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Neuroblastoma is a pediatric tumor that preferentially metastasizes to bone. Patients with bone metastases have a mortality rate >93%, indicating a need for novel treatment targets. Our laboratory has shown that type I insulin-like growth factor receptor (IGF-IR) expression and activation regulate neuroblastoma cell proliferation, motility, invasion, and survival, and that expression of the IGF-IR correlates with neuroblastoma tumorigenicity. Bone expresses large amounts of IGF ligands, and the IGF system is required for normal bone physiology. The current study addresses the role of the IGF system in neuroblastoma metastasis to bone. Upon reaching the bone marrow through the circulation, neuroblastoma cells must dock at the bone marrow endothelium, extravasate into the bone microenvironment, and destroy bone tissue to allow for tumor growth. This report examines the effects of high IGF-IR expression on neuroblastoma cell interaction with bone. The current data show that neuroblastoma cells with high IGF-IR expression, either endogenously or through transfection, adhere to human bone marrow endothelial cells and subsequently migrate toward both IGF-I and human bone stromal cells. High IGF-IR-expressing neuroblastoma cells adhere tightly to bone stromal cells, flatten, and extend processes. When neuroblastoma cells are injected directly into the tibiae of mice, those cells with increased IGF-IR form both osteolytic lesions within the tibiae and secondary tumors within other sites. These results support the hypothesis that IGF-IR expression in neuroblastoma cells increases tumor cell interaction with the bone microenvironment, resulting in greater formation of metastases.

Introduction: Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy., Subjects: A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m2 on Day 1 and 5-FU 1,000 mg/m2/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m2 on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed on patients with persistent or recurrent disease., Methods: Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing outcomes. Overall 3-year determinant survival was 87%, with median follow-up of 40 months., Results: Patients with an intact larynx demonstrated significantly higher (p = 0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This finding was consistent in the social-emotional (p = 0.007) and physical functioning domains (p = 0.03). No differences in V-RQOL scores were found in comparisons between early and late salvage laryngectomy. Multiple linear regression revealed that predictors of higher total V-RQOL scores include lower T stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since treatment (p = 0.01). Understandability of speech was better in patients with an intact larynx (p = 0.001). Overall swallowing function was comparable between groups. Multiple logistic regression revealed that longer duration since treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p = 0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public. Nutritional mode consisting of oral intake alone without nutritional supplements was achieved in 88.9% of patients with an intact larynx compared with 64.3% of laryngectomees (p = 0.09)., Conclusions: Voice-related quality of life is better in patients after chemoradiation therapy compared with salvage laryngectomy. Earlier salvage, although known to be associated with fewer surgical complications, did not result in improved voice; however, the number of patients analyzed is small. Overall swallowing function is good in all patients; however, patients with an intact larynx are more likely to obtain nutrition with oral intake alone without supplements. Such measures of function and quality of life are important endpoints to help judge overall effectiveness as newer, more aggressive treatment protocols with added toxicities are developed and evaluated.

Introduction: Tracheal suction catheters (TSCs) are used to clear mucus from an endotracheal tube (ETT). The clearance rate is critical because airway mucus stasis leads to obstruction, but prolonged catheter suctioning can lead to hypoxemia. The rate of mucus clearance from an ETT is thought to be influenced by the properties of the mucus, the pressure used to suction the mucus, and the diameter of the catheter. In this study, different adult TSCs were evaluated for their ability to suction mucus simulants that had properties similar to airway mucus., Methods: Six different 14F TSC designs were evaluated. All catheters had the same end hole size, but the two side holes were sized at 3 mm, 4 mm, or 5 mm. A coagulant (Polyox Water Soluble Resin Coagulant NF; Dow Chemical Company; Cary, NC) was mixed with water at concentrations of 0.5%, 1.5%, and 3.0% to simulate mucus or sputum. Suction effectiveness was evaluated by the mass percentage of the coagulant suctioned over 10 s at 100 mm Hg from an 8.0 ETT., Measurements and Results: The 1.5% and 3.0% simulants had properties comparable to human airway mucus and sputum. Suction effectiveness was less with the 3.0% coagulant simulant compared with the 1.5% and 0.5% simulants. Suction effectiveness was greater (p < 0.01) with TSCs that had nonparallel holes and a side hole diameter of 5 mm when tested with the 1.5% and 3.0% simulants. However, no best catheter could be identified among TSCs when tested with the more liquid-like 0.5% simulant., Conclusions: Greater TSC side hole diameter and nonparallel positioning was important for suctioning mucus simulants that are similar to mucus or sputum. The distance between side holes, end hole size, suction force, and duration of suctioning were not tested but could also have an effect on TSC performance.

Objectives: A cross-sectional observational study was designed to evaluate patient satisfaction after stapedotomy., Methods: Two validated questionnaires, the Psychosocial Impact of Assistive Devices Scale (PIADS) and the Hearing Handicap Inventory (HHI), were used to assess patients for whom audiometric data were available., Results: The response rate was 79%. The PIADS score showed that 96% of patients reported an improvement in quality of life. The HHI score, however, showed that 32% of patients still experienced a marked degree of handicap after surgery. The HHI scores correlated positively with postoperative audiometric data, and the PIADS scores correlated positively with the degree of change in audiometric data., Conclusions: The results of this study support the role of small fenestra stapedotomy as a primary treatment for otosclerosis. The study also identifies a certain subpopulation of patients with residual handicap who may require further aural rehabilitation.

Quality of life (QOL) considerations are uniquely important in head and neck oncology outcomes research due to the multidimensional impact of these tumors and their treatment. Patient variables, tumor variables and treatment variables must be considered comprehensively in order to maximize the validity of QOL outcome measures. There are a multitude of QOL instruments, which can be classified into: (1) general measures of health-related QOL, (2) general QOL instruments for patients with cancer, (3) disease-specific instruments for patients with head and neck cancer, (4) treatment-specific instruments and (5) symptom-specific instruments. This article will highlight commonly used validated QOL instruments in head and neck oncology.

A new series of short pyrrole tetraamides are described whose submicromolar DNA binding affinity is an essential component for their strong antibacterial activity. This class of compounds is related to the linked bis-netropsins and bis-distamycins, but here, only one amino-pyrrole-carboxamide unit and an amidine tail is connected to either side of a central dicarboxylic acid linker. The highest degree of DNA binding, measured by compound-induced changes in UV melting temperatures of an AT-rich DNA oligomer, was observed for flat, aromatic linkers with no inherent bent, i.e., terephthalic acid or 1,4-pyridine-dicarboxylic acid. However, the antibacterial activity is critically linked to the size of the N-alkyl substiutent of the pyrrole unit. None of the tetraamides with the commonly used methyl-pyrrole showed antibacterial activity. Isoamyl- or cyclopropylmethylene-substituted dipyrrole derivatives have the minimum inhibitory concentrations in the submicromolar range. In vitro toxicity against human T-cells was studied for all compounds. The degree to which compounds inhibited cell growth was neither directly correlated to DNA binding affinity nor directly correlated to antibacterial activity but seemed to depend strongly on the nature of the N-alkyl pyrrole substituents.

The genetic basis of familial Meniere's disease (MD) is unclear. We present a genetic investigation of six individuals in two families with familial MD. Linkage analysis was performed using polymorphic DNA markers linked to the human leukocyte antigen (HLA) locus that map to chromosome 6p. We have demonstrated the presence of anticipation in successive generations and the absence of HLA association. This is the second report of anticipation in familial MD in the literature, and it suggests that efforts should be directed toward finding a trinucleotide expansion as a possible genetic lesion in this uncommon disorder.