Graeme Clark Collection
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ItemNo Preview AvailableCan we prevent cochlear implant recipients from developing pneumococcal meningitis?(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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ItemPromoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes(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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ItemPneumococcal meningitis post-cochlear implantation: preventative measures.(Wiley, 2010-11)OBJECTIVE: Both clinical data and laboratory studies demonstrated the risk of pneumococcal meningitis post-cochlear implantation. This review examines strategies to prevent post-implant meningitis. DATA SOURCES: Medline/PubMed database; English articles after 1980. Search terms: cochlear implants, pneumococcus meningitis, streptococcus pneumonia, immunization, prevention. REVIEW METHODS: Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted. RESULTS: The presence of inner ear trauma as a result of surgical technique or cochlear implant electrode array design was associated with a higher risk of post-implant meningitis. Laboratory data demonstrated the effectiveness of pneumococcal vaccination in preventing meningitis induced via the hematogenous route of infection. Fibrous sealing around the electrode array at the cochleostomy site, and the use of antibiotic-coated electrode array reduced the risk of meningitis induced via an otogenic route. CONCLUSION: The recent scientific data support the U.S. Food and Drug Administration recommendation of pneumococcal vaccination for the prevention of meningitis in implant recipients. Nontraumatic cochlear implant design, surgical technique, and an adequate fibrous seal around the cochleostomy site further reduce the risk of meningitis.
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ItemPneumococcal meningitis post-cochlear implantation: potential routes of infection and pathophysiology.(Wiley, 2010-11)OBJECTIVE: This review describes the current concept of pneumococcal meningitis in cochlear implant recipients based on recent laboratory studies. It examines possible routes of Streptococcus pneumoniae infection to the meninges in cochlear implant recipients. It also provides insights into fundamental questions concerning the pathophysiology of pneumococcal meningitis in implant recipients. DATA SOURCES: Medline/PubMed database; English articles after 1960. Search terms: cochlear implants, meningitis, pneumococcus, streptococcus pneumonia. REVIEW METHODS: Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted. RESULTS: The incidence of pneumococcal meningitis in cochlear implant recipients is greater than that of an age-matched cohort in the general population. Based on the current clinical literature, it is difficult to determine whether cochlear implantation per se increases the risk of meningitis in subjects with no existing risk factors for acquiring the disease. As this question cannot be answered in humans, the study of implant-related infection must involve the use of laboratory animals in order for the research findings to be applicable to a clinical situation. The laboratory research demonstrated the routes of infection and the effects of the cochlear implant in lowering the threshold for pneumococcal meningitis. CONCLUSION: The laboratory data complement the existing clinical data on the risk of pneumococcal meningitis post-cochlear implantation.
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ItemNo Preview AvailablePolypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons(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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ItemThreshold shift: effects of cochlear implantation on the risk of pneumococcal meningitis( 2007)Unavailable due to copyright.
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ItemEffects of inner ear trauma on the risk of pneumococcal meningitis( 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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ItemAssessment of the protective effect of pneumococcal vaccination in preventing meningitis after cochlear implantation( 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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ItemProtective effects of local administration of ciprofloxacin on the risk of pneumococccal meningitis after cochlear implantation( 2006)Objectives: To determine whether ciprofloxacin retains its antimicrobial activity after storage with Healon at ambient temperature and at 37°C over 5 weeks and then to establish whether the application of ciprofloxacin/Healon onto scala tympani electrode arrays reduces the risk of meningitis in implanted rats inoculated with S. pneumoniae. Study Design: In vitro laboratory and in vivo animal studies Methods: The antibacterial activity of three concentrations of ciprofloxacin/Healon (7.5, 75, and 750 µg/mL) was examined over 5 weeks at both ambient temperature (23°C) and body temperature (37°C). Thirty-six rats (18 implanted with ciprofloxacin [750 mg/mL]/Healon-coated electrode array and 18 without the coating) were infected with S. pneumoniae 4 weeks after implantation by way of three different routes of infection (hematogenous, middle ear, and inner ear) and observed for the development of meningitis. Results: The antibacterial activity of ciprofloxacin/Healon was maintained over 5 weeks at both 23°C and 37°C. The implanted rats with the ciprofloxacin/Healon-coated electrode array were protected from meningitis when the bacteria were given by way of the hematogenous route (Fisher’s exact test, P = .008) but not when the bacteria were inoculated directly into the middle or inner ear. However, the time to develop meningitis was significantly longer in rats implanted with a coated array, irrespective of the route of inoculation (P < .05, log rank test). Conclusion: Our animal model demonstrated that a ciprofloxacin-coated electrode array can protect healthy implanted rats from meningitis when the route of infection is hematogenous and can delay the onset of meningitis when bacteria are inoculated directly into the middle or inner ear.
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ItemPneumococcal meningitis: development of a new animal model( 2006)Hypothesis: The rat is a suitable animal to establish a model for the study of pneumococcal meningitis postcochlear implantation. Background: There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis postimplantation and are based on relatively small animal numbers, making it difficult to assess the cause-and-effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant. Methods: Eighteen nonimplanted rats were infected with 1 x 10[to the power of 6] and 1 x 10[to the power of 8] colony-forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear, and i.p.) to examine for evidence of meningitis during 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 x 10[to the power of 10] CFU i.p., 3 x 10[to the power of 8] CFU middle ear, and I x 106 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. The histological pattern of cochlear infections for each of the three different inoculating routes were examined. Results: Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system via either the cochlear aqueduct or canaliculi perforantes of the osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent, and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal meningitis observed in 18 nonimplanted rats inoculated at a lower concentration of S. pneumoniae when observed for 24 hours postinoculation. Conclusion: Meningitis in implanted rats after inoculation with a clinical isolate of S. pneumoniae is possible via all three potential routes of infection via the upper respiratory tract. The lack of meningitis observed in the 18 nonimplanted rats suggests that longer postinoculation monitoring periods are required to ensure whether or not meningitis will develop. Based on this work, we have developed a new animal model that will allow quantitative risk assessment of meningitis postcochlear implantation, and the assessment of the efficacy of potential interventional strategies in future studies.