Transduction of the contralateral ear after adenovirus-mediated cochlear gene transfer.
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Cochlear gene transfer is a promising new approach for inner ear therapy. Previous studies have demonstrated hair cell protection with cochlear gene transfer not only in the inoculated, but also in the uninoculated ear. To characterize the kinetics of viral spread, we investigated the extent of transgene expression in the contralateral (uninoculated) cochlea after unilateral adenoviral cochlear gene transfer. We used a lacZ reporter gene vector, and demonstrated spread of the adenovirus into the cerebrospinal fluid (CSF) after cochlear inoculation of 25 microl viral vector. Direct virus application into the CSF resulted in transduction of both cochleae, whereas virus inoculation into the bloodstream did not. The cochlear aqueduct was identified as the most likely route of virus spread to the contralateral cochlea. These data enhance our understanding of the kinetics of virus-mediated transgene expression in the inner ear, and assist in the development of clinical applications for inner ear gene therapy. Our results showed a functional communication between the CSF and the perilymphatic space of the inner ear, that is not only of importance for otological gene transfer, but also for CNS gene transfer. Gene Therapy (2000) 7, 377-383. (+info)
MR cisternography of the cerebellopontine angle: comparison of three-dimensional fast asymmetrical spin-echo and three-dimensional constructive interference in the steady-state sequences.
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BACKGROUND AND PURPOSE: MR cisternography has been used as the noninvasive screening tool of the cerebellopontine angle. The purpose of this study was to directly compare two currently dominant types of sequences for heavily T2-weighted MR cisternography. METHODS: Three-dimensional fast asymmetric spin-echo (3D-FASE) sequences, which are 3D half-Fourier rapid acquisition with relaxation enhancement and 3D constructive interference in the steady-state (3D-CISS) sequences, were compared on a clinical 1.5-T MR unit using the same scan times. In five healthy volunteers, the contrast-to-noise ratio (C/N) between CSF and the cerebellum was measured at three locations. Then, for qualitative analysis, the quality of the labyrinth was scored on the original source multiplanar reformatted images, the virtual endoscopic images, and the maximum intensity projection (MIP) images. In 20 consecutive patients with suspected cerebellopontine angle tumors, visualization of the tumors was evaluated using 3D contrast-enhanced spoiled gradient-echo imaging as the standard of reference. RESULTS: Both sequences showed comparable mean C/N values; however, in qualitative analysis, the scores for 3D-CISS on the source, virtual endoscopic, and MIP images were significantly lower than those on the images obtained with 3D-FASE, owing to more prominent flow and magnetic susceptibility artifacts on the 3D-CISS sequences. In all subjects, discontinuity of the semicircular canals was seen on the virtual endoscopic and MIP images obtained with 3D-CISS, owing to susceptibility artifacts, but not on those obtained with 3D-FASE. All 12 tumors were detected by both sequences, but 3D-CISS gave one false-positive result. CONCLUSION: 3D-FASE is considered the method of choice because artifacts are reduced and specificity is increased. (+info)
Persistence of perilymph fistula mechanism in a completely paretic posterior semicircular canal.
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The three dimensional eye movements (search coil technique) of a patient with a completely paretic left posterior semicircular canal as a result of a perilymph fistula (PLF) were studied. The patient still exhibited pressure induced nystagmus that obeyed Ewald's first law. This finding cannot be explained by otolith stimulation, but might indicate that PLF mechanisms either persist in canal plugging or act on the ampulla by directly deflecting the cupula. (+info)
Cochlear aqueduct flow resistance depends on round window membrane position in guinea pigs.
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The resistance for fluid flow of the cochlear aqueduct was measured in guinea pigs for different positions of the round window membrane. These different positions were obtained by applying different constant pressures to the middle ear cavity. Fluid flow through the aqueduct was induced by small pressure steps superimposed on these constant pressures. It was found that the resistance for fluid flow through the aqueduct depended on the round window position but not on flow direction. The results can be explained by special fibrous structures that connect the round window with the entrance of the aqueduct. It was also found that the equilibrium inner ear pressure depends on middle ear pressure, indicating that the aqueduct does not connect the inner ear with a cavity with constant pressure. (+info)
Therapeutic regulation of gene expression in the inner ear using RNA interference.
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An overview is provided of the structural and molecular events causing the transformation of undifferentiated epidermal cells together with the underlying mesenchyme to become the complex, three-dimensional ear. While tremendous progress has been achieved in a few model systems, enough is not yet known about the comparative embryology of ear development to provide causal explanations of the adult structural differences among species. It is hoped that the changes in selector and/or structural genes, as well as changes in the spatiotemporal induction of structural gene activation, and possible changes in the interaction between the various embryonic sources which contribute to the ear, will soon be understood. The most promising new avenue for research appears to be studies which combine classical transplantation tissue experiments with modern gene expression analyses and modern in vitro assays of the role of putative morphogens or trophic factors. It is emphasized that it is not understood what is missing in the developmental program of those salamanders which have lost a basilar papilla. Direct comparison of gene expression patterns and xenoplastic transplantations in salamanders of comparable stages which either do or do not develop this organ should help to clarify the molecular events that have led to this major evolutionary novel feature of the vertebrate ear. (+info)
Enlarged cochlear aqueduct.
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Enlargement of the cochlear aqueduct is a controversial topic, with experienced investigators doubting its existence because of a lack of published cases. We describe the CT appearance of an enlarged cochlear aqueduct in a patient with advanced congenital inner ear anomalies and congenital hearing loss. The intent of this article is to present the CT appearance of a presumably enlarged cochlear aqueduct and to underscore the need to examine this structure in patients with congenital hearing loss. (+info)
Sudden hearing loss: frequency of abnormal findings on contrast-enhanced MR studies.
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BACKGROUND AND PURPOSE: Our purpose was to determine the frequency of abnormal findings on contrast-enhanced high-resolution MR imaging studies in patients with sudden hearing loss. METHODS: Seventy-eight consecutive patients with sudden hearing loss underwent contrast-enhanced MR imaging of the temporal bone, cerebellopontine angle, and brain. Additional tests included audiologic examination, electrocochleography, fistula tests, and serologic tests for viral agents and autoimmune disorders. RESULTS: Probable causes of the sudden hearing loss in these patients included viral or immune-mediated disease, Meniere disease, vascular disorder, syphilis, neoplasm, multiple sclerosis, and perilymphatic fistula. Twenty-four (31%) of the 78 patients were found to have abnormal imaging results early in the course of their work up and treatment. CONCLUSION: The prevalence of abnormal findings on contrast-enhanced MR studies is higher than previously reported in patients with sudden hearing loss. (+info)