Faculty Bibliography

OBJECTIVES: We studied the effect of transforming growth factor (TGF)-beta on immortalized human vocal fold fibroblasts. METHODS: Normal human vocal fold fibroblasts were subjected to sequential lentiviral transduction with genes for human telomerase (hTERT) and SV40 large T antigen in order to produce an 'immortalized' cell line of normal phenotype. After confirmation of vocal fold fibroblast transfection, these cells, referred to as HVOX, were treated with various concentrations of exogenous TGF-beta1 and assayed for collagen secretion, migration, and proliferation. In addition, components of the TGF-beta signaling pathway were examined in this cell line. RESULTS: TGF-beta stimulated collagen secretion and migration without altering proliferation of HVOX. HVOX constitutively expressed type I and II TGF-beta receptors, as well as messenger RNA for the Smad signaling proteins and for all TGF-beta isoforms. Exogenous TGF-beta1 induced temporally dependent alterations in Smad2 and Smad3 gene expression. TGF-beta increased Smad7 expression at both 4 and 24 hours. Prolonged exposure to TGF-beta decreased TGF-beta1 gene expression. CONCLUSIONS: Insight into the underlying pathophysiology of vocal fold fibrosis is likely to yield improved therapeutic strategies to mitigate vocal fold scarring. Our data suggest that TGF-beta signaling may be both paracrine and autocrine in this vocal fold fibroblast cell line, and we therefore propose that TGF-beta may be a reasonable target for therapies to prevent and/or treat vocal fold fibrosis, given its putative role in both acute and chronic vocal fold injury, as well as its effects on vocal fold fibroblasts

OBJECTIVE/HYPOTHESIS: Oxidative damage mediates the lower airway response to cigarette smoke (CS). In the vocal folds, the tissue phenotype is both distinct and largely uncharacterized. We sought to investigate the effects of CS on the oxidative status and fibroblast phenotype in the vocal folds. Specifically, we hypothesized that CS would induce a hypermetabolic fibroblast phenotype and altered oxidative metabolism potentially providing insight into the relationship among CS, Reinke's edema (RE), and malignancy. STUDY DESIGN: In vivo/in vitro. METHODS: Heme oxygenase (HO)-1 gene expression was examined in human tissue. In vitro, the effects of cigarette smoke condensate (CSC) on HO-1 gene expression and secretion was assayed. In addition, CS-mediated intracellular reactive oxygen species synthesis was quantified, and compared to the response in pulmonary fibroblasts (HFL). We then examined the effects of CSC on migration and proliferation in human vocal fold fibroblasts (HVOX). RESULTS:: HO-1 expression was approximately 4-fold higher in RE samples versus vocal fold polyps. CSC induced HO-1 gene expression and secretion in a time- and dose-dependent fashion in vitro. CSC also increased intracellular ROS in both HVOX and HFL. CSC decreased HVOX proliferation and migration in a dose-dependent manner. CONCLUSIONS: These data suggest that the fibroblast phenotype is influenced by smoke. Our data suggest that the antioxidant response in the vocal fold tissue may be one mechanism of chemoprotection, a putative explanation for the observation that RE rarely transforms to malignancy. In addition, CSC does not appear to induce a hypermetabolic fibroblast phenotype as expected

This paper presents an optimal path planning method of steerable electrode arrays for robot assisted cochlear implant surgery In this paper, the authors present a novel design of steerable electrode arrays that can actively bend at the up An embedded strand in the electrode array provides an active steering degrees of freedom (DoF) This paper addresses the calibration of the steerable electrode arrays and the optimal path planning for inserting it into planar and three dimensional scala tympani models The goal of the path planning is to minimize the intracochlear forces that the electrode array applies on the walls of the scala tympam during insertion This problem is solved by designing insertion path planning algorithms that provide best fit between the shape of the electrode aunty and the curved scala tympani during insertion Optimality measures that account fittape discrepancies between the steerable electrode array and the scala tympam are used to solve for the optimal path planning of the robot Different arrangements of DoF and insertion speed force feedback (ISFF) are simulated and experimentally validated in this paper A quality of insertion metric describing the gap between the steerable electrode array and the scala tympam model is presented and as correspondence to the insertion force is shown The results of using 1DoF 2DoF and 4DoF electrode array insertion setups are compared The 1DoE insertion setup fiver nonsteerable electrode arrays The 2DoF insertion setup uses single axis insertion with steerable electrode arrays. The 4DoF insertion setup allows full control of the insertion depth and the approach angle of the electrode with respect to the cochlea while using steerable electrode arrays It is shown that living steerable electrode arrays significantly reducer the maximal insertion force (59.6% or more) and effectively prevents buckling of the electrode array The 4DoF Insertion setup further reduces the maximal electrode insertion forces The results of using ISFF for steerable electrodes show a slight decrease in the insertion forcer in contrast to a slight increase for nonsteerable electrodes These results show that further research is required in order to determine the optimal ISFF control law and its effectiveness in reducing electrode invention fortes [DOI 10.1115/1.3039513]

Hedgehog signaling is often activated in tumors, yet it remains unclear how GLI2, a transcription factor activated by this pathway, acts as an oncogene. We show that GLI2 is a pleiotropic oncogene. The overexpression induces genomic instability and blocks differentiation, likely mediated in part by enhanced expression of the stem cell gene SOX2. GLI2 also induces transforming growth factor (TGF)B1-dependent transdifferentiation of foreskin and tongue, but not gingival fibroblasts into myofibroblasts, creating an environment permissive for invasion by keratinocytes, which are in various stages of differentiation having downregulated GLI2. Thus, upregulated GLI2 expression is sufficient to induce a number of the acquired characteristics of tumor cells; however, the stroma, in a tissue-specific manner, determines whether certain GLI2 oncogenic traits are expressed

OBJECTIVE: To determine whether a 3-day course of postoperative antibiotics is as effective as a 7-day course in reducing pain and reducing time to resumption of a normal diet and level of activity following pediatric tonsillectomy. DESIGN: A prospective, randomized, placebo-controlled trial. SETTING: Academic medical center. PATIENTS: Forty-nine patients were enrolled in the study. Preoperative demographic information was obtained. INTERVENTIONS: Tonsillectomy with or without adenoidectomy was performed by the senior author (J.J.) using electrocautery. Patients were randomized to receive either a 3- or 7-day course of amoxicillin. MAIN OUTCOME MEASURES: Parents were asked to record the following information: analgesic use for the first 7 postoperative days, postoperative days the child initiated his or her usual diet and level of activity, and medical treatment for oral hemorrhage or dehydration. RESULTS: Of the 49 patients, 26 were randomized to receive 7 days of postoperative antibiotics (group A) and 23 to receive 3 days of antibiotics, followed by 4 days of placebo (group B). Results were obtained for 47 of the enrolled patients (96%). No statistically significant difference was noted between the 2 groups with regard to postoperative pain or time to resumption of a normal diet and level of activity. CONCLUSION: A 3-day course of antibiotics following pediatric tonsillectomy is as effective as a 7-day course with regard to postoperative analgesic use and resumption of normal diet and level of activity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00662987

This study investigates the effect of the Nucleus CI24RE implant's neural response telemetry (NRT) system, which has less internal noise compared to its predecessor, the CI24M/R implant, on the NRT threshold (TNRT) profile across the array. CI24M/R measurements were simulated by ignoring CI24RE measurements with response amplitudes below 50 uV. Comparisons of the estimated TNRTs from the CI24RE measurements and the CI24M/R simulations suggest that, apart from a constant level difference, the TNRT profiles from the newer implant generally would not have differed very much from those of its predecessor. This view was also reflected by principal component analysis (PCA) results which revealed a 'shift' component similar to that reported by Smoorenburg et al (2002). On the whole, there is no indication that current practices of using the TNRT profiles for assisting with speech processor programming need to be revised for the CI24RE implant

The purpose of this report is to summarize the salient points made during a panel discussion at the 88th Annual Meeting of the American Broncho-Esophagological Association about the efficacy and oncological safety of endoscopic laser treatment of laryngeal cancer. Guidelines for endoscopic laser management of early glottic and supraglottic cancer, including contraindications for this treatment modality, are presented. On the basis of all currently available data, the panel, which critically considered the question of oncological safety, is of the opinion that endoscopic laser resections are oncologically safe when applied judiciously and by a skilled oncological surgeon. Relative contraindications for endoscopic laser resection of laryngeal cancer include instances in which the whole tumor cannot be visualized; large tumors that require removing too much of the functional laryngeal unit, severely decreasing airway protection and leading to aspiration; and cartilage invasion. Specific contraindications for supraglottic cancer include bilateral arytenoid involvement and direct extension into the neck