High-frequency Hearing Impairment Research Articles

Three deaf mice: mouse models for TECTA-based human hereditary deafness reveal domain-specific structural phenotypes in the tectorial membrane

Tecta is a modular, non-collagenous protein of the tectorial membrane (TM), an extracellular matrix of the cochlea essential for normal hearing. Missense mutations in Tecta cause dominant forms of non-syndromic deafness and a genotype–phenotype correlation has been reported in humans, with mutations in different Tecta domains causing mid- or high-frequency hearing impairments that are either stable or progressive. Three mutant mice were created as models for human Tecta mutations; the TectaL1820F,G1824D/+ mouse for zona pellucida (ZP) domain mutations causing stable mid-frequency hearing loss in a Belgian family, the TectaC1837G/+ mouse for a ZP-domain mutation underlying progressive mid-frequency hearing loss in a Spanish family and the TectaC1619S/+ mouse for a zonadhesin-like (ZA) domain mutation responsible for progressive, high-frequency hearing loss in a French family. Mutations in the ZP and ZA domains generate distinctly different changes in the structure of the TM. Auditory brainstem response thresholds in the 8–40 kHz range are elevated by 30–40 dB in the ZP-domain mutants, whilst those in the ZA-domain mutant are elevated by 20–30 dB. The phenotypes are stable and no evidence has been found for a progressive deterioration in TM structure or auditory function. Despite elevated auditory thresholds, the Tecta mutant mice all exhibit an enhanced tendency to have audiogenic seizures in response to white noise stimuli at low sound pressure levels (≤84 dB SPL), revealing a previously unrecognised consequence of Tecta mutations. These results, together with those from previous studies, establish an allelic series for Tecta unequivocally demonstrating an association between genotype and phenotype.

The Effect of Low-Pass Filtering on Identification of Nonsense Syllables in Quiet by School-Age Children With and Without Cochlear Dead Regions

The presence of cochlear dead regions (DRs) can have a significant effect on speech perception. Some studies have reported that adults do not benefit from amplification of frequencies well inside an extensive DR. However, the importance of high-frequency amplification for hearing-impaired children has been emphasized by many researchers. This study investigates the benefit of high-frequency amplification for children with various degrees of high-frequency hearing impairment, with and without DRs. The children, aged 8 to 13 years, were divided into two groups according to the severity of their hearing impairment. Group MS had moderate to severe impairment (9 ears without DRs and 3 ears with restricted DRs). Group SP had severe to profound hearing impairment (7 ears with DRs and 1 ear without a DR). The vowel-consonant-vowel stimuli were subjected to the frequency-gain characteristics prescribed by the desired sensation level fitting method and presented via headphones broadband and under various low-pass filtering conditions. Group MS benefited from high-frequency amplification whether or not a restricted DR was present. In contrast, ears in group SP with continuous extensive DRs showed limited benefit from high-frequency amplification. For the latter, performance improved with increasing cutoff frequency up to approximately 1 octave above the edge frequency of the DR and generally stayed the same, or deteriorated, with further increases in bandwidth. In one case of severe to profound hearing impairment without evidence of DRs, performance increased with increasing cutoff frequency up to 2 kHz and remained almost constant with further increases in bandwidth. For children with severe to profound hearing impairment and continuous high-frequency DRs commencing from approximately 1 kHz, applying amplification only for frequencies up to approximately 1 octave above the edge frequency of the DR may be of benefit. Tests with more participants are needed to confirm this finding.

The Reduced Cochlear Output and the Failure to Adapt the Central Auditory Response Causes Tinnitus in Noise Exposed Rats

Tinnitus is proposed to be caused by decreased central input from the cochlea, followed by increased spontaneous and evoked subcortical activity that is interpreted as compensation for increased responsiveness of central auditory circuits. We compared equally noise exposed rats separated into groups with and without tinnitus for differences in brain responsiveness relative to the degree of deafferentation in the periphery. We analyzed (1) the number of CtBP2/RIBEYE-positive particles in ribbon synapses of the inner hair cell (IHC) as a measure for deafferentation; (2) the fine structure of the amplitudes of auditory brainstem responses (ABR) reflecting differences in sound responses following decreased auditory nerve activity and (3) the expression of the activity-regulated gene Arc in the auditory cortex (AC) to identify long-lasting central activity following sensory deprivation. Following moderate trauma, 30% of animals exhibited tinnitus, similar to the tinnitus prevalence among hearing impaired humans. Although both tinnitus and no-tinnitus animals exhibited a reduced ABR wave I amplitude (generated by primary auditory nerve fibers), IHCs ribbon loss and high-frequency hearing impairment was more severe in tinnitus animals, associated with significantly reduced amplitudes of the more centrally generated wave IV and V and less intense staining of Arc mRNA and protein in the AC. The observed severe IHCs ribbon loss, the minimal restoration of ABR wave size, and reduced cortical Arc expression suggest that tinnitus is linked to a failure to adapt central circuits to reduced cochlear input.

Association between diabetes and hearing impairment in a large health check-up population

There have been few reports of evidence enabling estimation of the risk of association of diabetes with hearing impairment for the Japanese population. This cross-sectional study investigated the association in generally healthy Japanese (n = 2,753) who visited Saiseikai Central Hospital (Tokyo, Japan) for a health check-up. Logistic regression analysis was performed to calculate odds ratios for high-frequency and low-frequency hearing impairment among diabetic people compared with non-diabetic people. The results showed diabetes was associated with a 1.3-fold increase in the odds of high-frequency hearing impairment, after adjustment for age, gender, BMI, low HDL-cholesterol, abdominal obesity, hypertension, and smoking status. A significant association was not observed between diabetes and low-frequency hearing impairment. This study reported diabetes is associated with high-frequency hearing impairment irrespective of metabolic risk factors for a large health check-up population. The causal association was not confirmed because of the study design. Further research should be performed to determine the mechanism.

High-frequency hearing impairment assessed with cochlear microphonics

Conclusion: Cochlear microphonic (CM) measurements may potentially become a supplementary approach to otoacoustic emission (OAE) measurements for assessing low-frequency cochlear functions in the clinic. Objective: The objective of this study was to investigate the measurement of CMs in subjects with high-frequency hearing loss. Currently, CMs can be measured using electrocochleography (ECochG or ECoG) techniques. Both CMs and OAEs are cochlear responses, while auditory brainstem responses (ABRs) are not. However, there are inherent limitations associated with OAE measurements such as acoustic noise, which can conceal low-frequency OAEs measured in the clinic. However, CM measurements may not have these limitations. Methods: CMs were measured in human subjects using an ear canal electrode. The CMs were compared between the high-frequency hearing loss group and the normal-hearing control group. Distortion product OAEs (DPOAEs) and audiogram were also measured. Results: The DPOAE and audiogram measurements indicate that the subjects were correctly selected for the two groups. Low-frequency CM waveforms (CMWs) can be measured using ear canal electrodes in high-frequency hearing loss subjects. The difference in amplitudes of CMWs between the high-frequency hearing loss group and the normal-hearing group is insignificant at low frequencies but significant at high frequencies.

Effects of Repeated “Benign” Noise Exposures in Young CBA Mice: Shedding Light on Age-related Hearing Loss

Temporary hearing threshold shift (TTS) resulting from a "benign" noise exposure can cause irreversible auditory nerve afferent terminal damage and retraction. While hearing thresholds and acute tissue injury recover within 1-2 weeks after a noise overexposure, it is not clear if multiple TTS noise exposures would result in cumulative damage even though sufficient TTS recovery time is provided. Here, we tested whether repeated TTS noise exposures affected permanent hearing thresholds and examined how that related to inner ear histopathology. Despite a peak 35-40 dB TTS 24 hours after each noise exposure, a double dose (2 weeks apart) of 100 dB noise (8-16 kHz) exposures to young (4-week-old) CBA mice resulted in no permanent threshold shifts (PTS) and abnormal distortion product otoacoustic emissions (DPOAE). However, although auditory brainstem response (ABR) thresholds recovered fully in once- and twice-exposed animals, the growth function of ABR wave 1( p-p ) amplitude (synchronized spiral ganglion cell activity) was significantly reduced to a similar extent, suggesting that damage resulting from a second dose of the exposure was not proportional to that observed after the initial exposure. Estimate of surviving inner hair cell afferent terminals using immunostaining of presynaptic ribbons revealed ribbon loss of ∼ 40 % at the ∼ 23 kHz region after the first round of noise exposure, but no additional loss of ribbons after the second exposure. In contrast, a third dose of the same noise exposure resulted in not only TTS, but also PTS even in regions where DPOAEs were not affected. The pattern of PTS seen was not entirely tonotopically related to the noise band used. Instead, it resembled more to that of age-related hearing loss, i.e., high frequency hearing impairment towards the base of the cochlea. Interestingly, after a 3rd dose of the noise exposure, additional loss of ribbons (another ≈ 25 %) was observed, suggesting a cumulative detrimental effect from individual "benign" noise exposures, which should result in a significant deficit in central temporal processing.

NEW SOLUTIONS FOR HIGH-FREQUENCY HEARING IMPAIRMENT

The common observation that hearing impairment tends to affect sound perception at high frequencies more than at lower ones has led recently to the development and evaluation of a number of innovative signal-processing techniques. These include frequency-lowering schemes that aim to provide improved audibility and discriminability of sound components by shifting them into a frequency range where the listener has less impairment. For people who have usable low-frequency hearing, but insufficient high-frequency hearing for effective use of a frequency-lowering hearing instrument, cochlear implantation is rapidly becoming a well-accepted option. The use of a cochlear implant, in combination with an acoustic hearing aid either in the implanted ear or the opposite ear, can provide large perceptual benefits, especially for understanding speech in noise and for listening to music. Selecting and fitting the most appropriate configuration of hearing devices is critical in maximising the perceptual benefits for both children and adults with severe high-frequency hearing impairment.

Involuntary and Persistent Environmental Noise Influences Health and Hearing in Beirut, Lebanon

Objective. This study was conducted to assess the effects of involuntary and persistent noise exposure on health and hearing among Lebanese adults in Beirut, Lebanon, where people are exposed to noise from construction sites, power generators, honking cars, and motorcycles. Methods. Using a descriptive and exploratory design with mixed methods, participants were surveyed, interviewed, and tested for hearing while street noise levels were measured near their residents and work places. Results. Self-reports of 83 Lebanese adult, who lived and worked in Beirut, helped identify common patterns in experiences such as irritability, anger, headaches, and sleep disturbances due to noise annoyance. Of those tested, 30% suffered from high-frequency hearing impairment. Our results showed that environmental sound dB had increased by 12% and sound intensity by 400% above the maximum standard level when compared to the WHO report of 1999. Conclusion. Environmental noise contributes to premature hearing loss and potentiates systemic diseases among Lebanese.

A Technical Comparison of Digital Frequency-Lowering Algorithms Available in Two Current Hearing Aids

BackgroundRecently two major manufacturers of hearing aids introduced two distinct frequency-lowering techniques that were designed to compensate in part for the perceptual effects of high-frequency hearing impairments. The Widex “Audibility Extender” is a linear frequency transposition scheme, whereas the Phonak “SoundRecover” scheme employs nonlinear frequency compression. Although these schemes process sound signals in very different ways, studies investigating their use by both adults and children with hearing impairment have reported significant perceptual benefits. However, the modifications that these innovative schemes apply to sound signals have not previously been described or compared in detail.MethodsThe main aim of the present study was to analyze these schemes'technical performance by measuring outputs from each type of hearing aid with the frequency-lowering functions enabled and disabled. The input signals included sinusoids, flute sounds, and speech material. Spectral analyses were carried out on the output signals produced by the hearing aids in each condition.ConclusionsThe results of the analyses confirmed that each scheme was effective at lowering certain high-frequency acoustic signals, although both techniques also distorted some signals. Most importantly, the application of either frequency-lowering scheme would be expected to improve the audibility of many sounds having salient high-frequency components. Nevertheless, considerably different perceptual effects would be expected from these schemes, even when each hearing aid is fitted in accordance with the same audiometric configuration of hearing impairment. In general, these findings reinforce the need for appropriate selection and fitting of sound-processing schemes in modern hearing aids to suit the characteristics and preferences of individual listeners.

Risk factors for hearing impairment among U.S. adults with diabetes: National Health and Nutrition Examination Survey 1999-2004.

OBJECTIVEThe objective of this study was to examine the risk factors of low/mid-frequency and high-frequency hearing impairment among a nationally representative sample of diabetic adults.RESEARCH DESIGN AND METHODSData came from 536 participants, aged 20–69 years, with diagnosed or undiagnosed diabetes who completed audiometric testing during 1999–2004 in the National Health and Nutrition Examination Survey (NHANES). We defined hearing impairment as the pure-tone average >25 dB hearing level of pure-tone thresholds at low/mid-frequencies (500; 1,000; and 2,000 Hz) and high frequencies (3,000; 4,000; 6,000; and 8,000 Hz) and identified independent risk factors using logistic regression.RESULTSControlling for age, race/ethnicity, and marital status, odds ratios for associations with low/mid-frequency hearing impairment were 2.20 (95% CI 1.28–3.79) for HDL <40 mg/dL and 3.55 (1.57–8.03) for poor health. Controlling for age, race/ethnicity, sex, and income-to-poverty ratio, odds ratios for associations with high-frequency hearing impairment were 4.39 (1.26–15.26) for history of coronary heart disease and 4.42 (1.26–15.45) for peripheral neuropathy.CONCLUSIONSLow HDL, coronary heart disease, peripheral neuropathy, and having poor health are potentially preventable correlates of hearing impairment for people with diabetes. Glycemic control, years since diagnosis, and type of glycemic medication were not associated with hearing impairment.

Uncomfortable loudness levels in experienced unilateral and bilateral hearing aid users: Evidence of adaptive plasticity following asymmetrical sensory input?

Munro and Trotter [Inter J Audiol 45, 684-688, 2006] reported an asymmetry in uncomfortable loudness levels (ULLs) in a preliminary study using 12 experienced unilateral hearing aids users. The aim of the present study was to investigate ULLs in a larger sample of listeners with unilateral and bilateral hearing aid experience. Participants were adults with symmetrical high-frequency hearing impairment. There were 48 listeners with unilateral experience, 13 listeners with bilateral experience and a control group of 47 listeners with no hearing aid experience. The minimum duration of hearing aid experience was 2 years. ULLs were measured at 0.5, 1, 2 and 4 kHz. The unilateral group showed a statistically significant inter-aural asymmetry of 3-5 dB. Compared to the controls, there was a non-significant trend of higher ULLs in the fitted ear and lower ULLs in the not-fitted ear. ULLs in the bilateral group were symmetrical and similar to the control group. The findings suggest that changes in ULL may be a feature of asymmetrical sensory input and are consistent with a central gain mechanism.SumarioMunro y Rotter [Inter J Audiol 45, 684-688, 2006] reportaron asimetría en los niveles de molestia de intensidad subjetiva (ULLs) en un estudio preliminar, en el que participaron 12 usuarios experimentados unilaterales de auxiliares auditivos. El objetivo de este estudio fue investigar los ULLs en una muestra grande de usuarios, con experiencias uni o bilaterales. Los participantes fueron adultos con pérdida auditiva simétrica en frecuencias agudas y fueron 48 personas con experiencia unilateral, 13 con experiencia bilateral y un grupo control de 47 personas sin experiencia con auxiliares auditivos. La duración minima del uso de los auxiliares auditivos fue de 2 años. Se midieron las ULLs en 0.5, 1, 2 y 4 kHz. El grupo unilateral mostró una asimetría inter-aural de 3-5 dB, estadísticamente significativa. En comparación con los controles no hubo una tendencia significativa hacia mayores ULLs en el oído adaptado y menores ULLs en el oído sin auxiliar. Los ULLs en el grupo bilateral fueron simétricos y similares a los del grupo control. Estos hallazgos sugieren que los cambios en los ULL pueden ser un rasgo de estimulación sensorial asimétrico y que son consistentes con un mecanismo central de ganancia.

Potential mediators of diabetes-related hearing impairment in the U.S. population: National Health and Nutrition Examination Survey 1999-2004.

OBJECTIVEWe examined potential mediators of the reported association between diabetes and hearing impairment.RESEARCH DESIGN AND METHODSData come from 1,508 participants, aged 40–69 years, who completed audiometric testing during 1999–2004 in the National Health and Nutrition Examination Survey (NHANES). We defined hearing impairment as the pure-tone average >25 decibels hearing level of pure-tone thresholds at low/mid (500, 1,000, and 2,000 Hz) and high (3,000, 4,000, 6,000, and 8,000 Hz) frequencies. Using logistic regression, we examined whether controlling for vascular or neuropathic conditions, cardiovascular risk factors, glycemia, or inflammation diminished the association between diabetes and hearing impairment.RESULTSDiabetes was associated with a 100% increased odds of low/mid-frequency hearing impairment (odds ratio 2.03 [95% CI 1.32–3.10]) and a 67% increased odds of high-frequency hearing impairment (1.67 [1.14–2.44]) in preliminary models after controlling for age, sex, race/ethnicity, education, smoking, and occupational noise exposure. Adjusting for peripheral neuropathy attenuated the association with low/mid-frequency hearing impairment (1.70 [1.02–2.82]). Adjusting for albuminuria and C-reactive protein attenuated the association with high-frequency hearing impairment (1.54 [1.02–2.32] and 1.50 [1.01–2.23], respectively). Diabetes was not associated with high-frequency hearing impairment after controlling for A1C (1.09 [0.60–1.99]) but remained associated with low/mid-frequency impairment. We found no evidence suggesting that our observed relationship between diabetes and hearing impairment is due to hypertension or dyslipidemia.CONCLUSIONSMechanisms related to neuropathic or microvascular factors, inflammation, or hyperglycemia may be mediating the association of diabetes and hearing impairment.

Self-assessed auditory symptoms, noise exposure, and measured auditory function among healthy young Swedish men

The aim of the study was to estimate the prevalence of the exposure to ototraumatic factors and auditory symptoms, and to analyse the relations between these factors in a group of young healthy men. A total of 839 men, 19–22 years old, were recruited for the study when reporting for primary military service. A questionnaire was distributed and audiometry was performed. The prevalence of tinnitus, sensitivity to noise, and measured hearing impairment in the study group was 23.2%, 15.5%, and 14.5% respectively. Exposure to occupational noise often was reported by 21.4%, and playing loud music often by 16.5%. The young men who had experienced tinnitus after noise exposure had an elevated risk of high frequency hearing impairment, tinnitus, and sensitivity to noise. Those who played loud music had elevated prevalence values of tinnitus but not of hearing impairment. In this young group we observed high prevalence values of ototraumatic factors and auditory symptoms. We also observed significant correlations between tinnitus after noise exposure, self-assessed hearing symptoms, and hearing impairment.SumarioEl objetivo de este estudio fue estimar la prevalencia de la exposición de factores traumáticos al oído y síntomas auditivos y analizar las relaciones entre estos factores y un grupo de hombres jóvenes y sanos. Un total de 839 hombres entre 19 y 22 años fueron reclutados para el estudio al momento que se reportaban para el servicio militar primario. Se distribuyó un cuestionario y se realizó una audiometría. En el grupo de estudio hubo presencia de acufeno, sensibilidad al ruido y se midió hipoacusia en un 23.2%, 15.5% y 14.5% respectivamente. EL 21.4% reportó exposición frecuente a ruido y 16.5% tocaban música a alta intensidad. El joven que presentó acufeno después de haberse expuesto a ruido tenía un alto riesgo de hipoacusia en frecuencias agudas, acufeno y sensibilidad al ruido. Aquellos que tocaban música a alta intensidad tenían valores de prevalencia elevados para acufeno pero no para hipoacusia. En este grupo de jóvenes observamos altos valores de prevalencia para factores traumáticos para el oído y síntomas auditivos. También observamos correlaciones significativas entre acufeno y exposición a ruido, síntomas auto-evaluados e hipoacusia.

Audiometric and Vestibular Features in a Second Dutch DFNA20/26 Family with a Novel Mutation in ACTG1

We analyzed the phenotype in a 5-generation DFNA20/26 family with a novel missense mutation in the ACTG1 gene (c.151G>A) and compared the findings to previous reports on DFNA20/26 families. Audiometric data were collected from the family members of a Dutch kindred with the novel ACTG1 mutation. Cross-sectional and/or longitudinal analyses were performed on pure tone and speech audiometry data of the mutation carriers. Age-related typical audiograms were constructed. Vestibular examination was performed in all mutation carriers. Overall, high-frequency hearing impairment, most prominent at ages over 30 years, was observed with a progression rate of 1.1 to 2.1 dB/y, increasing with frequency. It ultimately resulted in residual hearing. Speech recognition scores remained good at given pure tone average (1, 2, and 4 kHz) levels, but were slightly poorer than those at similar levels in a group of patients with presbycusis. Vestibular examination did not reveal any consistent, statistically significant abnormalities. The audiometric phenotype of the Dutch DFNA20/26 family with a novel mutation in ACTG1 was largely consistent with previous reports on DFNA20/26. Considerable variations were found in audiogram configurations within the family. This is the first known DFNA20/26 family that has experienced tinnitus.

Mild and Variable Audiometric and Vestibular Features in a Third DFNA15 Family with a Novel Mutation in POU4F3

Cochleovestibular characteristics were investigated in a Dutch DFNA15 family with a novel POU4F3 mutation, L223P. A 4-generation pedigree was constructed of the Dutch family with the novel L223P POU4F3 mutation. Pure tone audiometric data were collected and analyzed cross-sectionally in mutation carriers. Age-related typical audiograms were derived. Vestibular examination was performed in most of the mutation carriers. The results were compared to those obtained from previously identified 884de18 and L289F POU4F3 mutation carriers. A novel mutation (L223P) in POU4F3 segregated with hearing impairment in the present family. Audiometric analysis generally showed an early-adult to midlife onset of hearing impairment. High-frequency hearing impairment was observed most frequently. Age-related typical audiograms showed a down-sloping configuration at ages of more than 30 years, with the fastest rate of progression at the high frequencies. Vestibular function tests revealed hypofunction of the vestibular labyrinth in 2 mutation carriers (not statistically significant). The clinical features in the present family with a POU4F3 mutation were fairly similar to those in the 2 previously described DFNA15 families, but the level of hearing impairment was milder, and there was no substantial vestibular dysfunction.

Cisplatin as a cornerstone of modern chemotherapy

35 years have passed since Higby and colleagues demonstrated the clinical activity of cisplatin in a broad spectrum of tumours. Although platinum derivatives are now familiar in medical oncology, this group’s land mark study, published in 1974, had a major eff ect on chemotherapy combinations over subsequent years. In 1965, Rosenberg and co-workers found that the discharge of an electric current from a platinum electrode inhibited the replication of Escherichia coli, before going on to isolate several platinum-containing compounds from the culture medium that were found to cause nucleic-acid alkylation. 4 years later, platinum derivatives were recognised as a new class of anti-cancer drugs with promising pre-clinical activity. Higby and colleagues investigated the activity of cisdiaminodichloroplatinum (DDP, cisplatin) in a phase I study. The trial was divided into two parts, although neither the exact number of patients treated nor the exact inclusion and exclusion criteria are explicitly mentioned in the paper. In the fi rst part of the study, cisplatin was infused intravenously over 3–5 min according to two diff erent schedules (50–100 mg/m2 as a single dose or 18–24 mg/m2 daily for 5 days). Irreversible renal toxicity occurred in fi ve of nine patients receiving cisplatin as a single dose and in two of fi ve patients treated with a daily dose for 5 days. Severe nausea and emesis occurred in almost all patients, and high-frequency hearing loss was noted in fi ve patients. Haematological toxicity was mild. Two patients with persistent increases in serum creatinine died; both patients had received gentamicin despite renal dysfunction. Pathological examination of kidney biopsy samples from both patients showed acute tubular necrosis lesions. In the second part of the study, patients received cisplatin 20 mg/m2 daily for 5 days. Of 11 patients with testicular tumours refractory to conventional therapy (doxorubicin and dactinomycin at this time), two complete and four partial responses were observed. Long-lasting responses were also seen in patients with anaplastic small-cell carcinoma of the thyroid and transitional-cell carcinoma of the bladder (one each). Hence, Higby and colleagues reported high response rates (close to 50%) in patients with testicular cancer, irrespective of histological subtype. By contrast, response rates in phase I oncology trials done between 1991 and 2002 were close to 10%, although death rates in modern phase I trials average 0·5%, probably lower than that reported by Higby and colleagues. In addition to effi cacy data, this study provided important information on cisplatin’s toxicity: a high emeto genic potential, acute and cumulative nephrotoxicity, and a risk of high-frequency hearing impairment. Peripheral neuropathy, another important toxicity of cisplatin, was later reported in patients receiving higher cumulative doses of the drug. Renal toxicity was subsequently shown to be reduced by osmotic diuresis and forced hydration. On the basis of this study, cisplatin became part of chemotherapy regimens that still constitute the gold standard for treatment of sarcomas and cancers of the testes, ovaries, bladder, head and neck, and lungs. During the 1980s and 1990s, other platinum derivatives devoid of renal toxicity—carboplatin and oxaliplatin—were developed, broadening the spectrum of activity of platinum derivatives, and establishing these drugs as a cornerstone of modern chemotherapy.

Diabetes and hearing impairment in the United States: audiometric evidence from the National Health and Nutrition Examination Survey, 1999 to 2004.

Diabetes might affect the vasculature and neural system of the inner ear, leading to hearing impairment. To determine whether hearing impairment is more prevalent among U.S. adults with diabetes. Cross-sectional analysis of nationally representative data. National Health and Nutrition Examination Survey, 1999 to 2004. 5140 noninstitutionalized adults age 20 to 69 years who had audiometric testing. Hearing impairment was assessed from the pure tone average of thresholds over low or mid-frequencies (500, 1000, and 2000 Hz) and high frequencies (3000, 4000, 6000, and 8000 Hz) and was defined as mild or greater severity (pure tone average >25 decibels hearing level [dB HL]) and moderate or greater severity (pure tone average >40 dB HL). Hearing impairment was more prevalent among adults with diabetes. Age-adjusted prevalence of low- or mid-frequency hearing impairment of mild or greater severity in the worse ear was 21.3% (95% CI, 15.0% to 27.5%) among 399 adults with diabetes compared with 9.4% (CI, 8.2% to 10.5%) among 4741 adults without diabetes. Similarly, age-adjusted prevalence of high-frequency hearing impairment of mild or greater severity in the worse ear was 54.1% (CI, 45.9% to 62.3%) among those with diabetes compared with 32.0% (CI, 30.5% to 33.5%) among those without diabetes. The association between diabetes and hearing impairment was independent of known risk factors for hearing impairment, such as noise exposure, ototoxic medication use, and smoking (adjusted odds ratios for low- or mid-frequency and high-frequency hearing impairment were 1.82 [CI, 1.27 to 2.60] and 2.16 [CI, 1.47 to 3.18], respectively). The diagnosis of diabetes was based on self-report. The investigators could not distinguish between type 1 and type 2 diabetes. Noise exposure was based on participant recall. Hearing impairment is common in adults with diabetes, and diabetes seems to be an independent risk factor for the condition.

Relation between Asymmetric Dimethylarginine (ADMA) and Hearing Loss in Patients with Renal Impairment

Background. Hearing loss is common in patients with CRF. The exact etiology of this complication is not known, and little can be done to ameliorate the disorder. ADMA is found to be high in CRF patients. We studied the relation between ADMA and hearing loss in patients with CRF under conservative treatment. Methods. The study was carried out on 40 patients with renal impairment under conservative treatment (group 1) and 30 normal control subjects (group 2). For both groups' medical history and examination, biochemical tests, otological examination, pure tone audiometry, high sensitivity CRP, and asymmetric dimethylarginine (ADMA) were completed. Results. High-frequency hearing impairment was the predominant auditory dysfunction in CRF patients who showed worse high-tone hearing level on pure tone audiometry as compared with the controls (p < .001). Multiple regression analysis for hearing level at high frequency in group 1 shows that significant determinants of hearing level are ADMA (p = 0.002), high sensitivity CRP (p = 0.02), duration of renal disease (p = 0.01), diabetes mellitus (p < 0.001), and serum creatinine (p = 0.008). No correlation was found between hearing loss with age, gender, smoking, hematocrit, or lipid parameters. Conclusion. Patients with CRF under conservative treatment often experience a significant frequency hearing loss. Such a hearing disorder is mainly affected by duration and degree of renal disease, presence of DM, and level of hsCRP and ADMA. There is a close correlation between ADMA and hearing loss. Thus, ADMA could be an important factor causing hearing loss in those patients. Modifying this factor can be of value to ameliorate this common complication.

Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II

Usher syndrome type II (USH2) is an autosomal recessive disorder, characterised by moderate to severe high-frequency hearing impairment, normal balance function and progressive visual impairment due to retinitis pigmentosa. Usher syndrome type IIa, the most common subtype, is defined by mutations in the USH2A gene encoding a short and a recently discovered long usherin isoform comprising 21 and 73 exons, respectively. More than 120 different disease-causing mutations have been reported, however, most of the previous reports concern mutations restricted to exons 1-21 of the USH2A gene. To explore the spectrum of USH2A disease-causing mutations among Scandinavian USH2 cases, patients from 118 unrelated families of which 27 previously had been found to carry mutations in exons 1-21 were subjected to extensive DNA sequence analysis of the full size USH2A gene. Altogether, 122 USH2A DNA sequence alterations were identified of which 57 were predicted to be disease-causing, 7 were considered to be of uncertain pathogenicity and 58 were predicted to be benign variants. Of 36 novel pathogenic USH2A mutations 31 were located in exons 22-73, specific to the long isoform. USH2A mutations were identified in 89/118 (75.4%) families. In 79/89 (88.8%) of these families two pathogenic mutations were identified whereas in 10/89 (11.2%) families the second mutation remained unidentified. In 5/118 (4.2%) families the USH phenotype could be explained by mutations in the USH3A gene. The results presented here provide a comprehensive picture of the genetic aetiology of Usher syndrome type IIA in Scandinavia as it is known to date.

Potential Ototoxicity of Aluminum in Hemodialysis Patients

Aluminum (Al) is a neurotoxin in both human and animal models. Al accumulation is usually observed in patients with end-stage renal disease (ESRD). To clarify whether Al also exhibits toxic effects on the specified neural organ of inner ear, we recruited hemodialysis (HD) patients to investigate the effect of serum Al level on the auditory physiology. Forty patients in maintenance HD as well as 40 age-matched healthy subjects without hearing complaints were enrolled. The auditory function tests, including pure-tone audiometry (PTA), distortion-product otoacoustic emissions (DPOAEs), and auditory brainstem response (ABR) were performed in all subjects. The serum Al levels determined within 3 months of auditory tests were used for analysis. High-frequency hearing impairment was the predominant auditory dysfunction in HD patients who showed worse high-tone hearing level on PTA and diminished amplitudes of DPOAEs at 3 K and 4 K as compared with the controls (P < .001). Age was a significant factor determining the auditory dysfunction in both HD patients and control subjects. After age correction, serum Al level correlated reversely with the amplitude of DPOAEs-2 K (P = .002), but not with amplitudes of DPOAEs-3 K, -4 K, hearing levels on PTA, or wave latencies on ABR. High-frequency hearing impairment is a common presentation in HD patients. Serum Al level correlates reversely with the amplitude of DPOAEs-2 K but not those of DPOAEs-3 K, -4 K, hearing levels on PTA, and wave latencies on ABR. Possibly, the correlation between the Al level and the high-frequency OAE results was obscured by the significantly diminished amplitudes of DPOAEs-3 K, -4 K in ESRD patients. These results implicate that the effect of Al is mainly of cochlear origin rather than of retrocochlear origin.