamil followed by quinine-induced death to the animal. We conclude that verapamil and quinine had no in vivo interaction with regard to the hearing ability.

Magnitude changes in transient evoked otoacoustic emissions and high-level 2f1-f2 distortion products in man during quinine administration.

Quinine reversibly affects the outer hair cells (OHC). It is therefore an ideal drug for studying OHC-related phenomena, such as transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). Pure-tone thresholds (PTTs), 1,000-4,000 Hz, TEOAEs, and DPOAEs were measured monaurally in 5 normal-hearing volunteers during quinine administration. DPOAE was evoked at 75 dB SPL (f2/f1 = 1.22) and analysed at 2f1-f2 with f2 at 6 frequencies (700-4,000 Hz), while TEOAE was obtained at 79 dB SPLp and analysed at the f2 frequencies (1/3 octave). The PTT-shift was flat, 10 dB, whereas the TEOAE-power and the global mean of the DPOAEs decreased 4.5 dB and 1.4 dB, respectively. No correlation was found between the intra-individual emission shifts. It is concluded that TEOAE is more sensitive than high-level DPOAE for identifying minor cochlear hearing losses. Support is given to the hypothesis that different sources are involved in generating DPOAEs at different evoking levels.

The concentration-effect relationship of quinine-induced hearing impairment.

Quinine-induced reversible hearing impairment at the frequencies of 1000 and 2000 Hz was investigated in healthy volunteers to analyze the plasma concentration-effect relationship of the drug. Six subjects were given two identical oral doses of quinine and a constant rate infusion of quinine over 6 hours (15 mg.kg-1) on three separate occasions. A simple pharmacodynamic model, E = k.C gamma (in which E is effect, k is a proportionality constant, C is drug concentration, and the exponent gamma is a fitting parameter), was found to describe well the relationship between hearing impairment and quinine concentrations in a hypothetical effect compartment. No statistical differences were found in the estimated parameters when the three dosings were compared, indicating that quinine-induced hearing impairment is independent of route of administration. The first-order rate constant (keo), linking plasma concentrations to the concentrations in the effect compartment, was (mean +/- SD) 0.71 +/- 0.19 and 0.99 +/- 0.37 hr-1 for 1000 and 2000 Hz, respectively. The corresponding values of k were 0.15 +/- 0.10 and 0.12 +/- 0.19 and the values of gamma were 2.13 +/- 0.57 and 3.44 +/- 1.04 for 1000 and 2000 Hz, respectively. Effect was also analyzed by semiparametric pharmacodynamic modeling, which gave results comparable to those obtained with the link model. We conclude that a simple power function is a reliable pharmacodynamic model for describing quinine-induced hearing impairment in healthy subjects.

Effects of quinine on the mechanical frequency response of the cupula in the fish lateral line.

Quinine induces changes in the motion of the cupula in the lateral line canal of the African knife-fish in response to sinusoidal water movements. Two different phases in the action of quinine on the cupular frequency response can be discerned. In the first phase the best frequency, i.e., the frequency at which the cupular vibratory displacement is maximal in response to constant-amplitude sinusoidal canal fluid displacement, shifts toward higher frequencies. During this phase, lasting about 70-100 min, the best frequency increases by a factor between 1.3 and 1.5. In the second phase, during roughly the following 90 min, the best frequency decreases gradually to a value 0.3-0.5 times that observed before the application of quinine.

The effects of quinine on the cochlear mechanics in the isolated temporal bone preparation.

Quinine is known to induce a reversible hearing loss and to evoke motile responses of isolated outer hair cells. To study the effect of quinine, mechanical tuning curves of the Hensen's cells were measured in the isolated cochlea preparation in response to acoustical stimuli applied to the ear before and after application of the drug. It was shown that 0.5-4 mM quinine increased the vibration amplitude at the peak of the mechanical resonance curves and increased the sharpness of tuning. The time course of the event depended on whether the scala media was opened or not. The results show that quinine alters the micromechanical tuning of the organ of Corti.

Hearing impairment related to plasma quinine concentration in healthy volunteers.

1. Hearing impairment was investigated in six healthy volunteers who received oral doses of 5, 10 and 15 mg kg-1 quinine single-blind and in random order. 2. The plasma concentration of quinine was followed for 48 h and the time course was fitted by a linear one compartment pharmacokinetic model. 3. Hearing thresholds were measured by pure tone audiometry. There was a delay between impairment in hearing and change in plasma quinine concentration. Thus the method of effect compartment modelling was applied. 4. The effect on hearing (L), measured as a shift in hearing threshold (dB), was used to estimate the rate constant for elimination of drug from the assumed effect compartment (ke0) and two parameters specifying the effect model (gamma and k). The effect model applied was L = 10 (log k + gamma x log Ce) where Ce is the calculated drug concentration in the effect compartment. This model is a logarithmic transform of a power expression equivalent to the Hill equation at the lower end of the effect range. In all experiments where there was a clear effect on hearing, convergence on a set of parameter estimates occurred, but inter- and intraindividual variability was large. The mean value of ke0 was 3.32 +/- 5.93 h-1 s.d., for gamma it was 1.73 +/- 1.14 s.d. and for k it was 0.59 +/- 0.66 s.d.

The effect of quinine on psychoacoustic tuning curves, stapedius reflexes and evoked otoacoustic emissions in healthy volunteers.

Quinine causes reversible hearing loss, closely related to the quinine plasma concentration. The effects of quinine on psychoacoustic tuning curves, stapedius reflex thresholds and evoked otoacoustic emissions were studied in healthy volunteers. The tuning curves became shallower, whereas reflex thresholds were unaffected. The shift in the emission thresholds paralleled that of the pure-tone thresholds. There were also qualitative changes in the emissions: 1) the exponent of the stimulus-response function changed from 0.34 to 0.56; 2) decay time shortened; 3) the power spectrum shifted towards lower frequencies. The results are discussed in relation to various aspects of cochlear performance and are suggested to depend on an outer hair cell dysfunction.

Ultrastructural changes in the outer hair cells of the guinea pig cochlea after exposure to quinine.

The outer hair cells have been shown to have motile properties which are likely to participate in the cochlear performance. Quinine is known to induce hearing loss as well as contraction of skeletal muscles. Isolated outer hair cells and isolated cochleae from guinea pigs have been exposed to quinine, which was also injected into living guinea pigs. When a physiological response was registered, the cells and cochleae were fixed and examined by transmission electron microscopy. In the isolated cells the formation of a central microtubule core occurred and in the cochleae a swelling of the subsurface cisternae in the outer hair cells was observed. The results are discussed in the context of a proposed effect of quinine on the contractile processes of the outer hair cells.

Audiometry as a possible indicator of quinine plasma concentration during treatment of malaria.

The spread of chloroquine-resistant malaria has led to a resurgence of quinine in clinical use. One of the well-known side effects of quinine, reversible hearing loss, is closely related to the plasma concentration. We suggest that this hearing effect could be used as an aid in therapy control when quinine drug assay is not available.

Quinine causes isolated outer hair cells to change length.

The outer hair cells have been shown to exhibit motile properties which are likely to participate in the cochlear performance. Quinine is known to induce hearing loss as well as contraction of skeletal muscle. Isolated outer hair cells were exposed to quinine and tetracaine. This resulted in a biphasic elongation-shortening response, quantitatively as well as qualitatively altered by tetracaine. These findings are in good agreement with similar studies on muscle.

Reversible hearing impairment related to quinine blood concentrations in guinea pigs.

The hearing ability was measured in anaesthetised guinea pigs by recording cochlear evoked potentials induced by standardised sound stimulation. The animals were given quinine intravenously and blood samples were withdrawn for assay of quinine. The shift in hearing threshold was closely related to the quinine blood concentration. The effect-concentration relationships were analysed according to the equation L = 10 (log k+a.log (s-b] which can be viewed as a special case of the Hill equation assuming that the stimulation (s) is of very low intensity compared to the stimulus at which half of the maximum response would be obtained and introducing an absolute limit for a stimulus at which no response is obtained.