Recent references related to Ototoxicity

Runge CF, Shupert CL, Horak FB, Zajac FE. Role of vestibular information in initiation of rapid postural responses. EBR 1998 122:403-412. Patients with acquired bilateral vestibular loss are as able as normal subjects to generate "hip strategy" type postural responses. This suggests that vestibular information is not necessary to trigger a "hip strategy". COMMENT: This correlates well with the clinical observation that after several years, imbalance may become rather subtle in patients with bilateral vestibular loss. Patients with recent vestibular loss (not studied here), are much more impaired.

Gwendeh B, Gibb AG, Aziz N, Kong N, Zahir Z. Vancomycin administration in continuous ambulatory peritoneal dialysis: the risk of ototoxicity. Otol HNS 1998:118:551-8. :In 16 patients on CAPD (chronic ambulatory peritoneal dialysis), including 22 episodes of treatment, there was no evidence for ototoxicity (audiometry, ENG). The authors suggest that vancomycin is likely not very ototoxic, but that co-administration of vancomycin with aminoglycosides may be more toxic. COMMENT: Seems reasonable.

Hirvonen TP, Aalto H, Pykko I, Jantti P, Juholoa M. Changes in the vestibulo-ocular reflex: a study of elderly day hospital patients. Clin Otolaryngol 23, 42-47, 1998. They report increased gain at high frequences in elderly (mean 82) day hospital patients, using the autorotation test. COMMENT: This is a strange result -- gain should go down, not up, as vestibular ganglion cells die with age. It is possible that active rotation, in which there is cervical input, doesn't track vestibular cell loss. If true, these patients might still have low gains for passive head movements. One might expect better visual performance then for active than passive head movement.

Mulheran M, Degg C. Comparison of distortion product OAE generation between a patient group requiring frequent gentamicin therapy and control subjects. Brit. J. Audiol 31(1):5-9, 1997. This paper reports that in patients with cystic fibrosis who were given many courses of gentamicin, there was a significant elevation of the 2f1-f2 distortion product at 4K. COMMENT: Using auditory testing to detect a vestibular ototoxin seems illogical.

Pandya A, Xia X, Radnaabazar J, Batsuuri J, Dangaansuren B, Fischel-Ghodsian N, Nance WE. Mutation in the mitochondrial 12s rRNA gene in two families from Mongolia with matrilineal aminoglycoside toxicity. J Med Gen 34(2):169-72, 1997.  COMMENTS: This paper provides further data confirming a mitochondrial mutation associated with a few cases of streptomycin induced deafness.

Wanamaker HH, Gruenwald L, Damm KJ, Ogata Y, Slepecky N. Dose-related vestibular and cochlear effects of transtympanic gentamicin. Am J Otol 19:170-179, 1998. COMMENTS: This paper documents that in the Mongolian gerbil, gentamicin affects vestibular and cochlear hair cells equivalently rather than being a selective vestibular ototoxicin. This pattern is similar to that found in the cat. More selective vestibular ototoxicity is certainly the usual case in humans, at least, when toxicity is measured by functional testing (audiometry and rotatory chair testing). Hearing can be completely preserved while vestibular function is completely eliminated.

Aran JM, Chappert C, Dulon D, Erre JP, Aurousseau. Uptake of amikacin by hair cells of guinea pig cochlea and vestibule and ototoxicity: comparison with gentamicin. Hearing Res 82(2):179-83, 1995. COMMENT: As with gentamicin, amikacin is rapidly taken up but very slowly cleared. Uptake patterns were similar for utricular and cristae ampullaris hair cells. The authors suggest that this means that selective ototoxicity cannot be explained by accumulation in hair cells.

Freeman S et al. Differential effect of the loop diuretic furosemide on short latency auditory and vestibular-evoked potentials. Am J. Otol, 20:41-45, 1999. COMMENTS: This study documents that furosemide (brand name is Lasix), temporarily diminishes auditory potentials, but not vestibular potentials. They speculate that this effect is based on differences in the amount of positive potentials across the hair cells between auditory and vestibular, with larger potentials experienced by auditory cells. These data, by themselves, do not say much about long term hearing impairment, but do point out an interesting difference between these types of hair cells that might explain the selectivity of other ototoxic agents.

Conlee JW, Bennett ML, Creel DJ. Differential effects of gentamicin on the distribution of cochlear function in albino and pigmented guinea pigs. Acta Otolaryngologica, 115(#) 367-74, 1995. Pigmented guinea pig cochleas were less sensitive to gentamicin. COMMENT: Albino human beings may also exhibit unusual sensitivity to gentamicin.

Conlon BJ, McSwain SD, Smith DW. Topical gentamicin and ethacryinic acid: effects on cochlear function. Laryngoscope 108(7):1087-9, 1998. These authors report that in animals, systemic ethacryinic acid potentiates toxicity of systemic gentamicin, but not of topical gentamicin. COMMENT: While the usefulness of this paper is limited as animal models of gentamicin toxicity don't seem to resemble very closely the situation in humans, it provides support for the idea that loop diuretics do not add to ototoxicity of ototopical agents.

Gillespie MB, Minor LB. Prognosis in bilateral vestibular hypofunction. Laryngoscope, 109, 1999, 35-41. 35 patient records were reviewed over a 2 year period. They concluded that poor outcome may be attributed to multiple medical comorbidities, vertigo, slowly progressive etiologies, and increased severity of vestibular loss as measured by an average gain of less than 0.2 and time constant less than 2 s. Comment: This is a useful study that demonstrates that there is a spectrum of outcomes, and that recovery is better in those who have less severe lesions.

Lopez I and others. The protective effect of brain-derived neurotrophic factor after gentamicin ototoxicity. Am J. Otol 20, 3, 1999, 317-324. Injections of BDNF directly into the perilymph were found to protect against Gentamicin ototoxicity in Chinchilla. Comment: while chinchilla's don't resemble human's that closely, and injections into the perilymph are certainly impractical as a clinical regiem, this study shows that there is feasibility in protective agents.

Casano R and others. Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications. Am. J. Otolaryngol 1999: 20:151-156. A family is described with abnormalities (961 thymidine deletion and variable inserted cytosines) in the 12S ribosomal RNA gene in mitochondria. This is a different mutation than the A1555G mutation previously described.

Kaplan DM, Marais J, Ogawa T, Kraus M, Rutka JA, Bance ML.Does high-frequency pseudo-random rotational chair testing increase the diagnostic yield of the eng caloric test in detecting bilateral vestibular loss in the dizzy patient? Laryngoscope 2001 Jun;111(6):959-63 . This paper reinforces the usual dogma that rotatory chair testing is the best way to diagnose bilateral loss.

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