Methodology for studying the effects of topically applied ear drops on otoacoustic emissions in guinea pigs

Testing of otoacoustic emissions (OAE) has been successfully applied to study outer hair cell function. We used this methodology to evaluate and compare the effect of topically applied normal saline, and gentamicin- and ciprofloxacin-containing drops into the middle ear of guinea pigs. All three solutions similarly decreased the distortion product OAE (DPOAE) and all three caused an inflammatory reaction in the guinea pig's middle-ear. OAE failed to detect adequately the ototoxicity of topically administered drops in this animal model because the opening of the bulla affected DPOAE, and both inflamed middle-ear mucosa and osteoneogenesis caused a decrease in DPOAE amplitude. This is the first report examining the influence of topically used otic drops on inner ear function as demonstrated by OAE.     

耳声发射应用于新生儿听力筛选的研究

目的 研究瞬态诱发耳声发射（ｔｒａｎｓｉｅｎｔ ｅｖｏｋｅｄ ｏｔｏａｃｏｕｓｔｉｃ ｅｍｉｓｓｉｏｎｓ，ＴＥＯＡＥ）产畸变产物耳声发射（ｄｉｓｔｏｒｔｉｏｎ ｐｒｏｄｕｃｔ ｏｔｏａｃｏｕｓｔｉｃ ｅｍｉｓｓｉｏｎｓ，ＤＰＯＡＥ）应用于新生儿听力筛选的可行性，控诉听力筛选的标准。方法 应用Ｃｅｌｅｓｔａ５０３型耳声发射分析仪对１０８名新生儿（２１６耳）进行ＴＥＯＡＥ和ＤＰＯＡＥ听力筛选，与听性脑     

Protective effect of thymoquinone against cisplatin-induced ototoxicity

The aim of this study was to investigate the potential protective effect of thymoquinone against cisplatin-induced ototoxicity. This study is a prospective, controlled experimental animal study. Experiments were performed on 30 healthy female Sprague-Dawley rats. Thirty animals were divided into three groups of 10 animals each. Group 1 received an intraperitoneal (i.p.) injection of cisplatin 15 mg/kg. Group 2 received i.p. thymoquinone 40 mg/kg/day for 2 days prior to cisplatin injection and third day i.p. cisplatin 15 mg/kg was administered concomitantly. Group 2 continued to receive i.p. thymoquinone until fifth day. Group 3 received i.p. thymoquinone 40 mg/kg/day for 5 days. Pretreatment distortion product otoacoustic emissions (DPOAE) and auditory brain stem responses (ABR) testing from both ears were obtained from the animals in all groups. After the baseline measurements, drugs were injected intraperitonally. After an observation period of 3 days, DPOAE measurements and ABR testing were obtained again and compared with the pretreatment values. There was no statistically significant difference between pre and post-treatment DPOAE responses and ABR thresholds group 2 and 3. However, group 1 demonstrated significant deterioration of the ABR thresholds and DPOAE responses. Our results suggest that DPOAE responses and ABR thresholds were preserved in the cisplatin plus TQ-treated group when compared with the group receiving cisplatin alone. According to these results, cisplatin-induced ototoxicity may be prevented by thymoquinone use in rats.     

Recovery from cisplatin-induced ototoxicity: a case report and review

We present a pediatric case report of cisplatin-induced ototoxicity with subsequent recovery. The patient experienced tinnitus and fluctuating mild high-frequency sensorineural hearing loss (SNHL) with a concomitant decrease in distortion product otoacoustic emissions (DPOAE). There was recovery of hearing loss and return of DPOAE at 1 year after completion of cisplatin therapy. Reports of recovery from cisplatin-induced ototoxicity in humans are limited in the literature, especially in the pediatric population. A review of cisplatin ototoxicity and mechanisms of recovery are discussed, with an emphasis on the particular chemotherapy regimen and dosing schedule in this case, given at 4-11 week intervals.     

The latency of evoked otoacoustic emissions: its relation to hearing loss and auditory evoked potentials.

The latencies of transient evoked otoacoustic emissions (TEOAE), distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) have been studied in 173 patients with cochlear hearing impairment. No systematic or significant correlation between the OAE latency and the hearing loss at the corresponding frequency could be found, whereas the ABR latencies increase by a small but significant amount with increasing hearing loss. This can be explained by a broadening of the excited area and its shifting towards a more apical position if the hair cell population in the basal turn is depleted. Because of the considerable intersubject variability of OAE latencies the data do not allow to decide whether they are not influenced by cochlear hearing loss or whether an effect is merely not observable. The large variability is attributed to the interindividual differences of OAE generation time and return delay whereas the travel time of the primary wave is less variable as can be seen from the low variability of ABR latencies.     

Cisplatin-induced ototoxicity and pharmacokinetics: preliminary findings in a dog model

The early effects of a clinical dose of cisplatin (100 mg/m2) on distortion-product otoacoustic emissions (DPOAE) thresholds and the relationship between DPOAE threshold shifts and changes in plasma concentrations of filterable and total platinum (Pt) following infusion of cisplatin in a dog model were investigated. The DPOAE thresholds (based on input-output function) were measured 2 days before a single high dose of cisplatin administration, and compared with measurements recorded 2 and 4 days after infusion. The results revealed DPOAE thresholds to be elevated by 4 days after the administration of cisplatin. However, this elevation could not be correlated with plasma concentrations of filterable and total Pt, which showed little variation over the 48-hour postinfusion period between animals. The present study demonstrated that DPOAE thresholds have the potential to be used as an indicator of cisplatin-induced ototoxicity, and cisplatin-induced ototoxicity could not be explained by plasma Pt kinetics in individual animals.     

Evaluation of Hearing Loss after Spinal Anesthesia with Otoacoustic Emissions

The aim of this study was to determine the degree and reversibility of hearing loss (HL) following spinal anesthesia with an objective audiometric test: otoacoustic emissions (OAE). Eleven patients (22 ears) who were undergoing surgery under spinal anesthesia were included in this study. Transient-evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) were evaluated 1 day before the operation and postoperative day 1, 2, and 15. DPOAE were recorded as DPgram and input/output functions (I/O). The emission amplitudes of the TEOAE and DPOAE of right and left ears were found to be affected immediately after the surgery and progressive improvement detected with full recovery within postoperative 15 days. These changes were mainly at around 1,500–3,000 Hz. None of the patients had permanent OAE amplitude deterioration. Transient HL may occur more often than it is generally assumed, and the symptoms might not be recognized. OAE is an effective and objective way of evaluating the HL in this particular group of patients. We suggest informing patients about this transient HL for medicolegal issues.     

后半规管阻塞前后豚鼠前庭及耳蜗功能的动态变化

目的 探讨机械性后半规管阻塞前后豚鼠前庭和耳蜗功能的动态变化。方法 采用２０只豚鼠建立单侧后半规管阻塞的动物模型,观察手术前后眼震电图,听性脑干反应,耳声发射等变化。结果 术后第１天,第３天豚鼠正弦摆动刺激术侧眼震反应,明显减术,术后第５天起双侧眼震恢复正常。术后早期ＡＢＲ阈值一度升高,第５天达高峰,ＡＢＲ阈值平均升高４．５ｄＢ。ＤＰＯＡＥ反应幅度无明显改变。结论 后半规管阻塞能选择性地消除后半规     

Age-specific changes in otoacoustic emission

The relation of age and external and middle ear parameters with otoacoustic emission (OAE) characteristics was studied. Ear canal equivalent volume (ECV), static compliance and tympanometric gradient were measured. Transient evoked OAE (TEOAE) and distortion product of OAE (DPOAE) were recorded. Measured parameters included: average TEOAE and DPOAE levels, TEOAE spectral peak level and DPOAE maximum level, TEOAE and DPOAE dominant frequencies as well as frequency corresponding to minimum DPOAE level. The analysis of variance demonstrated a significant interrelationship between subject's age and all TEOAE and DPOAE parameters. External and middle ear parameters had no significant influence on OAE. The only exception was ECV which had certain relation to TEOAE spectral peak frequency. The results obtained demonstrated that OAE age-related changes were predominantly determined by processes taking place within its generators system, i.e. at the outer hair cells level.     

The effect of various durations of noise exposure on auditory brainstem response, distortion product otoacoustic emissions and transient evoked otoacoustic emissions in rats

This study was designed to investigate the effect of various durations of noise exposure in animals on physiological responses from the cochlea which are also used clinically in humans: auditory brainstem response (ABR), transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). Rats were exposed to 113 dB SPL broad-band noise (12 h on/12 h off) for durations of 3, 6, 9, 12, 15 and 21 days, and tested 24 h after cessation of the noise and again after a period of 6 weeks. ABR threshold to click stimuli and to a 2-kHz tone burst (TB), TEOAE energy content and DPOAE amplitude in the exposed rats were compared to those in a group of control rats not exposed to noise. ABR thresholds (click and TB) were significantly elevated in all exposure duration groups compared to control rats. DPOAE amplitudes and TEOAE energy content were significantly reduced. The mean ABR thresholds following 21 days exposure were significantly greater (click = 100 dB pe SPL; TB = 115 dB pe SPL) than those following 3 days exposure (click = 86 dB pe SPL; TB = 91 dB pe SPL). Linear regression analysis between recorded responses and duration of noise exposure (days) showed a significant increase in ABR thresholds of approximately 0.8-- 1.4 dB/day. TEOAE and DPOAE responses showed no such dependence on noise duration and were already maximally reduced after only 3 days of exposure. This can be explained by the possibility that short noise exposures may cause damage to the early, more active stages of cochlear transduction (as shown by TEOAEs and DPOAEs). As the noise exposure continues, further damage may be induced at additional, later stages of the cochlear transduction cascade (as shown by ABR). Thus, ABR seems more sensitive to noise duration than OAE measures.     

耳声发射对侧抑制效应的频率特异性研究

目的　观察耳声发射对侧抑制效应是否有频率特异性。方法　分别测试７ 例正常人（１４耳） 畸变产物耳声发射（ＤＰＯＡＥ） 和２ 例正常人（２ 耳） 自发性耳声发射（ＳＯＡＥ） 的对侧抑制效应,对侧声刺激为窄带噪声（ＮＢＮ） 。结果　当对侧ＮＢＮ 中心频率等于ＤＰＯＡＥ 的初始音ｆ２ 频率和ＳＯＡＥ 频率时,ＤＰＯＡＥ 和ＳＯＡＥ 发生最大抑制。结论　本实验进一步表明耳声发射对侧抑制效应有频率特异性,提示内侧橄榄耳蜗系统和耳蜗外毛细胞参与了耳蜗频率特性的主动调谐过程,提高了耳蜗频率分辨率。文中讨论了频率特异性的发生机理     

Changes in transitory evoked otoacoustic emissions in chemotherapy with cisplatin and 5FU]

The aim of this study was to detect changes of transient evoked otoacoustic emissions (TEOAE) during chemotherapy with cisplatin and fluorouracil (5FU). A review of the literature reveals that the incidence of cisplatin ototoxicity varies from 9% to 50%; this variation is due to differences in doses, duration of administration, to the criteria for ototoxicity and on audiological methods. Three cycles of chemotherapy (1000 mg/m2 5FU from day 1 to 5 and 100 mg/m2 cisplatin on day 1) were given to 12 patients; the OAE were measured before chemotherapy and after each administration. In 86% of the ears measured we found changes in the TEOAE; the mean values for the amplitude of the TEOAE decreased about 13% after the end of the chemotherapy. Pure tone thresholds were reduced in almost 50% of the measured ears. The decrease of amplitude of TEOAE is an early sign of an ototoxic secondary effect, probably due to damage to the outer hair cells. TEOAE is a sensitive method for detecting ototoxicity in cisplatin-treated patients and more reliable than pure-tone audiometry or evoked acoustic potentials.     

次声波对豚鼠畸变产物耳声发射幅度的影响

目的观察强次声波暴露后豚鼠畸变产物耳声发射(DPOAE)的变化情况.方法将15只豚鼠置于频率8Hz、强度为135dB SPL的次声声场中连续暴露90分钟.分别于强次声波暴露前及暴露后即刻(2h内)、2天和5天做畸变产物耳声发射测试.结果强次声波暴露后豚鼠DPOAE的幅度值在各个频率段与暴露前相比均有明显的降低(p＜0.01),随着时间的推移,各个频率的幅度虽有一定的恢复,但仍明显低于暴露前水平(p＜0.01).结论强次声波可导致豚鼠耳蜗外毛细胞功能明显减退.     

The relationship between auditory threshold and evoked otoacoustic emissions

The aim of this study was to compare transiently evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) in normal hearing ears (n = 44) and ears with cochlear hearing loss (HL) to obtain defined data on qualitative and quantitative correlations. In addition, we wanted to determine the reliability with which a clinical examiner could predict a typical, idealized audiometric configuration from TEOAE measurements. In the hearing-impaired subjects (n = 149), a 50% reduction of OAE incidence was caused by a mean HL of 10.5 dB for TEOAE compared to 27 dB SPL for DPOAE. A 90% incidence reduction was found at a mean threshold elevation of 33 dB for TEOAE and 51 dB for DPOAE. Correlation between TEOAE amplitudes and HL was in general rather low (r = –0.1 to –0.5), while DPOAE amplitudes showed a slightly better correlation with HL (r = –0.3 to –0.6). In general, efforts to derive an audiogram from evoked OAE have been more promising for DPOAE than for TEOAE. However, our studies showed that approximately 40% of the ears with HL could be categorized correctly into one of five typical audiometric patterns from TEOAE measurements. Additionally, a cochlear HL in or near the medium frequency range was much more likely to cause a reduction in TEOAE than an isolated low- or high-frequency lesion. Accordingly, TEOAE were often preserved in ears with isolated HL in the high or low frequencies. Received: 7 May 1998 / Accepted: 25 September 1998     

Occupational exposure to noise decreases otoacoustic emission efferent suppression

With the discovery of otoacoustic emissions (OAEs), the efferent cochlear system has become accessible for investigation in humans. Recently, it has been suggested that contralateral sound activated OAE efferent suppression may provide an early indication of auditory damage due to exposure to noise. In this study, OAE efferent suppression in normally hearing subjects, occupationally exposed to noise, was compared with respective effects in healthy, non-exposed subjects. The noise-exposed group exhibited higher mean hearing thresholds at frequencies 4, 6 and 10 kHz (p < 0.01) and lower-level transient-evoked otoacoustic emission (TEOAE) and distortion-product otoacoustic emission (DPOAE) at a frequency of 4 kHz (not significant). TEOAE efferent suppression was moderately decreased, whereas DPOAE efferent suppression was negligible, in the exposed group compared to non-exposed subjects. The results of the study suggest that OAEs, particularly DPOAE contralateral suppression, are likely to become a valuable method for assessing early hearing damage caused by exposure to noise.     

Prevention of cisplatin ototoxicity using transtympanic N-acetylcysteine and lactate.

HYPOTHESIS: Transtympanic administration of the antioxidant N-acetylcysteine or lactated Ringer's solution onto the round window membrane will prevent cisplatin ototoxicity in the guinea pig model. BACKGROUND: Cochlear ototoxicity is a well-known side effect of cisplatin administration, with the mechanism of injury thought to rest in oxidative damage to the outer hair cells. However, previous attempts at transtympanic antioxidant delivery have met with varied success. We present an effective method of counteracting cisplatin ototoxicity via the transtympanic application of lactated Ringer's solution or N-acetylcysteine. METHODS: Baseline distortion product otoacoustic emission measurements were obtained. Intraperitoneal cisplatin was administered to a cumulative dose of 20 mg/kg. The middle ears were either untreated (control) or filled with normal saline (negative control), 2%N-acetylcysteine diluted in normal saline (treatment), or lactated Ringer's solution (treatment) via anterosuperior quadrant myringotomies. Posttreatment distortion product otoacoustic emissions were obtained. RESULTS: Animals in the untreated control group and the negative control normal saline group demonstrated consistent obliteration of distortion product otoacoustic emissions. However, those receiving either lactated Ringer's solution or 2%N-acetylcysteine diluted in normal saline demonstrated significant preservation of distortion product otoacoustic emissions. The treatment regimen was well tolerated, with minimal animal loss. CONCLUSION: We have demonstrated the efficacy of transtympanic lactated Ringer's solution and N-acetylcysteine in the prevention of cisplatin ototoxicity using a guinea pig model. The possible mechanisms for the high efficacy of lactated Ringer's solution are discussed in detail.     

Age dependence of otoacoustic emissions: the loss of amplitude is primarily caused by age-related hearing loss and not by aging alone

The amplitude of otoacoustic emissions (OAE) is known to decrease with increasing age, but it is still unclear whether this is due to aging alone or to age-related hearing loss. This study describes the exploration of a large database (5,142 patients from 0.4 to 89.8 years) collected in a routine clinical testing. Reliable pure tone audiograms, transitory evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) recordings were available from 5,424 ears without conductive loss, acute sudden deafness or retrocochlear disorder. From this database, group 1 with behavioral thresholds of 10 dB HL or better at all frequencies from 1 to 4 kHz and group 2 with age-accordant thresholds after ISO 7029 were formed. In both groups, the OAE amplitude decreased with increasing age, but in group 1, the effect was significant only for DPOAE recorded at 3 and 4 kHz. In group 2, the loss of amplitude was steeper and highly significant for TEOAE as well as DPOAE at all frequencies, but most pronounced at high frequencies. These findings support the hypothesis that the reduction of OAE amplitude with increasing age is primarily caused by age-linked hearing loss and not by aging alone.     

The effect of intratympanic vitamin C administration on cisplatin-induced ototoxicity

The Objective of this study is to investigate the effect of intratympanic injection of vitamin C on cisplatin-induced ototoxicity. The study included 24 albino adult female rats (48 ears). The study animals were divided into four groups each of which was composed of six animals including a control (intraperitoneal cisplatin), a cisplatin–saline (saline intratympanic + intraperitoneal cisplatin), a C vit (intratympanic vitamin C) and a cisplatin–C vit group (intraperitoneal cisplatin + intratympanic vitamin C). As two animals had died due to cisplatin-induced ototoxicity (one in the control and one in the cisplatin-saline group) they were excluded from the study. The experiment was terminated, performing distortion product otoacoustic emission (DPOAE) measurement prior to procedures and at the end of the experiment. The results of the statistical analysis were evaluated. In the cisplatin–C vit group, there were no significant decreases in DPOAE amplitudes at 2 kHz (p > 0.05). Although a decrease was observed in DPOAE amplitudes at 2.8, 4, 6, and 8 kHz frequencies, these amplitude reductions were significantly lower than the control group (p < 0.05). Intratympanic vit C infusion provided a protective effect against cisplatin-induced ototoxicity primarily at 2 kHz and at other frequencies (2.8, 4, 6, and 8 kHz), and it did not produce a toxic effect in the cochlea.     

新生儿听力普遍筛查模式的初步探讨

目的 寻找适合于中国国情的新生儿听力普遍筛查模式,获得新生儿听力损失发病的基本资料。方法 新生儿在出院前接受耳声发射（otoacoustic emissions,OAE)测试,通过者予以出院;对未通过者在1个月后再次复查OAE,仍未通过者行听性脑干反应（auditory brainstem response,ABR)检查。所有ABR检查不通过者在3个月内接受全面的听力学诊断和评估,以确定听力损失的性质和程度。耳声发射测试采用畸变产物耳声发射（distortion product otoacoustic emissions,DPOAE),通过标准：1．5－6kHz的5个测试频率中的4个信噪比大于6dB。ABR通过测试的标准为波V反应阈值≤35dBnHL。结果 2998例新生儿中2710位通过出院前的OAE测试,1个月后288例复查OAE,其中263例通过。需要ABR检查者共有25例,未通过者6例。经过全面的听力学诊断和评估,6例婴儿（占全体新生儿的2‰）有听力损失。结论 新生儿听力普查十分必要,OAE和ABR联合应用的两步筛查法是较适合的筛查模式。     

聋校学生中听神经病的调查研究

目的：获得南京聋人学校在校学生中听神经病的患病情况,并对其发病特征作初步探讨。方法：358名学生接受了耳科检查、声导抗及瞬态诱发性耳声发射（TEOAE）筛查,对通过TEOAE筛查的学生进行病史分析纯音测听、声导抗、诊断型TEOAE、DPOAE、ABR、ENG以及VEMP等全面的听力和前庭功能评估。结果：在可行听神经病评估的323名学生行TEOAE筛查时,1名学生单耳、2名学生双耳显示“通过”,经进一步检查,符合听神经病诊断。结论：听神经病并非罕见,在聋校中亦有发生,对其及早识别和科学干预,此类学生可能避免进入聋校,回归主流社会。