A soft-surgery approach to minimize hearing damage caused by the insertion of a cochlear implant electrode: a guinea pig animal model.

OBJECTIVE: A "soft surgery" technique was applied, using various types of specifically designed dummy electrodes, to mimic cochlear implantation in a guinea pig model, and the degree of hearing-preservation/cochlear damage was assessed. METHODS: Tricolor guinea pigs were divided into 3 groups: group A were implanted with electrodes without any contacts or wires (soft electrode), group B were implanted with electrodes having a metallic wire inside (stiff electrode), and group C underwent a cochleostomy procedure without implantation. Compound action potentials, in the range of 4 to 32 kHz, were used to assess electrophysiologic changes in the hearing function presurgery and postsurgery. Data were collected before surgery, at times t = 0 (immediately after surgery) and at 3, 7, 14, and 30 days. RESULTS: At low frequencies (4-8 kHz), an immediate elevation of hearing threshold was observed in all 3 groups. Higher threshold shifts were more consistent for group B implanted with a stiff electrode, in comparison to the other 2 groups. Animals from group C presented a recovery from hearing loss, starting 3 days after surgery. At high frequencies (16-32 kHz), the elevation of hearing threshold was higher, as compared with the data from the low frequencies. Group C animals presented oscillatory threshold shifts twice, and the recovery to normal threshold values occurred approximately at t = 14 days. CONCLUSION: The data suggest that cochleostomy is minimally harmful to the inner ear and that a soft electrode might better preserve the inner ear integrity than a rigid electrode.

Hearing threshold prediction with Auditory Steady State Responses and estimation of correction functions to compensate for differences with behavioral data, in adult subjects. Part 1: Audera and CHARTR EP devices.

BACKGROUND: The objective of the study was the evaluation and comparison of hearing threshold values extrapolated from Auditory Steady State Responses, using 2 commercial systems and the estimation of correction factors applicable to the ASSR data. MATERIAL/METHODS: One hundred ten subjects participated to the study. All subjects were initially examined with otoscopy, pure-tone audiometry and admittance. Data were acquired by 2 clinical systems the Audera (Viasys) and the CHARTR EP (ICS), using identical protocols. The acoustic stimuli consisted of single carrier frequencies at 1000, 2000 and 4000 Hz modulated at 40 Hz. RESULTS: The data show that the threshold estimates from both devices differ significantly from the measured behavioral thresholds. The ICS device presented significantly larger mean-ASSR estimated hearing level values at the tested frequencies, implying an underestimation of the hearing threshold. Both sets of prediction errors overestimated hearing levels for the normal group. The prediction errors were in all cases greater for the Audera than for the ICS. CONCLUSIONS: The errors encountered in the estimates of the 2 widely-used commercial devices suggest that the current ASSR protocols are not ready for a wide-range use and that significant developments in the area of threshold prediction/precision are necessary. If, on the other-hand, the ASSR predicted threshold is used on a purely consulting basis, as in hearing-aid fitting, then such errors might be acceptable in a clinical setting.

A new oral otoprotective agent. Part 1: Electrophysiology data from protection against noise-induced hearing loss.

BACKGROUND: Data from animal studies show that antioxidants can compensate against noise-induced stress and sensory hair cell death. The aim of this study was to evaluate the otoprotection efficacy of various versions of orally administered Acuval 400 against noise damage in a rat animal model. MATERIAL/METHODS: Fifty-five Sprague Dawley rats were divided into 4 groups: A) noise-exposed animals; B) animals exposed to noise and treated with the Acuval; C) animals exposed to noise and treated with a combination of Coenzyme Q10 and Acuval; D) animals treated only with Acuval and Coenzyme Q10 and with no exposure to noise. All solutions were administered orally 5 times: 24 and 2 hrs prior to noise exposure, and then daily for 3 days. The auditory function was assessed by measuring auditory brainstem responses (ABR) in the range from 2 to 32 kHz at times =1, 7, 14 and 21 days after noise exposure. RESULTS: At low frequencies (click and 4 kHz) animals from both A and B groups showed significant threshold shifts in the majority of the tested frequencies and tested times. For the same frequencies, animals from group C presented threshold levels similar to those from group D. At frequencies ≥ 8 kHz the protective performance of the 2 Acuval groups is more clearly distinguished from the noise group A. At 32 kHz the 2 Acuval groups perform equally well in terms of otoprotection. Animals in Group D did not show any significant differences in the hearing threshold during the experiment. CONCLUSIONS: The data of this study suggest that a solution containing Coenzyme Q10 and Acuval 400, administered orally, protects from noise-induced hearing loss.

Dose-dependent protection on cisplatin-induced ototoxicity - an electrophysiological study on the effect of three antioxidants in the Sprague-Dawley rat animal model.

BACKGROUND: Sprague-Dawley rats were used as an acute cisplatin ototoxicity model to compare the chemo-protective efficacy of 2 sulphur-containing antioxidants (D-methionine, N-L-acetylcysteine) and 1 seleno-organic compound (ebselen). Each putative chemo-protective agent was tested at 3 different dosages in order to assess the influence of dose on auditory preservation. MATERIAL/METHODS: A total of 40 Sprague-Dawley albino male rats were used in the study. Animals were divided into 10 groups, 3 groups of different doses for each protective agent and a cisplatin-treated control group. The animals were weight-matched before drug exposure to ensure similar weights in all groups. Auditory function was assessed with auditory brainstem responses and distortion product otoacoustic emissions at time zero and at 96 hours post-treatment. RESULTS: At the post-treatment follow-up no significant threshold change at 8 kHz was found in the D-Met- and NAC-treated groups. All ebselen-treated animals presented significant threshold elevations. At 12 and 16 kHz, only the groups treated with 300, 450 mg/kg of D-Met and 475 mg/kg of NAC presented thresholds comparable to the pre-treatment ABR data. The ebselen-treated animals presented significant threshold shifts and showed the highest threshold elevations. The DPOAE data analysis showed that only the animals from the 350 mg/kg D-met group presented lack of statistical differences between the pre and post recordings. CONCLUSIONS: Considering the outcome from the ABR and DPOAE analyses together, only the 350 mg/kg D-met group presented a complete auditory preservation against the 14 mg/kg cisplatin administered i.v. Data from ebselen pre-treated Sprague-Dawley albino male rats demonstrate that ebselen dosages up to 12 mg/kg given by i.p. administration lack auditory preservation in this species.

Estimation of pure-tone thresholds in adults using extrapolated distortion product otoacoustic emission input/output-functions and auditory steady state responses.

Pure-tone thresholds were used as the reference and compared with extrapolated distortion product otoacoustic emission input/output-functions and auditory steady state responses (ASSR) in hearing-impaired adults, using the Cochlea-Scan and Audera devices. Fifty-three subjects presenting sensorineural deficits were included in the study. The DPOAE data were recorded using the detailed Cochlea-Scan threshold modality, and ASSR responses were assessed at 1.0, 2.0, and 4.0 kHz. The comparison between DPOAE and ASSR threshold values indicated significant mean differences across all tested frequencies. Significant relationships were observed between the behavioral and the DPOAE measurements in the lower frequencies (1.5 and 2.0 kHz). The Cochlea-Scan algorithm seems to overestimate hearing threshold. Logistic regression models (probability of DPOAE response p = 0.9), suggested that the identifiable hearing levels are less than 34 dB HL (at 2.0 and 4.0 kHz) and less or equal to 38 and 40 dB HL at 1.5 and 6.0 kHz respectively. The Cochlea-Scan DPOAE protocols can be used in cases presenting mild hearing deficits (i.e.<40 dB HL).

Effect of noise conditioning on cisplatin-induced ototoxicity: a pilot study.

BACKGROUND: Cisplatin is a platinum-based chemotherapeutic agent that is highly effective in the treatment of cancer. Ototoxicity is an important dose-limiting adverse effect of cisplatin, in addition to nephrotoxicity. Studies have shown that cisplatin-induced ototoxicity is mainly a result of generated reactive oxygen species. Sulfur-containing compounds such as L-N acetylcysteine (L-NAC) and D-methionine (D-MET) have shown promising results as potent otoprotectors against cisplatin-induced ototoxicity in animal studies. MATERIAL/METHODS: In this study, we investigated a method to increase the efficacy of L-NAC and D-MET without increasing dose. Sprague Dawley rats were noise conditioned for 15 minutes immediately after intraperitoneal injection of 275 mg/kg L-NAC or 300 mg/kg D-MET. Another set of rats received 275 mg/kg L-NAC or 300 mg/kg D-MET alone, and 1 group underwent noise conditioning alone. All 5 groups were administered 14 mg/kg cisplatin intravenously 1 hour after otoprotector injection or 45 minutes after noise conditioning. RESULTS: Otoprotectors and noise conditioning, alone or in combination, were analyzed for their ability to reduce cisplatin-induced ototoxicity. The results indicated that the combination of 275 mg/kg L-NAC and noise conditioning afforded more otoprotection than 275 mg/kg L-NAC alone. In the case of D-MET, 300 mg/kg plus noise conditioning was little better than 300 mg/kg D-MET alone. In addition, we found that noise conditioning alone showed otoprotection against cisplatin-induced ototoxicity. CONCLUSIONS: The ability of noise conditioning to protect against cisplatin-induced ototoxicity requires additional study.

Different strategies in treating noiseinduced hearing loss with N-acetylcysteine.

BACKGROUND: The cellular mechanisms leading to noise-induced hearing loss (NIHL) involve the generation of reactive oxygen species (ROS). Recent studies on glutathione (GSH) and N-acetylcysteine (NAC) show that they can protect the cochlea from ROS-derived damage, increasing the levels of endogenous cellular defences. The purpose of this study was to verify NAC's oto-protective efficacy and determine if drug administration timing influences the degree of oto-protection. MATERIAL/METHODS: Forty male Sprague Dawley albino rats were divided in four groups exposed to 8-kHz 105-dB SPL continuous noise. The groups were treated with diverse NAC administration modalities: group A received 4 injections during 48 hours (pre- and post-noise exposure), group B 1 injection prior to exposure, group C 1 injection 24 h after exposure, and group D served as untreated controls. The single injection dosage was 375 mg/kg; the controls received an equal volume of saline solution. Cochlear function was assessed by pre- and post-noise (after 168 hours) recordings of distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABR). DPOAEs were obtained by three different asymmetric protocols (P1=60-50, P2=50-40, P3=40-30 dB SPL) for frequencies of 4-16 kHz. ABR responses were elicited by tone-bursts at 8 and 16 kHz. RESULTS: The most important outcome of the study was that the administration of NAC significantly reduced the threshold shifts in the treated animals. NAC provided different degrees of threshold reduction according to the timing of the drug injection. CONCLUSIONS: The role played by the timing of NAC injection was important for the OHC protection index. From a DPOAE perspective, the best protection scheme was observed in the group receiving NAC after noise exposure, but full recovery of cochlear function was not observed in any of the tested groups.

The universal newborn hearing screening program at the University Hospital of Ferrara: focus on costs and software solutions.

In the present paper, the authors report the results of the Universal Newborn Hearing Screening (UNHS) project at the University Hospital of Ferrara. A total of 6,759 full-term newborns and a total of 1,016 NICU babies were tested at the University Hospital of Ferrara, from January 2000 to December 2006. The paper presents information from clinically acceptable screening procedures developed and tested during the 6 years of the program and addresses two questions pertinent to hearing screening: (i) the cost-estimate of a UNHS program based on European economical and administration premises and (ii) the development of a database-structure for the evaluation of the UNHS/NHS performance and the individual patient tracking.

Vocal problems among teachers: evaluation of a preventive voice program.

Vocal education programs for teachers may prevent the emergence of vocal disorders; however, only a few studies have tried to evaluate the effectiveness of these preventive programs, particularly in the long term. Two hundred and sixty-four subjects, mostly kindergarten and primary school female teachers, participated in a course on voice care, including a theoretical seminar (120 minutes) and a short voice group therapy (180 minutes, small groups of 20 subjects). For 3 months, they had to either attend the vocal ergonomics norms and, as psychological reinforcement, they had to make out a daily report of vocal abuse, or to follow the given exercises for a more efficient vocal technique, reporting on whether the time scheduled was respected or not. The effectiveness of the course was assessed in a group of 21 female teachers through a randomized controlled study. Evaluation comprehended stroboscopy, perceptual and electro-acoustical voice analysis, Voice Handicap Index, and a course benefit questionnaire. A group of 20 teachers matched for age, working years, hoarseness grade, and vocal demand served as a control group. At 3 months evaluation, participants demonstrated amelioration in the global dysphonia rates (P=0.0003), jitter (P=0.0001), shimmer (P=0.0001), MPT (P=0.0001), and VHI (P=0.0001). Twelve months after the course, the positive effects remained, although they were slightly reduced. In conclusion, a course inclusive of two lectures, a short group voice therapy, home-controlled voice exercises, and hygiene, represents a feasible and cost-effective primary prevention of voice disorders in a homogeneous and well-motivated population of teachers.

Local maximal stress hypothesis and computational plaque vulnerability index for atherosclerotic plaque assessment.

It is believed that atherosclerotic plaque rupture may be related to maximal stress conditions in the plaque. More careful examination of stress distributions in plaques reveals that it may be the local stress/strain behaviors at critical sites such as very thin plaque cap and locations with plaque cap weakness that are more closely related to plaque rupture risk. A "local maximal stress hypothesis" and a stress-based computational plaque vulnerability index (CPVI) are proposed to assess plaque vulnerability. A critical site selection (CSS) method is proposed to identify critical sites in the plaque and critical stress conditions which are be used to determine CPVI values. Our initial results based on 34 2D MRI slices from 14 human coronary plaque samples indicate that CPVI plaque assessment has an 85% agreement rate (91% if the square root of stress values is used) with assessment given by histopathological analysis. Large-scale and long-term patient studies are needed to further validate our findings for more accurate quantitative plaque vulnerability assessment.

Electrophysiological findings in the Sprague-Dawley rat induced by moderate-dose carboplatin.

Carboplatin is a second generation platinum-containing anti-tumor drug which selectively alters the micromechanical function of the inner hair cells (IHCs) of the organ of Corti in the chinchilla. Data from a recent study [Wake et al., Acta Otolaryngol. 116 (1996) 374-381], using the chinchilla model, have suggested that a moderate dose of carboplatin alters the efferent feedback loop gain of the OHCs. The present study was designed to evaluate the possible 'efferent feedback alteration mechanism' in the Sprague-Dawley rat using distortion product otoacoustic emissions (DPOAEs). A moderate dose of carboplatin (50 mg/kg body weight) was administered by a 30 min i.p. infusion. Pre- and 72-h post-treatment DPOAE and auditory brainstem response (ABR) recordings were acquired from a group of 12 rats. The animals were anesthetized with a ketamine-atropin anesthesia administered in two consecutive phases. The DPOAE responses (cubic distortion products) were recorded with four asymmetrical protocols: P1=60-50, P2=50-40, P3=40-30 and P4=30-20 dB SPL (sound pressure level), in the frequency range from 4.0 to 16 kHz. ABR responses were obtained for bipolar clicks and tone pips at the frequencies 8.0, 10.0, 20.0 and 30 kHz using stimuli in the range from 100 to 30 dB SPL. Significant ABR threshold shifts of 15 dB were observed at 30 kHz, and shifts of 10 dB at 20, 16 and 10 kHz. The comparison of pre- and post-treatment DPOAE responses did not reveal any significant changes for protocols P1, P2 and P4. Data from the P3 protocol indicated a decrease of the DPOAE amplitude. The findings from the rat model suggest that (a) moderate doses of carboplatin do not affect the efferent feedback loop OHC function and (b) the cochlear susceptibility to carboplatin across species is different, even at moderate-dose regimes.

Comparison of the return-to-the-origin probability and the apparent diffusion coefficient of water as indicators of necrosis in RIF-1 tumors.

Two model-independent measures of diffusion, the apparent diffusion coefficient (ADC) and return-to-the-origin probability enhancement (R) were compared for their ability to detect tissue necrosis in RIF-1 murine tumors. Both reflect the degree of restriction experienced by the endogenous water molecules; however, the ADC is calculated from the initial linear slope of the diffusion attenuation curve, while R is calculated from data that includes the non-monoexponential part of the curve. In spectroscopic studies (n = 9), neither the ADC nor R showed a strong correlation with tumor volume. In imaging studies (n = 14), ADC, R, and T(2) were calculated on a pixel-by-pixel basis. There, the mean ADC and mean R for the entire imaging slice showed reasonable correlation with necrotic tumor fraction (r(2) = 0.679 and -0.665, respectively). The mean T(2) value yielded a poor correlation (r(2) = 0.436). Regions-of-interest were chosen from areas identified as either necrotic or viable and the resulting sets of ADC and R-values were subjected to discriminant analysis to determine the identification error rate. The error was greater for R than for the ADC (P < 0.001). Therefore, in this application, the use of the non-monoexponential part of the diffusion attenuation curve does not provide additional identification power.

Evaluation of anesthesia effects in a rat animal model using otoacoustic emission protocols.

Anesthesia effects on otoacoustic emission (OAE) recordings were evaluated in a group of 72 Sprague-Dawley rats (mean weight 225+/-20 gr). Two anesthesia dosages (high and normal) and two anesthetic protocols (ketamine-xylazine, ketamine-xylazine-atropine) were tested. Transient evoked OAE (TEOAE) and distortion product OAE (DPOAE) responses were recorded in 10 min intervals, for a total period of 60 min. Analyses of the data with repeated measure models indicated the following: (1) The animals receiving a high dose of anesthesia (cumulative dose 66.6 mg of ketamine and 13.2 mg of xylazine/kg of body weight) presented significant alterations of the TEOAE response level and the signal to noise ratio at 3.0 kHz; (2) the animals receiving a normal dose of ketamine-xylazine anesthesia (cumulative dose 50 mg of ketamine and 10 mg of xylazine/kg of body weight) presented TEOAE and DPOAE responses invariant in terms of time; (3) significant differences were observed in the DPOAE responses from animals anesthetized with ketamine-xylazine and ketamine-xylazine-atropine. The data support the hypothesis that the ketamine anesthesia OAE suppressing mechanism is related to middle-ear mechanics.

Ototoxic effects of cisplatin in a Sprague-Dawley rat animal model as revealed by ABR and transiently evoked otoacoustic emission measurements.

The ototoxic effects of cisplatin in a Sprague-Dawley rat model were evaluated by recordings of auditory brainstem responses (ABR) and transiently evoked otoacoustic emissions (TEOAEs). The ABR responses were evoked from alternating clicks and 8, 10, 12, 16, 20 and 30 kHz tone pips in a range from 40 to 100 dB SPL range. The TEOAEs were recorded with a non-linear protocol, and were evoked by a 63.5 dB SPL click stimulus. Twenty five male Sprague-Dawley rats were used in the study, 20 animals were treated with cisplatin (16 mg/kg, body weight) and five animals served as controls. The data showed that 72 h after the cisplatin administration, the TEOAE and ABR variables were significantly altered. The relationship between the ABR and TEOAE variables was shown to be non-linear. The most significant relationships were observed between the TEOAE correlation and the ABR threshold values at 10, 12, and 16 kHz.