Design  A molecular biology study. The VEGF-C coding sequence was cloned into an expression vector and stably transfected into the SCCHN cell line SCC116 to create the SCC116-VEGFC line. RNA interference (RNAi) was used to block VEGF-C expression. An adenoviral system for expressing VEGF-C RNAi was developed and tested.

Setting  An academic hospital laboratory.

Main Outcome Measures  Relative VEGF-C RNA levels were determined by real-time quantitative reverse transcriptase–polymerase chain reaction, and protein expression was evaluated by Western blot. Cellular invasion was evaluated by 24-hour semipermeable membrane transit assay.

Results  SCC116-VEGFC cells had markedly increased expression of VEGF-C protein and RNA compared with normal SCC116 controls. SCC116-VEGFC cells produced marked increases in cellular invasion and motility compared with SCC116 cells. Blockade of VEGF-C expression by transfection of a VEGF-C RNAi expression plasmid into both SCC116 and SCC116-VEGFC cells induced a 38% decrease in SCCHN invasion and motility as tested by a semipermeable membrane invasion assay. We developed an adenoviral expression system for VEGF-C RNAi, which also induced a dose-dependent decrease in cellular invasion in the highly invasive DM12 cell line.

Conclusions  These studies demonstrate that intracellular VEGF-C levels modulate in vitro SCCHN motility and invasion. Further work is needed to clarify the specific receptors and signaling pathways that are involved in SCCHN motility. Molecular therapies that inhibit the VEGF-C pathway may have clinical potential in the treatment of lymphatic metastasis in SCCHN.

Design  Marker expression and clinical outcome.

Patients  Pretreatment tumor biopsy specimens were analyzed from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Study.

Main Outcome Measures  Expression of p53 (OMIM TP53) and Bcl-xL (OMIM 600039) in pretreatment biopsy specimens was assessed for correlation with chemotherapy response, laryngeal preservation, and survival.

Results  Higher rates of larynx preservation were observed in patients whose tumors expressed p53 vs those that did not (80% [36 of 45 patients] vs 59% [24 of 41 patients], P =.03). Higher rates of larynx preservation were also observed in patients whose tumors expressed low levels of Bcl-xL vs high levels of Bcl-xL (90% [18 of 20 patients] vs 60% [30 of 50 patients], P =.02). Patients were categorized into 3 risk groups (low, intermediate, and high) based on their tumor p53 and Bcl-xL expression status. Patients whose tumors had the high-risk biomarker profile (low p53 expression and high Bcl-xL expression) were less likely to preserve their larynx than patients whose tumors had the intermediate-risk biomarker profile (high p53 expression and low or high Bcl-xL expression) or the low-risk biomarker profile (low p53 expression and low Bcl-xL expression). The larynx preservation rates were 100% (10 of 10 patients), 77% (26 of 34 patients), and 54% (7 of 13 patients) for the low-risk, intermediate-risk, and high-risk groups, respectively (P =.04, Fisher exact test).

Conclusion  Tumor expression of p53 and Bcl-xL is a strong predictor of successful larynx preservation in patients treated with induction chemotherapy and followed by radiation therapy in responding tumors.

Design  Retrospective cohort analysis using the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. The Surveillance, Epidemiology, and End Results data were used to design 5 cohorts of patients with laryngeal cancer: 1977-1978, 1983-1984, 1989-1990, 1995-1996, and 2001-2002. Five-year survival rates were analyzed according to tumor site, stage, and grade; age at diagnosis; and treatment strategy. The joinpoint regression model was used to assess survival trends and their statistical significance.

Results  Among patients with supraglottic cancer, 5-year relative survival rates for distant disease worsened over time while rates for local and regional disease did not change (P  = .01 and P > .05, respectively). For localized glottic cancer, survival remained stable from 1977-1978 to 2001-2002. However, patients with regional and distant glottic cancer demonstrated a significant decrease in survival in the past 3 decades (P < .001). This trend was independent of treatment strategy. Finally, the proportion of well-differentiated tumors in patients with regional laryngeal cancer decreased over time (P < .001 for supraglottic and P = .007 for glottic).

Conclusions  A decreasing 5-year survival trend was found among patients with glottic cancer who had regional disease and in all patients with distant disease. Histopathologic trends not previously reported in those with laryngeal cancer seem to parallel those seen in other tobacco-related cancers. These trends may reflect the effect of birth cohorts and implicate the relationship between carcinogenic exposure and host factors, rather than the influence of treatment.

Design  Cohort study with retrospective data analysis.

Setting  Voice clinic of a tertiary medical center.

Patients  Complete data for 45 patients diagnosed with idiopathic or iatrogenic UVFP. The LEMG was performed between 3 weeks and 6 months from the onset of symptoms.

Main Outcome Measure  At least 6 months after symptom onset and 3 months after LEMG.

Results  Thirteen subjects showed resolved vocal fold motion (29%), and 32 had persistent vocal fold paralysis (71%). According to the LEMG decision rules proposed by Munin et al in 2003, the predictive values for positive results, negative results, sensitivity, specificity, and accuracy of LEMG were 78.9%, 71.4%, 93.8%, 38.5%, and 77.8%, respectively. We found the false-positive rate to be as high as 50% if LEMG was performed less than 2 months after symptom onset, and only 7.7% if LEMG was performed at least 2 months after symptom onset. After excluding 14 LEMG data recorded at less than 2 months, the predictive values for positive results, negative results, sensitivity, specificity, and accuracy of LEMG were 92.3%, 60%, 92.3%, 60.0%, and 87.1%, respectively. The predictive values of positive results and accuracy significantly improved without compromising sensitivity.

Conclusion  This study confirms that LEMG is a clinically useful tool that can offer prognostic information for UVFP especially if it is done at least 2 months after symptom onset.

Design  A retrospective evaluation of patient records was completed to determine the percentage and the demographics of TMD patients in a clinical setting. A prospective analysis was done on the self-reported prevalence of previously studied and new aural symptoms of 78 TMD study patients compared with 78 control patients without TMD.

Setting  A private otolaryngology practice in a rural Arizona town.

Patients  Patients with TMD and aural symptoms.

Results  Ten percent of all new otolaryngology clinic patients were diagnosed as having TMD. Of the 78 patients, 27 (35%) listed the ear as one of their sites of pain. The prevalence of each of the 8 aural symptoms assessed was significantly higher in TMD patients compared with controls (P < .001). A warm and/or fluid sensation in the ear and a stuffed cotton sensation in the ear were the most indicative symptoms of TMD because they had the highest relative risk ratios in TMD patients. Aural symptoms of loud noise sensitivity and cold air/wind sensitivity are also relevant and were approximately 5 times more frequent in TMD subjects than in controls.

Conclusions  Patients with TMD are a significant component of otolaryngology practice. There are previously uninvestigated aural symptoms that occur much more frequently in TMD patients than in patients without TMD.

Design  Prospective case-control study.

Setting  Outpatient clinic in a tertiary neuro-otology department.

Patients  Seventeen healthy volunteers (mean age, 35.5 years), 9 patients with PVD (mean age, 43.1 years), and 10 patients with MD (mean age, 50.7 years) were included in the analysis.

Interventions  All subjects had a detailed neuro-otological evaluation. Twelve replicate readings of SVV and SVH were taken for each subject, with random preset angles, 6 in the clockwise and 6 in the counterclockwise direction.

Main Outcome Measure  The SVV and SVH values were correlated with clinical features and the direction of the preset angle.

Results  The 2 subjects with PVD who had abnormal mean SVV and SVH values had symptoms of dysequilibrium and otolithic involvement. The 5 patients in the MD group who had abnormal mean SVV and SVH values had either recent acute vertiginous attacks or total canal paresis on the affected side. A previously unreported finding, to our knowledge, is that the SVV value depends on the direction of the preset angle in all subject groups, more so in the PVD and MD groups compared with controls. The SVV is inclined toward the direction of the preset angle. A weaker relation is seen between the SVH and preset angle.

Conclusion  The preset angle should be considered when comparing SVV and SVH values.

Design  Validation of the mutation by its exclusion in more than 300 individuals with normal hearing.

Setting  A laboratory of genetics of hearing loss research, clinical genetics laboratories, an otolaryngology department at Tel Aviv University, and medical centers in Israel.

Patients  A patient with nonsyndromic hearing loss and enlarged vestibular aqueduct, 203 deaf probands, and 310 controls with normal hearing.

Interventions  Sequencing the SLC26A4 gene in the patient with nonsyndromic hearing loss and enlarged vestibular aqueduct. Transfection of yellow fluorescent protein (YFP) constructs into mammalian COS7 cells. Designing a computational model of the human SLC26A4 protein.

Main Outcome Measure  Detection of a novel c.1458_1459insT SLC26A4 mutation.

Results  A computational model of the human pendrin protein suggests that the novel c.1458_1459insT mutation leads to a prematurely truncated protein, p.Ile487TyrfsX39. Mammalian COS7 cells transfected with the YFP-1458_1459insT construct showed mislocalization of the mutant protein.

Conclusions  A novel SLC26A4 mutation was detected in Israel. Because current estimates demonstrate that SLC26A4 mutations are involved in up to 4% of nonsyndromic deafness, our findings emphasize the importance of adding a molecular test for the SLC26A4 gene in the diagnosis of deafness, particularly when bone abnormalities are involved, to the list of genes screened in Israel and elsewhere in the world.

Design  Retrospective medical record review.

Setting  Tertiary children's hospital.

Patients  The study population comprised 108 patients younger than 18 years old.

Intervention  Medical record review of patients with a discharge diagnosis of RPI (International Classification of Diseases, Ninth Revision code 478.24).

Main Outcome Measures  Cases from June 1997 to May 2001 were compared with those from June 2001 to May 2005 to examine changes in the incidence, bacteriology, and complications of RPI.

Results  The number of RPI cases doubled from 36 to 72 in the final 4 years. In the first 4 years, no isolates of methicillin-resistant Staphylococcus aureus (MRSA) were found, and 1 patient developed mediastinitis. In the last 4 years, 8 of 25 patients (32%) with positive cultures had MRSA isolated, and 7 cases of mediastinitis occurred. Of the 8 children with cultures positive for MRSA, 6 developed mediastinitis. The median age for all children with RPI was 32.5 months (n = 108). The median age for children with MRSA and mediastinitis was 6.5 months (n = 8) and 5.5 months (n = 8), respectively.

Conclusions  An alarming increase in the number of RPI cases occurred over the final 4 years. Methicillin-resistant S aureus is now a significant pathogen in patients with RPI at our institution. Documented local increases in community-associated MRSA infections and universal sensitivity to clindamycin suggest that community-associated MRSA is responsible for the change in bacteriology. A high correlation exists between MRSA infection and mediastinitis. Patients with MRSA infections are younger and may be vulnerable to developing mediastinitis because of immature immune systems. A higher index of suspicion is needed for MRSA, especially in patients younger than 1 year.

Design  Retrospective chart review.

Setting  Tertiary care children's hospital.

Patients  Thirty-nine children, with a mean age of 18 months at the time of evaluation, were evaluated for stridor.

Main Outcome Measures  Diagnoses made by airway fluoroscopy and endoscopy. The medical records of patients who had undergone both airway fluoroscopy and airway endoscopy for the evaluation of stridor over a 5-year period were reviewed. The sensitivity, specificity, and positive and negative predictive values of airway fluoroscopy in the diagnosis of laryngomalacia, tracheomalacia, airway stenosis at any level, and airway mass lesions were determined using endoscopic evaluation as the "gold standard."

Results  Twenty-three of 39 patients (59%) received a different diagnosis by airway endoscopy than by airway fluoroscopy. The sensitivity of airway fluoroscopy in the diagnosis of laryngomalacia, tracheomalacia, airway stenosis, and an airway mass was 27%, 20%, 69%, and 43%, respectively. The specificity for the same diagnoses was 100%, 94%, 100%, and 100%, respectively.

Conclusions  Airway fluoroscopy appears to be reliable in the diagnosis of laryngomalacia, tracheomalacia, airway stenosis, and airway masses because of its high specificity. However, its sensitivity in detecting these common causes of stridor is poor. Negative fluoroscopic study results require further diagnostic evaluation if the clinical indication exists; therefore, the value of fluoroscopy as a screening tool remains uncertain.

Design  In this retrospective analysis, patients who underwent septoplasty without turbinate surgery from May 1, 2003, through April 30, 2006, were studied. The thicknesses and cross-sectional areas of mucosa and conchal bones were measured with computed tomography before the operations and at least 1 year after the operations.

Setting  University hospital.

Patients  A total of 20 patients who presented with a chief concern of nasal obstruction.

Main Outcome Measures  The thicknesses of the medial mucosa, bone, and lateral mucosa and the cross-sectional area of turbinate before and after septoplasty were compared using the Wilcoxon signed rank test. P < .05 was considered statistically significant.

Results  The medial mucosa and cross-sectional area of the inferior turbinate on the concave side of the septum were significantly decreased by septoplasty (both, P = .01), and the medial mucosa and cross-sectional area of the inferior turbinate on the convex side of the septum were significantly increased by septoplasty (P = .01). The thicknesses and cross-sectional areas of the conchal bone on the concave and convex sides of the septum were not affected by septoplasty.

Conclusion  After septoplasty, inferior turbinate hypertrophy, especially in the medial mucosa, may reverse.

Design  In vitro study.

Setting  Tertiary care rhinology clinic.

Patients  We conducted RV infection experiments on the organ cultures of NPs and inferior turbinate mucosae from 16 patients with CRS/NP and sphenoid sinus and inferior turbinate mucosae from 19 patients who underwent transsphenoidal pituitary surgery.

Main Outcome Measures  Successful RV-16 infection was determined by positive identification of RV on the surface fluid of organ culture using seminested reverse transcriptase–polymerase chain reaction. Effects of RV on interleukin 6 (IL-6) and IL-8 secretion were measured by enzyme-linked immunosorbent assay.

Results  The successful RV infection was achievable in 9 of 16 NP samples (56.3%) and 9 of 16 turbinate samples (56.3%) from patients with CRS/NP compared with 11 of 19 sphenoid sinus samples (57.9%) and 15 of 19 turbinate samples (78.9%) from normal subjects. The RV infection increased IL-6 and IL-8 secretion 236% and 173%, respectively, in NP samples, and 218% and 178%, respectively, in turbinate samples from patients with CRS/NP; compared with 231% and 145%, respectively, in sphenoid mucosa samples, and 181% and 148%, respectively, in turbinate samples from normal subjects. However, there were no statistical differences among the 4 groups.

Conclusion  These in vitro findings suggest that subjects with CRS/NP mucosa might not be more susceptible to RV infection, and did not secrete more cytokines in response to rhinovirus infection, than those with normal mucosa.

Design  Prospective, longitudinal cohort study.

Patients  Fifty-one consecutive patients with obstructive sleep apnea (50 men and 1 woman; mean age, 39 years; mean [SD] apnea-hypopnea index, 37.4 [28.9] events/h; and mean ± SD body mass index [calculated as weight in kilograms divided by height in meters squared], 26.0 [3.5]) with symptoms of nasal obstruction due to a deviated nasal septum.

Intervention  Septomeatoplasty.

Outcome Measures  Surgical outcomes were measured using the Snore Outcomes Survey, the Epworth Sleepiness Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) 3 months after surgery. We compared baseline and postoperative scores. Normative SF-36 data obtained from 4591 age- and sex-matched adults were used as references.

Results  Nasal obstruction symptoms significantly improved (mean [SD] visual analog scale score, –5.2 [1.4]; P < .001). Assessments also showed significant improvement in the Snore Outcomes Survey (P < .001) and Epworth Sleepiness Scale (P < .001) scores and 6 of the 8 SF-36 subscale scores (P < .05). Remarkable improvements were observed in disease-specific Snore Outcomes Survey (by 43.1%), Epworth Sleepiness Scale (by 27.3%), and generic SF-36 role-emotional (by 30.4%) and role-physical (by 20.7%) QOL subscales. The postoperative role-emotional, bodily pain, and social function dimensions of health were indistinguishable from referential population data (P > .05).

Conclusions  Correction of an obstructed nasal airway significantly improves disease-specific and generic QOL in adult patients with obstructive sleep apnea who also have nasal obstruction symptoms. After nasal surgery, patients may experience greater improvement in snoring and daytime sleepiness than in other generic health status. Our findings substantiate the role of nasal surgery in treating patients with obstructive sleep apnea and nasal obstruction.