Innate immunity gene single nucleotide polymorphisms and otitis media.

OBJECTIVE: Toll-like receptors (TLR) activate the innate immune system. Single nucleotide polymorphisms (SNPs) in TLR genes are linked to increased susceptibility to infections. TLR4-deficient mice have increased incidence and duration of otitis media. We hypothesize that SNPs in TLR genes are more common in otitis-prone children than in children without a history of otitis media. METHODS: Cases (n=70) included children undergoing surgery for otitis media. Control subjects (n=70) included children undergoing surgery for non-otologic indication. Genomic DNA was extracted from blood samples. RT-PCR genotyping was performed for TLR2 (rs5743708), TLR4 (rs4986790 and rs4986791), TLR9 (rs5743836 & rs187084), and CD14 (rs2569190). RESULTS: There were no significant differences between the groups in family history, day care, smoke exposure, allergies or prevalence of the SNPs. The most common pre-op diagnosis in control subjects was obstructive sleep apnea (OSA). CONCLUSIONS: TLR2, TLR4, TLR9 and CD14 gene SNPs were not more prevalent in otitis-prone children.

Management of complete esophageal stricture after treatment of head and neck cancer using combined anterograde retrograde esophageal dilation.

BACKGROUND: Complete esophageal stricture is a difficult problem to manage. There is limited literature to support clinical decision-making. To evaluate outcomes and efficacy, we performed a retrospective medical chart review of patients who received combined anterograde retrograde esophageal dilation (CARD) between 2002 and 2009 at our institution. METHODS: Fifteen patients were identified who developed a stricture requiring CARD after treatment for head and neck cancers. Outcomes were pretreatment and posttreatment diet, gastrostomy tube status, and operative complications. RESULTS: Six of 15 patients were gastrostomy tube-free at last follow-up and 11 of 15 patients were taking oral nutrition. There were 4 complications. One patient died. Two gastrostomy tube site complications occurred. One patient sustained a dental injury. CONCLUSION: CARD offers benefit to most patients. Despite risks associated with the procedure, CARD should be considered by the clinician and patient in management of complete esophageal stricture.

Fatal central venous air embolism: a rare complication of esophageal dilation by rendezvous.

BACKGROUND: Esophageal dilation by rendezvous is a useful technique for the treatment of complicated esophageal strictures. METHODS AND RESULTS: We present a case of a 74-year-old man with chronic dysphagia caused by a complete cervical esophageal stricture that developed after external beam radiotherapy for treatment of papillary thyroid carcinoma. During attempted dilation using the rendezvous technique, the patient suffered a fatal pulmonary air embolism. The technique of esophageal dilation by rendezvous, complications, and risk factors for development of venous air embolism are discussed. CONCLUSION: To the best of our knowledge, this is the first report in the literature of fatal venous air embolism after dilation by rendezvous.

Adenoid cystic carcinoma of the subglottic larynx: a case report and review of the literature.

Laryngeal adenoid cystic carcinoma (ACC) is a rare clinical entity that poses a number of diagnostic and therapeutic challenges. We present a case of ACC of the subglottic larynx, and we review its diagnosis and management. We also discuss the workup of submucosal masses of the subglottic larynx, with an emphasis on clinical and radiologic diagnosis, surgical treatment, radiotherapy, and emerging therapies. The presence of a submucosal mass in the subglottic larynx should raise suspicion for the presence of ACC.

Contrast-enhanced MDCT characteristics of parathyroid adenomas.

OBJECTIVE: Minimally invasive directed parathyroidectomy has replaced conventional surgical techniques aimed at exploring all four glands in the bilateral neck. These changes have created the need for better preoperative imaging localization techniques. In this article, we describe the CT imaging characteristics of surgically confirmed adenomas and review anatomy and embryology to aid the radiologist in successfully identifying adenomas using contrast-enhanced CT. CONCLUSION: Knowledge of normal CT appearance, contrast enhancement, and expected location are critical to correct interpretation of parathyroid adenoma at CT.

The role of computed tomography for localization of parathyroid adenomas.

OBJECTIVE/HYPOTHESIS: The purpose of this study was to evaluate the use of computed tomography (CT) for localization of parathyroid adenomas (PA) when first-line imaging is indeterminate. STUDY DESIGN: Retrospective case series. METHODS: A search of operating room and radiology records identified 223 surgical explorations for primary hyperparathyroidism. Adenoma locations on CT, ultrasound, and nuclear scintigraphy were correlated with an independent review of operative records. RESULTS: The presence of adenoma in the correct side and quadrant of the neck was predicted by CT in 89% and 77% of studies, respectively. When first-line studies were indeterminate, the positive predictive value of CT for localization of PA to the correct side and quadrant of the neck was 87% and 69%, respectively. CONCLUSIONS: When first-line localization studies are indeterminate in patients with primary hyperparathyroidism, CT is a valuable, rapid, and widely available imaging modality that can be used to localize PA.

Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation.

Proper distribution of mitochondria within axons and at synapses is critical for neuronal function. While one-third of axonal mitochondria are mobile, a large proportion remains in a stationary phase. However, the mechanisms controlling mitochondrial docking within axons remain elusive. Here, we report a role for axon-targeted syntaphilin (SNPH) in mitochondrial docking through its interaction with microtubules. Axonal mitochondria that contain exogenously or endogenously expressed SNPH lose mobility. Deletion of the mouse snph gene results in a substantially higher proportion of axonal mitochondria in the mobile state and reduces the density of mitochondria in axons. The snph mutant neurons exhibit enhanced short-term facilitation during prolonged stimulation, probably by affecting calcium signaling at presynaptic boutons. This phenotype is fully rescued by reintroducing the snph gene into the mutant neurons. These findings demonstrate a molecular mechanism for controlling mitochondrial docking in axons that has a physiological impact on synaptic function.

EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors.

Cellular protein degradation pathways can be utilized by viruses to establish an environment that favors their propagation. Here we report that the Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) directly functions as a component of the EC5S ubiquitin complex targeting the tumor suppressors von Hippel-Lindau (VHL) and p53 for degradation. We have characterized a suppressor of cytokine signaling box-like motif within LANA composed of an Elongin B and C box and a Cullin box, which is spatially located at its amino and carboxyl termini. This motif is necessary for LANA interaction with the Cul5-Elongin BC complex, to promote polyubiquitylation of cellular substrates VHL and p53 in vitro via its amino- and carboxyl-terminal binding domain, respectively. In transfected cells as well as KSHV-infected B lymphoma cells, LANA expression stimulates degradation of VHL and p53. Additionally, specific RNA interference-mediated LANA knockdown stabilized VHL and p53 in primary effusion lymphoma cells. Thus, manipulation of tumor suppressors by LANA potentially provides a favorable environment for progression of KSHV-infected tumor cells.

Regional and developmental regulation of syntaphilin expression in the brain: a candidate molecular element of synaptic functional differentiation.

The conserved nature of the basic machinery underlying synaptic function makes it necessary to search for other factors--structural and molecular--that could account for the tremendous diversity found among synapses even within a single neuron. Syntaphilin is a presynaptic membrane protein previously described as a molecular clamp that controls free syntaxin-1A and dynamin-1 availability, and thereby regulates synaptic vesicle exocytosis and endocytosis at the nerve terminal. In this study, we report our finding that syntaphilin expression is developmentally regulated, and show that syntaphilin is expressed most prominently in the mature rat brain, in areas that have been previously characterized to undergo synaptic plastic change. We also find that syntaphilin undergoes divergent subcellular targeting to the mitochondrial outer membrane and the synaptic plasma membrane, giving rise to two neuronal subpopulations of the protein that are modified in their relative enrichment with synaptic maturation and with the formation of cell contacts. Finally, we demonstrate that syntaphilin expression is initiated with induction of neuronal differentiation in PC12 cells. Given its biochemical and functional properties, the spatially and temporally limited nature of syntaphilin expression provides evidence that syntaphilin could be a molecular element of synaptic functional differentiation.