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Biomedical subjects

R K Shepherd

Publications and source records attributed to R K Shepherd.

At least 73 records · Page 4Linked to original sources
PubMed1993

Profound hearing loss in the cat following the single co-administration of kanamycin and ethacrynic acid.

Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) has previously been shown to produce a rapid and profound hearing loss in guinea pigs. In the present study we describe a modified technique for developing a profound hearing loss in cats. By monitoring the animal's hearing status during the intravenous infusion of EA the technique minimizes the effects of individual variability to the drug regime. Seven cats received a subcutaneous injection of KA (300 mg/kg) followed by intravenous infusion of EA (1 mg/min). Click-evoked auditory brainstem responses (ABRs) were recorded to monitor the animal's hearing during the infusion. When the ABR thresholds rose rapidly to levels in excess of 90 dB SPL the infusion of EA was stopped. This occurred at EA doses of 10-25 mg/kg, indicating considerable individual variability to the deafening procedure. However, there was a strong negative correlation (r = -0.93) between the EA dose and body weight which accounted for much of this variability. Subsequent ABR monitoring showed that this profound hearing loss was both bilateral and permanent. Significantly, blood urea and creatinine levels, monitored for periods of up to three days after the procedure, remained within the normal range. Furthermore, there was no clinical evidence of renal dysfunction as indicated by weight loss or oliguria. Cochlear histopathology, examined after a two months to three year survival period, showed an absence of all inner and outer hair cells in the majority of cochleas. The extent of loss of spiral ganglion cells was dependent on their distance from the round window and the period of survival following the deafening procedure. Clearly, the degeneration of spiral ganglion cells continued for several years following the initial insult. Finally, we observed no evidence of renal histopathology. In conclusion, the co-administration of KA and EA produces a profound hearing loss in cats without evidence of renal impairment. Monitoring the animal's hearing status during the procedure ensures that the dose of EA can be optimised for individual animals. Moreover, it may be possible to adapt this procedure to produce animal models with controlled high frequency hearing losses.

Animals↗
PubMed1993

Electrical stimulation of the auditory nerve: the effect of electrode position on neural excitation.

Histological studies have shown that the Melbourne/Cochlear electrode array lies along the outer wall of the scala tympani and is therefore some distance from the residual VIIIth nerve elements. In order to investigate the influence of electrode position on neural excitation we systematically varied the position of the electrode array within the cat scala tympani while recording electrically evoked auditory brainstem responses (EABRs). Using both normal hearing and long-term deafened animals, we observed significant reductions in EABR thresholds as the electrode array was moved from the outer wall towards the modiolus. Further threshold reductions were observed when the array was placed underneath the osseous spiral lamina (OSL) close to the peripheral dendrites. These changes were independent of the bipolar inter-electrode separation, and were observed over a wide range of cochlear pathologies varying from normal to a moderate spiral ganglion cell loss. Interestingly, the one animal exhibiting extensive neural loss showed no correlation between EABR threshold and electrode position. There was also a general decrease in the gradient of the EABR input-output function as the electrode array was moved closer to the neural elements. This was, however, only statistically significant when the electrode was positioned adjacent to the peripheral dendrites. Significant reductions in EABR threshold were also observed as the inter-electrode spacing of the bipolar electrodes was increased. The gradient of the EABR input-output function also increased with increasing inter-electrode spacing, although again, this was only significant when the electrode array was positioned close to the neural elements. The present results indicate that the optimum placement of a Melbourne/Cochlear electrode array is adjacent to the peripheral dendrites. However, such a site would be difficult to achieve in practice while minimizing insertion trauma. An array lying adjacent to the modiolus would be a safe alternative while ensuring a significant reduction in threshold compared with the existing site (outer wall). This placement should result in more localized neural excitation patterns, an increase in the number of bipolar electrodes available, together with an increase in their dynamic range. These changes may lead to further improvements in speech perception among cochlear implant patients.

Animals↗
PubMed1993

Effect of chronic electrical stimulation on cochlear nucleus neuron size in normal hearing kittens.

Very young cochlear-implant candidates may have undetected islands of residual hearing. Would the maturation of these functioning auditory neurons be affected by chronic cochlear stimulation? This was tested by examining neuron sizes in the cochlear nuclei of young, normal hearing kittens with and without chronic cochlear stimulation. Six animals received bilateral intra- or extracochlear implants and were electrically stimulated unilaterally for periods of 1,000-1,500 hours. After sacrifice, cross-sectional areas of approximately 11,000 neurons somata in the cochlear nuclei were measured with an image-analysis system. There were statistically significant differences between stimulated and unstimulated nuclei, especially the posteroventral cochlear nucleus (PVCN), in individual cats, but the directions of the differences were inconsistent. Overall, there was no significant effect of electrical stimulation on soma size. These results indicate that chronic electrical stimulation of the auditory nerve has no positive or negative trophic effects on otherwise innervated, maturing cochlear nucleus neurons.

Animals↗
PubMed1993

The postnatal growth of the temporal bone and its implications for cochlear implantation in children.

The postnatal growth of the human temporal bone was examined by direct anatomical measurements on 60 cadaver specimens of all ages. The bones were dissected as one would perform cochlear implant surgery using a posterior tympanotomy approach. Nineteen anatomical/surgical landmarks with implications for cochlear implant surgery were identified on each bone and the distance between these points measured. The temporal bone was found to be a complex structure, phylogenetically, anatomically and functionally consisting of four different parts with independent postnatal development. The inner and middle ears were adult size at birth. The external auditory canal and most parts of the temporal bone were subject to significant lateral growth. The size of the pneumatised mastoid increased in all directions. In the facial recess, however, no postnatal growth was observed. Between birth and adulthood an average of 12 mm (SD 5 mm) of growth was seen directly between the sino-dural angle and the round window, the landmarks approximating the implantation site for the receiver-stimulator and the electrode entry point into the inner ear. However, if an electrode leadwire is fixed at a cortical fixation site such as the posterosuperior point of Macewen's triangle, the leadwire would be subject to approximately 20 mm of growth. These results indicate that a paediatric cochlear implant design incorporating an expandable leadwire to accommodate this growth should allow up to 25 mm of leadwire lengthening. The fossa incudis showed no growth relative to the round window and was found to be a convenient fixation site for the electrode array close to the cochlea. From an anatomical and surgical point of view, cochlear implantation in very young children is feasible, provided the electrode array is secured and the design accommodates for controlled leadwire lengthening.

Adolescent↗
PubMed1993

Evaluation of expandable leadwires for pediatric cochlear implants.

The development of cochlear implants for use in very young children (1-2 years old) will require techniques designed to accommodate temporal bone growth. Previous anatomic studies have shown that the leadwire of a cochlear implant must be capable of expanding up to 20 mm between the round window and the implanted receiver-stimulator in response to skull growth. In the present study morphologic and biomechanical evaluation of five expandable leadwire designs was conducted following their implantation in young cats. Two helical shaped leadwire designs frequently exhibited extensive fibrous tissue adhesions and broke during long-term implantation. In contrast, thin, flexible Silastic envelopes were effective in minimizing tissue adhesions. Residual V- and Z-shaped leadwires, placed in these envelopes, showed little evidence of fibrous tissue adhesions following implantation periods of up to 2 years. Moreover, these leadwires readily expanded both during the growth of the animal and when biomechanical expansion studies performed at the completion of the implant period. These expandable leadwire designs appear to be appropriate candidates for use in pediatric cochlear implants.

Animals↗
PubMed1992

Cochleotopic selectivity of a multichannel scala tympani electrode array using the 2-deoxyglucose technique.

The 2-deoxyglucose (2-DG) technique was used to study the cochleotopic selectivity of a multichannel scala tympani electrode array in four cats with another acting as an unstimulated control. Each animal was unilaterally deafened and a multichannel electrode array inserted 6 mm into the scala tympani. Thresholds to electrical stimulation were determined by recording electrically evoked auditory brainstem responses (EABRs). Each animal was injected with 2-DG, and electrically stimulated using bipolar electrodes located either distal or proximal to the round window. The contralateral ear was stimulated with acoustic tone pips at frequencies that matched the electrode place. Stimulation of both distal and proximal bipolar electrodes at 3 x EABR threshold, evoked localized 2-DG labelling in both ipsilateral cochlear nucleus (CN) and the contralateral inferior colliculus (IC), which was very similar in orientation and breadth to labelling evoked by the contralateral tone pips. The cochleotopic position of labelling to proximal stimulation was located in the 24-26 kHz region of each structure, whereas the distal labelling was located around 12 kHz. Distal stimulation at 10 x EABR threshold produced very broad 2-DG labelling in IC centered around the 12 kHz place. The present 2-DG results clearly illustrate cochleotopic selectivity using multichannel bipolar scala tympani electrodes. The extent of this selectivity is dependent on electrical stimulus levels. The 2-DG technique has great potential in evaluating the efficacy of new electrode array designs.

Acoustic Stimulation↗
PubMed1992

Cochlear pathology following chronic electrical stimulation of the auditory nerve. I: Normal hearing kittens.

The present study examines the histopathological effects of long-term intracochlear electrical stimulation in young normal hearing animals. Eight-week old kittens were implanted with scala tympani electrode arrays and stimulated for periods of up to 1500 h using charge balanced biphasic current pulses at charge densities in the range 21-52 microC cm-2 geom. per phase. Both click and electrically evoked auditory brainstem responses were periodically recorded to monitor the status of the hair cell and spiral ganglion cell populations. In addition, the impedance of the stimulating electrodes was measured daily to monitor their electrical characteristics during chronic implantation. Histopathological examination of the cochleas showed no evidence of stimulus induced damage to cochlear structures when compared with implanted, unstimulated control cochleas. Indeed, there was no statistically significant difference in the ganglion cell density adjacent to the stimulating electrodes when compared with a similar population in implanted control cochleas. In addition, hair cell loss, which was restricted to regions adjacent to the electrode array, was not influenced by the degree of electrical stimulation. These histopathological findings were consistent with the evoked potential recordings. Finally, electrode impedance data correlated well with the degree of tissue growth observed within the scala tympani. The present findings indicate that the young mammalian cochlea is no more susceptible to cochlear pathology following chronic implantation and electrical stimulation than is the adult.

Animals↗
PubMed1991

Scanning electron microscopy of platinum scala tympani electrodes following chronic stimulation in patients.

Platinum (Pt) electrodes from three auditory prostheses (Cochlear Pty Ltd) were examined for evidence of corrosion following implantation periods of up to 1000 days. These devices were used for periods ranging from 1600 to 10,400 h and developed maximum charge densities of 0.257 microC mm-2 geom. per phase. Scanning electron microscopy of the surface of the 66 stimulated electrodes examined showed no evidence of definitive Pt corrosion. Their surface features were essentially identical to control (unstimulated) electrodes. In addition, there was no evidence of any change in the surface morphology of the Silastic carrier adjacent to the stimulating electrodes. These results indicate that Pt is a suitable electrode material for neural prostheses that use relatively large surface area electrodes (0.1-1.0 mm2) and low to moderate charge densities (0.01-0.26 microC mm-2 geom. per phase).

Biocompatible Materials↗
PubMed1991

Electrical stimulation of the auditory nerve in deaf kittens: effects on cochlear nucleus morphology.

The present study examines the effects of long-term electrical stimulation of the auditory nerve on the morphology of neurons in the cochlear nucleus in young, sensorineural deaf animals. Kittens, systemically deafened using kanamycin and ethacrynic acid, received bilateral cochlear implants and were stimulated unilaterally for periods of up to four months. After sacrifice, cross-sectional areas of neuron somata were measured with an image-analysis system and compared using nonparametric statistics. The areas of cell somata within the anteroventral cochlear nucleus (AVCN) on the stimulated side were significantly larger than those of corresponding somata on the control, unstimulated side (P less than 0.001). However, there was no statistically significant difference among dorsal cochlear nucleus (DCN) neurons. These results indicate that long-term electrical stimulation of the auditory nerve can at least partially negate some effects of early postnatal auditory deprivation at the level of the cochlear nucleus.

Animals↗
PubMed1991

Cochlear pathology following chronic electrical stimulation using non charge balanced stimuli.

During the course of a chronic intracochlear electrical stimulation study using charge balanced biphasic current pulses, one animal inadvertently received a short period of direct current (DC) stimulation at a level of approximately 1 microA. Subsequent, the animal was chronically stimulated using a poorly charge balanced waveform that produced a DC level of approximately 2 microA. Extensive pathological changes were observed within the cochlea. These changes included widespread spiral ganglion cell loss and new bone growth that extended throughout all turns of the cochlea. Significant changes in the morphology of the electrically evoked auditory brainstem response (EABR) were associated with these pathological changes. EABRs recorded prior to the DC stimulation exhibited a normal waveform morphology. However, responses recorded during the course of the DC stimulation were dominated by a short latency response believed to be vestibular in origin. The response thresholds were also significantly higher than levels recorded before the DC stimulation. In contrast, the contralateral cochlea, stimulated using charge balanced stimuli, showed no evidence of adverse pathological changes. Furthermore, EABRs evoked from this cochlea remained stable throughout the chronic stimulation period. Although preliminary, the present results illustrate the adverse nature of poorly charge balanced electrical stimuli. These results have important implications for both the design of neural prostheses and the use of DC stimuli to suppress tinnitus in patients.

Animals↗
PubMed1991

Multichannel cochlear implantation in children: a summary of current work at the University of Melbourne.

This paper summarizes research work relating to multichannel cochlear implantation in children at the University of Melbourne. Ongoing safety studies relating to the implantation of young children are discussed. Results of these studies suggest that special design considerations are necessary for a prosthesis to be implanted in children under the age of 2 years. Results of clinical assessment of implanted children and adolescents are also discussed in terms of speech perception, speech production, and language development, and some possible predictive factors are suggested. Preliminary data suggests that a high proportion of young children can achieve open-set speech perception with the cochlear implant given appropriate training and support. Initial results with adults using new speech processing hardware and a new coding scheme are also presented. These suggest that improved speech perception in quiet and competing noise is possible with the new system.

Adolescent↗
PubMed1990

Dimensions of the scala tympani in the human and cat with reference to cochlear implants.

The width, height, and cross-sectional area of the scala tympani in both the human and cat were measured to provide dimensional information relevant to the design of scala tympani electrode arrays. Both the height and width of the human scala tympani decreased rapidly within the first 1.5 mm from the round window. Thereafter, they exhibit a gradual reduction in their dimension with increasing distance from the round window. The cross-sectional area of the human scala tympani reflects the changes observed in both the height and width. In contrast, the cat scala tympani exhibits a rapid decrease in its dimensions over the first 6 to 8 mm from the round window. However, beyond this point the cat scala tympani also exhibits a more gradual decrease in its dimensions. Finally, the width of the scala tympani, in both human and cat, is consistently greater than the height.

Anatomy, Comparative↗
PubMed1989

A farming systems study of abortion in dairy cattle on the Atherton Tableland. 3. Metabolic factors.

An association with a rank correlation of 0.55 (p = 0.06) was obtained between monthly rainfall and monthly abortions for a group of 24 farms in tropical Australia where cows grazed predominantly summer rain-dependent pasture. A similar association was found among cows grazing nitrogen-fertilised, irrigated pasture in winter in the same area. On farms with irrigated pasture the first service conception and abortion rates in herds which grazed intensively during the night (abortion 8.9%; first service conception 42.9%) differed significantly from those which grazed during the day (abortion 6.4%; first service conception 52.9%), and this suggested that increased abortion rates and decreased first conception rates may be part of the one syndrome. An hypothesis was developed that the feeding of immature nitrogen-fertilised pasture, rich in protein and stimulated by rain or irrigation, is associated with an increased abortion rate and a depressed conception rate. Other evidence included an increased susceptibility of first lactation cows to abortion, a lower abortion rate in late pregnant dry cows fed more mature pasture, a 20% repeat abortion rate in the population sampled and the lack of conclusive evidence for infectious and selected non-infectious agents. There were no other observed clinical signs in most aborting cows.

Abortion, Veterinary↗
PubMed1989

An evaluation of calf castration by intra-testicular injection of a lactic acid solution.

This experiment evaluated intra-testicular injection of a sclerosing drug, lactic acid, for castration of bulls. Its use was compared in 58 Brahman cross calves (50 to 128kg) with the general practice of open surgical castration. Chemical castration appeared to be more painful than surgical castration, though post-operative swelling and pain appeared similar for both methods. Chemical castration took 3 times longer than surgical castration (58 sec v 20 sec; P less than 0.01). Scrotal necrosis occurred in 25% of chemically-castrated calves and appeared due to drug leakage from the testes under the high pressure of injection. Healing time for chemical castrates was approximately twice that for surgical castrates. Five chemically-castrated calves (18%) retained one testis. Though all 5 were rendered sterile, each maintained androgenesis. This led to secondary male behaviour which caused management problems. Castration method did not influence post-operative growth. It is concluded that lactic acid administration is not a suitable alternative to the open surgical technique for castration of Brahman cross calves.

Animals↗
PubMed1988

The biologic safety of the Cochlear Corporation multiple-electrode intracochlear implant.

Studies have been undertaken to confirm the biologic safety of the Cochlear Corporation multi-electrode intracochlear implant. The materials used are biocompatible. The electrode array is flexible: it can be inserted with minimal or no trauma, providing the insertion is stopped when resistance is first felt. An atraumatic insertion is facilitated if a good view is obtained along the scala tympani of the basal turn of the cochlea by drilling through the crista fenestrae. The passage of the electrode around the cochlea can be facilitated if the electrode is rotated during insertion (clockwise for the left and anticlockwise for the right cochlea). The electrode can be explanted and another one reinserted with minimal or no trauma. A seal established around the electrode after an implantation period of 2 weeks can prevent infection extending from the middle to the inner ear. The electrical stimulus parameters produced by the Nucleus receiver-stimulator cause no loss of spiral ganglion cells or corrosion of the platinum band electrodes. Long-term stimulation has been carried out for up to 8 years in patients without affecting their clinical performance.

Animals↗