Mechanisms of aminoglycoside ototoxity in humans
thesisposted on 15.12.2014, 10:33 by S. A. Burr
Aminoglycoside ototoxcity is a common clinical problem. One patient group suitable for study are those with cystic fibrosis (CF).;The mechanistic approach adopted here has been to separate out differences in: auditory sensitivity (attributed to the whole auditory pathway and measured by pure tone audiometry); cochlear selectivity (attributed to inner and outer hair cells and measured by frequency resolution); and outer hair cells and measured by frequency resolution); and outer hair cell function (as measured by oto-acoustic emissions).;106 control subjects and 78 patients were tested. Over the range of ages investigated (from 10-37 years for most tests) there was only a correlation with age (p ,0.05) for high frequency pure tone thresholds at 10, 12, 14 and 16 kHz, and mean differences in frequency resolution at 4 and 8 kHz. There were numerous factors confounding the establishment of any dose-response relationship. In particular, there were found to be almost insurmountable problems associated with the retrospective calculation of patient aminoglycoside exposure. Nevertheless, 7.7 % of patients (control adjusted) did have high frequency sensorineural hearing loss that coincided in onset frequency with deficits in distortion-product oto-acoustic emissions. Also, aminoglycoside exposed patients as a group had significantly more saturating distortion-product input-output functions (p < 0.05). Surprisingly no more subtle changes were apparent. However, these physiological findings are still consistent with progressive damage affecting outer before inner hair cells. It would appear that most CF patients may be protected in some way, unless predisposed to ototoxicity by some additional risk factor(s).