Graeme Clark Collection

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    Clinical findings for a group of infants and young children with auditory neuropathy
    RANCE, GARY ; Beer, David E. ; Cone-Wesson, Barbara ; Shepherd, Robert K. ; Dowell, Richard C. ; King, Alison M. ; Rickards, Field W. ; Clark, Graeme M. ( 1999)
    Objective: To examine the prevalence of auditory neuropathy in a group of infants at risk for hearing impairment and to present an overview of the clinical findings for affected children. Design: Results for 20 subjects who showed repeatable cochlear microphonic potentials in the absence of click-evoked auditory brain stem responses are included in this study. Behavioral and steady state evoked potential thresholds were established in each case. Where possible, otoacoustic emission and speech perception results (unaided and aided) also were obtained. Results: One in 433 (0.23%) of the children in our series had evidence of auditory neuropathy. The audiometric findings for these subjects varied significantly, with behavioural thresholds ranging from normal to profound levels. Discrimination skills were also variable. Approximately half of the subjects showed little understanding, or even awareness, of speech inputs in both the unaided and aided conditions. There were, however, a number of children who could score at significant levels on speech discrimination tasks and who benefited from the provision of amplification. Conclusion: The results suggest that auditory neuropathy is more common in the infant population than previously suspected. The effects of neuropathy on auditory function appear to be idiosyncratic, producing significant variations in both the detection and discrimination of auditory signals. As such, the management of children with this disorder must allow for individual differences.
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    Chronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli
    Shepherd, Robert K. ; Linahan, N. ; Xu, J. ; Clark, Graeme M. ; Araki, S. ( 1999)
    This study was designed to evaluate the pathophysiological response of the cochlea following long-term intracochlear electrical stimulation using a poorly charge-balanced stimulus regime, leading to direct current (DC) levels >0.1 µA. Four normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods up to 2200 h. Stimuli consisted of 50 µs monophasic current pulses presented at 2000 pulses per second (pps) per channel, and resulted in DC levels of 0.4-2.8 µA. Both acoustic and electrical (EABR) evoked potentials were periodically recorded during the stimulation program. Frequency-specific stimuli indicated that an extensive and widespread hearing loss occurred over the 4-24 KHz region in all stimulated cochleae, although the 2 KHz region exhibited thresholds close to normal in some animals, despite long-term implantation and chronic stimulation. Longitudinal EABRs showed a statistically significant increase in threshold for three of the four animals. Histopathological evaluation of the cochleae revealed a highly significant reduction in ganglion cell density in stimulated cochleae compared with their controls. Spiral ganglion cell loss was significantly correlated with the degree of inflammation, duration of electrical stimulation, and the level of DC. In conclusion, the present study highlights the potential for neural damage following stimulation using poorly charge-balanced stimuli.
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    Synergy between TGF-ß3 and NT-3 to promote the survival of spiral ganglia neurones in vitro
    Marzella, P. L. ; Clark, Graeme M. ; Shepherd, R. K. ; Bartlett, P. F. ; Kilpatrick, T. J. ( 1998)
    Transforming growth factor-βs (TGF-βs) have been implicated in normal inner ear development and in promoting neuronal survival. Early rat post-natal spiral ganglion cells (SGC) in dissociated cell culture were used as a model of auditory innervation to test the trophic factors TGF-βs and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings from this study suggest that TGF-βs supports neuronal survival in a concentration-dependent manner. Moreover TGF-βs and NT-3-potentiated spiral ganglion neuronal survival in a synergistic fashion.
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    Effects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens
    Araki, Susumu ; Kawano, Atsushi ; Seldon, H. Lee ; Shepherd, Robert K. ; Funasaka, Sotaro ; Clark, Graeme M. ( 1998)
    We have studied spiral ganglion cell (SGC) survival and soma size in neonatally pharmacologically deafened kittens. They were implanted with a four-electrode array in the left cochlea at 100 to 180 or more days of age. Eight animals were chronically stimulated approximately 1000 hours over approximately 60 days with charge-balanced, biphasic current pulses; three were unstimulated controls. Using three-dimensional computer-aided reconstruction of the cochlea, the SGC position and cross-sectional area were stored. SGC position was mapped to the organ of Corti by perpendicular projections, starting from the basal end. The basal region of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1 mm of the length of the organ of Corti) and soma size for stimulated cochleae were compared statistically with implanted but unstimulated cochleae. There was no evidence of an effect of electrical stimulation on SGC survival under this protocol and with this duration. On the other hand, the cell size on the stimulated side was significantly larger than the control side in the middle segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after prolonged auditory deprivation; however, these changes may be partially moderated after chronic intracochlear electrical stimulation.
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    Chronic electrical stimulation of the auditory nerve at high rates: I. Effect on residual hearing [Abstract]
    Xu, J. ; Shepherd, R. K. ; Clark, Graeme M. ( 1996)
    In addition to direct excitation of auditory nerve fibres, cochlear implant patients with small amounts of residual hearing may receive important additional auditory cues via electrophonic activation of hair cells 1. Before incorporating electrophonic hearing into speech processing strategies, the extent of hair cell survival following cochlear implantation must first be determined. We have recently demonstrated widespread survival of hair cells apical to electrode arrays implanted for periods of up to three years, the present report describes the effects of chronic electrical stimulation on hair cell survival.
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    Chronic electrical stimulation of the auditory nerve at high rates: II. Cochlear pathophysiology [Abstract]
    Shepherd, R. K. ; Xu, J. ; Clark, Graeme M. ( 1996)
    A major factor in the improved performance of cochlear implant patients has been the use of high stimulus rate speech processing strategies. While these strategies show clear clinical advantage, we know little of their long-term safety. Indeed, recent studies have indicated that high stimulus rates at intensities above clinical limits, can result in neural damage as a result of prolonged neuronal hyperactivity. The present study was designed to evaluate the effects of chronic electrical stimulation of the auditory nerve at high rates, using intensities within clinical limits.
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    Spatial representation of the cochlea within the inferior colliculus of neonatally deafened kittens following chronic electrical stimulation of the auditory nerve [Abstract]
    Shepherd, R. K. ; Martin, R. L. ; Brown, M. ; Clark, Graeme M. ( 1995)
    The orderly tonotopic representation of the cochlea is accurately reproduced within the central auditory system of normal hearing animals. Any degradation of this representation as a result of a neonatal hearing loss or chronic electrical stimulation during development could have important implications for the use of multichannel cochlear implants in young children. In the present study we have used 2-deoxyglucose autoradiography (2-00) to examine the topographic representation of the cochlea within the inferior colliculus (IC) of neonatally deafened kittens following periods of chronic intracochlear electrical stimulation.
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    Cochlear histopatholgic characteristics following long-term implantation: safety studies in the young monkey
    Burton, Martin J. ; Shepherd, Robert K. ; Clark, Graeme M. ( 1996)
    Objective: To evaluate the safety of cochlear implantation in children 2 years of age or younger using a non-human primate model.
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    Cochlear implants in children: the value of cochleostomy seals in the prevention of labyrinthitis following pneumococcal otitis media
    Dahm, M. C. ; Webb, R. L. ; Clark, Graeme M. ; Franz, B. K-H. ; Shepherd, R. K. ; Burton, M. J. ; ROBINS-BROWNE, R. ( 1995)
    Cochlea implantation at an early age is important in rehabilitating profoundly hearing impaired children. Given the incidence of pneumococcal otitis media in young children, there has been concern that cochlear implantation could increase the possibility of otitis media, leading to labyrinthitis in this age group. Clinical experience has not indicated an increase in the frequency of otitis media and labyrinthitis in implanted adults or children over two years. However, labyrinthitis has occurred in implanted animals with otitis media. In order to assess the impact of cochlear implants on the occurrence of labyrinthitis, pneumococcal otitis media was induced in 21 kittens. Thirty-two kitten cochleas were implanted, of which 9 had a fascial graft and 9 a Gelfoam® graft. Nine control cochleas were unimplanted. Labyrinthitis occurred in 44% of unimplanted controls. 50% of implanted ungrafted cochleas, and 6% of implanted grafted cochleas. There was no statistically significant difference between the incidence of labyrinthitis in the implanted cochleas and the unimplanted controls. However there was a statistically significant difference between the ungrafted and grafted cochleas, but not between the two types of graft.