Hearing loss is associated with administration of some life-threatening medications. Cis-platinum is an effective anti-neoplastic agent which is more likely to cause hearing loss in children than in adults receiving proportionate doses. Also, children who develop hearing loss as a result of cis-platinum, tend to have more severe changes in hearing than do adults. Hearing loss in children can have devastating long-term ramifications on language acquisition, cognitive development and socialization, particularly if the hearing impairment goes unrecognized. As a pediatric otolaryngologist, I am interested in preventing the handicapping effects of acquired hearing loss in children. The proposed experiments address age-related differences in susceptibility to hearing loss after cis-platinum administration. The central goal of these experiments is to better understand the factors of increased developmental sensitivity to hearing loss, so that it may be effectively prevented. Animals pass through a phase of development during which they are more susceptible to hearing loss after exposure to ototoxic agents; exposure before or after this period is not as likely to cause hearing loss. In the proposed research, an animal model will be developed using the Mongolian gerbil (Marinas angiocholitis) because it undergoes postnatal maturation of the auditory function. Distortion product otoacoustic emissions, auditory brain stem responses, and endocochlear potentials will be measured to determine the site(s) of action of cis-platinum within the peripheral auditory system at different developmental stages. Serum levels of cis-platinum will be measured to determine if higher blood levels of cis-platinum are found during the period of increased sensitivity. The data will provide insight into the age-dependent effects of cis-platinum. A clinical protocol is designed to: 1) define the sensitive period to cis- platinum ototoxicity and 2) assess the role of distortion product otoacoustic emissions in monitoring ototoxicity in children. Children receiving cis-platinum will be evaluated prospectively, using distortion product otoacoustic emissions and age-appropriate audiometric testing. Early identification of hearing loss in children is critical in minimizing its handicapping effects. The University of Washington and Children's Hospital and Medical Center provide an environment which would allow me to develop this research interest because of the availability of outstanding mentors and the institutional commitment to academic medicine.
