Faculty Bibliography

Oxidative stress has been implicated as a cause of hair cell damage after ischemia reperfusion injury, noise trauma, and ototoxic injury. Oxidative stress can induce both apoptosis or necrosis depending on the degree of exposure. To study how reactive oxygen species (ROS) interacts with hair cells, we have developed an in vitro model of oxidative stress using organ of Corti cultures exposed to physiologically relevant concentrations of hydrogen peroxide (H(2) O(2) ). Treatment of organ of Corti cultures with low concentrations of H(2) O(2) results in loss of outer hair cells in the basal turn of the explant. Higher concentrations of peroxide result in more extensive outer hair cell injury as well as loss of inner hair cells. Early outer hair cell death appears to occur though apoptosis as demonstrated by staining of activated caspase. The effect of oxidative stress on mitochondrial function is a key determinant of degree of damage. Oxidative stress results in reduction of the mitochondrial membrane potential and reduction of mitochondrial produced antioxidants. Low doses of oxidative stress induce changes in mitochondrial gene expression and induce mitochondrial DNA deletions. Recurrent oxidative stress or inhibition of mitochondrial function significantly enhanced hair cell death. This tissue culture model of oxidative hair cell injury maintains a pattern of injury similar to what is observed in vivo after oxidative injury and can be used to study the effects of ROS on hair cells over the time period of the culture.

OBJECTIVE: The objective of this study was to review our pediatric emergency department's (ED's) utilization of computed tomography (CT) in the diagnosis of peritonsillar abscess (PTA) and treatment outcomes. METHODS: This study used case series with chart review. RESULTS: From January 2007 to January 2009, 148 patients were seen in our ED for possible PTA. Mean age at presentation was 11.8 years (range, 10 months to 18 years); 81 (54.7%) of 148 were females. Computed tomography was ordered in 96 (64.9%) of 148 patients, of which 73 (49.3%) 148 were confirmed to have PTA. Mean age of patients who underwent CT was younger when compared with those who did not have CT performed (mean, 11 vs 13 years; P = 0.02). Unilateral PTA was found in 65 (43.9%) of 148, bilateral in 8 (5.4%) of 148, and intratonsillar in 25 patients (16.9%). Concomitant CT findings of parapharyngeal space involvement were found in 19 (12.8%), and retropharyngeal space involvement in 11 (7.4%). Admission was necessary for 104 (71.2%) of 148 patients, whereas 42 were discharged from the ED. Transoral needle aspiration and/or incision and drainage were performed in the ED in 41 patients, with purulence identified in 33 (80.5%) of 41. Rapid strep testing was positive in 40 (32%) of 124 patients tested. Operative treatment was necessary in 44 patients (29.7%), 34 underwent incision and drainage, and 10 underwent quinsy tonsillectomy. CONCLUSIONS: Computed tomography is commonly utilized in the ED for the evaluation of PTA and is ordered more often in younger children.

PURPOSE: This dedicated QTc study was designed to evaluate the effect of the mammalian target of rapamycin inhibitor, ridaforolimus, on the QTc interval in patients with advanced malignancies. METHODS: We conducted a fixed-sequence, single-blind, placebo-controlled study. Patients (n = 23) received placebo on day 1 and a single 100-mg oral dose of ridaforolimus on day 2 in the fasted state. Holter electrocardiogram (ECG) monitoring was performed for 24 h after each treatment, and blood ridaforolimus concentrations were measured for 24 h after dosing. The ECGs were interpreted in a blinded fashion, and the QT interval was corrected using Fridericia's formula (QTcF). After a washout of at least 5 days, 22 patients went on to receive a therapeutic regimen of ridaforolimus (40 mg orally once daily for 5 days per week). RESULTS: The upper limit of the two-sided 90 % confidence interval for the placebo-adjusted mean change from baseline in QTcF was <10 ms at each time point. No patient had a QTcF change from baseline >30 ms or QTcF interval >480 ms. Geometric mean exposure to ridaforolimus after the single 100-mg dose was comparable to previous experience with the therapeutic regimen. There appeared to be no clear relationship between individual QTcF change from baseline and ridaforolimus blood concentrations. Ridaforolimus was generally well tolerated, with adverse events consistent with prior studies. CONCLUSIONS: Administration of the single 100-mg dose of ridaforolimus did not cause a clinically meaningful prolongation of QTcF, suggesting that patients treated with ridaforolimus have a low likelihood of delayed ventricular repolarization.

OBJECTIVES/HYPOTHESIS: To validate a clinical assessment score for pediatric sleep-disordered breathing. STUDY DESIGN: Prospective instrument validation. METHODS: One hundred children scheduled for overnight polysomnography were evaluated by a standardized history and physical examination and assigned a clinical assessment score. Parents completed the Obstructive Sleep Apnea (OSA)-18, the Pediatric Quality of Life Inventory (PedsQL) 4.0, and the Child Behavior Checklist questionnaires. Children with positive polysomnography underwent adenotonsillectomy or adenoidectomy. The identical assessments were performed at a mean follow-up of 8 months. RESULTS: Item reduction yielded a score of 15 items (Clinical Assessment Score-15 [CAS-15]) that demonstrated the best internal consistency and predictive utility (Cronbach alpha = .80). Intraclass correlation (ICC) demonstrated good intrarater (ICC, 0.78; 95% confidence interval [CI], 0.58 to 0.89) and inter-rater agreement (ICC, 0.65; 95% CI, 0.26 to 0.84). All change scores were significantly improved after surgery. Effect sizes were large for the CAS-15 (2.6), OSA-18 (2.4), and apnea-hypopnea index (1.4), and moderate for the Child Behavior Checklist (0.7) and PedsQL 4.0 (-0.5). Moderate to strong correlation was found between the initial CAS-15 scores and the external measures (|r| between 0.32 and 0.65). Receiver operating characteristic curves were constructed to determine the optimal initial CAS-15 score for predicting positive polysomnography. The area under the curve was 0.77 (95% CI, 0.67 to 0.87); and a score >/=32 yielded a sensitivity of 77.3% (95% CI, 65.3 to 86.7) and a specificity of 60.7% (95% CI, 40.6 to 78.5). CONCLUSIONS: The CAS-15 proved useful in an office setting and correctly diagnosed 72% of referred children when compared to polysomnography. It correlated well with external measures and demonstrated a good response to clinical change.

Objective: Glucocorticoids are commonly used treatments in otolaryngology, but guidelines about their use are vague and irregular. We sought to assess clinical practices with regard to glucocorticoid use for patients with laryngeal disease and to ascertain factors driving clinician drug choice. Method: A web-based survey was distributed to otolaryngologists via email using the Ear, Nose, and Throat (ENT) Journal database. This survey was composed of 20 questions and collected the following data from respondents: 1) indications for the use of glucocorticoids in their practice, 2) decision-making process influencing the choice of glucocorticoid, 3) background and demographics. Results: Two hundred eight otolaryngologists completed the survey, with 99% (n = 196) reporting that glucocorticoids were valuable to their practice. "Previous experience/results," "familiarity," and "use in practice" (n = 144, 114, and 79, respectively) were commonly cited reasons for choosing a particular glucocorticoid, whereas pharmacokinetic profile and "academic literature" were infrequently cited concerns. Only 54.4% (n = 106) of respondents said that they were more likely to prescribe glucocorticoids for vocal performers as compared to other patients. Additionally, most respondents said side effects only "occasionally" prevented them from prescribing glucocorticoids to patients. Conclusion: These results suggest that glucocorticoid prescription practices vary greatly between otolaryngologists, and drug choice is driven primarily by clinician preference rather than more objective factors. These findings indicate a need for further research about this powerful class of drugs, and the importance of establishing clear, appropriate guidelines regarding their use.

This study examines behavioral and physiological measures of pitch matching in cochlear implant (CI) users who have residual hearing in the contralateral ear. Subjects adjusted the frequency of an acoustic tone to match the pitch percept elicited by electrical stimulation in the other ear, when stimulation was alternating across two ears. In general, the selected acoustic frequencies did not line up perfectly with the center frequencies of the analysis bands corresponding to each stimulation electrode. Similar alternating electro-acoustic stimuli were used to record Auditory Evoked Potentials on 8 NH subjects and 3 CI patients. NH subjects were presented with a fixed tone in one ear, while tones in the other ear varied within a few octaves from the fixed tone. CI patients were stimulated with six different audible tones including their pitch-matched tones, while receiving electrical stimulation in the electrode. N1 latency for NH subjects was minimized when the same frequency was presented to both ears. Similarly, N1 latency for CI patients who are able to pitch match was minimized when the tone was at the pitch matched frequency of the stimulated electrode. These results suggest that N1 latency can be a possible objective measure of pitch matching. (Work supported by NIH/NIDCD 1K25DC010834-01;PI:Tan, PSC-CUNY;PI:Martin, and NIH/NIDCD R01-DC03937;PI:Svirsky.).