Intrasaccular injection of aminoglycosides: a novel method for temporary damaging fish inner ear hair cells

Fish models are increasingly being used for hearing research investigations. Aminoglycoside antibiotics that are used for damaging the inner ear hair cells can have systemic side effects leading to death of study animals. This study aimed to compare two methods: i) systemic (intravenous) and ii) local (intrasaccular) gentamicin administration for induction of inner ear hair cell damage in the Atlantic cod, Gadus morhua (L.). Hair cell damage was assessed using scanning electron microscopy; hair cell density, prevalence of immature hair cells and kinocilia length were measured. Gentamicin-treated fish were compared with control and sham fish. Intravenous gentamicin led to dose-dependent mortality caused by nephrotoxicity. The only visible effect after treatment was more immature hair cells and shorter kinocilia, the effect on hair cell density was equivocal. Following intrasaccular gentamicin treatment, fish mortality was negligible, and hair cells were damaged regardless of dose. Here, we observed decreased hair cell density, high prevalence of immature hair cells, and significantly shortened kinocilia. Conclusion: intrasaccular injection is preferable to intravenous injection of gentamicin for the study of ototoxicity in the Atlantic cod

Damage and functional recovery of the Atlantic cod (Gadus morhua) inner ear hair cells following local injection of gentamicin

This study addresses the ultrastructural and functional damage and subsequent recovery of the inner ear in the Atlantic cod following intrasaccular gentamicin injection. Inner ear damage was assessed using SEM and measurements of AEP following 250-Hz pure-tone stimuli. Data from gentamicin-treated fish were compared with control (no injection) and sham (injection of saline) fish. Control fish had normal response thresholds associated with welldeveloped hair cell bundles in their macula sacculi. Sham fish had higher response thresholds compared with control fish during the first week post-intervention, but response thresholds were subsequently normal. Treated fish displayed significant inner ear damage associated with an increased average AEP threshold on the third day following treatment. Thereafter, inner ear tissue displayed signs of progressive regeneration until it was comparable to controls from the 14th day. Response thresholds were similar to those of control fish from the 17th day following treatment. These observations suggest that the macula sacculi of Atlantic cod can regenerate towards a near-complete functional and ultrastructural recovery within 17-21 days following ototoxic gentamicin treatment

Hearing loss and tinnitus in rock musicians: A Norwegian survey

Our focus in this study was to assess hearing thresholds and the prevalence and characteristics of tinnitus in a large group of rock musicians based in Norway. A further objective was to assess related factors such as exposure, instrument category, and the preventive effect of hearing protection. The study was a cross-sectional survey of rock musicians selected at random from a defined cohort of musicians. A random control group was included for comparison. We recruited 111 active musicians from the Oslo region, and a control group of 40 nonmusicians from the student population at the University of TromsØ. The subjects were investigated using clinical examination, pure tone audiometry, tympanometry, and a questionnaire. We observed a hearing loss in 37.8% of the rock musicians. Significantly poorer hearing thresholds were seen at most pure-tone frequencies in musicians than controls, with the most pronounced threshold shift at 6 kHz. The use of hearing protection, in particular custom-fitted earplugs, has a preventive effect but a minority of rock musicians apply them consistently. The degree of musical performance exposure was inversely related to the degree of hearing loss in our sample. Bass and guitar players had higher hearing thresholds than vocalists. We observed a 20% prevalence of chronic tinnitus but none of the affected musicians had severe tinnitus symptomatology. There was no statistical association between permanent tinnitus and hearing loss in our sample. We observed an increased prevalence of hearing loss and tinnitus in our sample of Norwegian rock musicians but the causal relationship between musical exposure and hearing loss or tinnitus is ambiguous. We recommend the use of hearing protection in rock musicians

Transient evoked otoacoustic emissions in rock musicians

<p><i>Objective</i>: Our focus in this study was the assessment of transient evoked otoacoustic emissions (TEOAEs) in a large group of rock musicians. A further objective was to analyse tinnitus among rock musicians as related to TEOAEs. <i>Design</i>: The study was a cross-sectional survey of rock musicians selected at random. A control group was included at random for comparison. <i>Study sample</i>: We recruited 111 musicians and a control group of 40 non-musicians. Testing was conducted by using clinical examination, pure tone audiometry, TEOAEs and a questionnaire. <i>Results</i>: TEOAE SNR in the half-octave frequency band centred on 4 kHz was significantly lower bilaterally in musicians than controls. This effect was strongly predicted by age and pure-tone hearing threshold levels in the 3–6 kHz range. Bilateral hearing thresholds were significantly higher at 6 kHz in musicians. Twenty percent of the musicians had permanent tinnitus. There was no association between the TEOAE parameters and permanent tinnitus. <i>Conclusions</i>: Our results suggest an incipient hearing loss at 6 kHz in rock musicians. Loss of TEOAE SNR in the 4 kHz half-octave frequency band was observed, but it was related to higher mean 3–6 kHz hearing thresholds and age. A large proportion of rock musicians have permanent tinnitus.</p

Hearing in schoolchildren after neonatal exposure to a high-dose gentamicin regimen

OBJECTIVE: To assess the association between gentamicin exposure in the neonatal period and hearing in school age. METHODS: This study included children exposed to a high-dose (6 mg/kg) gentamicin regimen as neonates (2004–2012), invited for follow-up at school age, and a healthy age-matched control group. We assessed hearing with pure tone audiometry including the extended high-frequency (EHF) range. Outcomes were average hearing thresholds in the midfrequencies (0.5–4 kHz) and the EHFs (9–16 kHz). The measures of gentamicin exposure were cumulative dose and highest trough plasma concentration. We used linear regression models to assess the impact of gentamicin exposure, and other peri- and postnatal morbidities, on hearing thresholds. RESULTS: A total of 219 gentamicin-exposed and 33 healthy-control children were included in the audiological analysis. In the gentamicin cohort, 39 (17%) had a birth weight <1500 g. Median cumulative doses and trough plasma concentrations were 30 (interquartile range 24–42) mg/kg and 1.0 (interquartile range 0.7–1.2) mg/L, respectively. Median hearing thresholds for the midfrequencies and the EHFs were 2.5 (0 to 6.3) dB hearing level and −1.7 (−5.0 to 5.0) dB hearing level, both of which were within the normal range. In an adjusted analysis, increasing hearing thresholds were associated with lower birth weight and postnatal middle-ear disease but not level of gentamicin exposure. After adjusting for birth weight, there was no difference in hearing threshold between the gentamicin-exposed cohort and healthy controls. CONCLUSIONS: Exposure to a high-dose gentamicin regimen in the neonatal period was not associated with an increase in hearing thresholds in schoolchildren being able to complete audiometry

Aminoglycoside antibiotics and the sensory hair cells of inner ear and lateral line system in the Atlantic cod, Gadus morhua: effects on fish hearing threshold

The aims of the present study were to investigate: a) the potential involvement of the fish lateral line system in hearing at 250 Hz and b) the possible regeneration of the inner ear hair cells in the Atlantic cod (Gadus morhua). The inner ear and lateral line system of the Atlantic cod were inactivated using ototoxic aminoglycoside antibiotics by injection (gentamicin) or bath (gentamicin and streptomycin), respectively. Hearing thresholds were measured in the fish using the Auditory Brainstem Response (ABR) technique at 10, respectively 17 - 20 days following antibiotic treatment. Results were compared between groups of individuals i) with inner ear damage, ii) with lateral line system altered, iii) placebo (immersion in fresh sea water) and iv) control. The sound stimuli applied were series of 2000 five-cycle (2-1-2) 250 Hz tone bursts delivered using a Brüel & Kjær (Nærum, Denmark) loudspeaker. ABRs were measured using a filter set at 30-3000 Hz, a gain of 100 000 and visual interpretation using the Bio-Logic AEP software. Sound stimulus level was reduced until threshold was attained. To check the tissue status of the inner ear and lateral line system, hair cells from sensory maculae were visualized using scanning electron microscope (SEM). Ten days after treatment, hearing thresholds of placebo and lateral line damaged cods did not differ from controls fish (p = 0.387 and p = 0.095, respectively), whereas the fish that received intravenous gentamicin injection had significantly elevated hearing thresholds compared to controls (p < 0.0001). SEM analyses further demonstrated that, 10 days following antibiotic treatment, cod inner ear hair cells were damaged, as well as lateral line hair cells and more particularly in the case of canal neuromasts. There was no hearing effect or microscopic tissue damage in untreated fish. From the 17th day after treatment, ABR measurements showed that some of the gentamicin treated fish had regained hearing thresholds comparable to the control cods (p = 0.535), and this was associated with an apparent regeneration of hair cells in the sensory maculae of their inner ear. This study indicates a capacity for inner ear hair cell regeneration in Atlantic cod, and illustrates the advantages of the ABR-method for investigation of fish hearing after intervention on the inner ear, and during the hair cell regeneration process. The present work further suggests that the lateral line system is not involved in cod hearing at 250 Hz

Localization of Staphylococcus aureus in tissue from the nasal vestibule in healthy carriers

Abstract Background Colonization of the body is an important step in Staphylococcus aureus infection. S. aureus colonizes skin and mucous membranes in humans and several animal species. One important ecological niche of S. aureus is the anterior nares. More than 60% of the S. aureus in the nose are found in vestibulum nasi. Our aim was to describe the localization of S. aureus in nasal tissue from healthy carriers. Methods Punch skin biopsies were taken from vestibulum nasi from healthy volunteers (S. aureus carriers and non−/intermittent carriers, n = 39) attending the population-based Tromsø 6 study. The tissue samples were processed as frozen sections before immunostaining with a specific S. aureus antibody, and finally evaluated by a confocal laser-scanning microscope. Results Our results suggest that S. aureus colonize both the upper and lower layers of the epidermis within the nasal epithelium of healthy individuals. The number of S. aureus in epidermis was surprisingly low. Intracellular localization of S. aureus in nasal tissue from healthy individuals was also detected. Conclusions Knowledge of the exact localization of S. aureus in nasal tissue is important for the understanding of the host responses against S. aureus. Our results may have consequences for the eradication strategy of S. aureus in carriers, and further work can provide us with tools for targeted prevention of S. aureus colonisation and infection