ABSTRACT
Current therapy for patients with hereditary absence of cochlear hair cells, who have severe or profound deafness, is restricted to cochlear implantation, a procedure that requires survival of the auditory nerve. Mouse mutations that serve as models for genetic deafness can be utilized for developing and enhancing therapies for hereditary deafness. A mouse with Pou4f3 loss of function has no hair cells and a subsequent, progressive degeneration of auditory neurons. Here we tested the influence of neurotrophin gene therapy on auditory nerve survival and peripheral sprouting in Pou4f3 mouse ears. BDNF gene transfer enhanced preservation of auditory neurons compared to control ears, in which nearly all neurons degenerated. Surviving neurons in treated ears exhibited pronounced sprouting of nerve fibers into the auditory epithelium, despite the absence of hair cells. This enhanced nerve survival and regenerative sprouting may improve the outcome of cochlear implant therapy in patients with hereditary deafness.
Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Deafness/therapy , Homeodomain Proteins/genetics , Transcription Factor Brn-3C/genetics , Adenoviridae/genetics , Animals , Brain-Derived Neurotrophic Factor/metabolism , Cell Survival , Cochlear Implantation , Cochlear Nerve/metabolism , Cochlear Nerve/pathology , Genetic Therapy , Homeodomain Proteins/metabolism , Mice , Mutation , Nerve Fibers/physiology , Spiral Ganglion/cytology , Spiral Ganglion/physiology , Transcription Factor Brn-3C/metabolismABSTRACT
OBJECTIVE: Research has found low concordance of personality disorder diagnoses made during depression versus after remission and made using patient versus collateral informants, but little is known about the reliability of personality disorder (PD) diagnoses made during depression using patient and collateral reports. METHOD: A total of 168 patients were evaluated for PDs during depression and following response using patient and close informant reports. kappa coefficients of inter-informant and test-retest reliability were calculated. RESULTS: After depression response, the proportion diagnosed with cluster A and C PDs fell by both patient and close informant report, and overall inter-informant reliability declined. Overall test-retest reliability did not differ between patients and informants. CONCLUSION: Collateral informants do not improve the reliability of PD diagnoses made during depressive episodes.