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PubMed2003

Acrylonitrile produces transient cochlear function loss and potentiates permanent noise-induced hearing loss.

There is growing evidence that agents that produce oxidative stress in the cochlea have significant ototoxic potential by themselves and can potentiate noise-induced hearing loss as well. Acrylonitrile (ACN) metabolism entails conjugation with glutathione, resulting in rapid and pronounced depletion of this important antioxidant in many organs including brain, liver, and kidney. ACN metabolism also results in cyanide (CN) formation through a secondary oxidative pathway. The results of two physiological experiments are reported here. First, the acute effects of ACN (50 mg/kg sc) on auditory sensitivity are assessed using a within subject study. In the second study, persistent effects of ACN alone (50 mg/kg, sc and 2 x 50 mg/kg, sc) and ACN in combination with noise exposure (8 h, 108 dB octave-band noise) are evaluated using threshold sensitivity as the dependent measure. Auditory threshold shift and absolute thresholds were determined using the compound action potential (CAP) amplitude. Acute ACN administration produces a loss in auditory threshold sensitivity that reached a maximum 10-20 min following sc injection. Auditory thresholds returned to control levels 75-100 min following exposure. In the study of permanent auditory threshold shifts, ACN plus noise increased auditory threshold impairment relative to rats receiving noise only when thresholds were assessed 3 weeks following exposure. ACN by itself did not produce permanent threshold impairment 3 weeks following administration. Assays were undertaken in separate groups of rats to track the elevation in blood CN and the depletion of total glutathione in cochlea, brain, and liver following ACN treatment. Systemic blood CN levels were not significantly elevated until 60-120 min following injection, and cochlear glutathione levels showed significant depletion as little as 15 min after injection and remained depressed for about 4 h. The results confirm the prediction that ACN is acutely ototoxic and can enhance noise-induced hearing loss.

Acrylonitrile↗

PubMed1994

Progressive hair cell loss induced by toluene exposure.

Rats were exposed to toluene by inhalation (1400 ppm, 16 h/d, 8 days) and sacrificed for morphological investigations at 3 and 5 days after the start of the exposure, and 4 days and 6 weeks after the end of the exposure. The cochleae were removed and prepared for light microscopy and scanning electron microscopy. After 3 days of toluene exposure no loss of hair cells was found. A slight loss in the third row outer hair cells was observed after 5 days of exposure. Four days after the 8-day long exposure a loss of hair cells was found in all 3 rows of outer hair cells, mainly in the middle and upper turns of the cochlea. Six weeks post-exposure the damage on the hair cells had progressed towards the basal part of the cochlea, and a 50-100% loss of outer hair cells together with some loss of inner hair cells were seen. A fairly good correlation was found between the frequency regions showing loss of hair cells and the threshold shifts previously measured by auditory brainstem responses and distortion product otoacoustic emissions in the same rats at corresponding times (Johnson and Canlon, 1994). These results indicate that the outer hair cells in the middle frequency region of the cochlea, were primarily affected by toluene exposure. However, after a long post-exposure period the damage extended basally and apically and some damage to the inner hair cells was seen.

Acoustic Stimulation↗

PubMed1983

Locomotor activity, auditory startle and shock thresholds in spontaneously hypertensive rats.

A group of SHRs and a group of WKY normotensive controls were compared sequentially on open-field behavior, Y-maze activity, responsiveness and habituation of the auditory startle response, and shock thresholds. In the open field and Y maze the SHRs were more active than the WKYs, but the locomotor activity of the SHRs decreased more within sessions. However, the SHRs could be described as showing more, less or the same between-session habituation depending upon the apparatus and the portion of the session analyzed. The SHRs were less responsive than controls on the auditory startle response measure, and they did not differ from controls on startle-response habituation. The SHRs were less responsive than controls at low shock levels but more responsive at high shock levels. The relationship between SHRs and WKYs on the responsiveness dimension depended upon the modality and intensity of the stimulus, the response characteristics of the test situation, and the time sample of behavior taken.

Animals↗

PubMed1991

Human auditory system response to pulsed radiofrequency energy in RF coils for magnetic resonance at 2.4 to 170 MHz.

The threshold conditions for an auditory perception of pulsed radiofrequency (RF) energy absorption in the human head have been studied on six volunteers with RF coils for magnetic resonance (MR) imaging. For homogeneous RF exposure with MR head coils in the 2.4- to 170-MHz range and pulse widths 3 microseconds less than or equal to Tp less than 100 microseconds, the auditory thresholds were observed at 16 +/- 4 mJ pulse energy. Localized RF exposure with optimized surface coils positioned flush with the ear lowers the auditory threshold to only 3 +/- 0.6 mJ. The hearing threshold of RF pulses with Tp greater than 200 microseconds occurs at more or less constant peak power levels of typically 150 +/- 50 W for head coils and as low as 20 W for surface coils. The results from this study confirm theoretical predictions from a thermoelastic expansion model and compare well with reported thresholds from near field antenna measurements at 425 to 3000 MHz. Details of the threshold dependence on RF pulse length reveal primary sites of RF to acoustic energy conversion at the mastoid and temporal bone region and the outer layer of the brain from where thermoelastically generated pressure transients excite audible pressure waves at the resonance modes of the skull around 1.7 kHz and of the brain around 11 kHz. If not masked by usually dominating noise from switched gradients, the conditions for hearing RF pulses, as applied to head coils in MR studies with flip angle alpha at main field B0, is given by Tp/ms less than or equal to 0.4 (alpha/pi)B0/[T]. At peak power levels up to 15 kW presently available in clinical MR systems, there is no evidence known for detrimental health effects arising from the RF auditory phenomenon which is a secondary cause associated with primary RF to thermal energy conversion in body tissues. To avoid the RF-evoked sound pressure levels in the head rising above the discomfort threshold at 110 dB SPL, an upper limit of 30 kW applied peak pulse power is suggested for head coils and 6 kW for surface coils.

Auditory Perception↗

PubMed1984

Masked and unmasked pure-tone thresholds of infants and adults: development of auditory frequency selectivity and sensitivity.

Detection thresholds for pure tones (1000 Hz and 4000 Hz) in noise and in quiet were estimated for infants at 6 months and 12 months of age and for adults. A visually reinforced head-turn procedure under control of a PDP-11/03 minicomputer was used. An adaptive protocol with a 5-dB step size was employed for the threshold estimates. Infant thresholds were poorer than adult thresholds in each condition. In noise, infant-adult differences were 8 dB (6-month-old infants) and 6 dB (12-month-old infants) at each frequency. In quiet, infant-adult differences were 14 dB (6-month-old infants) and 12 dB (12-month-old infants) at 1000 Hz but were only 7 dB (6-month-old infants) and 5 dB (12-month-old infants) at 4000 Hz. The masking data suggest that infants are at only a slight disadvantage in detecting a target in a background of noise and are consistent with a frequency selectivity mechanism that is proportional to that of adults. The detection-in-quiet data, with greater correspondence among the groups at 4000 Hz than at 1000 Hz, support the notion that hearing sensitivity varies with frequency in a different way in infants than in adults. Data on task performance reveal significant age effects, and the possibility that such effects have biased the observed differences in the estimates of sensory function among the groups is considered.

Acoustic Impedance Tests↗

PubMed2001

Energy-independent factors influencing noise-induced hearing loss in the chinchilla model.

The effects on hearing and the sensory cell population of four continuous, non-Gaussian noise exposures each having an A-weighted L(eq)=100 dB SPL were compared to the effects of an energy-equivalent Gaussian noise. The non-Gaussian noise conditions were characterized by the statistical metric, kurtosis (beta), computed on the unfiltered, beta(t), and the filtered, beta(f), time-domain signals. The chinchilla (n=58) was used as the animal model. Hearing thresholds were estimated using auditory-evoked potentials (AEP) recorded from the inferior colliculus and sensory cell populations were obtained from surface preparation histology. Despite equivalent exposure energies, the four non-Gaussian conditions produced considerably greater hearing and sensory cell loss than did the Gaussian condition. The magnitude of this excess trauma produced by the non-Gaussian noise was dependent on the frequency content, but not on the average energy content of the impacts which gave the noise its non-Gaussian character. These results indicate that beta(t) is an appropriate index of the increased hazard of exposure to non-Gaussian noises and that beta(f) may be useful in the prediction of the place-specific additional outer hair cell loss produced by non-Gaussian exposures. The results also suggest that energy-based metrics, while necessary for the prediction of noise-induced hearing loss, are not sufficient.

Animals↗

PubMed2005

Hearing threshold estimation in infants using auditory steady-state responses.

Successful early intervention in children with permanent hearing loss requires assessment techniques that can accurately reflect the behavioral audiogram in infancy. This retrospective study compared auditory steady-state response (ASSR) findings from subjects tested in the first three months of life with subsequently obtained behavioral hearing levels. ASSR audiograms were established using amplitude and frequency modulated tones at octave frequencies (500 Hz to 4 kHz). Results obtained from 575 subjects including 285 with normal hearing, 271 with sensorineural hearing loss, and 19 with auditory neuropathy-type hearing loss are presented. ASSR and behavioral hearing thresholds for subjects in the normal and sensorineural groups were highly correlated, with Pearson r values exceeding 0.95 at each of the test frequencies. In contrast, ASSR thresholds in children with AN-type hearing loss did not accurately reflect the behavioral audiogram. Overall, the findings indicate that ASSR testing can offer useful insights into the hearing acuity of children tested in infancy.

Acoustic Stimulation↗

PubMed2004

Ototoxic protection of sodium thiosulfate: daily vs constant infusion.

OBJECTIVE: Compare the effect of a daily dose of sodium thiosulfate (STS) to continuous infusion of STS on Hartley albino guinea pig (HAGP) on cisplatin (CP)-induced sensorineural hearing loss. Study design Prospective randomized pilot study comparing a single daily dose of STS to a constant controlled infusion of STS given the middle ear space (MES) with an ototoxic regimen of CP. The hearing thresholds will be obtained by auditory brainstem response (ABR) 1 week before and after treatment. Treatment effects on responses at 2, 8, and 16 kHz signals will be investigated by an analysis of variance with one between subjects' condition and two within subjects' conditions. SETTING: Basic science laboratory. RESULTS: STS protection resulted in significantly less hearing loss post-treatment for the protected ears. Guinea pigs with continuous infusion of STS demonstrated less loss in the protected ear than those who received the single daily dose. As expected, hearing loss at 2 kHz was less than that at 8 and 16 kHz. CONCLUSION: A continuous infusion of STS directly to the MES is better than a single daily dose of STS to the MES in reducing the ototoxicity of CP. SIGNIFICANCE: Any targeted protection, whether by continuous infusion or daily dose, is better than no protection against the sensorineural hearing loss of CP.

Animals↗

PubMed2002

Susceptibility to acoustic trauma in young and aged gerbils.

The effect of age on susceptibility to noise-induced hearing loss (NIHL), the effect of gender on the interaction of age-related hearing loss (ARHL) and NIHL, and the relative contributions of ARHL and NIHL to total hearing loss are poorly understood. The issues are difficult to resolve empirically in human subjects because of lack of control over extrinsic variables and for ethical reasons. Accordingly, these issues were examined in a well-studied animal model of both ARHL and NIHL, the Mongolian gerbil. Animals were exposed to an intense tone (3.5 kHz, 113 dB SPL, 1 h) either as young adults (6-8 months) or near the end of the average lifespan of the species (34-38 months). Hearing thresholds were determined with the auditory brainstem response (ABR). ARHL was approximately 5-10 dB, with slightly more observed in males at 16 kHz (p<0.05). NIHL of approximately 15-20 dB was similar for the young and old groups, suggesting no differences in susceptibility as a function of age. There were no gender differences in NIHL. The relative contributions of ARHL and NIHL to total hearing loss in aged, noise-exposed gerbils were predicted by an addition of ARHL and NIHL in dB, similar to an international standard on hearing loss allocation, ISO-1999 [Determination of Occupational Noise Exposure and Estimation of Noise-Induced Hearing Impairment (1990)]. Previous evaluations of ISO-1999 using the gerbil animal model concluded that addition of ARHL and NIHL in dB overpredicts total hearing loss. However, in these studies, ARHL was large and nearly equal to NIHL. In the current study, where ARHL was much less than NIHL, addition of the two factors in dB, as recommended by ISO-1999, results in fairly accurate predictions of total hearing loss.

Age Factors↗

PubMed2000

Hearing thresholds under acute hypoxia and relationship to slowing in the auditory modality.

BACKGROUND: Acute hypoxia slows reaction time to visual stimuli and it has been proposed that this slowing can be accounted for by a decrease in perceived brightness. Auditory slowing could be accounted for in an analogous manner if hypoxia decreases perceived loudness, as reflected by an increase in pure-tone thresholds. However, evidence concerning the effects of hypoxia on auditory thresholds is contradictory and we performed an experiment to clarify this issue. Pilot work suggested that thresholds were raised due to noise from our breathing apparatus used to deliver the low O2 mixtures and we eliminated this artifact by measuring thresholds while the subjects held their breath. METHODS: The six subjects breathed either air as a control through an oro-nasal mask or low O2 mixtures to maintain arterial blood oxygen saturation at 74% while thresholds between 500-4000 Hz were measured with an audiometer during breathholding. RESULTS: Hypoxia produced a statistically significant but practically insignificant decrease in thresholds of 1 dB across all frequencies tested. CONCLUSIONS: Our results are consistent with the view that audition is relatively insensitive to hypoxia and that the slowing observed with auditory stimuli cannot be accounted for by an increase in auditory thresholds. Some alternative hypotheses which could account for this slowing are proposed.

Adult↗

PubMed1977

Auditory reaction time and absolute threshold in cat.

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Animals↗

PubMed1999

Steroid-responsive cochlear dysfunction in the MRL/lpr autoimmune mouse.

Corticosteroids historically have been used to treat autoimmune sensorineural hearing loss, although little is known of how steroids restore normal inner ear function. Therefore, to identify a potential model for this field of research, this study examined the effects of prednisolone on auditory brain stem response thresholds in the MRL/lpr mouse model of autoimmune sensorineural hearing loss. Mice treated with prednisolone after auditory threshold elevations demonstrated significant improvement and stabilization of thresholds compared with untreated controls. MRL/lpr mice treated with steroids before the onset of autoimmune disease and cochlear dysfunction demonstrated decreased serum immune complexes, higher survival rates, and lower auditory thresholds compared with untreated controls. These positive results suggest the autoimmune mouse may be useful for studies of steroid-responsive mechanisms of the cochlea in autoimmune sensorineural hearing loss, as well as any hearing disorder in which steroid therapy is currently used.

Animals↗

PubMed2002

Sex- and age-related elevation of cochlear nerve envelope response (CNER) and auditory brainstem response (ABR) thresholds in C57BL/6 mice.

The C57BL/6 mouse has long been considered, in scores of published studies, as a model of early adult-onset, progressive sensorineural hearing loss (presbycusis). The auditory brainstem response (ABR) has most often been used in these studies as a measure of functional loss. Whereas the ABR measures the response to a rapid acoustic onset, the cochlear nerve envelope response (CNER) measures the ability of cochlear nerve axons to respond to the low frequency modulations of the entire acoustic waveform, acoustic changes that are utilized in vocalizations and music. The present study compared the ability of these two measures to assess presbycusis in male and female C57BL/6 mice, at ages ranging from 50 to 400 days. Thresholds to the CNER were almost invariably more sensitive than the ABR, in response to stimulus frequencies ranging from 8 to 56 kHz. By 100 days of age, mice showed elevation of thresholds in response to high frequency stimuli, and this loss was greater in females than in males. These trends persisted for both measures over the next 300 days, involving successively lower frequencies.

Aging↗

PubMed1982

Auditory masking effects on lingual vibrotactile thresholds as a function of age.

Auditory masking effects on lingual vibrotactile thresholds were examined across three groups of 10 subjects each. The first group included children 13 yr. of age or younger, the second group young college age adults, and the third group elderly individuals 66 yr. of age or older. Lingual vibrotactile thresholds were obtained from each group at a frequency of 250 Hz, under experimental conditions of no-masking, narrow-band masking, and wide-band masking. Results showed statistically significant threshold differences between the elderly group and the other two groups for all three experimental conditions. A difference was also detected between experimental conditions when an over-all statistical analysis was performed, but this difference disappeared under more stringent post hoc examination. Results are discussed with respect to current literature on aging and appropriate simplified procedures are recommended for future lingual vibrotactile threshold testing.

Adolescent↗

PubMedDate not supplied

Frequency-specific auditory brainstem responses in adults with sensorineural hearing loss.

The purpose of this study was to investigate the prediction of pure tone thresholds from auditory brainstem response (ABR) thresholds to tone bursts in noise using two formulae: (1) a correction factor based on the average difference between pure tone thresholds and ABR thresholds, and (2) a regression equation describing the relationship between pure tone thresholds and ABR thresholds. Twenty subjects with mild to moderate sensorineural hearing loss were tested with tone bursts having 1 millisecond rise-plateau-fall times in highpass noise (500 Hz) and notch noise (1000, 2000, and 4000 Hz). The data revealed that the pure tone-ABR threshold difference systematically decreased as frequency increased. Mean differences were approximately 25 dB at 500 Hz and 1000 Hz, 15 dB at 2000 Hz, and 10 dB at 4000 Hz. Using these correction factors, approximately 90 per cent of pure tone thresholds were predicted within +/- 10 dB at 2000 Hz and 4000 Hz, and within +/- 20 dB at 500 Hz and 1000 Hz. Similar results were found using the regression formulae. The results suggest that ABR thresholds to tone bursts in noise may provide valuable information on the auditory sensitivity and audiometric configuration of difficult-to-test patients.

Aged↗

PubMed2006

Threshold estimation in children using auditory steady-state responses to multiple simultaneous stimuli.

OBJECTIVE: It was the aim of this study to explore the use of auditory steady-state response (ASSR) to multiple simultaneous stimuli for threshold estimation in young children. METHOD: The subjects consisted of 40 children, aged from 6 months to 5 years, with variant degrees of sensorineural hearing loss. Simultaneous tonepips (0.5, 1, 2 and 4 kHz) with an amplitude modulated at different rates from 77 to 103 Hz were presented to both ears by insert phones. All children were tested with ASSR and age-appropriate behavioral tests. RESULTS: We found that (1) ASSR thresholds were usually higher than behavioral thresholds with a difference of 8-15 dB, (2) the behavioral thresholds were significantly correlated with ASSR thresholds (p = 0.000), and (3) there was a great difference between ASSR thresholds and behavioral thresholds found in a child with auditory neuropathy. CONCLUSION: Being objective, frequency specific and well correlated with behavioral thresholds, ASSR to multiple simultaneous stimuli was proven to be a good tool to predict behavioral hearing thresholds.

Acoustic Stimulation↗

PubMed1992

The role of frequency selectivity in measures of auditory and vibrotactile temporal resolution.

The purpose of this study was to compare the role of frequency selectivity in measures of auditory and vibrotactile temporal resolution. In the first experiment, temporal modulation transfer functions for a sinusoidally amplitude modulated (SAM) 250-Hz carrier revealed auditory modulation thresholds significantly lower than corresponding vibrotactile modulation thresholds at SAM frequencies greater than or equal to 100 Hz. In the second experiment, auditory and vibrotactile gap detection thresholds were measured by presenting silent gaps bounded by markers of the same or different frequency. The marker frequency F1 = 250 Hz preceded the silent gap and marker frequencies after the silent gap included F2 = 250, 255, 263, 310, and 325 Hz. Auditory gap detection thresholds were lower than corresponding vibrotactile thresholds for F2 markers less than or equal to 263 Hz, but were greater than the corresponding vibrotactile gap detection thresholds for F2 markers greater than or equal to 310 Hz. When the auditory gap detection thresholds were transformed into filter attenuation values, the results were modeled well by a constant-percentage (10%) bandwidth filter centered on F1. The vibrotactile gap detection thresholds, however, were independent of marker frequency separation. In a third experiment, auditory and vibrotactile rate difference limens (RDLs) were measured for a 250-Hz carrier at SAM rates less than or equal to 100 Hz. Auditory RDLs were lower than corresponding vibrotactile RDLs for standard rates greater than 10 Hz. Combination tones may have confounded auditory performance for standard rates of 80 and 100 Hz. The results from these experiments revealed that frequency selectivity influences auditory measures of temporal resolution, but there was no evidence of frequency selectivity affecting vibrotactile temporal resolution.

Adult↗

PubMed2000

Treatment of chronic suppurative otitis media with topical tobramycin and dexamethasone.

OBJECTIVES: To investigate the safety and efficacy of a topical combination of tobramycin and dexamethasone in a primate model of chronic suppurative otitis media (CSOM) and to explore the contribution of the added topical steroid for the treatment of CSOM. DESIGN: Blinded, randomized, placebo-controlled trial. SUBJECTS: Sixty juvenile cynomolgus monkeys randomized into the following 6 treatment groups of 10 monkeys each: 0.3% tobramycin (group 1), combined 0.3% tobramycin-0.1% dexamethasone (group 2), combined 1.0% tobramycin-0.33% dexamethasone (group 3), 0.1% dexamethasone (group 4), vehicle (group 5), and phosphate-buffered saline solution (group 6). INTERVENTIONS: Chronic suppurative otitis media was established by inoculating the right ear with Pseudomonas aeruginosa. After 4 weeks of drainage, animals were treated according to the group assignment with 3 drops twice daily for 7 weeks. Hearing thresholds were monitored with repeated auditory brainstem response testing (ABR), and clinical response was monitored with repeated otoscopic examinations and cultures throughout the study. Cytocochleograms were evaluated for quantification of outer hair cell loss. RESULTS: Rapid resolution of otorrhea and eradication of P aeruginosa occurred in all groups receiving tobramycin. The inclusion of dexamethasone accelerated the resolution of otorrhea and negative yields of cultures compared with tobramycin alone. Otorrhea and positive culture findings persisted in the groups not treated with topical antibiotic. Results of ABRs at 4 and 8 weeks and cytocochleograms for outer cell hair loss were not affected by drug administration. Perilymph samples collected at the end of the study showed no detectable tobramycin. CONCLUSIONS: Combined tobramycin-dexamethasone ear drops were safe and effective in the monkey CSOM model. Dexamethasone enhanced the efficacy of tobramycin.

Administration, Topical↗