Graeme Clark Collection
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ItemPartial hearing loss in the macaque following the co-administration of kanamycin and ethacrynic acid( 1994)Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) rapidly produces a profound hearing loss in the cat while maintaining normal renal function [Xu et al., Hear. Res. 70, 205-215 (1993)]. In the present paper we have applied this deafening procedure to the old world monkey Macaca fascicularis (macaque). Following the co-administration of KA and EA, the hearing loss in the macaque developed far slower than we observed in the cat. Moreover, unlike the cat, there was evidence of a partial recovery in the animal’s hearing, resulting in a bilaterally symmetrical high frequency hearing loss. The extent of this hearing loss was dependent on the dose of the EA administered. Finally, the most unexpected result of the present study was the degree of acute nephrotoxicity experienced by these animals following the drug administration. The sensitivity of this species to renal failure restricted the dose of EA that could be safely administered. In conclusion, the co-administration of KA and EA cannot reliably produce a profound hearing loss in the macaque. While it can produce a dose dependent high frequency hearing loss the animal will also experience acute renal failure that requires careful management.
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ItemProfound hearing loss in the cat following the single co-administration of kanamycin and ethacrynic acid( 1993)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.
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ItemTinnitus management in the profoundly and totally deaf( 1993)Tinnitus is a common symptom of many cochlear or auditory system pathologies. Since tinnitus is frequently associated with a sensorineural hearing loss, it is not surprising that a large proportion of profoundly and totally deaf patients describe tinnitus as a symptom. The clinical management of severe tinnitus in these patients is discussed with particular emphasis on the use of electrical stimulation. While cochlear implants appear to provide a measure of relief when being used, significant improvements in the management of severe tinnitus will only occur when we have a greater understanding of the underlying pathophysiology, diagnostic procedures that can accurately establish the site of tinnitus generation, and more objective clinical trial procedures that include the use of controls.
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ItemProgressive ototoxicity of neomycin monitored using derived brainstem response audiometry( 1985)Progressive hearing loss following the systemic administration of neomycin was investigated using derived brainstem response audiometry. Cats were given three to five times the maximum recommended clinical dose of neomycin over a period of 10 days. Their hearing was monitored prior to and during the administration of the drug, and periodically following its completion. The results of this study showed that the induced hearing loss generally proceeded from high to low frequencies as an advancing lesion, with regions apical to the lesion functioning normally. Although considerable variability in response to the drug existed among animals, the evoked responses from both ears of each animal showed close bilateral symmetry during the deafening process. Futhermore, the present results highlight the long-term ongoing ototoxicity associated with neomycin, and the importance of monitoring high frequencies for initial signs of an aminoglycoside induced hearing loss.
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ItemRapid and permanent hearing loss in cats following co-administration of kanamycin and ethacrynic acid [Abstract]( 1990)A safe, simple and effective technique for producing profound-totally deaf animal models in both young and adult cats is required for auditory prosthesis related research. Exposure to loud noises can result in a partial hearing loss, the degree of which varies significantly among animals. Long-term systemic injection of an aminoglycoside ototoxic drug frequently results in renal dysfunction and can show significant variation in response among animals (Shepherd & Clark, 1985). Finally, direct infusion of ototoxic drugs produces extensive and highly variable cochlear pathology, unsuitable for auditory prosthesis research.