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Bedside high frequency monitoring for ototoxicity
Otolaryngology Head and Neck Surgery Volume 117 Number 2
of the medications. This work demonstrates a simple and reliable way of examining hearing, which will help make these sustained release devices available to patients who suffer from diseases of the inner ear. Poster 29
Bedside High Frequency Monitoring for Ototoxicity BELINDA C. SINKS, MA (presenter), and JOEL A, GOEBEL, MD, St. Louis, Me.
Auditory threshold changes due to administration of ototoxic medications and the benefits of high-frequency (8 to 18 Khz) audiometry to monitor changes in hearing sensitivity have been well documented in the literature. We have previously demonstrated that in normally hearing adults no significant differences were observed between threshold measured in a sound suite versus a typical hospital room with excellent test-retest reliability, using high-fidelity headphones (Valente et al. 1992). Further trials revealed acceptable test-retest reliability in persons with sensorineural hearing impairment when tested in a typical hospital room environment (Sinks et al. 1994). The present study evaluated the utility of bedside highfrequency testing for detection of subclinical ototoxicity in 50 patients (92 ears) undergoing cis-platin or gentamicin treatment. Each patient was tested on three separate occasions at the bedside with ambient noise measurement obtained prior to each test. Results showed a significant threshold shift in nine patients during the course of therapy. The relationship of this objective finding to the patient's symptom of hearing loss and the ambient noise level during testing will be discussed in detail. We believe that bedside ototoxic monitoring is a useful and reliable tool for detecting early threshold changes and preventing clinical hearing loss when ambient noise levels are not excessive. (Supported by the American Hearing Research Foundation Grant no. 45207.)
Research Forum - - Monday
P93
paper reviews three sets of experiments that illustrate the protective potential of augmenting antioxidant defenses of the cochlea. In the first set of experiments rat pup organ of Corti explants were exposed to toxic levels of cisplatin, resulting in a 70% loss of hair ceils. When antioxidant defenses were augmented either by adding different antioxidant molecules or an antioxidant plus an adenosine analog (R-HA) to the culture medium prior to and during the administration of cisplatin, there was a highly significant (>90%) protection of hair cells from cisplatin destruction. In a related set of in vitro experiments with the same cisplatin model, a combination of neurotrophin (BDNF) and antioxidant (D-methionine) was utilized in an attempt to protect both auditory neurons and hair cells from cisplatin destruction. BDNF protected the auditory neurons while D-methionine protected the auditory hair cells, and an additive effect was seen with a combination of BDNF plus D-methionine for protection from cisplatin neurotoxicity. A third set of experiments utilized an in vivo model of noise-induced hearing loss in chinchilla. Saline (control) or R - H A was placed on the round window membrane for 30 minutes. Following closure of the bulla, the chinchillas were exposed to 4 kHz noise at 105 dB SPL for 48 hours. The ears treated with R-PIA showed significantly lower temporary threshold shifts and reduced permanent threshold shifts and greater recovery of DPOAE, as well as 50% less outer hair cell loss compared with saline-treated controls. The antioxidant system thus appears to play a basic and important role in inner ear defense, since it is involved in limiting damage from a wide variety of insults. Augmentation of this system holds promise for preventing hearing loss in a number of clinical applications. Poster 31
WR2721 Protection From Cisplatin Ototoxicity ANIL K, GUPTA, MD (presenter), BRIAN W. BLAKLEY,MD, PhD, and MICHAEL W. CHURCH, PhD, Detroit, Mich.
Poster 30
Augmentation of the Inner Ear Antioxidant Defense System: A Strategy for Preventing Toxic and Traumatic Cochlear Injury RICK KOPKE, MD (presenter), THOMAS R. VAN DE WATER, PhD, RAMIN GABAIZEDEH, HOWARD M. STEINMAN, PhD, DONALD HENDERSON, PhD, and JOSEPH G. FEGHALI, MD, San Diego, Calif,, and Bronx, Clarence, and New York, N.Y.
Evidence is accumulating that both toxins and noise may damage cochlear hair cells through the generation of reactive oxygen species (ROS). If unchecked, ROS can react with and damage cellular protein, DNA, and unsaturated lipids, leading to cell death. The cochlear stria vascularis and organ of Corti possess a system of antioxidant enzymes and molecules that defend against these ROS, which can be augmented pharmacologically. This
Amifostine (WR2721) was initially developed as a protector against radiation-induced toxicity. The compound has been found to have protective effects from the neuropathic and renal toxicity of cisplatin. Its possible use as a protector from auditory toxicity is assessed. We have previously found that, at a low dose (18 mg/kg), WR2721 was not protective. This study assessed the efficacy of WR2721 in larger doses in ameliorating cisplatin-induced ototoxicity. Syrian Golden hamsters were split into four groups and given cisplatin injections every 3 days (3 mg/kg/dose). They were given WR2721 at five doses, ranging from 20 to 200 mg/kg, 30 minutes before cisplatin. Dose-dependent protection of WR2721 was found by using auditory brainstem threshold (ABR) testing. We conclude that WR2721 may have a role in protection from cisplatininduced hearing loss.
of the medications. This work demonstrates a simple and reliable way of examining hearing, which will help make these sustained release devices available to patients who suffer from diseases of the inner ear. Poster 29
Bedside High Frequency Monitoring for Ototoxicity BELINDA C. SINKS, MA (presenter), and JOEL A, GOEBEL, MD, St. Louis, Me.
Auditory threshold changes due to administration of ototoxic medications and the benefits of high-frequency (8 to 18 Khz) audiometry to monitor changes in hearing sensitivity have been well documented in the literature. We have previously demonstrated that in normally hearing adults no significant differences were observed between threshold measured in a sound suite versus a typical hospital room with excellent test-retest reliability, using high-fidelity headphones (Valente et al. 1992). Further trials revealed acceptable test-retest reliability in persons with sensorineural hearing impairment when tested in a typical hospital room environment (Sinks et al. 1994). The present study evaluated the utility of bedside highfrequency testing for detection of subclinical ototoxicity in 50 patients (92 ears) undergoing cis-platin or gentamicin treatment. Each patient was tested on three separate occasions at the bedside with ambient noise measurement obtained prior to each test. Results showed a significant threshold shift in nine patients during the course of therapy. The relationship of this objective finding to the patient's symptom of hearing loss and the ambient noise level during testing will be discussed in detail. We believe that bedside ototoxic monitoring is a useful and reliable tool for detecting early threshold changes and preventing clinical hearing loss when ambient noise levels are not excessive. (Supported by the American Hearing Research Foundation Grant no. 45207.)
Research Forum - - Monday
P93
paper reviews three sets of experiments that illustrate the protective potential of augmenting antioxidant defenses of the cochlea. In the first set of experiments rat pup organ of Corti explants were exposed to toxic levels of cisplatin, resulting in a 70% loss of hair ceils. When antioxidant defenses were augmented either by adding different antioxidant molecules or an antioxidant plus an adenosine analog (R-HA) to the culture medium prior to and during the administration of cisplatin, there was a highly significant (>90%) protection of hair cells from cisplatin destruction. In a related set of in vitro experiments with the same cisplatin model, a combination of neurotrophin (BDNF) and antioxidant (D-methionine) was utilized in an attempt to protect both auditory neurons and hair cells from cisplatin destruction. BDNF protected the auditory neurons while D-methionine protected the auditory hair cells, and an additive effect was seen with a combination of BDNF plus D-methionine for protection from cisplatin neurotoxicity. A third set of experiments utilized an in vivo model of noise-induced hearing loss in chinchilla. Saline (control) or R - H A was placed on the round window membrane for 30 minutes. Following closure of the bulla, the chinchillas were exposed to 4 kHz noise at 105 dB SPL for 48 hours. The ears treated with R-PIA showed significantly lower temporary threshold shifts and reduced permanent threshold shifts and greater recovery of DPOAE, as well as 50% less outer hair cell loss compared with saline-treated controls. The antioxidant system thus appears to play a basic and important role in inner ear defense, since it is involved in limiting damage from a wide variety of insults. Augmentation of this system holds promise for preventing hearing loss in a number of clinical applications. Poster 31
WR2721 Protection From Cisplatin Ototoxicity ANIL K, GUPTA, MD (presenter), BRIAN W. BLAKLEY,MD, PhD, and MICHAEL W. CHURCH, PhD, Detroit, Mich.
Poster 30
Augmentation of the Inner Ear Antioxidant Defense System: A Strategy for Preventing Toxic and Traumatic Cochlear Injury RICK KOPKE, MD (presenter), THOMAS R. VAN DE WATER, PhD, RAMIN GABAIZEDEH, HOWARD M. STEINMAN, PhD, DONALD HENDERSON, PhD, and JOSEPH G. FEGHALI, MD, San Diego, Calif,, and Bronx, Clarence, and New York, N.Y.
Evidence is accumulating that both toxins and noise may damage cochlear hair cells through the generation of reactive oxygen species (ROS). If unchecked, ROS can react with and damage cellular protein, DNA, and unsaturated lipids, leading to cell death. The cochlear stria vascularis and organ of Corti possess a system of antioxidant enzymes and molecules that defend against these ROS, which can be augmented pharmacologically. This
Amifostine (WR2721) was initially developed as a protector against radiation-induced toxicity. The compound has been found to have protective effects from the neuropathic and renal toxicity of cisplatin. Its possible use as a protector from auditory toxicity is assessed. We have previously found that, at a low dose (18 mg/kg), WR2721 was not protective. This study assessed the efficacy of WR2721 in larger doses in ameliorating cisplatin-induced ototoxicity. Syrian Golden hamsters were split into four groups and given cisplatin injections every 3 days (3 mg/kg/dose). They were given WR2721 at five doses, ranging from 20 to 200 mg/kg, 30 minutes before cisplatin. Dose-dependent protection of WR2721 was found by using auditory brainstem threshold (ABR) testing. We conclude that WR2721 may have a role in protection from cisplatininduced hearing loss.