Molecular analysis of aquaporin genes 1 to 4 in patients with Menière's disease.

BACKGROUND: Menière's Disease (MD) is an episodic cochleovestibular dysfunction of unknown etiology, still lacking a specific test and therapy. The proposed theories on the pathophysiology include genetic factors and factors relating to inner ear homeostasis. Various aquaporins (AQP), water channels, expressed in the inner ear and the vestibular organ, are involved in homeostasis. Mutations in AQP genes could result in disturbed inner ear homeostasis and endolymphatic hydrops, and therefore be involved in the pathogenesis of MD. AIM: To search for mutations in AQP1 to 4 in patients suffering from MD. METHODS: In patients with definite MD, DNA was extracted from whole blood. The coding sequences of AQP1 to 4 were amplified by PCR reaction and sequenced. RESULTS: One sequence alteration, homozygous c.105G->C (conservative change without alteration of amino acid) in AQP3 was detected in 11 out of 34 patients but not in 100 control chromosomes. CONCLUSION: By itself the detected alteration is unlikely to play a role in the pathogenesis of MD. However, together with an additional modifying gene an effect can not be excluded. Additional regions (introns, splice-sites) and other genes involved in inner ear homeostasis need to be analyzed to identify a possible molecular alteration in MD.

Long-term assessment after implantation of the Vibrant Soundbridge device.

OBJECTIVE: To present long-term results with a semi-implantable middle ear implant, the Vibrant Soundbridge (VSB), and analyze pre- and post-operative results of audiologic tests. STUDY DESIGN: Retrospective chart review with additional patient interview and audiologic testing. SETTING: One tertiary referral center. SUBJECTS: Twenty patients who met the selection criteria of the manufacturer were evaluated at least two years after implantation. INTERVENTIONS: Monaural Implantation of the VSB in 20 patients, in two of these 20 patients implantation of the second ear in a second stage. RESULTS: Assessment of benefit and satisfaction using the standardized International Outcome Inventory for Hearing Aids, the Glasgow Benefit Inventory, and Visual Analogue Scales in all patients. Fifteen patients agreed to undergo audiologic testing at follow-up including pure-tone- and speech audiometry in silence and noise. The majority of patients (13/20) reported to be satisfied or very satisfied with the VSB. Aided speech perception was comparable between the VSB and the hearing aid preoperatively. When compared to the preoperative audiograms, residual hearing from 0.5-4 kHz was significantly worse in the operated ear with 8 dB (Wilcoxon signed rank test p < 0.001) but only 2.6 dB in the non-operated ear (Wilcoxon signed rank test, p > 0.05). Major surgical complications did not occur. Permanent alteration in taste occurred in three patients and revision surgery was necessary in another three patients. CONCLUSION: Satisfaction with the VSB was not superior to conventional hearing aids in subjective and in audiometric terms. Because of its impact on residual hearing and the requirement of implantation middle ear surgery, implantation of the VSB should be limited to patients with relevant side effects of hearing aids, e.g., severe chronic otitis externa.

Audiologic testing and molecular analysis of 12S rRNA in patients receiving aminoglycosides.

BACKGROUND: Pathogenic mutations in the mitochondrial genome are associated with a wide variety of maternally inherited human diseases including sensorineural hearing loss (HL). A specific mutation, m.1555A>G in the mitochondrial 12S rRNA gene, is associated with predisposition to aminoglycoside ototoxicity and HL. Mutation screening in this gene has been recommended before use of aminoglycosides as a preventative strategy to reduce the risk of ototoxicity. OBJECTIVE: To study the incidence of mutations in the 12S rRNA gene in patients being treated with aminoglycosides and its correlation with ototoxicity. METHODS: Patients undergoing treatment with aminoglycosides were prospectively enrolled in this study (n = 27). Total dosage administered and therapeutic levels of the antibiotic were noted. All patients underwent high-frequency pure-tone audiometry pre- and posttherapy and sequencing of the 12S rRNA gene. In addition, 12S rRNA gene was also sequenced in 50 controls to characterize population specific polymorphisms. RESULTS: Five of 27 patients suffered from HL involving the high frequencies: four mild and one moderate. Only one of the five patients with ototoxicity harbored two sequence alterations in 12S rRNA of uncertain pathogenicity. The m.1555A>G and m.961delTInsCn mutations were not detected. CONCLUSIONS: High-frequency pure-tone audiometry is critical for detection of aminoglycoside-induced HL. In the Swiss population, screening for mutations in the 12S rRNA gene, before the initiation of aminoglycoside therapy, is not supported by this limited study. A larger multicenter and multicultural study is warranted to more definitively address this critical clinical issue.

Is there addiction to loud music? Findings in a group of non-professional pop/rock musicians.

Listening to loud music may be connected to addictive behavior possibly leading to damaging effects on the cochlea. We hypothesized that members of non-professional pop/rock bands with regular exposure to loud music are more likely to show an addictive-like behavior for loud music than matched control subjects. Fifty non-professional musicians and 50 matched control subjects were asked to complete the Northeastern Music Listening Survey (NEMLS) with two basic components. The first comprises an adaptation of the validated Michigan Alcohol Screening Test (MAST) to study the addictive-like behavior towards loud music. The second comprises the criteria outlined by the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Society for the diagnosis of substance dependence. The NEMLS was scored using the same point system as used in the MAST. The DSM-IV criteria for substance dependence were met by nine of the musician group and by one control subject. Seven of these nine musicians also had a positive NEMLS score. Traits of addictive-like behavior to loud music were detected more often in members of nonprofessional pop/rock bands than in control subjects.

Comparison of ultrasound-guided core-needle biopsy and fine-needle aspiration in the assessment of head and neck lesions.

BACKGROUND: Core-needle biopsy (CNB) has been successfully applied in other medical specialties, but its value is undetermined in otolaryngology. METHODS: This prospective study includes 75 patients, who were seen at our institution with a cervical mass. The results of CNB were compared with those of fine-needle aspiration (FNA) in the 68 histologically verified cases. RESULTS: CNB was superior to FNA providing a specific diagnosis (90% vs 66%) and achieved a higher accuracy in identifying true neoplasms (100% vs 93%) and detecting malignancy (99% vs 90%). However, the sensitivity and specificity did not differ significantly between both methods. CONCLUSIONS: Sonography and if necessary FNA should continue to be the investigation method of first choice for head and neck lesions. The main indication for CNB is after repeated failures of FNA to provide a diagnosis. It can also be performed in patients who are not surgical candidates or in those who refuse surgery.

An assessment of threshold shifts in nonprofessional pop/rock musicians using conventional and extended high-frequency audiometry.

The clinical value of extended high-frequency audiometry for the detection of noise-induced hearing loss has not been established conclusively. The purpose of this study was to assess the relative temporary threshold shift (TTS) in two frequency regions (conventional versus extended high frequency). In this exploratory study, pure-tone thresholds from 0.5 to 14 kHz were measured in both ears of 16 nonprofessional pop/rock musicians (mean age, 35 yr; range, 27 to 49 yr), before and after a 90-minute rehearsal session. All had experienced repeated exposures to intense sound levels during at least 5 yr of their musical careers. After the rehearsal, median threshold levels were found to be significantly poorer for frequencies from 0.5 to 8 kHz (Wilcoxon signed rank test, p

Acoustic measures of low-frequency noise in extended high-frequency audiometry.

A very high signal-to-noise ratio is required for equipment designed for extended high-frequency audiometry because listeners with almost no hearing ability in the extended high-frequency range may have normal hearing sensitivity in the lower frequencies. Two commercially available systems designed for pure-tone audiometry were evaluated both in the conventional and extended high-frequency range. Unwanted lower frequency signals greater than the noise floor occurred predominantly at presentation levels of approximately 110 dB SPL or higher. Test tones in the extended high-frequency range should be restricted to levels that are not associated with lower frequency noise.

Hearing in nonprofessional pop/rock musicians.

OBJECTIVE: The purpose of this study was to evaluate the hearing and subjective auditory symptoms in a group of nonprofessional pop/rock musicians who had experienced repeated exposures to intense sound levels during at least 5 yr of musical activity. DESIGN: An evaluation of both ears in 42 nonprofessional pop/rock musicians included pure-tone audiometry in the conventional and extended high-frequency range, the measurement of uncomfortable loudness levels, and an assessment of tinnitus and hypersensitivity to sound. Exclusion criteria were (a) the occurrence of acoustic trauma, (b) excessive noise exposure during occupational activities, (c) a history of recurrent otitis media, (d) previous ear surgery, (e) a fracture of the cranium, (f) ingestion of potentially ototoxic drugs, and (g) reported hearing difficulties within the immediate family. These audiometric results were then compared with a control group of 20 otologically normal young adults with no history of long-term noise exposure. RESULTS: After adjusting for age and gender, relative to ISO 7029, the mean hearing threshold in the frequency range of 3 to 8 kHz was 6 dB in the musicians and 1.5 dB in the control group. This difference was statistically significant (Mann-Whitney rank sum test, p < 0.001). A significant difference was also observed between musicians using regular hearing protection during their activities (average 3 to 8 kHz thresholds = 2.4 dB) and musicians who never used such hearing protection (average 3 to 8 kHz thresholds = 8.2 dB), after adjusting for age and gender (Mann-Whitney rank sum test, p = 0.006). Eleven of the musicians (26%) were found to be hypersensitive to sound, and seven (17%) presented with tinnitus. Tinnitus assessment, however, did not reveal any clinically significant psychological distress in these individuals. CONCLUSIONS: Tinnitus and hypersensitivity to sound were observed in a significant minority within a group of nonprofessional pop/rock musicians who had experienced repeated exposure to intense sound levels over at least 5 yr but with minimal impact on their lives. Moreover, hearing loss was minimal in the subjects who always used ear protection, being only 0.9 dB higher than the control group. In contrast, hearing loss was significantly more pronounced, at 6.7 dB higher than the control group, in those musicians who never used ear protection. Continued education about the risk to hearing and the benefits of the persistent use of ear protection is warranted for musicians who are exposed frequently to intense sound levels.

Automated pure-tone threshold estimations from extrapolated distortion product otoacoustic emission (DPOAE) input/output functions.

A promising approach to the prediction of pure-tone thresholds through the estimation of DPOAE thresholds by input/output functions was recently published by Boege and Janssen [J. Acoust. Soc. Am. 111, 1810-1818 (2002)]. On the basis of their results, a device that enables automated measurements of these thresholds was recently developed. The purpose of the current study was to evaluate the reliability of this instrument for the objective assessment of hearing loss in 101 ears with either normal hearing or with cochlear hearing loss of up to 50 dB HL. The median difference between pure-tone hearing and DPOAE thresholds was approximately 2 dB. For individual subjects, however, DPOAE thresholds differed from pure-tone thresholds by up to 40 dB. We find, therefore, that the clinical benefits of this method are probably limited.

Incapacitating hypersensitivity to one's own body sounds due to a dehiscence of bone overlying the superior semicircular canal. A case report.

We present a case study of a 49-year-old patient with an 8-year history of hypersensitivity to sound produced by intrinsic but not extrinsic sources. Findings that indicated an organic problem were: a supranormal bone conduction threshold of -25 to -15 dB HL from 0.25 to 1 kHz with an air-bone gap of 15 to 45 dB HL, a lower threshold and larger amplitude for vestibular-evoked myogenic potentials, eye movement reactions to sound and trunk pitch sway in response to sound. Results of immitance audiometry and otoacoustic emission testing were within normal limits and indicative of intact middle ear conductance. A high-resolution CT scan of the temporal bone demonstrated a dehiscence of bone overlying the superior semicircular canal. These findings support previous research indicating that auditory energy reaches the cochleo-vestibular receptor systems more easily via transmission through cerebrospinal fluid than through bone. Therefore, a dehiscence of the bone overlying the superior semicircular canal may lead to hypersensitivity to intrinsic sound. We recommend that similar findings in other patients be followed up with an evaluation of middle ear function and the temporal bone with high-resolution CT scan.

Otoacoustic emissions and extended high-frequency hearing sensitivity in young adults.

The relationship between hearing sensitivity in the extended high-frequency region (8-16 kHz) and (1) the presence of synchronized spontaneous otoacoustic emissions (SSOAEs) and (2) the strength of click-evoked and distortion product otoacoustic emissions (CEOAEs and DPOAEs) was investigated in 104 ears of 57 young adults. The age range was confined to 16 to 19 years. All subjects had normal hearing in the conventional audiometric frequency range (0.5-8 kHz). Ears with detected SSOAEs had better hearing sensitivity in the extended high-frequency region and also higher levels of CEOAEs and DPOAEs than ears with undetected SSOAEs. The results support the hypothesis that the presence of SSOAEs is indicative of an ear with highly normal cochlear function over a broad frequency range.

Test-retest reliability of pure-tone thresholds from 0.5 to 16 kHz using Sennheiser HDA 200 and Etymotic Research ER-2 earphones.

OBJECTIVE: The purposes of the study were: (1) To evaluate the intrasession test-retest reliability of pure-tone thresholds measured in the 0.5-16 kHz frequency range for a group of otologically healthy subjects using Sennheiser HDA 200 circumaural and Etymotic Research ER-2 insert earphones and (2) to compare the data with existing criteria of significant threshold shifts related to ototoxicity and noise-induced hearing loss. DESIGN: Auditory thresholds in the frequency range from 0.5 to 6 kHz and in the extended high-frequency range from 8 to 16 kHz were measured in one ear of 138 otologically healthy subjects (77 women, 61 men; mean age, 24.4 yr; range, 12-51 yr) using HDA 200 and ER-2 earphones. For each subject, measurements of thresholds were obtained twice for both transducers during the same test session. For analysis, the extended high-frequency range from 8 to 16 kHz was subdivided into 8 to 12.5 and 14 to 16 kHz ranges. Data for each frequency and frequency range were analyzed separately. RESULTS: There were no significant differences in repeatability for the two transducer types for all frequency ranges. The intrasession variability increased slightly, but significantly, as frequency increased with the greatest amount of variability in the 14 to 16 kHz range. Analyzing each individual frequency, variability was increased particularly at 16 kHz. At each individual frequency and for both transducer types, intrasession test-retest repeatability from 0.5 to 6 kHz and 8 to 16 kHz was within 10 dB for >99% and >94% of measurements, respectively. The results indicated a false-positive rate of <3% in reference to the criteria for cochleotoxicity for both transducer types. In reference to the Occupational Safety and Health Administration Standard Threshold Shift criteria for noise-induced hazards, the results showed a minor false-positive rate of <1% for the HDA 200. CONCLUSION: Repeatability was similar for both transducer types. Intrasession test-retest repeatability from 0.5 to 12.5 kHz at each individual frequency including the frequency range susceptible to noise-induced hearing loss was excellent for both transducers. Repeatability was slightly, but significantly poorer in the frequency range from 14 to 16 kHz compared with the frequency ranges from 0.5 to 6 or 8 to 12.5 kHz. Measurements in the extended high-frequency range from 8 to 14 kHz, but not up to 16 kHz, may be recommended for monitoring purposes.

Rate of false-positive results for threshold shifts during initial treatment with aminoglycosides.

Specific recommendations from the American Speech-Language Hearing Association (1994) exist for the audiometric surveillance of patients receiving aminoglycoside therapy. However, these recommendations are not based primarily on test-retest repeatability in often seriously ill patients. The probability of ototoxicity is very low during the first three days of aminoglycoside therapy, and significant threshold shifts can be assumed to represent a false-positive result. Baseline thresholds were measured in 28 patients before or not later than 24 h after the beginning of aminoglycoside therapy. These measurements were repeated in 22 patients during the first three days of the drug administration. Three out of 22 patients fulfilled the American Speech-Language-Hearing Association's (1994) criteria for cochleotoxicity making up a false-positive rate of 13%. In actual patients, the false-positive rate of audiometric surveillance during ototoxic drug administration may be substantially higher than in healthy subjects when these criteria are used.