Faculty Bibliography

The MHC-encoded cofactor DM catalyzes endosomal loading of peptides onto MHC class II molecules. Despite evidence from in vitro experiments that DM acts to selectively edit the repertoire of class II:peptide complexes, the consequence of DM expression in vivo, or a predictive pattern of DM activity in the specificity of CD4 T cell responses has remained unresolved. Therefore, to characterize DM function in vivo we used wild-type (WT) or DM-deficient (DM(-/-)) mice of the H-2(d) MHC haplotype and tested the hypothesis that DM promotes narrowing of the repertoire of class II:peptide complexes displayed by APC, leading to a correspondingly selective CD4 T cell response. Surprisingly, our results indicated that DM(-/-) mice do not exhibit a broadened CD4 T cell response relative to WT mice, but rather shift their immunodominance pattern to new peptides, a pattern associated with a change in class II isotype-restriction. Specifically, we found that CD4 T cell responses in WT mice were primarily restricted to the I-A class II molecule, whereas DM(-/-) mice recognize peptides in the context of I-E. The observed shift in isotype-restriction appeared to be due in part to a modification in the peripheral CD4 T cell repertoire available for peptide recognition.

OBJECTIVES: This study compares normal and pathologic voices using a novel voice analysis algorithm that examines pitch deviation during connected speech. The study evaluates the clinical potential of the algorithm as a mechanism to distinguish between normal and pathologic voices using connected speech. METHODS: Adult vocalizations from normal subjects and patients with known benign free-edge vocal fold lesions were analyzed. Recordings had been previously obtained in quiet under controlled conditions. Two phrases and sustained /a/ were recorded per subject. The subject populations consisted of 10 normal and 31 abnormal subjects. The voice analysis algorithm generated 2-dimensional patterns that represent pitch deviation in time and under variable window widths. Measures were collected from these patterns for window widths between 10 and 250 ms. For comparison, jitter and shimmer measures were collected from sustained /a/ by means of the Computerized Speech Lab (CSL). A t-test and tests of sensitivity and specificity assessed discrimination between normal and abnormal populations. RESULTS: More than 58% of the measures collected from connected speech outperformed the CSL jitter and shimmer measures in population discrimination. Twenty-five percent of the experimental measures (including /a/) indicated significantly different populations (p < .01%). CONCLUSIONS: The results demonstrate that the algorithm distinguishes between normal and abnormal populations by use of samples of connected speech

BACKGROUND: In the neck, the recipient vessels most frequently used for microsurgical reconstruction are compromised by prior surgery and radiation. METHODS: We conducted a retrospective chart review of all patients who underwent microvascular reconstruction between July 2001 and June 2005. Donor vessels, vein grafts, and flap survival were examined. RESULTS: Fourteen of 197 patients (7%) were identified with a vessel-depleted neck. All patients had undergone a prior neck dissection and radiation (100%) or chemoradiation (42%). Free flap revascularization was achieved using the transverse cervical artery with a vein graft and a cephalic vein (4 patients), thoracoacromial artery and cephalic vein (3 patients), internal mammary artery and vein (3 patients), and inferior thyroid artery and cephalic vein (1 case). In 3 patients, the reverse flow thoracodorsal artery and cephalic vein were used to vascularize the scapular flap. CONCLUSION: The cephalic vein, transverse cervical, internal mammary, and thoracoacromial vessels represent reliable alternatives in the vessel-depleted neck.

The effect of membrane electrical activity on spiral ganglion neuron (SGN) neurite growth remains unknown despite its relevance to cochlear implant technology. We demonstrate that membrane depolarization delays the initial formation and inhibits the subsequent extension of cultured SGN neurites. This inhibition depends directly on the level of depolarization with higher levels of depolarization causing retraction of existing neurites. Cultured SGNs express subunits for L-type, N-type, and P/Q type voltage-gated calcium channels (VGCCs) and removal of extracellular Ca(2+) or treatment with a combination of L-type, N-type, and P/Q-type VGCC antagonists rescues SGN neurite growth under depolarizing conditions. By measuring the fluorescence intensity of SGNs loaded with the fluorogenic calpain substrate t-butoxy carbonyl-Leu-Met-chloromethylaminocoumarin (20 muM), we demonstrate that depolarization activates calpains. Calpeptin (15 muM), a calpain inhibitor, prevents calpain activation by depolarization and rescues neurite growth in depolarized SGNs suggesting that calpain activation contributes to the inhibition of neurite growth by depolarization

PURPOSE OF REVIEW/OBJECTIVE:Pressure is mounting on physicians to adopt electronic medical records. The field of health information technology is evolving rapidly with innovations and policies often outpacing science. We sought to review research and discussions about electronic medical records from the past year to keep abreast of these changes. RECENT FINDINGS/RESULTS:Original scientific research, especially from otolaryngologists, is lacking in this field. Adoption rates are slowly increasing, but more of the burden is shouldered by physicians despite policy efforts and the clear benefits to third-party payers. Scientific research from the past year suggests lack of improvements and even decreasing quality of healthcare with electronic medical record adoption in the ambulatory care setting. The increasing prevalence and standardization of electronic medical record systems results in a new set of problems including rising costs, audits, difficulties in transition and public concerns about security of information. SUMMARY/CONCLUSIONS:As major players in healthcare continue to push for adoption, increased effort must be made to demonstrate actual improvements in patient care in the ambulatory care setting. More scientific studies are needed to demonstrate what features of electronic medical records actually improve patient care. Otolaryngologists should help each other by disseminating research about improvement in patient outcomes with their systems since current adoption and outcomes policies do not apply to specialists.

BACKGROUND: Radiation alone or concurrent chemoradiation can result in severe swallowing disorders. This manuscript defines the swallowing disorders occurring at pretreatment and 3 and 12 months after completion of radiation or chemoradiation. METHODS: Forty-eight patients (10 women and 38 men) participated in this study involving videofluorographic evaluation of oropharyngeal swallow at the 3 time points. RESULTS: At baseline, patients had some swallow disorders, probably related to presence of their tumor. At 3 months posttreatment, frequency of reduced tongue base retraction, slow or delayed laryngeal vestibule closure, and reduced laryngeal elevation increased from baseline. Some disorders continued at 12 months posttreatment. Functional swallow decreased over time in patients treated with chemoradiation, but not those treated with radiation alone. DISCUSSION: Chemoradiation results in fewer functional swallowers than radiation alone at 12 months posttreatment completion

OBJECTIVE: Various energy delivery systems have been utilized to treat superficial rhytids in the aging face. The Intense Ultrasound System (IUS) is a novel modality capable of transcutaneously delivering controlled thermal energy at various depths while sparing the overlying tissues. The purpose of this feasibility study was to evaluate the response of porcine tissues to various IUS energy source conditions. Further evaluation was performed of the built-in imaging capabilities of the device. MATERIALS AND METHODS: Simulations were performed on ex vivo porcine tissues to estimate the thermal dose distribution in tissues after IUS exposures to determine the unique source settings that would produce thermal injury zones (TIZs) at given depths. Exposures were performed at escalating power settings and different exposure times (in the range of 1-7.6 J) using three IUS handpieces with unique frequencies and focal depths. Ultrasound imaging was performed before and after IUS exposures to detect changes in tissue consistency. Porcine tissues were examined using nitro-blue tetrazolium chloride (NBTC) staining sensitive for thermal lesions, both grossly and histologically. The dimensions and depth of the TIZs were measured from digital photographs and compared. RESULTS: IUS can reliably achieve discrete, TIZ at various depths within tissue without surface disruption. Changes in the TIZ dimensions and shape were observed as source settings were varied. As the source energy was increased, the thermal lesions became larger by growing proximally towards the tissue surface. Maximum lesion depth closely approximated the pre-set focal depth of a given handpiece. Ultrasound imaging detected well-demarcated TIZ at depths within the porcine muscle tissue. CONCLUSION: This study demonstrates the response of porcine tissue to various energy dose levels of Intense Ultrasound. Further study, especially on human facial tissue, is necessary in order to understand the utility of this modality in treating the aging face and potentially, other cosmetic applications

OBJECTIVE: To assess word recognition and pitch-scaling abilities of cochlear implant users first implanted with a Nucleus 10-mm Hybrid electrode array and then reimplanted with a full length Nucleus Freedom array after loss of residual hearing. BACKGROUND: Although electroacoustic stimulation is a promising treatment for patients with residual low-frequency hearing,a small subset of them lose that residual hearing. It is not clear whether these patients would be better served by leaving in the 10-mm array and providing electric stimulation through it, or by replacing it with a standard full-length array. METHODS: Word recognition and pitch-scaling abilities were measured in 2 users of hybrid cochlear implants who lost their residual hearing in the implanted ear after a few months. Tests were repeated over several months, first with a 10-mm array, and after, these patients were reimplanted with a full array. The word recognition task consisted of 2 50-word consonant nucleus consonant (CNC) lists. In the pitch-scaling task, 6 electrodes were stimulated in pseudorandom order, and patients assigned a pitch value to the sensation elicited by each electrode. RESULTS: Shortly after reimplantation with the full electrode array, speech understanding was much better than with the 10-mm array. Patients improved their ability to perform the pitch-scaling task over time with the full array, although their performance on that task was variable, and the improvements were often small. CONCLUSION: 1) Short electrode arrays may help preserve residual hearing but may also provide less benefit than traditional cochlear implants for some patients. 2) Pitch percepts in response to electric stimulation may be modified by experience