Is there a close relationship between changes in amplitudes of distortion product otoacoustic emissions and hair cell damage after exposure to realistic industrial noise in guinea pigs?

In long-term experiments in awake guinea pigs (n=12), distortion product otoacoustic emissions (DPOAEs) at various frequencies were measured repeatedly over 6–8 months. About 9 weeks after the first measurement, the animals were exposed to industrial noise (car industry, maximal intensity about 110 dB SPL) for 2 h. The amplitudes of DPOAE were measured prior to noise exposure and 10 min, 70 min, 1 day and 2 days after the noise exposure and then once every week. Three to four months after noise exposure, the animals were killed, and the cochleae were prepared for scanning electron microscopy. The row of inner hair cells (IHCs) was complete in all animals, while the rows of outer hair cells (OHCs) showed a considerable hair cell loss in some of the animals without a correlation to the change in amplitudes of DPOAE. However, a closer relationship between the decline of amplitudes of DPOAE and the number of missing and changed OHCs (fused stereocilia bundles, missing tip links) could be established. The number of lost OHC does not reflect the decline in DPOAE in all cases. This discrepancy must be considered when the degree of hearing loss needs to be established from changed DPOAE.     

Assessment of the efficacy of a local steroid rescue treatment administered 2 days after a moderate noise-induced trauma in guinea pig

Objectives: Intratympanic injection of corticosteroids membrane after noise-induced hearing loss is an accepted alternative to general administration. We investigated the effect on hearing of a hyaluronic acid gel with liposomes loaded with dexamethasone (DexP) administered into the middle ear.

Methods: An acute acoustic trauma was performed to 13 guinea pigs for a period of 1?h on Day ?2. Two 2 days after the noise trauma, the animals were then assigned randomly to four experimental groups: control without gel, gel injection, gel-containing free DexP, gel-containing DexP loaded into liposomes. Auditory thresholds were measured with Auditory Brainstem Response before Day ?2 and at Day 0, Day 7 and Day 30 after noise trauma.

Results: Seven days after, a complete hearing recovery was observed in the control group at all frequencies apart from 8?kHz, and no recovery was observed in the three groups receiving a gel injection. Thirty days after trauma, all of the animals had recovered normal hearing, apart from at the 8-kHz frequency, with similar auditory thresholds.

Conclusions: Local DexP administration 48?h after a mild acoustic trauma did not improve hearing recovery, even with a sustained release in a specific gel formulation designed for inner ear therapy.     

The effect of Ginkgo biloba on the expression of intermediate–early antigen (c-fos) in the experimentally induced anosmic mouse

Objective

Treatment of olfactory dysfunction is very difficult and has limited modality. Treatment with steroids has been used in patients with olfactory dysfunction but the side effects of steroid need to be weighed against its potential benefits. In the present study, the effect of systemic administration of dexamethasone and EGb 761 on damage to olfactory mucosa produced by zinc sulfate was examined. Expression of the immediate-early antigen (IEG), c-fos, in the olfactory bulb and piriform cortex was used to determine the effects of treatment.

Methods

Young adult CD1 mice (6 to 8 weeks old, male) were used. After anosmic mice were made by bilateral intranasal irrigation with 0.2 ml of 5% (0.17 M) zinc sulfate, anosmia was confirmed by a food finding test. Four groups of anosmic mice were studied: a steroid group (steroid injection group, n = 12), an EGb group (EGb injection group, n = 12), a steroid-EGb group (steroid and EGb injection group, n = 12), and a control group (anosmic mice and no Tx. n = 12). The olfactory bulb and piriform cortex of four mice in each group were obtained at 1, 2, and 3 weeks after instillation of zinc sulfate by cardiac perfusion, and immunohistochemical staining for c-fos was also performed to evaluate brain activity. In approximately 10 well-defined glomeruli of the olfactory bulb and in one side of the piriform cortex, c-fos (+) cells were counted. Statistical analyses were performed by Kruskal–Wallis one-way analysis of variance (ANOVA) by rank.

Results

In all experimental groups, c-fos (+) cells increased in a time-dependent manner. The combination treatment of steroid and EGb was the most effective and the no-treatment group the least effective 1 week later after zinc sulfate irrigation. However, 3 weeks later after zinc sulfate irrigation, there was no statistically significant differences in the number of c-fos positive cells among all 4 groups (3 treatment groups and the control group).

Conclusion

The combination treatment of EGb and steroid enhanced the regeneration of the olfactory pathway after olfactory mucosal injury by zinc sulfate. Our study suggests that EGb could be an effective treatment option for olfactory dysfunction.     

Level alterations of the 2f 1–f 2 distortion product due to hypoxia in the guinea pig depend on the stimulus frequency

Increased intracranial pressure (ICP) is known to affect the levels of distortion product otoacoustic emissions (DPOAEs) in a frequency-specific manner. DPOAEs might, therefore, be used for monitoring the ICP non-invasively. Hypoxia can also cause alterations of DPOAE levels, which can be distinguished from ICP-related changes only, when their characteristics, in particular frequency specificity, are known in detail. DPOAEs at f ₂ = 2, 4, 8, 12 and 16 kHz and oxygen saturation (SaO₂) were continuously monitored in nine spontaneously breathing guinea pigs, anaesthetized by i.m. administration of midazolam, medetomidin and fentanyl, during the respiration of a gas mixture of N₂O and O₂ containing either 30% O₂ or 13% O₂. Fourteen hypoxic intervals in eight animals were included into final data analysis. Characteristic hypoxic level alterations with a level decrease and a remarkable level destabilization during hypoxia, and a pronounced reversible level decrease after reoxygenation were observed at the frequencies of 4, 8 and 16 kHz. At 2 and 12 kHz, the only reproducible effect of hypoxia was an increased fluctuation of the DPOAE level, which was significantly less pronounced compared with the other frequencies (P < 0.05 for 12 vs. 16 and 8 kHz and for 2 vs. 16 kHz). DPOAE level alterations due to hypoxia depend on the frequency in guinea pigs. Studies in human are warranted to improve non-invasive ICP monitoring with DPOAE by the detection of hypoxia-related changes.     

The importance of being specific–a meta-analysis evaluating the effect of antibiotics in acute otitis media

Background

Whether acute otitis media (AOM) should be the cause for antibiotic treatment has been a matter of debate during the last decades. Treatment guidelines are based on less than twenty trials that have found the effect of antibiotics on symptomatic outcomes in AOM, such as pain, to be very modest. Two recent trials found a more substantial effect of antibiotics when they looked at treatment failure as the outcome. That the effect varies with the chosen outcome may not only be because the true effect is different but also because different outcomes are more or less specific for the disease in question.

Objective

The purpose of this study was to perform a meta-analysis to calculate a composite risk ratio for treatment failure in AOM and also to investigate whether the specificity of treatment failure as an outcome differs from that of symptomatic outcomes, such as pain.

Methods

Trials evaluating the effect of antibiotics in AOM and reporting the number of treatment failures were identified and a fixed-effects meta-analysis was performed. In addition, the literature was searched for articles providing direct or indirect figures on the specificity of different outcomes in AOM trials. A hypothetical study was designed to show how differences in sensitivity/specificity of inclusion/outcome criteria affect the results of a trial.

Results

The meta-analysis yielded a composite risk ratio of 0.4 (95% CI 0.35–0.48), p < 0.001 for the effect of antibiotics on treatment failure. Based on data from the literature, the specificity of treatment failure was estimated to 92–100%. The hypothetical study showed how a non-specific outcome biases the effect estimate towards the null, whereas other kinds of misclassification only decrease precision.

Conclusion

Future trials should focus on improving diagnostic criteria to increase precision but primarily, they should focus on choosing a specific outcome in order not to get a biased effect estimate.