Faculty Bibliography

By a focus on three essential elements of language: phonology, semantics, and syntax, a time frame for critical/sensitive periods of language development is presented as a model of central auditory nervous system flexibility. Several studies support the hypothesis that the critical/sensitive period of phonology is from the 6th month of fetal life through the 12th month of infancy. Data indicate that the critical/sensitive periods for syntax run through the 4th year of life, and for semantics through the 15th or 16th year of life. The data indicate that there is a time dependent series of functions in sequence that is based on responsive adaptations made by the CNS to pyschophysical and electrophysiological stimuli.

HYPOTHESIS: Cisplatin causes the generation of reactive oxygen species (ROS), which interferes with the antioxidant defense system of Corti's organ and results in damage to the hair cells. BACKGROUND: Cisplatin is a widely used chemotherapeutic agent with the dose-limiting side effect of ototoxicity. Evidence is accumulating that cisplatin interferes with the antioxidant defense system of Corti's organ. METHODS: Organotypic explants of P-3 rat organ of Corti were the in vitro model system. Presence of intact auditory hair cells and stereocilia bundle integrity was assayed by phalloidin-FITC staining. Fluorescent dye probes detected H2O2 and intracellular thiol [e.g., glutathione (GSH)]. Spectrophotometric analysis determined antioxidant enzyme levels. RESULTS: There was a rapid dose-dependent cisplatin cytotoxicity in the explants after 48 h of exposure. An accumulation of H2O2 and a reduction of GSH levels were observed within cisplatin-exposed hair cells. L-buthionine sulfoximine, an inhibitor of GSH formation, enhanced cisplatin ototoxicity, whereas N6-(2-phenylisopropyl) adenosine, an adenosine agonist, elevated antioxidant enzyme levels and ameliorated cisplatin toxicity. The following molecules protected hair cells from cisplatin-induced damage: GSH; glutathione diethyl ester (GSHe); ebselen (EBS); 4-methylthiobenzoic acid (MTBA); and D-methionine (D-MET). EBS, MTBA, and D-MET in vitro protection correlates with in vivo protection in rats. CONCLUSIONS: Organotypic culture of Corti's organ has been validated as a model for studying cisplatin toxicity and for screening otoprotective molecules. Some of the events that contribute to cisplatin's ability to damage auditory hair cells are generation of ROS (e.g., H2O2), depletion of intracellular GSH, and interference with antioxidant enzymes within the cochlea. Agents that bolster the cochlea's antioxidant system can prevent cisplatin destruction of auditory hair cells. Identified protective agents may prove to be clinically useful in limiting or completely protecting from cisplatin ototoxicity.

Recent advances in the study of the genetic basis of hearing loss include the mapping of several nonsyndromic deafness genes and the cloning and characterization of several genes for syndromic deafness. It is now clear that some types of Usher syndrome are caused by a mutation in a gene for a myosin protein, that Jervall Lange Neilson syndrome is caused by a mutant gene for a potassium channel protein, and that the mutant gene underlying branchial-oto-renal syndrome is similar to the eyes absent gene in drosophila. These developments mark concrete progress towards understanding cochlear molecular physiology and towards the creation of clinically useful tests for inherited hearing loss

The purpose of this study was to determine the effectiveness of specialty pads as an intervention to reduce the incidence of intraoperatively acquired pressure sores. A convenience sample (N = 361) was drawn from all inpatients who underwent cardiothoracic or major vascular surgery on the standard operating room table (group 1), the air-filled pad (group 2), or the specialty foam pad (group 3). This sample was inclusive of 100% of patients during the study period who met the criteria. The incidence of pressure sore development was seven in group 1, zero in group 2, and one in group 3. There was at statistically significant difference (p = 0.0003) between group 1 and group 2. Additionally, a statistically significant difference (p = 0.0003) was found between group 1 and group 3. The foam pad and the air-filled pad were effective interventions for reducing the risk of intraoperatively acquired pressure sores.