Noise-induced hearing loss - An examination of the methods of assessment in a cross-sectional study of 87 industrial workers.

OBJECTIVES: The surveillance of noise-induced hearing loss (NIHL) according to the Health and Safety Executive (HSE) differs from the medico-legal criteria used to assess NIHL. Our study compares the two systems and proposes a novel method of simplifying the medico-legal criteria and applying it to ascertain noise-induced hearing loss. DESIGN: The anonymised audiograms of a group of 87 industrial workers from a single site were analysed with both methods. RESULTS: The comparison showed approximately one-third of the workers assessed in this study had their noise-induced hearing loss underestimated by the HSE criteria. The majority of these individuals were over 40 years of age. CONCLUSIONS: The HSE criteria for noise-induced hearing loss need review and re-alignment with the medico-legal criteria to address the discrepancy between the two systems.

Comparison of distortion product otoacoustic emissions and pure tone audiometry in occupational screening for auditory deficit due to noise exposure.

OBJECTIVE: To examine whether distortion product otoacoustic emissions can serve as a replacement for pure tone audiometry in longitudinal screening for occupational noise exposure related auditory deficit. METHODS: A retrospective review was conducted of pure tone audiometry and distortion product otoacoustic emission data obtained sequentially during mandatory screening of brickyard workers (n = 16). Individual pure tone audiometry thresholds were compared with distortion product otoacoustic emission amplitudes, and a correlation of these measurements was conducted. RESULTS: Pure tone audiometry threshold elevation was identified in 13 out of 16 workers. When distortion product otoacoustic emission amplitudes were compared with pure tone audiometry thresholds at matched frequencies, no evidence of a robust relationship was apparent. Seven out of 16 workers had substantial distortion product otoacoustic emissions with elevated pure tone audiometry thresholds. CONCLUSION: No clinically relevant predictive relationship between distortion product otoacoustic emission amplitude and pure tone audiometry threshold was apparent. These results do not support the replacement of pure tone audiometry with distortion product otoacoustic emissions in screening. Distortion product otoacoustic emissions at frequencies associated with elevated pure tone audiometry thresholds are evidence of intact outer hair cell function, suggesting that sites distinct from these contribute to auditory deficit following ototrauma.

Voltage-gated sodium channel expression in rat spiral ganglion neurons.

The spiral ganglion neurons (SGN) provide the afferent innervation of the hair cells in the organ of Corti and relay auditory information from the inner ear to the brain. Voltage-gated sodium channels (Na(V)) initiate and propagate action potentials that encode this sensory information but little is known regarding the subtypes expressed in these cells. We have used RT-PCR and immunohistochemistry to study the compliment and anatomical distribution of Na(V) channels in rodent SGN. Na(V)1.1, Na(V)1.6 and Na(V)1.7 were all detected at the mRNA level. Fluorescence or streptavidin-horseradish peroxidase immunohistochemistry extended these findings, demonstrating predominant localisation of Na(V)1.6 and Na(V)1.7 on SGN cell bodies and Na(V)1.1 on axonal processes. Dual labelling with peripherin demonstrated higher Na(V)1.6 and Na(V)1.7 expression on Type I rather than Type II neurons. These results provide evidence for selective expression and variations in the distribution of VGSC in the rodent SGN, which may guide further studies into afferent function in the auditory pathway and therapeutic approaches for diseases such as hearing loss and tinnitus.

The acute effects of tetrahydrocannabinol on auditory threshold and frequency resolution in human subjects.

AIMS: The study was designed to investigate the acute effects of ingested tetrahydrocannabinol (THC) on auditory function. METHODS: Eight male subjects (aged 22-30 years), who had previous experience of cannabis use, took part in this study. They performed air conduction pure tone audiometry in both ears over 0.5-8 kHz. A simple test of frequency selectivity by detecting a 4-kHz tone under two masking noise conditions was also carried out in one ear. Three test sessions at weekly intervals were carried out, at the start of which they ingested a capsule containing either placebo, or 7.5 or 15 mg of THC. These were administered in a randomized cross-over, double-blind manner. Auditory testing as described above was carried out 2 hours after ingestion. Blood samples were also obtained at this time point and assayed for delta 9- and 11-OH-THC levels. RESULTS: No significant changes in threshold or frequency resolution were seen with the dosages employed in this study. CONCLUSIONS: This suggests that THC at the plasma levels attained in this study does not have profound effect on the processing of elementary stimuli by the auditory pathway.

Occurrence and risk of cochleotoxicity in cystic fibrosis patients receiving repeated high-dose aminoglycoside therapy.

Cystic fibrosis (CF) patients receive repeated courses of aminoglycoside therapy. These patients would consequently be expected to be more susceptible to cochleotoxicity, a recognized side effect with single courses of aminoglycoside therapy. The primary aim of this retrospective study was to establish the incidence and severity of auditory deficit in CF patients. Standard (0.25- to 8-kHz) and high-frequency (10- to 16-kHz) pure-tone audiometry was carried out in 70 CF patients, and the results were compared with the results from 91 control subjects. These subjects were further divided into pediatric and adult groups. Of 70 CF patients, 12 (1 pediatric) displayed hearing loss considered to be caused by repeated exposure to aminoglycosides. There was a nonlinear relationship between the courses of therapy received and the incidence of hearing loss. The severity of the loss did not appear to be related to the number of courses received. Assuming the risk of loss to be independent for each course, preliminary estimates of per course risk of hearing loss were less than 2%. Upon comparison with previous clinical studies and experimental work, these findings suggest that the incidence of cochleotoxicity in CF patients is considerably lower than would be expected, suggesting that the CF condition may confer protection against aminoglycoside cochleotoxicity.

Pharmacological protection of auditory function against noise and hypoxia with MK 801

INTRODUCTION: Pharmacological protection of cochlear function is one of the most exciting goals of inner ear medicine. The selective glutamate antagonist MK 801 may be neuro-protective to the cochlea.1 This study aims to investigate whether round window administration of MK 801 protects cochlear function against a combination of noise and atmostpheric hypoxia. METHODS: Eight guinea-pigs were studied. Round Window E. Catheters (Durect Inc., USA) were implanted through a trans-bulla approach and EcoG thresholds determined at 8, 16, 24 and 30 kHz. Artificial perilymph (n = 4) or 10 mM MK 801 (n = 4) was then perfused onto the round window membrane. After 15 min the anaesthetized animals were exposed to 100 dB white noise in 11.5-12. 5% atmospheric oxygen. Thresholds were determined before and 15 min after exposure. RESULTS: The mean threshold shifts from pre-perfusion at 8, 16, 24 and 30 kHz were 40, 33, 35 and 17 dB, respectively (in control animals) and 29, 28, 33 and 41 dB, respectively (in treated animals). A marginal protective effect was demonstrated at 8 kHz (P = 0.06). The 30-kHz thresholds in the treated group fell by 61 dB before noise exposure compared to < 1 dB in the controls (P = 0.0007), suggesting that at high frequencies, 10 mM MK 801 may itself be ototoxic. CONCLUSIONS: These results partially support existing data suggesting that pharmacological protection against noise/hypoxia is possible. Administration of round window NMDA antagonists may affect normal auditory threshold making detailed evaluation of the toxicity of potential inner ear therapies essential before clinical use is contemplated.

Blood flow in the external auditory canal and tympanic membrane as assess by laser doppler blood flowmetry

INTRODUCTION: Procedures within the external meatus and tympanum constitute a large part of otological surgery. Successful healing after procedures on the tympanic membrane will in large part be dependent on the integrity of local blood flow. However, there appear to have been relatively few studies investigating blood flow in the external auditory meatus and tympanum in normal subjects and those with conditions requiring surgery, e.g. tympanoplasty. The aim of this study is to obtain such data using Laser Doppler Blood Flowmetry. METHOD: Control volunteers (n = 30) and patients requiring tympanoplasty (n = 20) were recruited for the study. Laser Doppler Blood Flowmetry was performed in all patients using a commercially available system (Periflux 5000, Perimed AB, Sweden) at four sites: (1) preauricular skin; (2) cartilaginous ear canal; (3) bony ear canal; and (4) tympanic membrane. Mesotympanic temperature was also measured using a Braun Infrared thermometer. Blood flow (flux) was measured as RBC density 'speed following internal calibration. RESULTS: Analysis revealed that in both the control subjects and pretympanoplasty patients, the ranking of blood flow at the sites was 3, 2, 1 and 4 (highest to lowest). Comparing matched sites, there were no significant differences between the two groups. The amplitude of flow was not found to be correlated with mesotympanic temperature. CONCLUSION: Grafts applied to repair perforations of the tympanic membrane are likely to obtain the majority of their blood supply from the bony external auditory meatus rather than that tympanic membrane. Further studies are ongoing to define local blood flow patterns in order to optimize the results of tympanoplasty.

The effects of quinine on cochlear nerve fibre activity in the guinea pig.

The effect of quinine on single cochlear nerve fibre activity (n = 38) was measured in four pigmented guinea pigs, which were given 10-30 mg/kg of quinine intravenously. The frequency tuning curves of these fibres exhibited significant increases in the thresholds of both 'tip' and 'tails' regions of the frequency tuning curve, but these changes did not appear to be accompanied by significant changes in tuning, as measured by the Q'10'dB. In comparison with control fibres (n = 178) from 13 untreated animals, significant changes in the proportion of low:high spontaneous rates (SR) were also seen. Using a boundary criterion of 25 sp/s, this rate changed from 26:74% to 47:53% in control and quinine-poisoned fibres, respectively. Independent of changes in the spontaneous rate, significant increases in the mean absolute refractory period from 0.85 to 1 ms were measured following quinine administration. The absence of a significant effect on fibre tuning whilst threshold was elevated indicates that quinine does not affect the integrity of the cochlear amplifier, though appears to affect cochlear sensitivity.

The effect of 1,3-dinitrobenzene on the functioning of the auditory pathway in the rat.

1,3-Dinitrobenzene (DNB) has previously been shown to be neuropathic, causing gliovascular lesioning in the rat brainstem, with the nuclei of the auditory pathway being particularly affected. Lesion severity was shown to be dependent on functional activity, which could be markedly decreased within one pathway by monaurally reducing sensory input. The aim of this study was to characterise the changes in electrophysiological and vascular function associated with this asymmetric lesioning. Depth electrodes located in the inferior colliculi were used to measure wave II and IV of the auditory evoked response (AER) and collicular blood flow. These were measured up to eight days after DNB exposure in rats, in which preexisting reduction in sensory input in one ear was achieved by tympanic membrane rupture. Significant increases of between 14-27 dB were seen in the mean stimulus level required to generate a 50% isoamplitude response for wave IV in the intact (ie vulnerable) pathway over days 1-8 post DNB. No significant changes in this response for the other AER waves were seen over the same recording period. Significant increases in blood flow were seen in the inferior colliculi up to 24 hours after the final dose of DNB. Differences in increased flow between the colliculi were also highly significant, with peak increases of 200% and 80% seen in the intact and protected sides respectively. This difference shows that DNB enhanced blood flow appears to reflect the severity of the DNB induced functional deficit. In both cases, disturbance to normal glial function in maintaining K+ homeostasis, may underlie the neurophysiological deficit and the increase in blood flow seen at the level of the inferior colliculi. These asymmetric functional changes were also parallelled by the differential lesion severity between the protected and unprotected pathways. Hence, protection against DNB glial lesion severity by reduction in sensory input, and consequently metabolic demand, is paralleled by the early vascular response and functional neuronal deficit seen over the eight day post DNB recording period.

The effect of gentamicin and furosemide given in combination on cochlear potentials in the guinea pig.

Single doses of gentamicin and furosemide given in combination result in a rapid and profound loss of cochlear function. In this study, measurement of three gross cochlear potentials (cochlear microphonics, compound action potentials and the endocochlear potential) were carried out in order to determine the ototoxic sites of action of the drugs given in combination. The rapidity and severity of the cochlear deficit is dose dependent and with the doses employed in this study (80 mg/kg gentamicin i.v. 80 mg/kg furosemide i.v.), complete loss of cochlear function is seen after about 72 hours. Twenty-four hours after i.v. administration of the drugs, significant increases in compound action potential thresholds between 6 and 32 kHz were seen. In contrast, over this frequency range the generation of cochlear microphonics in response to stimulus levels of 70 dB SPL appeared to be unaffected. The endocochlear potential remained unaffected at 24 and 72 hours after administration. These findings are taken as evidence that the primary site of ototoxic action of the two drugs in combination may be at the level of the inner hair cells and/or the afferent synapse.

Comparison of distortion product OAE generation between a patient group requiring frequent gentamicin therapy and control subjects.

Although the animal models used to characterize aminoglycoside ototoxicity are well developed, the initial stages of the ototoxic process of this important group of antibiotics in humans are less well understood. A group that receives frequent aminoglycoside therapy are cystic fibrosis (CF) patients, who may receive cumulative doses of gentamicin over 200 g in their lifetime. Consequently they represent a group in which it is particularly appropriate to monitor regularly auditory function. In this preliminary study, 15 young (aged 9-18 years) CF patients had their pure tone thresholds measured over 0.25-12 kHz. Their distortion product otoacoustic emission (DPOAE) growth functions were also measured at f2 = 2, 4 and 6 kHz with f2/f1 = 1.22. These results were compared with those obtained from 36 control volunteers of similar age. Fourteen of the CF patients had normal hearing (pure tone audiogram (PTA) thresholds < or = 10 dB HL over 0.25-8 kHz). In this group, there was a significant elevation of the stimulus levels required to generate a 2f1-f2 DPOAE < or = 10 dB SPL at 4 kHz. This elevation may represent one of the earliest changes in outer hair cell performance caused by gentamicin, although it may also be due to the CF condition itself. Whilst this measurement alone cannot be taken to indicate any serious cochlear dysfunction, it may have some clinical use as an early indicator or marker of functional deficit in the cochlea.