An optimized, clinically relevant mouse model of cisplatin-induced ototoxicity.

Cisplatin-induced ototoxicity results in significant, permanent hearing loss in pediatric and adult cancer survivors. Elucidating the mechanisms underlying cisplatin-induced hearing loss as well as the development of therapies to reduce and/or reverse cisplatin ototoxicity have been impeded by suboptimal animal models. Clinically, cisplatin is most commonly administered in multi-dose, multi-cycle protocols. However, many animal studies are conducted using single injections of high-dose cisplatin, which is not reflective of clinical cisplatin administration protocols. Significant limitations of both high-dose, single-injection protocols and previous multi-dose protocols in rodent models include high mortality rates and relatively small changes in hearing sensitivity. These limitations restrict assessment of both long-term changes in hearing sensitivity and effects of potential protective therapies. Here, we present a detailed method for an optimized mouse model of cisplatin ototoxicity that utilizes a multi-cycle administration protocol that better approximates the type and degree of hearing loss observed clinically. This protocol results in significant hearing loss with very low mortality. This mouse model of cisplatin ototoxicity provides a platform for examining mechanisms of cisplatin-induced hearing loss as well as developing therapies to protect the hearing of cancer patients receiving cisplatin therapy.

Basic characteristics of click-evoked otoacoustic emissions in infants and children.

Since Kemp [J. Acoust. Soc. Am. 64, 1386-1391 (1978)] first described click-evoked otoacoustic emissions (COAEs), researchers have advocated their use as an excellent tool for diagnosing hearing loss in infants and children. However, there are few detailed reports of COAEs in this population, and those that do exist suggest that there are age-dependent differences. The purpose of the current study was to determine basic characteristics of COAEs in infants, toddlers, children, and young adults and to define any differences among age groups. An additional goal was to ensure that spontaneous otoacoustic emissions (SOAEs) did not confound any possible developmental effects. COAEs and SOAEs were measured from one ear of 223 normal-hearing subjects. COAE input/ output functions indicated that children aged less than one year have higher COAE levels than older children and adults. Children aged 1-5 yr had higher COAE levels than those aged 12-17 yr and adults. These differences were independent of level and SOAE status, but were dependent on frequency. The results of this study suggest that different clinical norms may be necessary for children aged less than 6 years.

Basic characteristics of distortion product otoacoustic emissions in infants and children.

Distortion-product otoacoustic emissions at the 2 f1-f2 frequency (DPOAEs) are being advocated as a clinical tool for diagnosis of peripheral auditory pathology. Because they can be measured quickly and noninvasively, they may be an excellent method for identifying hearing loss in infants and children. However, few studies have examined the characteristics of DPOAEs in infants and children or detailed if, and how, their responses differ from those of adults. The purpose of the current study was to determine basic characteristics of DPOAEs in infants, toddlers, children, and young adults and to define any differences among age groups. An additional goal was to ensure that the presence of spontaneous otoacoustic emissions (SOAEs) did not confound any developmental effect. DPOAE input/output (I/O) functions at seven f2 frequencies and SOAEs were measured from one ear of 196 subjects. Children aged less than 1 yr had significantly higher mean DPOAE levels than older children and adults, and children aged 1-3 yr had higher mean DPOAE levels than teens and adults. These differences were dependent on frequency but were independent of f2 level and SOAE status. At every f2 frequency, groups of individuals having SOAEs had higher mean DPOAE levels than those not having SOAEs.

COAE thresholds: 1. Effects of equal-amplitude versus subtraction methods.

Although research has demonstrated that click-evoked otoacoustic emissions (COAEs) elicited by high-level stimuli are useful for identifying hearing loss, the ability of COAEs to predict behavioral thresholds has not been adequately tested. Results of studies comparing COAE thresholds and behavioral thresholds have been equivocal, perhaps due to the need for a more rigorous approach to COAE threshold estimation. The present study was designed to address several methodological concerns in COAE threshold testing, particularly the effects of two methods of stimulus presentation on COAE testing and threshold calculation. In an attempt to make COAE threshold estimation consistent across participants, COAE threshold calculations were based on mean noise floor levels across participants. COAE and noise floor levels were measured in 15 participants using both equal-amplitude clicks and a subtraction method. Broadband COAEs were analyzed into 1/3 octave bands, so that input/output functions could be examined and COAE thresholds could be calculated for each 1/3 octave band. Comparison of the two stimulus methods indicated several differences. Mean noise floor levels for the equal-amplitude method were approximately 6 dB lower than those measured for the subtraction method across frequency. In many cases COAEs evoked using the equal-amplitude method were higher in amplitude than those evoked using the subtraction method. COAE thresholds measured using the equal-amplitude click stimuli were significantly lower than those measured using the subtraction method. The significantly higher thresholds obtained using the subtraction method may be attributed in part to the reduction of COAE amplitude by the subtraction procedure, and not merely to the higher noise level. Slopes of the input/output functions were not significantly different between the two stimulus methods. These results suggest that the equal-amplitude method is preferable for COAE threshold testing because lower noise floor and larger amplitude COAEs may be obtained in the same test time.

A simplified system of human milk banking.

A simplified system of human milk banking, from milk supplied from home or hospital, has been evaluated for use in a neonatal intensive care unit. Twenty milk samples were obtained at a single expression using a standard hand pump and divided into three parts. Analyses were performed on the raw milk and on samples stored at -20 degrees C for 1 week and 1 month. No pathogens were isolated from any samples and the counts of Staphylococcus albus in the raw milk remained unchanged after storage. 19% of the cells in the original milk survived freezing and remained viable. There was a loss of bacteriostatic activity after storage for one month but significantly less than that caused by pasteurization. No change in levels of IgA, IgM, IgF, lactoferrin, lysozyme, C3 and C4 was apparent and concentrations of amino acids and fatty acids also remained unchanged after storage. We conclude that milk can be safely and conveniently stored by this method without loss or damage to the components of raw breast milk important for preterm and sick infants.