Biomedical subjects

Stephen O'Leary

Publications and source records attributed to Stephen O'Leary.

12 recordsLinked to original sources

PubMed2006

Optimising the incorporation and release of a neurotrophic factor using conducting polypyrrole.

In this study, a neurotrophin delivery system based on an inherently conducting polymer (ICP) has been developed. Direct incorporation of neurotrophin-3 (NT-3) was investigated and controlled release was tested under various electrochemical conditions. The loading capacity and amount of NT-3 released from the polymer was determined using (125)I-labelled NT-3. Electrochemical stimulation of polypyrrole by pulsed voltage, pulsed current or cyclic voltammetry promoted the release of NT-3 at a greater rate than natural diffusion of NT-3. NT-3 was released from polypyrrole as an initial burst in the first 24 h followed by prolonged release over a subsequent 6 days of sampling. The amount of NT-3 incorporated into the polymer could be controlled by varying the polymerisation time, with longer growth periods incorporating more NT-3. The NT-3 release results indicated that the polymers grown for longer released a lower percentage of the incorporated NT-3 compared to the polymers grown for shorter times. Polymer-based neurotrophin delivery systems have the potential to be incorporated into future treatments for nerve injuries to prevent nerve degradation and promote nerve protection.

Delayed-Action Preparations↗

PubMed2006

The effect of polypyrrole with incorporated neurotrophin-3 on the promotion of neurite outgrowth from auditory neurons.

This research aims to improve the nerve-electrode interface of the cochlear implant using polymer technology to encourage neuron survival, elongation and adhesion to the electrodes. Polypyrrole (Ppy) doped with p-toluene sulphonate (pTS) is an electroactive polymer into which neurotrophin-3 (NT3) can be incorporated. Ppy/pTS+/-NT3 was synthesised over gold electrodes and used as a surface for auditory neuron explant culture. Neurite outgrowth from explants grown on Ppy/pTS was equivalent to tissue culture plastic but improved with the incorporation of NT3 (Ppy/pTS/NT3). Electrical stimulation of Ppy/pTS/NT3 with a biphasic current pulse, as used in cochlear implants, significantly improved neurite outgrowth from explants. Using (125)I-NT3, it was shown that low levels of NT3 passively diffused from Ppy/pTS/NT3 during normal incubation and that electrical stimulation enhanced the release of biologically active NT3 in quantities adequate for neuron survival. Furthermore, Ppy/pTS/NT3 and its constituents were not toxic to auditory neurons and the Ppy/pTS/NT3 coating on gold electrodes did not alter impedance. If applied to the cochlear implant, Ppy/pTS/NT3 will provide a biocompatible, low-impedance substrate for storage and release of NT3 to help protect auditory neurons from degradation after sensorineural hearing loss and encourage neurite outgrowth towards the electrodes.

Animals↗

PubMed2006

Inner ear therapy for neural preservation.

A gradual loss of auditory neurons often occurs following sensorineural hearing loss. Since the cochlear implant must stimulate the remaining auditory neuron population, it would be beneficial to preserve as many auditory neurons as possible. Neurotrophic factors protect auditory neurons from degradation after sensorineural hearing loss in experimental animals, but have not yet been translated into the clinical setting. Current experimental and clinical techniques for drug delivery to the inner ear are examined in this review, covering the routes for drug delivery to the cochlea and the delivery systems used to introduce them. Duration of treatment, drug diffusion, effectiveness and safety are discussed with references to how they may be translated to the implementation of neurotrophic factor treatment for neural preservation.

Animals↗

PubMed2006

Presentation and management of aural foreign bodies in two Australian emergency departments.

OBJECTIVE: To survey and compare the type and management of foreign bodies found in adult and paediatric ears presenting to an Australian otorhinolaryngology and a general ED. METHODS: Retrospective case study with data collated from two centres. Chart reviews of a total of 330 patients presenting with aural foreign bodies to the ED of the Royal Victorian Eye and Ear Hospital and the ED of The Bendigo Hospital, both situated in the state of Victoria, Australia, were surveyed for patient demographics, foreign body description and referral and removal pattern. RESULTS: Two hundred and seventeen adults and 113 children were included in the study. The most common foreign bodies in children were beads, cotton tips, insects and paper, and in adults cotton tips, insects, cotton wool and silicone ear plugs. Flying insects were far more common in the Australian population than cockroaches found in surveys in other countries. Children were significantly more likely to have initially been seen by their Local Medical Officer than adults (P < 0.001) and to require a general anaesthetic for removal of the object(s) (P < 0.001). Adults were more likely to have associated otitis externa at the time of presentation (P < 0.05). CONCLUSIONS: Aural foreign bodies are a frequent presentation to the ED. Recognition of patients requiring early specialist referral is important. Adults present with a different profile of aural foreign objects to children and require different management. The use of cotton tips or cotton wool in the external ear canal and silicone ear plugs should be discouraged.

Adolescent↗

PubMed2005

A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support.

Degeneration of spiral ganglion neurons (SGNs) in the cochlea following sensorineural hearing loss is preventable by the infusion of neurotrophins into the scala tympani. This study investigates the trophic effects and distribution of a single bolus infusion of neurotrophin-3 (NT3) into the scala tympani of the cochlea. The left cochleae of 28-day deafened guinea pigs were infused with 0, 100 or 140 ng 125I NT3 via a cochleostomy in the scala tympani of the basal turn. Seven days post-infusion, cochlear sections were processed for measurements of trophic effects on SGNs and autoradiography. A single infusion of NT3 increased the soma size of SGNs in a dose-dependent and significant manner but did not contribute to SGN survival. Following infusion of 140 ng 125I NT3 into the cochlea, 0.31% of the total 125I NT3 signal in the basal turn was detected in Rosenthal's canal, 2.4% was in peripheral processes and 0.35% was in the modiolar auditory nerve. Despite influencing SGN soma size, 125I NT3 was not observed to accumulate in SGN cell bodies. The data suggest that only a small proportion of neurotrophins infused into the scala tympani diffuses to the SGNs and their processes and produces trophic effects on SGN cell bodies.

Animals↗

PubMed2005

Delivery of neurotrophin-3 to the cochlea using alginate beads.

OBJECTIVE: The aim of this study was to design a novel cochlear neurotrophin (NT) delivery system for the rescue of auditory neurons after ototoxicity-induced deafening. BACKGROUND: NT-3 is a trophic growth factor that promotes the survival of the auditory nerve and may have a potential therapeutic role in slowing neuron loss in progressive deafness, especially as an adjunct to the current cochlear implant. Beads made from alginate are biodegradable, slow release substances that can be placed at the round window or inside the cochlea. This study investigated the loading properties, release kinetics, and implantation potential of alginate beads loaded with NT-3. METHODS: Alginate beads were prepared using an ionic gelation technique and postloaded with NT-3. Release of NT-3 was measured using enzyme-linked immunosorbent assay over 5 days. Alginate beads were implanted into deafened guinea pigs for 28 days, after which survival of auditory neurons was assessed. RESULTS: Enzyme-linked immunosorbent assay studies demonstrated a 98% to 99% loading of NT-3 with a slow, partial release over 5 days in Ringer's solution. Furthermore, the addition of heparin to the delivery system modulated NT-3 release to a steadier pattern. Implantation of alginate-heparin beads in guinea pig cochleae produced minimal local tissue reaction. NT-3 loaded beads implanted at both the round window and within the scala tympani of the basal turn provided auditory neurons significant protection from degradation and apoptosis compared with unloaded beads or untreated cochleae. CONCLUSIONS: This study demonstrates alginate beads to be a safe, biodegradable and effective delivery system for NT-3 to the cochlea.

Alginates↗

PubMed2005

Postoperative bleeding after diathermy and dissection tonsillectomy.

OBJECTIVE: To analyze the incidence and pattern of bleeding after tonsillectomy performed by either cold dissection or diathermy. DESIGN: A prospective, nonrandomized cohort study of postoperative hemorrhage after tonsillectomy. METHODS: Monthly reporting of the number of tonsillectomies and postoperative bleeds from otolaryngologists working in rural areas of Victoria, Australia over a 2.5 year period. Criteria for bleeding were either 1) repeat anesthesia and surgery because of hemorrhage (including return to theater from the recovery room), or 2) readmission to hospital because of bleeding, or 3) blood transfusion to replace blood loss. Main outcome measures were the incidence, volume, and time course of postoperative hemorrhage. RESULTS: The number of bilateral tonsillectomies with removal by cold-blunt dissection was 3,087. In this group, there were 57 (1.85%) bleeds. The number of bilateral tonsillectomies with removal by diathermy dissection was 1,557. In this group, there were 37 (2.38%) bleeds. If cold dissection is taken as the "control" and diathermy tonsillectomy as the "treatment" group, the relative risk of bleeding after diathermy tonsillectomy is 1.30 (95% confidence interval 0.88-1.93). The pattern of bleeding after each technique differs significantly over time, with more reactionary bleeds in the dissection group and more bleeds between 4 to 7 postoperative days after diathermy. When bleeding occurred, it was in excess of 500 mL in 16% of dissection cases and 43% of diathermy tonsillectomies. CONCLUSIONS: The difference in the risk of bleeding after each technique did not reach statistical significance, but the temporal pattern of hemorrhage differed, and more bleeds exceeding 500 mL were seen in the diathermy group.

Adolescent↗

PubMed2005

A networked haptic virtual environment for teaching temporal bone surgery.

This paper describes a computer system for teaching temporal bone surgery using networked haptic work benches. The system enables an instructor and student to collaboratively explore and drill a volumetric bone model including significant anatomical features. Subjective evaluations by otologists have been favourable, and experimental trials are planned.

Australia↗

PubMed2004

Tracing neurotrophin-3 diffusion and uptake in the guinea pig cochlea.

Neurotrophin therapy in the cochlea can potentially slow or reverse the degeneration of the auditory nerve that occurs during progressive deafness. Studies were performed to trace the diffusion and uptake of neurotrophin-3 (NT-3) following infusion into the cochlea. NT-3 labeled with (125)I or coated onto fluorescent microspheres was introduced into the basal turn of normal hearing and deafened guinea pig cochleae via a single slow-rate injection. Cochleae were examined between 2 h and 28 days post-infusion by autoradiography or fluorescent microscopy to determine the number of turns labeled by NT-3, identify individual cells and tissues receiving NT-3 and quantify the proportion of signal in each tissue. In general, long-term infusions were required for all cochlear turns to receive NT-3. (125)I NT-3 signal was strongest in cells lining the perilymphatic space of the scala tympani, basilar membrane, osseous spiral lamina and spiral ligament. Signal in the peripheral nerve tract and Rosenthal's canal was only 1.3-2.1 times background levels of radiation. NT-3 microspheres were detected within neural areas of the cochlea (nerve tract and Rosenthal's canal) in all cases, but not within neuronal cell bodies. NT-3 microspheres remained in the cochlea for at least 28 days, suggesting a low clearance rate within cochlear tissues.

Analysis of Variance↗

PubMed2002

Randomized trial on the treatment of oedematous acute otitis externa using ear wicks or ribbon gauze: clinical outcome and cost.

Acute otitis externa is a common condition that can be extremely painful. When there is considerable canal oedema, packing is necessary to facilitate the passage of medication. The experience at the Royal Victoria Eye and Ear Hospital is that ear wicks generally require removal in two to three days by medical staff and can be labour intensive as they often involve serial removals following re-insertions. Alternatively, medicated ribbon gauze is cheap and can be removed by the patient at home. Ear wick and mediated ribbon gauze were investigated by a prospective randomized trial involving 94 patients. Fewer out-patient visits were required for the ribbon gauze group (two vs. three, p<0.0001) with considerably less material and labour costs than the wick group. Similar resolution rates were achieved (70 per cent vs. 64 per cent, p = 0.58). Following development of guidelines, the proportion of otitis externa patient reviews in the accident and emergency department declined from 49 per cent to 36 per cent. Compared with the ear wick, medicated ribbon gauze is a cost-effective method of treating oedematous acute otitis externa.

Acute Disease↗

PubMed2002

Revision surgery for chronic otitis media: recurrent-residual disease and hearing.

The aim of this study was to determine the effect of surgical approach, intact canal wall (ICW) or canal wall down (CWD), upon the success of revision surgery for chronic otitis media (COM). A retrospective analysis of 367 patients (including 65 children aged <15 years) who underwent revision tympanoplasty because of persistent disease was performed. Single-staged tympanoplasty was performed, preserving the canal wall when present. Hearing was reconstructed with allograft incus. Follow-up ranged from one to 15 years. Hearing was determined by pre- and post-operative air-bone gaps. Post-operative re-perforation, aural discharge and/or cholesteatoma rates were similar for CWD and ICW. Cholesteatoma could present following the revision, even though it was not apparent at surgery. Following tympanoplasty, the final hearing was not significantly affected by the surgical approach or presence of cholesteatoma. Improvement in hearing was adversely affected by cholesteatoma or an absent stapes suprastructure. Revision ICW and CWD operations were both successful in controlling signs of COM. Cholesteatoma is a peripheral risk in COM and may become apparent after revision surgery.

Adult↗

PubMedDate not supplied

Effects of insertion depth of cochlear implant electrodes upon speech perception.

OBJECTIVE: To investigate whether the insertion depth of a cochlear implant array affects postoperative speech perception. DESIGN: The subjects were 48 postlingually deaf adults who received either the Nucleus 22 or the Nucleus 24 cochlear implant with a straight array. A postoperative radiograph of the cochlear electrode was used to estimate insertion depth, as either the angle of the electrode tip (angle) or the intracochlear length of the electrode (length). Other estimates of insertion depth included the numbers of active electrodes and channels used by the speech processor. Electrode depth, together with the duration of deafness, hearing aid usage, pre-operative speech perception score and pre-operative pure-tone averages were independent variables in a forward stepwise multiple regression analysis, where the dependent variables were postoperative CNC words and CNC phonemes. RESULTS: Duration of deafness and insertion depth (angle, insertion length or active electrodes) were the predictive variables for CNC words or CNC phonemes. Angle was the best 'depth-related' predictor of postoperative speech perception. An even clearer relationship was found between CUNY sentences in noise and angle, in a subset of 26 patients. CONCLUSION: Depth of electrode insertion affects postoperative speech perception.

Adult↗