EFFECT OF OTOTOXICITY ON AUDITORY EVOKED POTENTIALS

拟议研究的重点是检查急性和慢性影响 耳毒性制剂对耳蜗电生理活动的影响， 通过无创耳蜗电图（ECOG）检查第VIII神经和脑干 和听性脑干反应（ABR）。 首要目的是 确定ECOG或ABR的变化是否可用于预测即将发生的 听力损失或提供听力损失的早期识别之前， 不可逆的 如果这些措施确实提供了这样的指标， 病人的护理可以得到改善。 实验将开始， 鼓膜非侵入性ECOG记录技术的发展 膜（TM）和耳道的龙猫需要为随后的 耳毒性的慢性动物研究。 同时记录的非侵入性 和侵入性测量的总和电位（SP）的幅度，行动 然后，将计算潜在（AP）幅度、AP潜伏期和AP阈值。 比较了 无创性ECOG记录技术的发展， 动物将消除手术的需要，特别是重复手术 ，在五月的动物研究，由我们自己和他人。 因此，需要 用于术后镇痛药和抗生素以及无菌手术室 可以显着减少以及可能的动物痛苦， 实验 然后，非侵入性记录技术在 动物和以前开发的非侵入性记录技术， 成年人的TM将用于检查耳毒性的慢性效应 药物对SP振幅、AP振幅、SP/AP振幅比、AP 潜伏期-强度函数、AP输入-输出函数、AP和ABR 听性脑干的阈值、适应和I-V间期 反应 在成年人中，行为测听阈值也将 被监控。 在动物中，将进行耳蜗组织学检查 牺牲之后。 在第三年，我们计划扩大动物研究， 包括耳毒性和频率选择性单个单位研究 在单个单位记录、ECOG记录或两者中。 此外，本发明还提供了一种方法， 我们计划扩大非侵入性耳蜗电图的发展， 婴儿和新生儿的技术。 婴儿和新生儿接受 然后耳毒性剂可以被包括用于研究。 在整个赠款期间 期间，P.I.将参加化学，药理学和 电镜 同时，她将指导和监督 耳鼻喉科住院医师、医学生和药理学博士 在ECOG、ABR和耳毒性领域的学生。

The focus of the proposed study is to examine the acute and chronic effects of ototoxic preparations on the electrophysiologic activity of the cochlea, VIII nerve, and brainstem through noninvasive electrocochleography (ECOG) and the auditory brainstem response (ABR). The primary purpose is to determine if changes in the ECOG or ABR can be used to predict impending hearing loss or provide early identification of a hearing loss before it is irreversible. If these measures do provide such an indicant, the efficacy of patient care may be enhanced. Experiments will begin with the development of noninvasive ECOG recording techniques from the tympanic membrane (TM) and ear canal of chinchillas needed for the subsequent chronic animal study of ototoxicity. Simultaneously recorded noninvasive and invasive measures of the summating potential (SP) amplitude, action potential (AP) amplitude, AP latency, and AP threshold will then be compared. Development of noninvasive ECOG recording techniques in these animals will eliminate the need for surgery, particularly repeated surgery , in may animal studies by ourselves and others. Consequently, the need for postoperative analgesics and antibiotics and sterile operating rooms could be markedly curtailed as well as possible animal suffering in chronic experiments. Then the noninvasive recording techniques developed in animals and previously developed noninvasive recording techniques from the TM in adult humans will be used to examine the chronic effects of ototoxic agents on SP amplitude, AP amplitude, the SP/AP amplitude ratio, AP latency-intensity functions, AP input-output functions, AP and ABR threshold and adaptation and the I-V interval of the auditory brainstem response. In the human adults, behavioral audiometric thresholds will also be monitored. In the animals, histology of the cochlea will be performed after sacrifice. In the third year, we plan to expand animal studies to include single unit studies of ototoxicity, and frequency selectivity either in single unit recordings, ECOG recordings, or both. In addition, we plan to expand the development of noninvasive electrocochleographic techniques to infants and neonates. Infants and neonates receiving ototoxic agents could then be included for study. Throughout the grant period the P.I. will take formal coursework in chemistry, pharmacology, and electron microscopy. Simultaneously, she will teach and supervise otolaryngology residents, medical students, and pharmacology doctoral students in the area of ECOG, ABR, and ototoxicity.