The aim of this study is to outline the mechanisms leading cochlear cells to die. We utilized an immortalized cell line (OC-k3 cells) derived from the organ of Corti of transgenic mice in order to perform in-depth biochemical studies with no limitations on sample size and number. We probed these cells with cisplatin and gentamicin, two drugs which display in vivo undesired ototoxic side-effects. We investigated cell viability, reactive oxygen species (ROS) production and glutathione (GSH) levels and tested the effects of different concentrations of cisplatin and gentamicin from 0 to 48 h. Results show that cells undergo a dose- and treatment-time-dependent apoptosis characterized by nuclear fragmentation, integrity of the cell membrane and mitochondria, and absence of DNA endonuclease activity. During the early part of treatment, ROS production increases and intracellular GSH decreases, probably due to the activation of protein kinase C alpha. Use of antioxidants such as N-acetylcysteine, GSH and vitamin C rescues cells from apoptosis almost completely. Overall, these data indicate that ROS generation might play a central role in inducing inner ear cell apoptosis and may have an additive role in the ageing process.

The stria vascularis (SV) of 3-, 8- and 18-month-old C57 mice was examined with a fluorescence microscope in order to evaluate the capillary density and vessel diameter. The capillary density was significantly reduced in 18-month-old mice compared to 3-month-old (P<0.001) and to 8-month-old (P<0.001) mice. The difference between 3- and 18-month-old mice was significant for the basal, middle and apical cochlear turns, while the difference between 8- and 18-month-old mice was significant only for the middle and basal turns. Vessel diameter within the whole SV was significantly reduced in all turns in 18-month-old mice (P<0.01) versus 3-month-old animals, while vessel diameter was reduced only in the basal turn in 8-month-old versus 3-month-old mice. The results suggest that previously described histopathological changes in the organ of Corti of C57 mice may be related to modifications of strial capillaries.

Because of their short lifespan and genetic homogeneity, mice can provide valuable insights into the biological basis of age-related hearing loss. In C57BL/6 mice, hair cell loss begins around 1-2 months of age and progresses rapidly along a base-to-apex gradient, whereas CBA mice show relatively little hair cell loss until late in life. This anatomical difference is reflected in dehydrogenase histochemistry, an indirect measure of aerobic energy metabolism. A small, but significant, decrease in hair cell dehydrogenase staining occurred in CBA mice between 1.5 and 18 months of age. Significantly, dehydrogenase levels in 1.5-month C57 mice were substantially lower than in CBA mice of any age. Thus, deficits in aerobic energy metabolism presage degeneration of the hair cells. The superoxide radical, O2*-, a normal byproduct of cellular metabolism, is potentially toxic and can cause cellular damage if it is not inactivated by superoxide dismutases. Cytosolic copper/zinc superoxide dismutase (SOD1) is highly expressed in the cochlea. Knockout mutant mice with a single (HET) or double deletion (KO) of the Sod1 gene coding for SOD1 showed greater age-related losses than wild-type (WT) mice. KO mice had the worst hearing, WT the best, and HETs were intermediate. KOs exhibited considerably greater hair cell loss than WT mice; however, losses in KOs were only slightly greater than in HETs. KO mice showed significantly greater loss of spiral ganglion cells and nerve fibers than WT mice. These results indicate that SOD1 and O2*- play important roles in age-related hearing loss. Intervention strategies targeting O2*- may reduce age-related hearing loss.

Transiently evoked otoacoustic emissions (TEOAEs) without and with contralateral acoustical stimulation, were recorded on 52 subjects ranging from 20 to 78 years. Subject selection was based on the hearing levels from 0.5 to 4 kHz being better than 25 dB HL, normal tympanograms and stapedial reflexes, presence of TEOAEs in at least one ear and no history of otological disease, noise exposure, ototoxic drugs, metabolic disease associated with hearing loss or a family history of hearing loss. The ear with better audiological thresholds was selected as the test ear. If there was no difference between the ears, the ear with stronger TEOAEs was selected. Subjects were divided into five age groups: 20-34 years (n=12, mean age 23.7), 35-44 (n=11, mean age 39.7), 45-54 (n=8, mean age 48.1), 55-64 (n=10, mean age 60), 65-78 (n=11, mean age 71). TEOAEs were never absent in the first two groups, but they were absent in two ears in the 45-54 group, and in one ear of the 55-64 and 65-78 groups. Mean TEOAE amplitude decreased with age, but the differences between the five groups were not significant. Contralateral white noise suppressed emission amplitude, but the amount of suppression was not significantly different between the five groups. A linear regression analysis showed a significant correlation between age and hearing levels, and a negative correlation between age and TEOAE amplitude. In addition, a significant negative correlation between hearing threshold and TEOAE amplitude was evident. No effect of age on the amplitude of the efferent suppression was found.

The aim of the current study was to evaluate the performance of elderly subjects in advanced tests that assess primary cochlear functions (temporal summation, frequency selectivity, cochlear mechanics) and relate them to speech recognition scores. The results show that measures of primary cochlear function in elderly subjects are worse than in young adults, suggesting that receptor failure primarily involved presbyacusis'. Moreover, the data suggest that significant changes in the conductive structures within the inner ear could be involved in age-related hearing loss. Peripheral function deterioration seems to be highly relevant for speech recognition; in fact, it was found that the elderly with the poorest speech recognition scores also had the worst frequency selectivity.

The aim of this study was to determine whether participation restrictions and contextual factors could be elicited in an elderly hearing-impaired population using an open-ended questionnaire. The study also tested the value of the World Health Organization's ICF in the classification of the problems experienced by the elderly hearing-impaired. To this end, we administered the 'Life Effects Questionnaire', in which the subjects were asked to list the effects of their hearing loss on their lives. With this approach, significantly more participation restrictions, environmental factors and personal factors were elicited than with a traditional approach. ICF proved useful in classifying these, but the Activity and Participation Scales had a major weakness in terms of non-communication-related hearing problems. Furthermore, a high proportion of the responses came into the personal factors, for which a formal classification does not exist within ICF. This highlights a significant need in that classification.

An epidemiological study comparing speech audiometry with self-assessed hearing disability and an analysis of other factors influencing the quality of life was conducted. In the Veneto region (Italy), a representative sample of 2700 independently living individuals of 65 years of age and older was selected for the study. All participants were administered a comprehensive questionnaire and a brief examination at their home, including a general physical examination, speech audiometry, Sanders' Speech Disability test, part I and III, Mini Mental State Examination, CES-D scale for depression, visual acuity, self-reported diseases and physical function. Auditory function was worst in the older individuals: auditory performance was within acceptable limits up to the 75-79 age group, while it rapidly deteriorates in the older groups. This trend is consistent with self-reported auditory disability (Sanders' test). A detailed analysis of the type of errors made in the speech audiometry was conducted for each subject. Speech audiometry is a good indicator of real hearing difficulties faced by the elderly, and it might be preferred to pure-tone audiometry, since hearing deficits with age are not always limited to an increased detection threshold, but include other aspects of hearing such as distortion of sounds, comprehension of speech and noise discrimination.

Questions about the clinical effectiveness of tinnitus services are of considerable interest to health professionals and health care providers alike in view of the chronic nature of tinnitus, the diversity of tinnitus-related problems, and the range of costs of different approaches to the clinical management of tinnitus. This study sought to identify the views of patients with tinnitus, who attended a specialist tinnitus clinic in Wales, about their satisfaction with that service. One hundred and forty-eight patients returned an open-ended mail-out questionnaire that asked them to list the perceived benefits and shortcomings of attendance at the specialist clinic. The respondents were classified as current or very recent attenders (43 per cent) and those who had first attended between 18 to 60 months earlier (57 per cent). Respondents cited an average of 2.8 benefits compared to only 0.8 perceived shortcomings per respondent. Major areas of perceived benefit included technical assistance, in the form of hearing aid or tinnitus masker fitting, and the general therapeutic nature of the consultation(s) with clinic staff. Statistically significant differences were found in some volunteered benefits in relation to gender and patient status as a current or previous attender. More than one-quarter of the respondents (28.4 per cent) stated that there were no shortcomings to their clinic attendance. The main volunteered shortcoming was lack of treatment effectiveness. The study showed that tinnitus clinic attendance resulted in many of the patients' individually expressed complaints being addressed effectively. Further, the study's findings confirmed the effectiveness of the provision of information and counselling as a fundamental form of tinnitus management for a substantial proportion of patients with tinnitus.

In 1999, the World Health Organization issued a document (Beta-2 ICIDH-2) that outlines proposed revisions to the original International Classification of Impairments, Disabilities, and Handicaps. The document, issued for trial purposes, is significant in that it redefines the theoretical context in which audiological research into hearing disability has operated since 1980 and will develop in the future. The purpose of this article is threefold. First, it provides an introductory descriptive overview of the primary disablement dimensions outlined in the Beta-2 version of the ICIDH-2 framework. Second, in discussing the implications of the revised framework for audiology, the article highlights particular classification issues that require clarification if the framework is to be applied effectively in audiological research and practice. Third, the article evaluates the revised framework in the context of recent conceptual developments in audiological research and raises a number of issues for further discussion and investigation. The article concludes that the Beta-2 ICIDH-2 represents a significant advance on the original ICIDH classification framework on three counts. First, much of the rationale underpinning the revised framework, particularly its redefinition of the primary disablement dimensions, is consistent with recent conceptual developments in audiological research into hearing disablements. Second, the framework offers specific pointers for the development of current audiological research and practice. One potential line of enquiry focuses attention on specific ICIDH-2 dimensions that are currently under-represented in audiological literature, namely, the participation and contextual factors dimensions. Another potential line of enquiry focuses attention on issues pertaining to the measurement of function, specifically the inclusion of "positive" outcome indicators in assessment. Finally, the publication of the revised ICIDH-2 framework offers a standard frame of reference from which to conduct larger debates in the audiological literature about the nature and purpose of audiological rehabilitation and the influence of the ecological perspective on the rehabilitative process.

Contralateral broadband noise (BBN) elevates ipsilateral auditory thresholds (central masking) and reduces the amplitude of ipsilateral brainstem auditory evoked potentials (BAEPs). Binaural interactions are complex psychophysical phenomena, but binaural interaction components are easily extracted from BAEPs to monaural versus binaural click stimulation. However, contralateral, or binaural, acoustical stimulation is known to activate simultaneously the crossed and uncrossed medial olivocochlear (MOC) efferent systems and decrease activity in both cochleas. Particularly, contralateral BBN stimulation suppresses in part ipsilateral peripheral activity. What is the role of such contralaterally induced peripheral suppression in the overall changes in central BAEPs observed during contralateral masking or binaural stimulation? Compound action potentials (CAPs) of the auditory nerve and BAEPs were recorded simultaneously in awake guinea pigs from electrodes chronically implanted on the round window of the cochlea and the surface of the brain. Peripheral and central measures of contralateral masking and binaural interactions were obtained from responses to monaural or binaural clicks, with or without contralateral BBN, recorded before, during, and after the reversible blockade of the MOC function following a single intramuscular injection of gentamicin. Contralateral BBN effectively reduced the amplitudes of CAP and of all BAEP peaks. CAP to ipsilateral click did not, however, change significantly from monaural to binaural click stimulation; still, normal binaural interaction components developed in the BAEPs. When the medial efferent function was blocked by gentamicin, the normal contralateral BBN suppression of CAP and of the earliest BAEP peak was lost; however, the later BAEP peaks were suppressed by contralateral BBN as before gentamicin, and the central binaural interaction components were unchanged. In these experimental conditions, the MOC efferent system seems to play little role in centrally recorded contralateral masking and binaural interactions.

Cochlear implantation has been performed for almost two decades at the Vienna University Hospital. Until 1994, single-channel implants were used (Ball-Electrode, SC6/2SC6, Vienna/Epoxy, Med-E1, Innsbruck, Austria). The development of multi-channel devices (Combi 40/40+), which provide significantly improved speech recognition performance, led to the reimplantation of some patients who had previously received single-channel implants. It was of particular interest to find out if there was a deterioration of the central "learning process" by the reimplantation from the analogue single-channel device to the tonotopic pulsatile multi-channel stimulation. In this study, we attempted to demonstrate that single-channel implants have an impact on the neural organisation of the auditory system. Two groups of post-lingually deaf adult patients were tested. Group A had previously received single-channel implants and were reimplanted with the new Combi 40/40+ cochlear implant (Med-E1, Innsbruck, Austria) in the same ear. Group B was implanted only with the Combi 40/40+. Six different speech recognition tests were subsequently performed on all patients, and the two groups performed similarly. Furthermore, it was discovered that group A obtained significant speech recognition improvement (p<0.05) with monosyllabic words and number tests 1 month following reimplantation.

This study provided tympanometric data on rhesus monkeys (Macaca mulatta) and more support for this monkey as a good model for human peripheral auditory function. There have been few published reports concerning middle ear function in rhesus monkeys, and these experiments addressed that need. In the first experiment, peak acoustic admittance (Ytm) and ear-canal volume (Vea) were measured in 17 older adult monkeys and 16 younger adult monkeys. In the second experiment, middle ear resonance frequency was measured in eight younger adult monkeys and four older adult monkeys. Overall, peak Ytm, Vea, and resonance frequency were similar for monkeys and humans. Specifically, peak mean Ytm and mean Vea in monkeys were comparable to those values in human children. There was a trend for older monkeys to have decreased peak Ytm and Vea, but these trends did not reach statistical significance. There was a significant sex effect similar to what has been reported in humans. Male monkeys had larger peak Ytm values and larger Vea values compared with female monkeys regardless of age. Finally, there were no significant age or sex effects on resonance frequency.

This study examined the effect of the number of accepted responses in transient evoked otoacoustic emissions on the results of neonatal hearing screening programmes. The ILO88 Otodynamics Analyzer Quickscreen programme was used for all testing, and a three-stage procedure was adopted by averaging 20, 30, and 260 low-noise samples in total. The results were recorded after each stage of the testing in those cases in which, after the first 20 accepted responses, the "pass" criteria were met. Under these circumstances, 117 ears were included in the study from a total number of 334 screened ears. It was concluded that 20 averaged quiet responses are adequate for screened newborn babies to pass the test if the conditions of the "pass" criteria are fulfilled at this stage. In the rest of the newborn babies, testing should be continued using a larger number of clicks. For diagnostic and clinical purposes, the full 260 quiet samples must be used since the results indicated statistically better scores in response and reproducibility measures after the 260 averaged responses.

The amplitude compression function in a speech processor for cochlear implants maps the wide acoustical dynamic range of sounds into the smaller electrical dynamic range available on the implanted electrodes. In this study, we examined the effects of systematic variations of the acoustical dynamic range of the compression function on speech recognition with cochlear implants. Statistical measures of the amplitude distribution of speech sounds were made in each channel of a research speech processor providing more than 50 dB of input signal-to-noise ratio. Several systematic variations of the dynamic range of the compression function were implemented on this basis, and speech recognition was determined using vowel and consonant identification tests in three experienced cochlear implant users. Results demonstrated that the acoustical dynamic range of the compression function does have a significant effect on speech recognition with cochlear implants. They suggest that a dynamic range of about 45 dB is necessary for optimal speech recognition.

The present study aims to evaluate tone decay (auditory adaptation) in Digisonic cochlear implant patients, and to compare tone decay results with speech recognition performance. The following criteria are evaluated: tone decay occurrence, place effect, pulse rate effect, and correlation with speech recognition. A great variability in tone decay was found among the subjects. The amount of tone decay, measured as a percentage of the electrical dynamic range, depends to some extent on electrode location, which may be linked with the frequency dependence of acoustical tone decay. However, it is likely that acoustically and electrically evoked adaptation does not involve the same process. Also, an effect of pulse rate was found. However, no relationship between the amount of tone decay and speech recognition abilities was observed. Evaluation of tone decay in cochlear implant patients might not only allow further evaluation of the condition of their auditory system, but also provide a means to determine preoperatively the specific characteristics of a subject's residual auditory capacities.