Graeme Clark Collection

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    Effects of intracochlear factors on spiral ganglion cells and auditory brain stem response after long-term electrical stimulation in deafened kittens
    Araki, Susumu ; Kawano, Atsushi ; Seldon, H. Lee ; Shepherd, Robert K. ; Funasaka, Sotaro ; Clark, Graeme M. ( 2000)
    Using an animal model, we have studied the response of the auditory brain stem to cochlear implantation and the effect of intracochlear factors on this response. Neonatally, pharmacologically deafened cats (100 to more than 180 days old) were implanted with a 4-electrode array in both cochleas. Then, the left cochlea of each cat was electrically stimulated for total periods of up to 1000 hours. After a terminal 14C-2-deoxyglucose (2DG) experiment, the fraction of the right inferior colliculus with a significant accumulation of 2DG label was calculated. Using 3-dimensional computer-aided reconstruction, we examined the cochleas of these animals for spiral ganglion cell (SGC) survival and intracochlear factors such as electrode positions, degeneration of the organ of Corti, and the degree of fibrosis of the scala tympani. The distribution of each parameter was calculated along the organ of Corti from the basal end. There was a positive correlation between SGC survival and the level of fibrosis in the scala tympani, and a negative correlation between SGC survival and the degree of organ of Corti degeneration. Finally, there was a negative correlation between the 2DG-labeled inferior colliculus volume fraction and the degree of fibrosis, particularly in the 1-mm region nearest the pair of electrodes, and presumably in the basal turn.
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    Meningitis after cochlear implantation: the risk is low, and preventive measures can reduce this further
    Wei, Benjamin P. C. ; Clark, Graeme M. ; O'Leary, Stephen J. ; Shepherd, Robert K. ; Robins-Browne, Roy M. ( 2007)
    Since the 1980s, more than 80 000 people have received cochlear implants worldwide. These implants are designed to enable people who are severely or profoundly deaf to experience sound and speech. Since 1990, implantation has become standard treatment for people who cannot communicate effectively despite well fitted hearing aids. Children who are deaf when they are born can perceive sound and learn to speak if they receive cochlear implants at a young age (ideally under 18 months). The use of cochlear implants has been thought to be safe. But since 2002 the number of patients with meningitis related to cochlear implantation has increased worldwide. Mortality and neurological complications after meningitis are high. We need to investigate the reasons for this and look at measures to reduce them.
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    Threshold shift: effects of cochlear implantation on the risk of pneumococcal meningitis
    Wei, Benjamin P. C. ; Shepherd, Robert K. ; Robins-Browne, Roy M. ; Clark, Graeme M. ; O'Leary, Stephen J. ( 2007)
    Unavailable due to copyright.
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    Effects of inner ear trauma on the risk of pneumococcal meningitis
    Wei, Benjamin P. C. ; Shepherd, Robert K. ; Robins-Browne, Roy M. ; Clark, Graeme M. ; O'LEARY, STEPHEN ( 2007)
    Objective: To examine the risk of pneumococcal meningitis in healthy rats that received a severe surgical trauma to the modiolus and osseous spiral lamina or the standard insertion technique for acute cochlear implantation. Design: Interventional animal studies. Subjects: Fifty-four otologically normal adult Hooded- Wistar rats. Interventions: Fifty-four rats (18 of which received a cochleostomy alone; 18, a cochleostomy and acute cochlear implantation using standard surgical techniques; and 18, a cochleostomy followed by severe inner ear trauma) were infected 4 weeks after surgery with Streptococcus pneumoniae via 3 different routes (hematogenous, middle ear, and inner ear) to represent all potential routes of bacterial infection from the upper respiratory tract to the meninges in cochlear implant recipients with meningitis. Results: Severe trauma to the osseous spiral lamina and modiolus increased the risk of pneumococcal meningitis when the bacteria were given via the middle or inner ear (Fisher exact test, P<.05). However, the risk of meningitis did not change when the bacteria were given via the hematogenous route. Acute electrode insertion did not alter the risk of subsequent pneumococcal meningitis for any route of infection. Conclusions: Severe inner ear surgical trauma to the osseous spiral lamina and modiolus can increase the risk of pneumococcal meningitis. Therefore, every effort should be made to ensure that cochlear implant design and insertion technique cause minimal trauma to the bony structures of the inner ear to reduce the risk of pneumococcalmeningitis.
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    Assessment of the protective effect of pneumococcal vaccination in preventing meningitis after cochlear implantation
    Wei, Benjamin P. C. ; Robins-Browne, Roy M. ; Shepherd, Robert K. ; AZZOPARDI, KRISTY ; Clark, Graeme M. ; O'Leary, Stephen J. ( 2007)
    Objectives: To examine if a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) reduces the risk of meningitis in healthy rats after cochlear implantation. Design: Interventional animal study. Interventions: Thirty-six rats (18 immunized and 18 unimmunized) received cochlear implantations and were then infected with Streptococcus pneumoniae via 3 different routes (hematogenous, middle ear, and inner ear) in numbers sufficient to induce meningitis. Results: The rats with implants that received PPV23 were protected from meningitis when the bacteria were delivered via the hematogenous and middle-ear routes (Fisher exact test P<.05). However, the protective effect of the vaccine in the rats with implants was only moderate when the bacteria were inoculated directly into the inner ear. Conclusions: Our animal model clearly demonstrates that immunization can protect healthy rats with a cochlear implant from meningitis caused by a vaccine-covered serotype. This finding supports the notion that all current and future implant recipients should be vaccinated against S pneumoniae.
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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.