Cochlear gene transfer studies in animal models have utilized mainly two delivery methods: direct injection through the round window membrane (RWM) or intracochlear infusion through a cochleostomy. However, the surgical trauma, inflammation, and hearing loss associated with these methods lead us to investigate a less invasive delivery method. Herein, we studied the feasibility of a vector transgene-soaked gelatin sponge, Gelfoam, for transgene delivery into the mouse cochlea through an intact RWM. The Gelfoam absorbed with liposomes and adenovirus, but not with adeno-associated virus (AAV), was successful in mediating transgene expression across an intact RWM in a variety of cochlear tissues. The Gelfoam technique proved to be an easy, atraumatic, and effective, but vector-dependent, method of delivering transgenes through an intact RWM. Compared with the more invasive gene delivery methods, this technique represents a safer and a more clinically viable route of cochlear gene delivery in humans.

White and Asian children with severe to profound SNHL had higher proportionate rates of cochlear implantation than black and Hispanic children in 1997. Implanted children were more likely to live in areas (represented by ZIP codes) with higher median incomes. Although there was a disparity in rate of cochlear implantation based on race/ethnicity and surrogate measures of SES, these data did not allow the authors to determine the causes for these differences.

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In this large cohort of patients, we found no difference in the odds of flap re-exploration or failure based on venous anastomotic configuration. Reconstructive surgeons should have both anastomotic techniques in their repertoire to optimize the success of every flap.

Lateral retrocanthal orbitotomy is a new approach that provides extended access to the entire lateral orbit. The technique is rapid and can be extended in a single continuous incision to the medial orbit. The structural integrity of the lateral retinaculum is preserved, which appears to improve the postoperative cosmetic and functional result.

A large American family has been mapped to the DFNA2 locus. However, mutation screening of CX31 and KCNQ4, the two genes associated with deafness at this locus, did not identify any mutations. The purpose of this report was to characterize the otologic and audiometric phenotype of this large American family with non-syndromic, autosomal-dominant sensorineural hereditary hearing impairment (HHI). Anamnestic data were obtained, pure-tone audiometry was performed and transient-evoked otoacoustic emissions were recorded. The findings in affected family members were compared to those in unaffected family members and to the respective p50 thresholds of the normal age-matched population. Mutational analysis of the CX26 gene was also performed. The affected members of this family demonstrated progressive symmetric sensorineural hearing impairment. The hearing loss was downward sloping, with mild-to-moderate loss in the low and mid frequencies and severe-to-profound loss in frequencies > 4,000 Hz. The onset of disease was predominantly in the first or early in the second decade. Hearing impairment progressed at approximately 1 dB per year across all frequencies. Transient-evoked otoacoustic emissions revealed a minimal response over all frequencies in affected members but robust responses in all unaffected members. Mutation in the CX26 gene was not present. The affected frequencies observed in this family were similar to those in the original family mapped to DFNA2; however, the age of onset of disease was different and the hearing loss progressed at a slower rate. Therefore, this family provides clinical evidence of genetic heterogeneity at the DFNA2 locus and can serve as a model for age-related hearing loss.

A large American family has been mapped to the DFNA2 locus. However, mutation screening of CX31 and KCNQ4, the two genes associated with deafness at this locus, did not identify any mutations. The purpose of this report was to characterize the otologic and audiometric phenotype of this large American family with non-syndromic, autosomal-dominant sensorineural hereditary hearing impairment (HHI). Anamnestic data were obtained, pure-tone audiometry was performed and transient-evoked otoacoustic emissions were recorded. The findings in affected family members were compared to those in unaffected family members and to the respective p50 thresholds of the normal age-matched population. Mutational analysis of the CX26 gene was also performed. The affected members of this family demonstrated progressive symmetric sensorineural hearing impairment. The hearing loss was downward sloping, with mild-to-moderate loss in the low and mid frequencies and severe-to-profound loss in frequencies > 4,000 Hz. The onset of disease was predominantly in the first or early in the second decade. Hearing impairment progressed at approximately 1 dB per year across all frequencies. Transient-evoked otoacoustic emissions revealed a minimal response over all frequencies in affected members but robust responses in all unaffected members. Mutation in the CX26 gene was not present. The affected frequencies observed in this family were similar to those in the original family mapped to DFNA2; however, the age of onset of disease was different and the hearing loss progressed at a slower rate. Therefore, this family provides clinical evidence of genetic heterogeneity at the DFNA2 locus and can serve as a model for age-related hearing loss.

The goal of this study was to determine the relationship between psychophysical measures of electric hearing and neural survival in Nucleus-22 cochlear implant users.Methods: The temporal bones of 2 subjects with Nucleus-22 cochlear implants were obtained at autopsy. Histologic procedures were used to quantify spiral ganglion cell survival as a function of longitudinal cochlear distance and to estimate the radial distance between each electrode and the spiral ganglion cells in Rosenthal's canal. Psychophysical measures of threshold, maximum acceptable loudness level, and dynamic range were obtained for each stimulable electrode prior to death. Both subjects were tested with short phase-duration (200 microseconds per phase) pulses; subject 2 was also tested with long phase-duration (1260 microseconds per phase) pulses.Results: Correlation coefficients were calculated for threshold, maximum acceptable loudness level, and dynamic range and spiral ganglion cell density as a function of distance along Rosenthal's canal. No significant correlations were observed in subject 1, who had extensive neo-ossification in the basal and middle turns of the cochlea. Weak correlations were observed in subject 2, but relationships were in unexpected directions: Spiral ganglion cell density was positively correlated with threshold (r ϭ 0.502, P Ͻ 0.05) and negatively correlated with dynamic range (r ϭ Ϫ0.533, P Ͻ 0.05). Radial distance was not correlated with any of the psychophysical measures in either subject.Conclusion: There was no consistent relationship among threshold, maximum acceptable loudness level and dynamic range, and spiral ganglion cell survival in the 2 Nucleus-22 cochlear implant users studied.Significance: These data suggest a complex relationship among neural survival, electrode location, and behavioral measures of hearing, and indicates that threshold, maximum acceptable loudness level, and dynamic range are influenced by factors other than the proximity and number of surviving sprial ganglion cells.