Faculty Bibliography

OBJECTIVES: We sought to better characterize pathologic changes that occur in the human vocal fold after radiotherapy for head and neck cancer. METHODS: In a blinded, controlled study of archived tissue, we evaluated postirradiation salvage laryngectomy vocal fold tissue without evidence of malignant disease. Clinical and demographic patient data were collected. In a blinded fashion, irradiated tissue was compared to nonirradiated, benign control tissue. Histomorphometric analysis was used to assess muscle and collagen organization, superficial lamina propria (SLP) and vocal ligament thickness, vocalis muscle fiber area, collagen content, and hyaluronic acid content. Immunohistochemical analysis was used to assess the content of type I collagen, type IV collagen, vimentin, fibronectin, alpha-smooth muscle actin, matrix metalloproteinase 9, and laminin. RESULTS: Twenty irradiated vocal folds were evaluated and compared to control specimens. Collagen and muscle disorganization was noted in the irradiated specimens. The SLP and vocal ligament thicknesses and the mean muscle fiber diameters did not differ significantly. The SLP fibronectin and the vocalis muscle and SLP collagen content were significantly increased in the irradiated vocal folds, and the SLP collagen content increased significantly with time between irradiation and resection. The laminin content of irradiated vocalis muscles was significantly decreased. CONCLUSIONS: Radiotherapy results in significant vocal fold tissue changes. Having more precisely defined these changes, we plan continued investigation seeking targeted preventive and therapeutic interventions for improved vocal quality following radiotherapy.

Perception of the impact of voice disorders may differ across different cultural backgrounds. This study investigated the difference in the perception of the impact of voice disorders between the American (Pittsburgh) and Chinese (Hong Kong) cultures. Study Design and Setting: Sixty dysphonic subjects from Hong Kong, China, and 60 dysphonic subjects from Pittsburgh, USA, were recruited to complete the Chinese and English versions of the Voice Activity and Participation Profile (VAPP), respectively. Data analyses using independent t tests were conducted on (1) the total profile scores; (b) total activity limitation score (ALS) and total participation restriction score (PRS); (c) section scores of job, daily communication, and social communication; and (d) section ALS and section PRS. Results: Hong Kong subjects showed significantly higher scores than the Pittsburgh subjects in total profile and other subsections except in the job PRS. Conclusion: Results support the possible influence of individualist and collectivist cultures on the perceived impact of voice disorders on the activity and participation.

Although Reinke's space, or layer, is a critical laryngeal structure, and the eponym is in current use in both clinical and research milieus, little is known about the life of the eponymist, German anatomist Friedrich Berthold Reinke. Extensive investigation of the archives at the University of Rostock and other sources, as well as multinational collaboration, has yielded unique insight into the personal and professional life of this pioneer who, among other things, identified and characterized the subepithelial space of the vocal fold and structures in the Leydig cells of the testicles and ovaries. This breadth of investigation reflects Reinke's intellectual curiosity and broad-ranging interest as well as his scientific environment. Without question, Reinke's observations of the human vocal fold are substantive contributions, without which modern laryngology could not have evolved. In 2009, at the 90th anniversary of Reinke's death, we summarize his achievements to express our appreciation for his singular brilliance and fundamental contribution to laryngology.

In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation modes. For sequential VCs, the interpulse interval (IPI) varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud, loudness-balanced levels at a 250 pulse per second per electrode (ppse) stimulation rate. On average, CI subjects were able to reliably discriminate between sequential and simultaneous VCs. While there was no significant effect of IPI or stimulation mode on VC discrimination, some subjects exhibited better VC discrimination with BP + 1 stimulation. Subjects' discrimination between sequential and simultaneous VCs was correlated with electrode discrimination, suggesting that spatial selectivity may influence perception of sequential VCs. To maintain equal loudness, sequential VC amplitudes were nearly double those of simultaneous VCs, presumably resulting in a broader spread of excitation. These results suggest that perceptual differences between simultaneous and sequential VCs might be explained by differences in the spread of excitation.

A portable real-time speech processor that implements an acoustic simulation model of a cochlear implant (CI) has been developed on the Apple iPhone / iPod Touch to permit testing and experimentation under extended exposure in real-world environments. This simulator allows for both a variable number of noise band channels and electrode insertion depth. Utilizing this portable CI simulator, we tested perceptual learning in normal hearing listeners by measuring word and sentence comprehension behaviorally before and after 2 weeks of exposure. To evaluate changes in neural activation related to adaptation to transformed speech, fMRI was also conducted. Differences in brain activation after training occurred in the inferior frontal gyrus and areas related to language processing. A 15-20% improvement in word and sentence comprehension of cochlear implant simulated speech was also observed. These results demonstrate the effectiveness of a portable CI simulator as a research tool and provide new information about the physiological changes that accompany perceptual learning of degraded auditory input.

Laryngomalacia is a common source of stridor and can lead to significant upper airway obstruction and feeding disturbances in infants. We describe a unique case of supraglottic dysgenesis presenting as laryngomalacia featuring a prominent "s-shaped" epiglottis with both posterior edges fused to the right aryepiglottic fold/arytenoid complex. Although this anomaly is not accounted for in any of the current laryngomalacia classification schemes, modified laser supraglottoplasty was a satisfactory approach leading to successful decannulation. Laryngeal embryology and possible timing of the pathogenesis of this rare occurrence are reviewed as well.

BACKGROUND: The head and neck is the most common site of mucosal melanoma, a cancer with poor prognosis. In contrast to cutaneous melanoma, mucosal melanoma of the head and neck (MMHN) is uncommon, with limited data regarding outcomes and prognostic factors drawn from small, single-institution case series. In order to identify factors predictive of survival, we analyzed MMHN outcomes in a large US cohort. METHODS: MMHN cases (n = 815) diagnosed in the USA between 1973 and 2007 were analyzed in the Surveillance, Epidemiology, and End Results registry, and cause of death was individually determined in 778 (95.5%) cases. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to analyze prognostic variables. RESULTS: Disease-specific survival status was determined in 778 (95.5%) cases. The 5- and 10-year rates of overall survival (OS) were 25.2 and 12.2%; disease-specific survival (DSS), 32.4 and 19.3%. On multivariable analysis, anatomic primary site was an independent predictor of OS and DSS, with tumors in the nasal cavity and oral cavity associated with survival superior to tumors in the nasopharynx and paranasal sinuses. Age > 70 years, tumor size, nodal status, and distant metastasis status were additional independent predictors of poorer survival. CONCLUSIONS: In this large cohort of patients with MMHN, we have identified several novel factors robustly predictive of overall and melanoma-specific survival.

European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major goal of current research. Here we show that type I and III infected macrophages, a cell type required for host immunity to Toxoplasma, are alternatively activated, while type II infected macrophages are classically activated. The Toxoplasma rhoptry kinase ROP16, which activates STAT6, is responsible for alternative activation. The Toxoplasma dense granule protein GRA15, which activates NF-kappaB, promotes classical activation by type II parasites. These effectors antagonistically regulate many of the same genes, and mice infected with type II parasites expressing type I ROP16 are protected against Toxoplasma-induced ileitis. Thus, polymorphisms in determinants that modulate macrophage activation influence the ability of Toxoplasma to establish a chronic infection.