The goals of this project are: (1) to determine the minimum dose of intratympanic gentamicin necessary to control vertigo in unilateral Meniere's disease, and (2) to determine what effects this dose has on the structure and function of the vestibular organs of the inner ear. Multiple intratympanic injections, if spaced 1 week apart and halted at the first signs of loss of vestibular function, can control vertigo in >90% of patients with no greater hearing loss than the disease itself causes. We will conduct a clinical trial in which gentamicin will be given every 2 weeks until vertigo is controlled. We wish to determine if lower total doses can control vertigo yet preserve some vestibular function as measured by 3-dimensional vestibulo-ocular reflexes, vestibular-evoked myogenic potentials, subjective visual vertical, and caloric tests. By following patients for one year we can also determine if some vestibular function returns over time. We also want to know what these doses of gentamicin do to the vestibular part of the inner ear and the vestibular nerve afferents. Are all or most of the hair cells destroyed? Do the vestibular nerve afferents stop responding? Is there some return of some function over time? If so, why? Do hair cells recover, do afferents become more sensitive, or does the brain adjust its responses to make up for the peripheral loss. These questions will be answered in an animal model. The candidate has a background in vestibular physiology and now seeks a long-term career in academic otolaryngology, focusing physiologic principles on clinical vestibular problems. The short-term goals are to master the fundamentals of clinical trial design and analysis, 3D eye movements, and afferent neurophysiology. Johns Hopkins is uniquely suited to this training because it has a core group devoted to vestibular research, and the mentor's laboratory has successfully used all of the techniques required.
| Migliaccio, Americo A; Minor, Lloyd B; Carey, John P (2008) Vergence-mediated modulation of the human angular vestibulo-ocular reflex is unaffected by canal plugging. Exp Brain Res 186:581-7 |
| Lyford-Pike, Sofia; Vogelheim, Casey; Chu, Eugene et al. (2007) Gentamicin is primarily localized in vestibular type I hair cells after intratympanic administration. J Assoc Res Otolaryngol 8:497-508 |
| Migliaccio, Americo A; Schubert, Michael C; Clendaniel, Richard A et al. (2006) Axis of eye rotation changes with head-pitch orientation during head impulses about earth-vertical. J Assoc Res Otolaryngol 7:140-50 |
| Migliaccio, Americo A; Della Santina, Charles C; Carey, John P et al. (2006) The effect of binocular eye position and head rotation plane on the human torsional vestibuloocular reflex. Vision Res 46:2475-86 |
| Hirvonen, Timo P; Minor, Lloyd B; Hullar, Timothy E et al. (2005) Effects of intratympanic gentamicin on vestibular afferents and hair cells in the chinchilla. J Neurophysiol 93:643-55 |
| Potyagaylo, Valeria L; Della Santina, Charley C; Minor, Lloyd B et al. (2005) Superior canal dehiscence is not due to cephalic displacement of the labyrinth. Ann N Y Acad Sci 1039:498-502 |
| Hullar, Timothy E; Della Santina, Charles C; Hirvonen, Timo et al. (2005) Responses of irregularly discharging chinchilla semicircular canal vestibular-nerve afferents during high-frequency head rotations. J Neurophysiol 93:2777-86 |
| Della Santina, Charles C; Potyagaylo, Valeria; Migliaccio, Americo A et al. (2005) Orientation of human semicircular canals measured by three-dimensional multiplanar CT reconstruction. J Assoc Res Otolaryngol 6:191-206 |
| Park, Hong Ju; Migliaccio, Americo A; Della Santina, Charley C et al. (2005) Search-coil head-thrust and caloric tests in Meniere's disease. Acta Otolaryngol 125:852-7 |
| Carey, J P; Cooper, T; Jallo, G I et al. (2005) Ototoxicity of carboplatin delivered locally in a monkey brainstem. Int J Toxicol 24:443-9 |
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