Profound, prelingual nonsyndromic deafness maps to chromosome 10q21 and is caused by a novel missense mutation in the Usher syndrome type IF gene PCDH15.

We studied a consanguineous family (Family A) from the island of Newfoundland with an autosomal recessive form of prelingual, profound, nonsyndromic sensorineural hearing loss. A genome-wide scan mapped the deafness trait to 10q21-22 (max LOD score of 4.0; D10S196) and fine mapping revealed a 16 Mb ancestral haplotype in deaf relatives.

Characterization of a new full length TMPRSS3 isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan.

Background: Mutant alleles of TMPRSS3 are associated with nonsyndromic recessive deafness (DFNB8/B10). TMPRSS3 encodes a predicted secreted serine protease, although the deduced amino acid sequence has no signal peptide. In this study, we searched for mutant alleles of TMPRSS3 in families from Pakistan and Newfoundland with recessive deafness co-segregating with DFNB8/B10 linked haplotypes and also more thoroughly characterized the genomic structure of TMPRSS3.

Irreversible ototoxicity associated with difluoromethylornithine.

Difluoromethylornithine (DFMO) is a potent, irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the synthesis of polyamines that promote cellular proliferation. DFMO has been tested as a potential cancer therapeutic and chemopreventive agent in clinical trials. Reversible hearing loss is a recognized toxicity of DFMO that usually occurs at doses above 2 g/m(2)/d, and generally when the cumulative dose exceeds 250 g/m(2).

Endolymphatic sac tumors in von Hippel-Lindau disease.

Object: Von Hippel-Lindau (VHL) disease is a hereditary multiple-neoplasia syndrome mapping to chromosome 3p25-26. Endolymphatic sac (ELS) tumors have been identified as a neoplastic manifestation of VHL disease. The purpose of this study was to evaluate comprehensively the natural history of inner ear disease in a large population of patients with confirmed or suspected VHL disease and to correlate the clinical features with the VHL genotype.

Audiologic manifestations of patients with post-treatment Lyme disease syndrome.

Objective: The purpose of this study was to characterize auditory function in patients diagnosed with post-treatment Lyme disease syndrome (PTLDS).

Design: Eighteen patients with PTLDS were evaluated and compared to a normal population. Evaluations consisted of pure tone and speech thresholds, word recognition (WRS), acoustic immittance battery, auditory brain stem response (ABR), and loudness discomfort level (LDL).

Auditory dysfunction in Stickler syndrome.

Objectives: To characterize the natural history and possible mechanisms of hearing loss in Stickler syndrome (OMIM 108300; or hereditary progressive arthro-ophthalmopathy) and to determine if the auditory phenotype is a useful discriminating feature for the differential diagnosis of this group of disorders.

Design: Multifamily study.

Setting: Outpatient audiology and otolaryngology clinics at the Warren Grant Magnuson Clinical Center of the National Institutes of Health, Rockville, Md.

Recommendations for cancer prevention trials using potentially ototoxic test agents.

Purpose: Preventive oncology applies pharmacologic agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy, a process that may require administration of agents over long periods of time. Although ototoxicity may be a tolerable side effect of anticancer or antimicrobial therapy, even modest ototoxicity may not be acceptable in agents developed for preventive oncology that are routinely administered to subjects who neither are, nor necessarily will become, clinically ill.

Materials And Methods: Age-related shifts in hearing may occur over the course of longterm or open-ended therapy; consequently, age-adjusted norms enable researchers to better distinguish hearing loss caused by drugs from that caused by aging.

Dosimetry measurements using a probe tube microphone in the ear canal.

Federal and international standards recommended use of microphone placement either on or in the vicinity of the shoulder for dosimetry to minimize deviations from the undisturbed sound field. Probe microphone measurements from the ear canal were compared to shoulder and chest measures in order to investigate the validity of current dosimetry methodologies. Six subjects were monitored in an industrial setting.

No specific effects of caloric stimulation on the visual-imagery processes of normal subjects.

Recent research indicates that neglect can be temporarily, but only partially, ameliorated by activating the contralateral hemisphere via caloric stimulation and other techniques. In this study, we evaluated whether caloric stimulation could be used to manipulate visual-imagery processes in normal subjects. 11 normal subjects participated in a quantitative visual-imagery task while undergoing caloric stimulation.

Safety of rapid-rate transcranial magnetic stimulation in normal volunteers.

In 9 normal volunteers, we studied the safety of rapid-rate transcranial magnetic stimulation (rTMS) applied to different scalp positions at various frequencies and intensities. Pure tone threshold audiometry showed temporary threshold shifts in 3 subjects. In the subject stimulated at the highest intensity, rTMS induced a focal, secondarily generalized seizure despite the absence of definite risk factors for seizures.

No evidence of hearing loss in humans due to transcranial magnetic stimulation.

Prompted by the description of hearing loss in rabbits exposed to the acoustic artifact of magnetic stimulation, we compared the results of audiologic studies before and after exposure to transcranial magnetic stimulation in humans. We found no evidence of temporary or permanent threshold shifts in any of the subjects, even in those exposed to transcranial magnetic stimulation repeatedly for several years. Risk of hearing loss from the acoustic artifact of magnetic stimulation, as evaluated by audiograms, tympanograms, acoustic reflexes, and auditory evoked potentials, seems to be small in humans.

The effect of probe tube reference placement on sound pressure level variability.

This study examined the effect of external microphone reference placement on peak sound pressure level (pSPL) and measurement variability. Nine normal subjects were seated in a double-walled sound suite, 1 m and 0 degrees azimuth from a wall-mounted speaker. Digitized Gaussian noise was presented at 80 dB pSPL with a 500 msec duration and was measured through a probe tube microphone assembly.