Graeme Clark Collection

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    Can we prevent cochlear implant recipients from developing pneumococcal meningitis?
    Wei, BPC ; Robins-Browne, RM ; Shepherd, RK ; Clark, GM ; O'Leary, SJ (Oxford University Press (OUP), 2008-01-01)
    The restoration of hearing to persons with severely or profoundly impaired hearing by means of a cochlear implant is one of the great achievements of bionics applied to medicine. However, pneumococcal meningitis in implant recipients has received high profile public attention as a result of the US Food and Drug Administration's public health notification and recent media attention. Worldwide, 118 of the 60,000 people who received cochlear implants over the past 20 years have acquired meningitis, causing deep concern in the international medical community. This review provides answers to pediatricians, internists, and infectious diseases doctors who have patients with cochlear implants and who have questions about the safety of the cochlear implant from both the clinical and scientific research perspectives. Both clinical and laboratory research support the notion that pneumococcal meningitis is more likely in patients who receive cochlear implantation, and that the surgical insertion technique and the cochlear implant design should be nontraumatic, and that all cochlear implant recipients should be offered vaccination against Streptococcus pneumoniae.
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    Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes
    Evans, AJ ; Thompson, BC ; Wallace, GG ; Millard, R ; O'Leary, SJ ; Clark, GM ; Shepherd, RK ; Richardson, RT (WILEY, 2009-10)
    Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day SGN explant assay found that neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p < 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants.
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    Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons
    Richardson, RT ; Wise, AK ; Thompson, BC ; Flynn, BO ; Atkinson, PJ ; Fretwell, NJ ; Fallon, JB ; Wallace, GG ; Shepherd, RK ; Clark, GM ; O'Leary, SJ (ELSEVIER SCI LTD, 2009-05)
    Sensorineural hearing loss is associated with gradual degeneration of spiral ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use. Combination of neurotrophin delivery to the cochlea and electrical stimulation from a cochlear implant protects SGNs, prompting research into neurotrophin-eluting polymer electrode coatings. The electrically conducting polypyrrole/para-toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm2 cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3 and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via aminoglycosides. The electrodes of a subgroup of these guinea pigs were electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of electrode insertion damage. However, guinea pigs implanted with electrically stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory brainstem response thresholds and greater SGN densities in implanted cochleae compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS-coated electrodes (p<0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue formation and did not affect electrode impedance. Drug-eluting conducting polymer coatings on cochlear implant electrodes present a clinically viable method to promote preservation of SGNs without adversely affecting the function of the cochlear implant.
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    Comparison of electrode position in the human cochlea using various perimodiolar electrode arrays
    TYKOCINSKI, MICHAEL ; Cohen, Lawrence T. ; Pyman, Brian C. ; Roland (Jr), Thomas ; Treaba, Claudiu ; PALAMARA, JOSEPH ; Dahm, Markus C. ; Shepherd, Robert K. ; XU, JIN ; Cowan, Robert S. ; Cohen, Noel L. ; Clark, Graeme M. ( 2000)
    Objective: This study was conducted to evaluate the insertion properties and intracochlear trajectories of three perimodiolar electrode array designs and to compare these designs with the standard Cochlear /Melbourne array. Background: Advantages to be expected of a perimodiolar electrode array include both a reduction in stimulus thresholds and an increase in dynamic range, resulting in a more localized stimulation pattern of the spiral ganglion cells, reduced power consumption, and, therefore, longer speech processor battery life. Methods: The test arrays were implanted into human temporal bones. Image analysis was performed on a radiograph taken after the insertion. The cochleas were then histologically processed with the electrode array in situ, and the resulting sections were subsequently assessed for position of the electrode array as well as insertion-related intracochlear damage. Results: All perimodiolar electrode arrays were inserted deeper and showed trajectories that were generally closer to the modiolus compared with the standard electrode array. However, although the precurved array designs did not show significant insertion trauma, the method of insertion needed improvement. After insertion of the straight electrode array with positioner, signs of severe insertion trauma in the majority o fimplanted cochleas were found. Conclusions: Although it was possible to position the electrode arrays close to the modiolus, none of the three perimodiolar designs investigated fulfilled satisfactorily all three criteria of being easy, safe, and a traumatic to implant.