Sound shock response in larval zebrafish: A convenient and high-throughput assessment of auditory function.

Given that hearing ability can be challenged in diverse ways, it is necessary to develop an easily conducted, high-throughput method for assessing potential auditory risks. Measuring the acoustic startle response (ASR) has become a critical behavioral method in hearing research using zebrafish (Danio rerio). In this study, changes in the activity of zebrafish larvae (10 days post fertilization (dpf)) due to exposure to a sudden easily-generated broad-band noise were automatically and objectively recorded and analyzed without building sophisticated equipments. A significant increase in activity was induced by the noise stimulation and the alterations were impaired by gentamicin. In addition, a clear dose-response trend was observed between gentamicin exposure and the impaired activity, and a similar phenomenon was observed between gentamicin exposure and damage to hair cells. Our results suggested that alterations in the activity induced by a broad-band noise can potentially be used as an efficient assay for assessing hearing ability.

A review of the progress and pitfalls of FDA policy process: Planning a pathway for pharmaceutical interventions for hearing loss development.

The Federal Food and Drug Administration, or FDA is generally considered a powerful gatekeeper, able to deliver or withhold life-saving cures and create or destroy economic windfalls. As the decades go by, and technologies, diseases, public health demands, and politics evolve, we can identify patterns of change, action and inter-action among some of these traditional stakeholders in the FDA's policy sphere. A careful examination of this agency's colorful history can shed light on central features of the agency's policy process, which has been quite receptive to its stakeholders and adaptive to change over the decades and, in turn, show the way for development in lanes which do not fit neatly into the current paradigms offered by the agency. This paper will explore the history of FDA policy process, through examination of seminal moments in FDA history, the prominent actors and focusing events within them, and the outcomes of those events, in an attempt to illuminate a pattern of behavior or processes by which a struggling field of pharmaceutical development such as interventions for hearing loss can advance.

Oral steroids for the resolution of otitis media with effusion (OME) in children (OSTRICH): study protocol for a randomised controlled trial.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear affecting about 80 % of children by the age of 4 years. While OME usually resolves spontaneously, it can affect speech, behaviour and development. Children with persistent hearing loss associated with OME are usually offered hearing aids or insertion of ventilation tubes through the tympanic membrane. Oral steroids may be a safe and effective treatment for OME, which could be delivered in primary care. Treatment with oral steroids has the potential to benefit large numbers of children and reduce the burden of care on them and on health services. However, previous trials have either been too small with too short a follow-up period, or of too poor quality to give a definite answer. The aim of the Oral Steroids for the Resolution of Otitis Media with Effusion in Children (OSTRICH) trial is to determine if a short course of oral steroids improves the hearing of children with OME in the short and longer term. METHODS/DESIGN: A total of 380 participants (children of 2 to 8 years of age) are recruited from Hospital Ear, Nose and Throat departments in Wales and England. A trained clinician seeks informed consent from parents of children with symptoms for at least 3 months that are attributable to OME and with confirmed bilateral hearing loss at study entry. Participants are randomised to a course of oral steroid or a matched placebo for 1 week. Outcomes include audiometry, tympanometry and otoscopy assessments; symptoms; adverse effects; functional health status; quality of life; resource use; and cost effectiveness. Participants are followed up at 5 weeks, and at 6 and 12 months after the day of randomisation. The primary outcome is audiometry-confirmed satisfactory hearing at 5 weeks. DISCUSSION: An important evidence gap exists regarding the clinical and cost effectiveness of short courses of oral steroid treatment for OME. Identifying an effective, safe, nonsurgical intervention for OME in children for use in primary care would be of great benefit to children, their families and the NHS. ISRCTN: ISRCTN49798431 (Registered 7 December 2012).

Effect of hypoglycemic anti-deafness capsules in diabetic patients with deafness and toxicological assessment in rats.

OBJECTIVE: Through experiment on animals and clinical trials to explore the safety and efficacy of hypoglycemic anti-deafness capsules on diabetic patients with deafness. METHODS: Total 296 patients with non-insulin dependent diabetes mellitus (NIDDM) were randomly divided into two groups. A treatment group of 164 patients (208 ears) was treated with hypoglycemic anti-deafness capsules based on TCM syndrome differentiation. A control group of 132 patients (184 ears) was treated with glibenclamide and conventional drug treatment for deafness. The following were observed: hearing, fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2hPG), 24 h urine glucose (24hUG), improvement of main symptoms, platelet function, and changes in superoxide dismutase (SOD) and lipid peroxide (LPO) levels. In animal studies, Kunming mice, weighing 18-22 g were used. Half of the mice were males and half were females. Wistar rats, weighing 80-120 g were used. Half of the rats were males and half were females. Male Wistar rats, weighing 200-220 g, were also used. Their acute and chronic toxicity was studied. RESULTS: The hearing improvement was 56.7% in the treatment group and 26.6% in the control group. FPG, 2hPG, and 24hUG were improved significantly (P < 0.05, P < 0.01, P < 0.01, respectively) in the treatment group and 2hPG and 24hUG improved significantly in the control group (P < 0.05, P < 0.05). The improvement in 2hPG and 24hUG in the treatment group was significantly greater than that in the control group P < 0.01).There was no significant difference in FPG between the two groups (P < 0.05). Main symptoms in the treatment group were significantly more improved than those in the control group (P < 0.05, P < 0.01). In the treatment group, platelet adhesion and aggregation, SOD, and LPO were all significantly improved from before treatment (P < 0.05, P < 0.01). However, in the control group, except LOP (P < 0.05), there were no significant differences from before treatment to after (P < 0.05). In animal studies, no obvious acute or long-term toxicity was observed from capsule administration. CONCLUSION: Through experiment on animals and clinical trials, we can found that hypoglycemic anti-deafness capsules could decrease blood glucose and serum triglycerides of alloxan-induced diabetic rats. This herbal capsule is effective for safely treating diabetic patients with deafness.

Assessment of the ototoxicity of docusate sodium (colace) in a guinea pig animal model.

OBJECTIVE: Docusate sodium (Colace) is an off-label ceruminolytic agent used to soften ear wax and relieve ear canal obstruction. At present, its effect on hearing in the presence of tympanic membrane (TM) perforation is not clear. The present study aimed to assess the safety of ototopic docusate sodium on hearing in the presence of TM perforation. STUDY DESIGN: A prospective, randomized, controlled trial in a guinea pig animal model. MATERIALS AND METHODS: Ten guinea pigs underwent bilateral myringotomy. In each animal, one ear received docusate sodium, serving as the experimental ear, and the other received normal saline as the control. Auditory brain response (ABR) was performed at baseline and then 1, 7, and 14 days following the application. RESULTS: At day 14 following application, there was no significant change in ABR thresholds at 8, 12, 16, 20, or 25 kHz. CONCLUSION: In guinea pigs with perforated TMs, docusate sodium does not seem to cause ototoxicity. Future clinical studies are required.

A weight of evidence approach for the assessment of the ototoxic potential of industrial chemicals.

There is accumulating epidemiological evidence that exposure to some solvents, metals, asphyxiants and other substances in humans is associated with an increased risk of acquiring hearing loss. Furthermore, simultaneous and successive exposure to certain chemicals along with noise can increase the susceptibility to noise-induced hearing loss. There are no regulations that require hearing monitoring of workers who are employed at locations in which occupational exposure to potentially ototoxic chemicals occurs in the absence of noise exposure. This project was undertaken to develop a toxicological database allowing the identification of possible ototoxic substances present in the work environment alone or in combination with noise exposure. Critical toxicological data were compiled for chemical substances included in the Quebec occupational health regulation. The data were evaluated only for noise exposure levels that can be encountered in the workplace and for realistic exposure concentrations up to the short-term exposure limit or ceiling value (CV) or 5 times the 8-h time-weighted average occupational exposure limit (TWA OEL) for human data and up to 100 times the 8-h TWA OEL or CV for animal studies. In total, 224 studies (in 150 articles of which 44 evaluated the combined exposure to noise and a chemical) covering 29 substances were evaluated using a weight of evidence approach. For the majority of cases where potential ototoxicity was previously proposed, there is a paucity of toxicological data in the primary literature. Human and animal studies indicate that lead, styrene, toluene and trichloroethylene are ototoxic and ethyl benzene, n-hexane and p-xylene are possibly ototoxic at concentrations that are relevant to the occupational setting. Carbon monoxide appears to exacerbate noise-induced hearing dysfunction. Toluene interacts with noise to induce more severe hearing losses than the noise alone.

[Assessment of efficacy and tolerance of tanakan during treatment of sensorineural bradyacuasia and tympanophonia].

The objective of the study was to evaluate efficacy and tolerance of tanakan during treatment of neurosensory hearing loss and subjective tinnitis supposedly of vascular etiology. The secondary purpose was to analyse late results of 3 month courses of therapy and changes in the clinical course of the disease during treatment and within 6 months after its termination. Tanakan was first given at a dose of 40 mg thrice daily for 90 days. Results of the treatment were estimated on days 90, 180, and 240. The second course (40 mg thrice daily for 90 days) was initiated 180 days after the end of the first one. The final outcome was evaluated on day 360. It was shown that monotherapy with tanakan effectively improved the hearing function and had the most pronounced beneficial effect on subjective tinnitus. Results of the treatment remained stable throughout the entire observation period (12 months).

Neonatal hearing assessment in very low birth weight infants exposed to antenatal steroids.

OBJECTIVE: We sought to evaluate neonatal hearing assessment by the otoacoustic emission (OAE) test in very low birth weight (VLBW) infants exposed to antenatal steroids. STUDY DESIGN: This is a retrospective cohort study of infants <1500 g delivered between July 1998 and July 2004 who completed hearing screens on discharge. All screens were performed by the OAE. Only infants who failed or passed the exam were included in the analysis. Infants with a partial or an inadequate exam were excluded. Neonates exposed to antenatal steroids were then compared to unexposed infants for the results of their OAE. RESULT: A total of 68,000 deliveries were performed during the study period. There were 703 VLBW infants who had hearing exams, of which 548 (78%) passed the screen, 95 (14%) failed and 59 (8%) were indeterminate. Gestational age, birth weight, score for neonatal acute physiology and severe intraventricular hemorrhage were associated with a failed screen (P<0.01). Antenatal steroid exposure was not associated with a failed screen (odds ratio: 0.83 (95% confidence interval 0.5-1.4), P=0.43). CONCLUSION: In our population, antenatal steroids were not associated with a positive or negative effect on hearing assessment of VLBW infants.

Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas.

A phase III clinical trial assessed the recurrence of adenomatous polyps after treatment for 36 months with difluoromethylornithine (DFMO) plus sulindac or matched placebos. Temporary hearing loss is a known toxicity of treatment with DFMO, thus a comprehensive approach was developed to analyze serial air conduction audiograms. The generalized estimating equation method estimated the mean difference between treatment arms with regard to change in air conduction pure tone thresholds while accounting for within-subject correlation due to repeated measurements at frequencies. Based on 290 subjects, there was an average difference of 0.50 dB between subjects treated with DFMO plus sulindac compared with those treated with placebo (95% confidence interval, -0.64 to 1.63 dB; P = 0.39), adjusted for baseline values, age, and frequencies. In the normal speech range of 500 to 3,000 Hz, an estimated difference of 0.99 dB (-0.17 to 2.14 dB; P = 0.09) was detected. Dose intensity did not add information to models. There were 14 of 151 (9.3%) in the DFMO plus sulindac group and 4 of 139 (2.9%) in the placebo group who experienced at least 15 dB hearing reduction from baseline in 2 or more consecutive frequencies across the entire range tested (P = 0.02). Follow-up air conduction done at least 6 months after end of treatment showed an adjusted mean difference in hearing thresholds of 1.08 dB (-0.81 to 2.96 dB; P = 0.26) between treatment arms. There was no significant difference in the proportion of subjects in the DFMO plus sulindac group who experienced clinically significant hearing loss compared with the placebo group. The estimated attributable risk of ototoxicity from exposure to the drug is 8.4% (95% confidence interval, -2.0% to 18.8%; P = 0.12). There is a <2 dB difference in mean threshold for patients treated with DFMO plus sulindac compared with those treated with placebo.

[Assessment of hearing organ ability in high-frequency auditory in patients suffering from chronic renal failure treated by haemodialysis and human recombinant erythropoietin (rhPEO)]. / Ocena wydolnosci narzadu sluchu w rozszerzonym zakresie czestotliwosci wysokich u osób chorych na przewlekla niewydolnosc nerek leczonych hemodializa i ludzka erytropoetyna uzyskana metoda rekombinacji genetycznej (rhEPO).

The problem of hearing loss occurrence in the course of chronic renal failure (CRF) was investigated in numerous research studies, attempting to explain both the etiological factors and treatment possibilities. According to various authors, the percentage of hearing loss occurrence in patients suffering from CRF differs between 20% and 80%. The idea of this paper is based on an observation that if peripheral blood parameters such; haemoglobin, amount of red blood cells improve when influenced by rhEPO, then tissue oxidation improvement connected with it causes also better metabolism of cilliar's cells, what helps to improve hearing. The purpose of this study has been to assess the influence of treatment with human recombinant erythropoietin obtained through genetic recombination and by haemodialysis upon the condition of the hearing organ in patients with CRF (as a result of both a single procedure and long-term treatment). 65 haemodialysed patients with chronic renal failure were enrolled in this study. 31 of them (with haematocrit value below 28%) were treated with rhEPO for 4 months (3 times a week, 4000 units). The remaining 34 patients (with haematocrit values of above 28%) were not treated with rhEPO. Impairment of hearing was found in 87.1% of the CRF patients examined, while the hearing loss in high frequency range (9-18 kHz) was significantly more pronounced than those observed in the conventional range. In 70% of the patients the hearing loss was the cochlear type. Thus, combining haemodialysis with recombinant human erythropoietin in treatment of CRF patients results in significant improvement of hearing, correlated with positive results in fighting anaemia. The improved hearing found is, most surely, related to better oxygen supply of ciliated cells of internal ear, resulting from improved oxygen supply in peripheral blood and tissues of the body, and may also be related to the centric activity of erythropoietin, as the presence of receptors for EPO was found in the central nervous system (CNS) neurocytes, and it was also proven that EPO is produced in CNS, probably in astrocytes.

Toluene ototoxicity in rats: assessment of the frequency of hearing deficit by electrocochleography.

To identify the frequency range most sensitive to toluene-induced auditory damage, the auditory function of adult Long-Evans rats exposed to 1750 ppm of toluene (6 h/day, 5 days/week, 4 weeks), was tested by recording auditory-evoked potentials directly from the round window of the cochlea. The present electrocochleographic findings do not support a specific mid- to high-frequency loss of auditory sensitivity. On the contrary, the electrophysiologic data, obtained for audiometric frequencies ranging from 2 to 32 kHz, showed a hearing deficit not only in the mid-frequency region (12-16 kHz), but also in the mid-low-frequency region (3-4 kHz). Actually, the effect of toluene was independent of the frequency in our experimental conditions. Histological analysis was consistent with electrophysiologic data because a broad loss of outer hair cells occurred in both mid- and mid-apical coil of the organ of Corti.

Future trends in aminoglycoside therapy.

The aminoglycosidic aminocyclitols have been utilized extensively for three decades. Nonetheless, the future use of this class of agents has been questioned of late. Recognized inadequacies of the aminoglycosides and the development of new antibiotics with significant activity against gram-negative bacilli are commonly cited reasons for the theorized decline of these compounds. However, resistance to newly developed antibiotics already has become evident. This insures a continuing role for the aminoglycosides in the treatment of nosocomial infections. Aminoglycosides will have continued use as empiric, potentially synergistic therapies for hospital-acquired infections in neutropenic patients with bacteremia, in enterococcal endovascular infections, and in patients with serious infections associated with Pseudomonas aeruginosa. Those factors that will influence the future role of aminoglycosides in these settings will include economic, administrative, and space pressures to restrict the number of antibiotics available in hospitals, the discovery of novel antibiotics, the utility of combination therapies employing an aminoglycoside and newly available drugs, the comparative toxicities of new antimicrobial regimens, and considerations of cost containment.

[Ototoxicity of micronomicin sulfate--audiometric assessment].

Micronomicin sulfate (MCR) is a new aminoglycoside antibiotic, and its antibacterial spectrum is similar to that of gentamicin (GM). According to the animal test, MCR has less ototoxicity than other aminoglycoside antibiotics such as GM. To check its clinical ototoxicity, MCR was given intramuscularly to 20 patients at dose of 120--240 mg/day, respectively for 2--8 days, and audiometry was carried out before and after administration of MCR. No evident change was detected between the preadministration hearing levels and the postadministration hearing levels. These data suggest that MCR is sufficiently safe in ototoxicity within dose of 120 mg/day for 4 days.