Neuronal erythropoietin overexpression is protective against kanamycin-induced hearing loss in mice.

Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet these agents indisputably are one of the cornerstones in antibiotic therapy. Hence, there is a demand for strategies to prevent aminoglycoside-induced ototoxicity, which are not available today. In vitro data suggests that the pleiotropic growth factor erythropoietin (EPO) is neuroprotective against aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO-overexpression in neuronal tissue to evaluate whether EPO could also in vivo protect from aminoglycoside-induced hearing loss. Auditory brainstem response (ABR) thresholds were measured in 12-weeks-old mice before and after treatment with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO-transgenic mice were significantly lower than in C57BL/6 mice (mean difference in ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8-23.4 dB, p = 0.003). Correspondingly, quantification of hair cells and spiral ganglion neurons by immunofluorescence revealed that EPO-transgenic mice had a significantly lower hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion, neuronal overexpression of EPO is protective against aminoglycoside-induce hearing loss, which is in accordance with its known neuroprotective effects in other organs, such as the eye or the brain.

Shooting history and presence of high-frequency hearing impairment in swedish hunters: A cross-sectional internet-based observational study.

The aim of this cross-sectional study among Swedish hunters was to examine the association between shooting history and presence of high-frequency hearing impairment (HFHI). All hunters registered with an e-mail address in the membership roster of the Swedish Hunters' Association were invited via e-mail to a secure website with a questionnaire and an Internet-based audiometry test. Associations, expressed as prevalence ratio (PR), were multivariately modelled using Poisson regression. The questionnaire was answered by 1771 hunters (age 11-91 years), and 202 of them also completed the audiometry test. Subjective severe hearing loss was reported by 195/1771 (11%), while 23/202 (11%) exhibited HFHI upon testing with Internet-based audiometry. As many as 328/1771 (19%) had never used hearing protection during hunting. In the preceding 5 years, 785/1771 (45%), had fired >6 unprotected gunshots with hunting rifle calibers. The adjusted PR of HFHI when reporting 1-6 such shots, relative to 0, was 1.5 [95% confidence interval (CI) 1.1-2.1; P = 0.02]. We could not verify any excessive HFHI prevalence among 89 hunters reporting unprotected exposure to such gunshot noise >6 times. Nor did the total number of reported rifle shots seem to matter. These findings support the notion of a wide variation in individual susceptibility to impulse noise; that significant sound energy, corresponding to unprotected noise from hunting rifle calibers, seems to be required; that susceptible individuals may sustain irreversible damage to the inner ear from just one or a few shots; and that use of hearing protection should be encouraged from the first shot with such weapons.

Reduction in high-frequency hearing loss following technical modifications to microvascular decompression for hemifacial spasm.

OBJECT: Microvascular decompression is a safe and effective procedure to treat hemifacial spasm, but the operation poses some risk to the patient's hearing. While severe sensorineural hearing loss across all frequencies occurs at a low rate in experienced hands, a recent study suggests that as many as one-half of patients who undergo this procedure may experience ipsilateral high-frequency hearing loss (HFHL), and as many as one-quarter may experience contralateral HFHL. While it has been suggested that drill-related noise may account for this finding, this study was designed to examine the effect of a number of techniques designed to protect the vestibulocochlear nerve from operative manipulation on the incidence of HFHL. METHODS: Pure-tone audiometry was performed both preoperatively and postoperatively on 67 patients who underwent microvascular decompression for hemifacial spasm during the study period. A change of greater than 10 dB at either 4 kHz or 8 kHz was considered to be HFHL. Additionally, the authors analyzed intraoperative brainstem auditory evoked potentials from this patient cohort. RESULTS: The incidence of ipsilateral HFHL in this cohort was 7.4%, while the incidence of contralateral HFHL was 4.5%. One patient (1.5%; also included in the HFHL group) experienced an ipsilateral nonserviceable hearing loss. CONCLUSIONS: The reduced incidence of HFHL in this study suggests that technical modifications including performing the procedure without the use of fixed retraction may greatly reduce, but not eliminate, the occurrence of HFHL following microvascular decompression for hemifacial spasm.

[Molecular mechanism of age-related hearing loss: toward its prevention].

Mitochondrial DNA (mtDNA) mutations/deletions and decline of mitochondrial function are considered to be associated with the development of age-related hearing loss (AHL). First, we examined age-related changes in gene expression profile in the cochlea of DBA/2J mouse. This mouse exhibited mild hearing loss at 2 months of age and became deaf by 8 months. Comprehensive gene expression analysis identified significant expression changes correlated with AHL in over 4000 cochlear genes. When compared to 2 month old mice, approximately 2,200 genes were downregulated and approximately 1,900 genes were upregulated in the cochlea of 8 month old mice. AHL-correlated genes in the cochlea of 8-month-old DBA/2J mice were statistically associated with 15 mitochondrial process categories, suggesting that AHL is associated with profound down-regulation of genes involved in the mitochondrial function in the cochlea of aged DBA/2J mice. Next, we assessed the role of accumulation of mtDNA mutations in the development of AHL using Polg (D257A) knock-in mouse, which exhibited increased spontaneous mtDNA mutation rates during aging and showed accelerated aging. They exhibited moderate hearing loss and degeneration and apoptosis in the cochlea by 9 month of age, while wild-type animals did not. MtDNA mutations were associated with transcriptional alterations consistent with impairment of energy metabolism, induction of apoptosis, and hearing dysfunction in the cochlea of aged mitochondrial mutator mice. Lastly, we examined if 26% calorie restriction (CR) could prevent AHL in C57BL/6 mice. CR mice retained normal hearing and showed no cochlear degeneration by 15 months of age, whereas control mice developed moderate hearing loss and cochlear degeneration due to increased apoptosis at 15 months of age. CR mice also showed a significant reduction in the number of TUNEL-positive cells and cleaved caspase-3-positive cells. Microarray analysis revealed that CR upregulated the expression of genes involved in mitochondrial and hearing function and downregulated that of apoptotic genes. Taken together, these findings suggest that accumulation of mtDNA mutations during aging leads to mitochondrial dysfunction and induces an apoptotic program, thereby causing AHL.

[Measurement of noise protection in functional magnetic resonance imaging]. / Messungen zum Lärmschutz bei der funktionellen MR-Tomographie.

BACKGROUND: Functional magnetic resonance imaging (fMRI) can detect changes in oxygen saturation of the brain. Fast changing high gradient fields are necessary which produce high levels of noise. In studies of the auditory cortex, auditory stimuli have to be perceived and discriminated against the noise level of the activated tomograph. MATERIAL AND METHODS: The generated frequency bands and their intensities during fMRI with a Siemens Magnetom Vision, 1.5 T, EPI sequence were measured in the outer ear canal of a dummy head. Noise attenuation was evaluated with four different noise muffs (simple/inexpensive products, quality product, specialized fMRI muffs). RESULTS: Without protection, peak noise levels reached up to 111 dB(A) near 1000 Hz in the dummy ear canal. Major noise attenuation was only found at higher frequencies (4000 Hz by about 25 dB; 8000 Hz by about 35 dB) with the quality product and the specialized fMRI muffs. CONCLUSION: Only quality noise products can sufficiently protect patients from high sound pressure levels of tomograph noise. If in the future higher gradient fields are applied at faster slew rates, acoustic stimuli can safely be applied only in combination with increased hearing protection systems in order to minimize the risk of noise trauma.

Aminoguanidine reduces cisplatin ototoxicity.

Cisplatin is known to cause high-frequency neurosensory hearing loss. While reactive oxygen species have been shown to play a role, reactive nitrogen species have been implicated, but not proven to be involved, in cisplatin ototoxicity. The purpose of the present study was to investigate the role of nitric oxide (*NO) in cisplatin ototoxicity by administering aminoguanidine (AG), a relatively specific inhibitor of inducible nitric oxide synthase (iNOS), in conjunction with cisplatin. Rats were injected with cisplatin, AG, or both. Auditory brainstem evoked responses (ABR) were measured before and 3 days after cisplatin administration. The cochlear tissue was then assayed for *NO and malondialdehyde. Cisplatin alone caused significant ABR threshold shifts at all stimuli tested, whereas AG alone caused no shifts. There was a significant reduction in threshold shift for clicks and 16 kHz tone bursts (but not 32 kHz) when AG was given with cisplatin. The malondialdehyde concentration (but not the *NO concentration) in the AG/cisplatin group was significantly lower than that of the cisplatin group. This suggests that AG reduces cisplatin ototoxicity by directly scavenging hydroxyl radicals. The iNOS pathway may play a role in the generation of free radicals and hearing loss resulting from cisplatin administration, but this conclusion was not supported by our data.

Combined feedback-feedforward active noise-reducing headset--the effect of the acoustics on broadband performance.

Active noise-reducing headsets that employ analog feedback control and provide good broadband attenuation are commercially available for a wide range of applications. Recent studies have explored the integration of an adaptive digital feedforward controller with the analog feedback controller to provide additional attenuation of periodic noise components. This paper presents an experimental study of such a combined control system, but with both feedback- and feedforward controllers attenuating broadband noise. Good performance is demonstrated in a reverberant sound field, while under direct sound-field conditions the attenuation performance of the feedforward controller is shown to be dependent on head position. The paper concludes with an analysis of the forward path delay showing how the passive attenuation mechanism improves broadband performance.

Audiometría de alta frecuencia: umbrales en relación con la edad / High frequency audiometric testing: thresholds related to age

Una aplicación cada vez más importante de la audiometría de alta frecuencia es la monitorización de los tratamientos considerados potencialmente ototóxicos.Sin embargo, establecer unos umbrales auditivos de alta frecuencia sigue siendo una tarea difícil, principalmente debido a la diversidad de los sistemas empleados y de los métodos de calibración.El objetivo de este estudio ha sido establecer unos umbrales auditivos de alta frecuencia en función de la edad, que puedan servir como parámetros de referencia. Estudiamos a 162 pacientes control que fueron sometidos a una audiometría tonal liminar de alta frecuencia, calculando los umbrales para las frecuencias comprendidas entre los 10 y 20 KHz.Los resultados se presentan en relación a grupos de edad, y sugieren, como otros autores, que los umbrales auditivos aumentan con la edad y con la frecuencia. Destacamos la contaminación medioambiental y la presbiacusia dentro del grupo de los principales factores etiológicos que justificarían este agravamiento progresivo de la capacidad auditiva con el tiempo. (AU)

Otoprotectant minimizes hearing defects caused by Pseudomonas aeruginosa exotoxin A.

Exotoxin A, produced by Pseudomonas aeruginosa (PaExoA), penetrates from the middle ear in to the cochlea and causes sensorineural hearing loss (SNHL). In this investigation we studied electrophysiological changes in the albino rat following instillation of PaExoA and N(G)-nitro-L-arginine methyl ester (L-NAME), a known inhibitor of nitric oxide synthesis, into the middle ear. Hearing thresholds were measured by auditory brainstem response (ABR) technique. Latency/intensity curves were constructed to distinguish between cochlear and conductive components of hearing loss. PaExoA caused damage to cochleae and SNHL, mainly at high frequencies. This impairment was blocked by (L-NAME). It would appear that nitric oxide may be a significant link in the mechanism of SNHL caused by bacterial toxin. L-NAME acts as an otoprotectant against the deleterious action of PaExoA.

Dexamethasone modifies the effect of Pseudomonas aeruginosa exotoxin A on hearing.

In the present study, the protective effect of dexamethasone was analysed following exposure of the cochlea to Pseudomonas aeruginosa Exotoxin A (PaExoA). Four groups of albino Sprague-Dawley rats were used. 20 microl saline was instilled through the tympanic membrane into the round window niche (group A, n = 4); 1 microg/20 microl dexamethasone sodium 21-phosphate (dexamethasone) solution was instilled (group B, n = 4); 1 microg/20 microl PaExoA solution was initially instilled followed 1 h later by 20 microl saline (group C, n = 6); and 1 microg/20 microl PaExoA solution was initially instilled followed 1 h later by 1 microg/20 microl dexamethasone solution (group D, n = 6). Frequency-specific (4, 8, 10, 12, 16 and 20 kHz) auditory brainstem responses (ABR) were used to ascertain the threshold prior to exposure and 1, 2, 3, and 5 days and 1 and 2 weeks afterwards. No threshold change was observed in groups A and B, whereas the animals in groups C and D showed some threshold elevation, that in D being smaller than that in C. There was a significant difference at the frequencies 12, 16 and 20 kHz, 2 and 5 days after exposure. The intensity-latency (I-L) curve showed that in group D the cochlear component almost disappeared at high frequency one week after exposure. Our results indicate that dexamethasone can modify the effect of PaExoA caused by non-specific inflammation.

Prevención de hipoacusias y de ruidos en la comunicación en escolares / Prevention of hearing loss and noise in the communication of school children

El ruido produce efectos negativos sobre el sujeto y su entorno. Los adolescentes son el grupo de más alto riesgo. Se han encontrado importantes pérdidas auditivas en menores de 20 años. Es este trabajo se investigaron los factores de riesgo sonoro a que está expuesta la población escolar del área del Centro de Salud número 6; se detectaron pacientes con patología auditiva y se trató de establecer una probable relación entre niveles de audición y exposición del ruido. Fueron evaluados 178 alumnos; la edad media fue de 11.6 años, el 59 por ciento eran varones y el 41 por ciento mujeres. Se efectuó una encuesta sobre exposición al ruido que fue contestada por 162 alumnos; 138 refirieron estar expuestos al ruido y 26 no estarlo. Las principales causas fueron: música y televisión en el hogar y los recreos y el momento de las comidas en la escuela. De los niños expuestos al ruido, 18 presentaron hipoacusias perceptivas y 7 hipoacusias conductivas; entre los no expuestos hubo 3 hipoacusias perceptivas y 2 conductivas, resultados estadísticamente no significativos. Treinta y cuatro alumnos presentaron acúfenos. A través del intercambio de información producido y la elaboración en el aspecto comunicacional se pudo iniciar la concientización sobre la problemática tratada. (AU)

Prevención de hipoacusias y de ruidos en la comunicación en escolares / Prevention of hearing loss and noise in the communication of school children

El ruido produce efectos negativos sobre el sujeto y su entorno. Los adolescentes son el grupo de más alto riesgo. Se han encontrado importantes pérdidas auditivas en menores de 20 años. Es este trabajo se investigaron los factores de riesgo sonoro a que está expuesta la población escolar del área del Centro de Salud número 6; se detectaron pacientes con patología auditiva y se trató de establecer una probable relación entre niveles de audición y exposición del ruido. Fueron evaluados 178 alumnos; la edad media fue de 11.6 años, el 59 por ciento eran varones y el 41 por ciento mujeres. Se efectuó una encuesta sobre exposición al ruido que fue contestada por 162 alumnos; 138 refirieron estar expuestos al ruido y 26 no estarlo. Las principales causas fueron: música y televisión en el hogar y los recreos y el momento de las comidas en la escuela. De los niños expuestos al ruido, 18 presentaron hipoacusias perceptivas y 7 hipoacusias conductivas; entre los no expuestos hubo 3 hipoacusias perceptivas y 2 conductivas, resultados estadísticamente no significativos. Treinta y cuatro alumnos presentaron acúfenos. A través del intercambio de información producido y la elaboración en el aspecto comunicacional se pudo iniciar la concientización sobre la problemática tratada.

[Hearing tests in extended high frequency range in pre-school age children. Initial results]. / Höruntersuchungen im erweiterten Hochtonbereich bei Kindern im Vorschulalter. Erste Ergebnisse.

Since reliable headphones are now available, clinical audiometry can also be performed in extended high frequencies (EHF). Hearing in frequencies over 10 kHz is more influenced by age, noise and toxicity. Thus it is useful to take additionally results in children to establish the normal hearing threshold. In the present study, 35 pre-school children (ages 4-7 years) were tested by EHF (8 kHz-16 kHz) using a new Sennheiser HDA-200 headphone. The hearing thresholds recorded corresponded to those of other studied. Median and standard deviations for 10 kHz were 25 dB(SPL) +/- 12 dB(SPL), 35 dB(SPL) +/- 12 dB(SPL) for 12.5 kHz and 50 dB(SPL) +/- 15 dB(SPL) for 16 kHz. In the older children (> 5 years), hearing thresholds could be more reliably determined and were 10 dB(SPL) better than in the younger children (< 5 years). Thresholds at 10 kHz-12.5 kHz corresponded to those found in adults, but were more sensitive by 5 dB(SPL)-15 dB(SPL) in the 14 kHz-16 kHz range.

Long-term sequelae of hearing impairment in congenital hypothyroidism.

Hearing loss and its functional consequences were evaluated retrospectively in children with congenital hypothyroidism. From a cohort of 101 children followed longitudinally to evaluate newborn screening, 75 with previous hearing tests were studied. Fifteen (20%) were found to have hearing problems. Of these, nine had unilateral or sensorineural loss mostly at high frequencies, five had a conductive loss, and one had both problems. Hearing impaired children differed from children with normal hearing in age of treatment onset (22 vs 14 days) but not disease severity or duration. A comparison of language and auditory processing skills at ages 3, 5, and 7 years revealed that early speech was delayed in hearing impaired children, whereas deficits persisted in later receptive language and auditory discrimination skills. Comparing hearing impaired children and children with normal hearing with matched control subjects at grade 3 showed that hearing impaired children were poorer readers because of less adequate phonologic processing skills.

Prevention of noise-induced hearing loss in the Canadian military.

A prospective study was undertaken to investigate the development of noise-induced hearing loss in Canadian military recruits, and to assess the effectiveness of the hearing conservation program currently in place. The participants were 134 men and women, 20 to 30 years of age, employed in four trades, three of these (infantry, artillery, and armour) associated with high noise levels. The data comprised audiometric measurements made at the time of entry and after 3 years of employment, and responses to a questionnaire mainly relating to noise exposure in the workplace and during leisure activities, and the utilization of personal hearing protective devices. The findings showed that group audiograms at entry and at the 3-year recall were characterized by a 6-kHz notch that was indicative of noise-induced hearing loss, although mean threshold values were within normal limits. By the 3-year recall, 11% of the infantry had sustained a mild-to-moderate hearing loss in the left ear, greater than 25-dB HL, that was consistent with the use of small-calibre weapons. Responses to the questionnaire indicated that, while subjects appreciated the potential benefit of wearing hearing protectors, instructions in their proper use and education on the hazards of noise exposure were poor. The results suggested methods to strengthen the existing scheme for hearing conservation to further minimize risk.

[Comparison of methods for early detection of noise vulnerability of the inner ear. Amplitude reduction of otoacoustic emissions are most sensitive at submaximal noise impulse exposure]. / Methodenvergleich zur Früherkennung einer Lärm-vulnerabilität des Innenohres. Amplitudenreduktion otoakustischer Emissionen am empfindlichsten bei subriskanter Impulsschallreizung.

Noise-induced temporary impairment of cochlear function was measured with several audiometric tests in order to evaluate which method best predicts a vulnerable cochlea. We tested 10 normally-hearing and 13 subjects who were positive for temporary threshold shifts (TTS). The latter were selected from 194 soldiers who demonstrated a TTS higher than 15 dB after regular training with firearms. Acoustic distortion products (DPOAE), click-evoked otoacoustic emissions (TEOAE), upper limit of hearing (ULH) and pure-tone and high-frequency audiometry were used to evaluate possible increased vulnerability of the cochlea. Tests were conducted at lower sound intensities (white noise, 90 dB SPL, 5 min; impact noise, 100 or 106 dB SPLs, 10 impulses/s, 5 min). Seventy per cent of the TTS-positive soldiers studied exhibited significant reductions of TEOAE amplitudes, whereas a stable emission was observed in all control subjects. DPOAE alterations were seen in 38% of the soldiers tested. These results indicate that TEOAE is the most sensitive, objective method for detecting a positive disturbance in cochlear function. Although the upper limit of hearing was also a very sensitive method, variability of this psychoacoustic method depended on the help and experience of the subjects being tested.

Development of resistance to hearing loss from high frequency noise.

The effect of interrupted exposure on the development of progressive resistance to hearing loss from exposure to high frequency noise was studied using monaural chinchillas. The animals were exposed to an octave band noise centered at 4 kHz at 85 dB SPL for 6 h a day for ten consecutive days. Hearing thresholds were measured using evoked potential recording before and after each exposure. Results indicated a reduction in threshold shift with repeated exposures. This reduction in threshold shift or 'toughening' was more rapid for the high frequency exposures than the 'toughening' from similar low frequency exposures.