PubMed Health⌕ Search

Biomedical subjects

Stephen J O'Leary

Publications and source records attributed to Stephen J O'Leary.

7 recordsLinked to original sources

Pneumococcal meningitis threshold model: A potential tool to assess infectious risk of new or existing inner ear surgical interventions.

HYPOTHESIS: A minimal threshold of Streptococcus pneumoniae is required to induce meningitis in healthy animals for intraperitoneal (hematogenous), middle ear, and inner ear inoculations, and this threshold may be altered via recent inner ear surgery. BACKGROUND: There has been an increase in the number of reported cases of cochlear implant-related pneumococcal meningitis since 2002. The pathogenesis of pneumococcal meningitis is complex and not completely understood. The bacteria can reach the central nervous system (CNS) from the upper respiratory tract mucosa via either hematogenous route or via the inner ear. The establishment of a threshold model for all potential routes of infection to the CNS in animals without cochlear implantation is an important first step to help us understand the pathogenesis of the disease in animals with cochlear implantation. METHODS: Fifty-four otologically normal adult Hooded Wistar rats (27 receiving cochleostomy and 27 controls) were inoculated with different amounts of bacterial counts via three different routes (intraperitoneal, middle ear, and inner ear). Rats were monitored during 5 days for signs of meningitis. Blood, cerebrospinal fluid, and middle ear swabs were taken for bacterial culture, and brains and cochleae were examined for signs of infection. RESULTS: The threshold of bacterial counts required to induce meningitis is lowest in rats receiving direct inner ear inoculation compared with both intraperitoneal and middle ear inoculation. There is no change in threshold between the group of rats with cochleostomy and the control (Fisher's exact test, p < 0.05). CONCLUSION: A minimal threshold of bacteria is required to induce meningitis in healthy animals and is different for three different routes of infection (intraperitoneal, middle ear, and inner ear). Cochleostomy performed 4 weeks before the inoculation did not reduce the threshold of bacteria required for meningitis in all three infectious routes. This threshold model will also serve as a valuable tool, assisting clinicians to quantitatively analyze if the presence of a cochlear implant or other CNS prostheses alter the risk of meningitis.

Animals↗

Cochlear implant and vestibular function.

OBJECTIVES: To document incidences of vestibular dysfunction after cochlear implantation and investigate why it occurs. This work was also motivated by a desire to provide the basis for better preoperative counseling and postoperative vestibular therapy to cochlear implant patients. SETTING: Melbourne Cochlear Implant Clinic at a tertiary referral hospital. STUDY DESIGN: Prospective observational study. PATIENTS: One hundred forty-six adult implant recipients, mean age, 60 years (range, 20-90 yr). MAIN OUTCOME MEASURES: Postoperative vestibular disturbance was defined as symptoms lasting for 1 week or longer after surgery. The differences in preoperative and postoperative vestibular function were measured from subjective assessments (Dizziness Handicap Inventory and Activity Balance Confidence questionnaires) and objective assessments (bithermal caloric tests). The position of the postoperative electrode was classified as "loose", "regular", or "tight" fitting. RESULTS: Thirty-two percent of patients reported vestibular disturbance and had poorer Dizziness Handicap Inventory, Activity Balance Confidence, and caloric results in the implanted ear after surgery. Patient age, cause, and preoperative caloric result did not predict postoperative vestibular symptoms. Recipients aged 70 years or older had significantly poorer caloric results on the implanted side after surgery that was not related to the intracochlear electrode position or surgical team. CONCLUSION: One-third of recipients can expect to experience a significant vestibular disturbance after surgery, regardless of age, cause, or preoperative caloric result. "Older" ears seem more prone to permanent injury after cochlear implantation.

Adult↗

Pneumococcal meningitis: development of a new animal model.

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 and 1 x 10 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 CFU i.p., 3 x 10 CFU middle ear, and 1 x 10 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.

Animals↗

Protective effects of local administration of ciprofloxacin on the risk of pneumococcal meningitis after cochlear implantation.

OBJECTIVES: To determine whether ciprofloxacin retains its antimicrobial activity after storage with Healon at ambient temperature and at 37 degrees 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 microg/mL) was examined over 5 weeks at both ambient temperature (23 degrees C) and body temperature (37 degrees 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 degrees C and 37 degrees 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.

Adjuvants, Immunologic↗

Partial recovery of cisplatin-induced hearing loss in the albino guinea pig in relation to cisplatin dose.

The objective of the present study was to further characterize cochlear recovery after cisplatin damage. We equipped albino guinea pigs with permanent round window electrodes. Cisplatin was injected i.p. on a daily basis at either 1.5 or 2.0 mg/kg/day. Treatment was stopped when the criterion of > or =40 dB loss in the compound action potential iso-response level at 8 kHz had occurred. Either shortly (1-3 days) or long (4 weeks or more) after this stop, the endocochlear potential (EP) was measured and all animals were sacrificed for histology. At a cisplatin dose of 2.0 mg/kg/day, the time needed to reach the criterion hearing loss varied from 5 to 11 days. With 1.5 mg/kg/day this period lasted longer, the cumulative dose being the first-order predictor. The cochlear potentials gradually recovered in the first 2 weeks after treatment. At the lower frequencies, recovery was often complete. At the higher frequencies complete recovery was never seen. EP was depressed when measured just after treatment but had normal values long after. Basal outer hair cell (OHC) loss was found for both the short and the long post-treatment period. Thus, loss and recovery of cochlear potentials can for a large part be explained by loss and recovery of the EP. Recovery is limited by permanent OHC loss.

Action Potentials↗

Recovery of hearing following cisplatin ototoxicity in the guinea pig.

BACKGROUND: To report a spontaneous recovery of hearing, following cisplatin ototoxicity in the guinea pig. The findings are related to the animal and human literature on recovery from hearing loss following cisplatin ototoxicity. MATERIALS AND METHODS: Hearing was measured from compound action potentials (CAP) evoked by acoustic tones, which were monitored daily from an electrode implanted onto the round window of the inner ear. Cisplatin was administered at 2 mg/kg/day intraperitoneally until a hearing loss occurred. RESULTS: A hearing loss occurred suddenly across the frequency range and recovered over the period 2-14 days after treatment. The endocochlear potential was significantly lower than normal before hearing recovery and normal following recovery. CONCLUSION: These findings suggest a pivotal role for the endocochlear potential in the hearing loss from cisplatin ototoxicity and its recovery, and a plausible mechanism for the hearing recovery sometimes reported in patients following cisplatin ototoxicity.

Animals↗

A post-traumatic nasal epidermoid: an endoscopic approach.

BACKGROUND: Epidermoid cysts are thought to arise as a result of implantation of epidermal cells into the deeper dermal elements. These cysts have previously been described postsurgery but not after accidental nasal trauma. METHODS: We outline a case of a nasal epidermoid occurring post-blunt nasal trauma and its subsequent excision. RESULTS: The lesion was excised successfully endoscopically without recourse to an open technique. CONCLUSION: We describe, for the first time, the successful intranasal removal of a post-traumatic epidermoid cyst via an endoscopic approach.

Adolescent↗