Long-term Effects of Carboplatin Brainstem Infusions on Hearing Thresholds in Monkeys

May, Bradford J.; Guarnieri, Michael; Carson, Benjamin S.; Bachani, Abdul; Jallo, George I.

doi:10.1001/archotol.130.12.1411

Cited by 8 publications

(5 citation statements)

References 21 publications

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“…Hearing thresholds were determined by ABR [8]. Apparatus and set-up were similar to that described by May et al [9]. Animals were placed inside an acoustic isolation chamber where they were exposed to clicks and tone pips at 2, 4, 6, and 8 kHz emitted from a free-field speaker.…”

Section: Methodsmentioning

confidence: 99%

Effects of semicircular canal electrode implantation on hearing in chinchillas

Tang¹,

Melvin²,

Santina

2009

Acta Oto-Laryngologica

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Conclusion-Implantation of vestibular prosthesis electrodes in chinchilla semicircular canal ampullae can be accomplished without significant loss of cochlear function; however, the risk of hearing loss with the current surgical technique is high.Objectives-To determine if it is possible to implant vestibular prosthesis electrodes into the labyrinth without damaging hearing, and to quantify the extent of hearing loss due to implantation.Method-The left semicircular canals of 6 chinchillas were implanted with 3 bipolar pairs of electrodes using a transmastoid approach. Right ears, which served as controls, were subjected to the same mastoid approach without fenestration and implantation. Auditory brainstem response hearing thresholds to free field clicks and tone pips at 2, 4, 6, and 8 kHz were measured bilaterally 3-9 weeks after implantation. Hearing thresholds were compared between sides and against data from 6 normal chinchillas.Results-4 implanted ears suffered severe hearing loss, with thresholds ranging from 5 to 11 SD above the mean threshold of sham surgery control ears across all tested stimuli. 2 implanted ears had preserved hearing, with thresholds remaining within 1 SD of the mean threshold of sham surgery control ears across nearly all stimulus frequencies.

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Section: Methodsmentioning

confidence: 99%

Effects of semicircular canal electrode implantation on hearing in chinchillas

Tang¹,

Melvin²,

Santina

2009

Acta Oto-Laryngologica

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“…Our previous suggestion that they might be secondary to the decreases of glutamate (Li et al, 2002) is not supported by their rapid occurrence after carboplatin treatment. There is recent evidence that carboplatin infused into the brain stem can have some eVects on central auditory neurons (May et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Amino acid concentrations in chinchilla cochlear nucleus at different times after carboplatin treatment

Godfrey

Ding

et al. 2005

Hearing Research

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“…The average hearing threshold was elevated 8.8 dB ( SD = 7.3 dB) in monkeys 6 to 8 (Table 3) 6 months after the infusion was stopped. The average threshold elevation increased to 10.7 dB 1 year after drug treatment, a loss that became statistically significant ( p < .05) (May et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Ototoxicity of Carboplatin Delivered Locally in a Monkey Brainstem

et al. 2005

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Ototoxicity is a common side effect of platinum-based chemotherapy. Intratumoral drug delivery theoretically could reduce the ototoxic effects of systemic drug infusions. However, local delivery to central nervous system (CNS) tumors might promote ototoxicity through drug release into cerebrospinal fluid (CSF). This report describes an examination of the cytoarchitecture of vestibular cells of cynomolgus monkeys that had chronic brainstem infusions with the maximum tolerated dose (MTD) of carboplatin. The brainstems of adult monkeys were infused for 30 days at 0.42 mu l/h with 0.025 to 0.25 mg/kg (MTD) of carboplatin. The vestibular sensory epithelia of eight drug-treated animals were isolated for microscopic examination of vestibular hair cells and support cells. Local infusions produced chronic elevated CSF levels of platinum, neurological symptoms, and radiographic evidence of pontine injury. Histology revealed significant cell damage at the infusion sites. Microscopic examinations of vestibular support cells and hair cells demonstrate a small reduction in cell counts in the drug-treated monkeys compared to a noninfused control animal. Parametric and nonparametric tests show no effect of dose in predicting the vestibular cell counts. In this single study of eight monkeys, a dose-dependent reduction of vestibular hair cells or support cells was not observed in animals infused with brainstem infusions of 0.025 to 0.25 mg/kg of carboplatin.

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Long-term Effects of Carboplatin Brainstem Infusions on Hearing Thresholds in Monkeys

Cited by 8 publications

References 21 publications

Effects of semicircular canal electrode implantation on hearing in chinchillas

Effects of semicircular canal electrode implantation on hearing in chinchillas

Amino acid concentrations in chinchilla cochlear nucleus at different times after carboplatin treatment

Ototoxicity of Carboplatin Delivered Locally in a Monkey Brainstem

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