Otitis media (OM) is a major cause of morbidity in the United States, and remains the primary cause of hearing loss in children. While antibiotic administration has proven to be an effective treatment regimen for OM caused by bacterial infection, middle ear effusion (MEE) and inflammation often persist after antibiotic treatment. Studies by the investigators and others have identified inflammatory mediators (IM's) which contribute to disease pathogenesis but our understanding of this process is incomplete. More recent developments in the physiological actions of IM's, newly developed techniques that allow assessment of the subcellular message for IM synthesis, and new pharmacological agents that act on those IMs allow us to address important questions related to the pathogenesis of OM such as: * What is the temporal sequence of expression of the various IMs and related chemical signals including inflammatory cytokines, adhesion molecules, and nitric oxide synthase (NOS) in experimental OM? * Does prophylactic treatment with pharmacological blockers of these IM's alter IM express-ion and/or the course of pathological events in OM? * Will therapy with pharmacological agents that affect these lM's moderate the course of OM and the development of MEE's? This project answers the first question through the study of,the role of proinflammatory cytokines, NOS and cell adhesion molecules in the pathogenesis of OM and MEE. New immunomodulating agents permit the investigation of the second and third questions through their use as pharmacological probes of pathophysiological events. These will be used in a rat model of OM to test the hypothesis that pharmacological intervention in the inflammatory responses mediated by cytokines, NOS and cell adhesion molecules can moderate the course of the early responses to infections and the development of MEE. Two dosing strategies will be tested: intervention one day prior to ME infection to test the efficacy of prophylactic administration and intervention concurrent with the administration of antibiotics to test treatment efficacy. These experiments will better define the cause of inflammation during OM, assess the modulating effects of pharmacological intervention and possibly identify promising therapeutic agents that can be tested in the clinical setting.
| Doyle, William J; Swarts, J Douglas (2010) Eustachian tube-Tensor veli palatini muscle-cranial base relationships in children and adults: an osteological study. Int J Pediatr Otorhinolaryngol 74:986-90 |
| Doyle, William J; Yuksel, Sancak; Banks, Juliane et al. (2007) Directional asymmetry in the measured nitrous oxide time constant for middle ear transmucosal gas exchange. Ann Otol Rhinol Laryngol 116:69-75 |
| Doyle, William J (2007) The mastoid as a functional rate-limiter of middle ear pressure change. Int J Pediatr Otorhinolaryngol 71:393-402 |
| Li-Korotky, Ha-Sheng; Kelly, Lori A; Piltcher, Otavio et al. (2007) Evaluation of microbial RNA extractions from Streptococcus pneumoniae. J Microbiol Methods 68:342-8 |
| Chad Kanick, S; Kasi, Sundeep; Douglas Swarts, J et al. (2006) Accuracy of CO2 conductance predicted using a morphometric model of the middle ear mucosa. Acta Otolaryngol 126:1252-9 |
| Yuksel, Sancak; Doyle, William J; Banks, Juliane et al. (2005) Nasal prostaglandin challenge increases N2O exchange from blood to middle ear. Auris Nasus Larynx 32:29-32 |
| Kanick, Stephen Chad; Doyle, William J; Ghadiali, Samir N et al. (2005) On morphometric measurement of oxygen diffusing capacity in middle ear gas exchange. J Appl Physiol 98:114-9 |
| Chen, Anton; Li, Ha-Sheng; Hebda, Patricia A et al. (2005) Gene expression profiles of early pneumococcal otitis media in the rat. Int J Pediatr Otorhinolaryngol 69:1383-93 |
| Casselbrant, Margaretha L; Mandel, Ellen M; Rockette, Howard E et al. (2004) The genetic component of middle ear disease in the first 5 years of life. Arch Otolaryngol Head Neck Surg 130:273-8 |
| Li-Korotky, Ha-Sheng; Swarts, J Douglas; Hebda, Patricia A et al. (2004) Cathepsin gene expression profile in rat acute pneumococcal otitis media. Laryngoscope 114:1032-6 |
Showing the most recent 10 out of 58 publications
