Biomedical subjects
George A Gates
Publications and source records attributed to George A Gates.
Dilating the clinical research stricture.
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Genomewide linkage analysis to presbycusis in the Framingham Heart Study.
OBJECTIVE: To identify chromosomal regions that show evidence of linkage to age-associated hearing impairment (presbycusis) in humans. DESIGN: We evaluated the genetic linkage between quantitative measures from audiometric examinations and markers from a genomewide scan in a population-based sample ascertained without respect to hearing status. PARTICIPANTS: Audiometric examinations were conducted on 2263 original cohort members and 2217 offspring cohort members of the National Heart, Lung, and Blood Institute's Framingham Heart Study. Of these, 1789 individuals were members of 328 extended pedigrees used for linkage analysis. The outcome traits for linkage analysis were pure-tone average at medium (0.5, 1.0, and 2.0 kHz) and low (0.25, 0.5, and 1.0 kHz) frequencies adjusted for cohort, sex, age, age squared, and age cubed. RESULTS: We found heritability (proportion of variance due to genes) of age-adjusted pure-tone average at medium and low frequencies to be 0.38 and 0.31, respectively. Genomewide linkage analysis identified several locations with suggestive evidence of linkage. Of particular interest are the regions 11p (maximum multipoint logarithm of odds [MLOD], 1.57), 11q13.5 (MLOD, 2.10), and 14q (MLOD, 1.55), which overlap with genes known to cause congenital deafness. CONCLUSIONS: There is evidence that genetic and environmental factors contribute to hearing loss in the mature human population. Several of the chromosomal locations identified overlap with loci known to cause congenital hearing loss. Further studies are needed to determine whether the same genes cause presbycusis and congenital hearing loss.
Screening for handicapping hearing loss in the elderly.
OBJECTIVE: To compare 2 screening methods for unrecognized handicapping hearing loss in the elderly. STUDY DESIGN: Cross-sectional study. POPULATION: Five hundred forty-six older individuals who underwent audiometry at biennial examination 22 of the Framingham Heart Study and who took the Hearing Handicap Inventory for the Elderly-Screening (HHIE-S) questionnaire. OUTCOMES MEASURED: The 2 screening methods were the 10-item HHIE-S and 1 global question: "Do you have a hearing problem now?" The gold standard was an audiogram showing a pure tone threshold of 40 dB HL or higher at 1 and 2 kHz in one ear or at 1 or 2 kHz in both ears. Both screening methods were compared with the gold standard in terms of sensitivity, specificity, and predictive values. The 10-item screening version of the HHIE-S (cutoff score between 8 and 10) had a sensitivity of 35% and a specificity of 94% for detecting the criterion hearing loss. The global subjective measure had greater sensitivity (71%) but lower specificity (71%) than the HHIE-S. Combining the global question and the HHIE-S items failed to improve the specificity of the global question or the sensitivity of the HHIE-S. CONCLUSIONS: The global measure of hearing loss was more effective than the detailed questionnaire in identifying older individuals with unrecognized handicapping hearing loss. Primary care physicians are encouraged to ask their patients whether they have a hearing problem and refer patients who do for formal hearing testing.
CT-derived estimation of cochlear morphology and electrode array position in relation to word recognition in Nucleus-22 recipients.
This study extended the findings of Ketten et al. [Ann. Otol. Rhinol. Laryngol. Suppl. 175:1-16 (1998)] by estimating the three-dimensional (3D) cochlear lengths, electrode array intracochlear insertion depths, and characteristic frequency ranges for 13 more Nucleus-22 implant recipients based on in vivo computed tomography (CT) scans. Array insertion depths were correlated with NU-6 word scores (obtained one year after SPEAK strategy use) by these patients and the 13 who used the SPEAK strategy from the Ketten et al. study. For these 26 patients, the range of cochlear lengths was 29.1-37.4 mm. Array insertion depth range was 11.9-25.9 mm, and array insertion depth estimated from the surgeon's report was 1.14 mm longer than CT-based estimates. Given the assumption that the human hearing range is fixed (20-20,000 Hz) regardless of cochlear length, characteristic frequencies at the most apical electrode (estimated with Greenwood's equation [Greenwood DD (1990) A cochlear frequency--position function of several species--29 years later. J Acoust. Soc. Am. 33: 1344-1356] and a patient-specific constant as) ranged from 308 to 3674 Hz. Patients' NU-6 word scores were significantly correlated with insertion depth as a percentage of total cochlear length (R = 0.452; r2 = 0.204; p = 0.020), suggesting that part of the variability in word recognition across implant recipients can be accounted for by the position of the electrode array in the cochlea. However, NU-6 scores ranged from 4% to 81% correct for patients with array insertion depths between 47% and 68% of total cochlear length. Lower scores appeared related to low spiral ganglion cell survival (e.g., lues), aberrant current paths that produced facial nerve stimulation by apical electrodes (i.e., otosclerosis), central auditory processing difficulty, below-average verbal abilities, and early Alzheimer's disease. Higher scores appeared related to patients' high-average to above-average verbal abilities. Because most patients' scores increased with SPEAK use, it is hypothesized that they accommodated to the shift in frequency of incoming sound to a higher pitch percept with the implant than would normally be perceived acoustically.
Effects of age on the distortion product otoacoustic emission growth functions.
Age-related hearing loss (presbycusis) is thought to result from age-related degeneration (aging) of the cochlea plus the cumulative effects of extrinsic damage (noise and other ototoxic agents) and intrinsic disorders (e.g. systemic diseases). Previous studies have implicated dysfunction of the hair cells (sensory presbycusis) as the principal mechanism of age-related hearing loss. However, recent evidence from quiet-reared gerbils suggests that cochlear aging results primarily from atrophy of the stria vascularis, which is associated with diminished endocochlear potential (EP), spiral ganglion atrophy, and a relatively flat audiometric loss, termed metabolic presbycusis. Because it is not currently possible to measure EP directly in the clinical setting, we wondered if cochlear metabolic dysfunction might be evidenced indirectly from existing clinical tests, specifically, the input-output (IO) growth function of the distortion product (DP) otoacoustic emissions in relation to behavioral hearing threshold levels (HTL). We anticipated finding discordance between the IO functions and HTL with either a greater decline with age in HTL than in IO functions if an age-related metabolic dysfunction of the cochlea was operant, or a greater loss of IO function than HTL if outer hair cell dysfunction was the dominant pathology. To address this supposition we analyzed existing auditory data from a large cohort of adults to determine the change with age in three aspects of the DP IO function: area under the curve, threshold, and slope. The analyses demonstrated a greater effect of age on HTL than on the DP IO measures. This effect supports the hypothesis that strial dysfunction is a substantive factor in cochlear aging. The etiology and mechanisms for this dysfunction are conjectural at present.
Is DFNA5 a susceptibility gene for age-related hearing impairment?
A mutation in DFNA5 leads to a type of hearing loss that closely resembles the frequently observed age-related hearing impairment (ARHI). The hearing loss is sensorineural, progressive and starts at the high frequencies. As DFNA5 was considered an excellent candidate ARHI susceptibility gene, we performed linkage analysis to a quantitive measure of high frequency hearing loss. However, no significant linkage between ARHI and microsatellite markers from the DFNA5 region could be detected. Subsequently, the DFNA5 coding region was analysed for single nucleotide polymorphisms (SNPs). Two SNPs leading to amino-acid substitutions (P142H and V207M) were selected for further analysis. Using these SNPs, an association study based on a collection of random individuals, and a case-control association study were performed. No significant differences in genotypes between good hearing and hearing impaired individuals could be detected in either study design. We conclude that there exists no strong association between DFNA5 and ARHI.
Central auditory dysfunction may precede the onset of clinical dementia in people with probable Alzheimer's disease.
OBJECTIVES: To document the prognostic significance of a central auditory speech-processing deficit for the subsequent onset of probable Alzheimer's disease. DESIGN: Prospective cohort study. SETTING: Framingham Heart Study. PARTICIPANTS: Seven hundred forty dementia-free volunteers from the Framingham Heart Study cohort with symmetric hearing thresholds at biennial examination 15 (1983-1985). MEASUREMENTS: The diagnosis of probable Alzheimer's disease was made prospectively using the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease Related Disorder Association criteria. A central auditory speech-processing deficit was defined as a score of 50% of less correct on the Synthetic Sentence Identification with Ipsilateral Competing Message test in at least one ear with normal word recognition ability in both ears. Cox proportional hazards regression assessed the relationship between a central auditory speech-processing deficit and the age at diagnosis of probable Alzheimer's disease. RESULTS: Forty subjects (5.4%) received a diagnosis of probable Alzheimer's disease during an average of 8.4 years (range 3-12) of follow-up; seven (17.5%) of these had a central auditory speech-processing deficit. The presence of a central auditory speech-processing deficit had an age-adjusted risk ratio for probable Alzheimer's disease of 10.8 (95% CI = 4.6-25.2), and the estimated risk ratio adjusted for age, gender, education level, apolipoprotein allele E4 presence, and hearing level was 23.3 (95% CI =6.6-82.7). A central auditory speech-processing deficit had a positive predictive value for subsequent probable Alzheimer's disease of 47% but the sensitivity was only 17.5%. CONCLUSION: Central auditory speech-processing deficits may be an early manifestation of probable Alzheimer's disease and may precede the onset of dementia diagnosis by many years.
Intermittent pressure therapy of intractable Ménière's disease using the Meniett device: a preliminary report.
HYPOTHESIS: Treatment with the Meniett device, which applies intermittent micropressure pulses to the inner ear through a tympanostomy tube, is effective in controlling vertigo in people with intractable Ménière's disease. STUDY DESIGN: Short-term, preliminary descriptive report. METHODS: Ten patients with intractable vertigo despite adequate medical therapy elected to use the Meniett device. After placement of a standard tympanostomy tube, the patient self-administers the Meniett device three times daily. RESULTS: The follow-up ranged from 3 to 11 months with an average of 8 months. All 10 patients responded to the therapy with vertigo control in 9 of 10 and a 50% reduction in the 10th case. There was a mean hearing gain of 6 dB, which was statistically significant. There were no major complications. Two subjects required tube reinsertion during the 8 months of follow-up. CONCLUSIONS: Use of the Meniett device is an effective and safe option for people with intractable vertigo from Ménière's disease.
Recent advances in otitis media. 1. Definitions, terminology, and classification of otitis media.
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Delayed facial palsy after resection of vestibular schwannoma.
OBJECT: In this study the authors investigate delayed facial palsy (DFP), which is an underreported phenomenon after surgery for vestibular schwannoma (VS). The authors identified 15 (4.8%) patients from a consecutive series of 314 who underwent surgery for VS between 1988 and 2000, and in whom DFP developed. Delayed facial palsy was defined as a deterioration of facial nerve function from House-Brackmann Grades 1 or 2 more than 3 days postoperatively. METHODS: All patients underwent intraoperative neurophysiological monitoring of facial nerve function. The average latency of DFP was 10.9 days (range 4-30 days). In six patients (40%) minor deterioration (< or = two House-Brackmann grades) had occurred at a mean of 10.2 days postsurgery, whereas in nine patients (60%) moderate deterioration (> or = three House-Brackmann grades) had occurred at a mean of 11.8 days postoperatively. Five (33%) of 15 patients recovered to Grade 1 of 2 function within 6 weeks of DFP onset. Of the 15 patients with DFP, 14 had completed 1 year of follow up at the time of this study. Twelve (80%) of these 15 patients recovered to Grade 1 or 2 function within 3 months, and 13 (93%) of 14 patients recovered within 1 year. In all cases, stimulation of the seventh cranial nerve on completion of tumor resection revealed the nerve to be intact, both anatomically and functionally, to proximal and distal stimulation at 0.1 mA. A smaller tumor diameter correlated with greater recovery of facial nerve function. There was no correlation between the latency or severity of or recovery from DFP, and the patient's age or sex, the surgical approach, frequency of neurotonic seventh nerve discharges, anatomical relationship of the facial nerve to the tumor, patient's history of tobacco use, or cardiovascular disease. CONCLUSIONS: It appears that DFP is an uncommon consequence of surgery for VS. Although excellent recovery of facial nerve function to its original postoperative status nearly always occurs after DFP, the magnitude and time course of the disorder were not predictors for subsequent recovery of facial nerve function.