Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.

Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB).

Allelic variants in TLR10 gene may influence bilateral affectation and clinical course of Meniere's disease.

Toll-like receptors trigger the innate immune response by activating various cell types such us macrophages and lymphocytes. We genotyped SNV of TLR3, TRL7, TLR8 and TLR10 in 863 Spanish and 150 Italian patients with Meniere's disease (MD) and 1,013 controls by using Taqman assays. Real-Time qPCR was used to measure the expression level of TLR10 in peripheral blood leukocytes.

Functional variants of MIF, INFG and TFNA genes are not associated with disease susceptibility or hearing loss progression in patients with Ménière's disease.

Variability in acute immune response genes could determine susceptibility or prognosis for Ménière's disease (MD). The cytokines tumor necrosis factor α (TNFα), macrophage migration inhibitory factor (MIF) and interferon γ (INFγ) are proinflammatory cytokines of the innate immune response. These cytokines mediate inflammation and have been previously associated with the inflammatory process in several autoimmune diseases.

Genetics of recurrent vertigo and vestibular disorders.

We present recent advances in the genetics of recurrent vertigo, including familial episodic ataxias, migraneous vertigo, bilateral vestibular hypofunction and Meniere's disease.Although several vestibular disorders are more common within families, the genetics of vestibulopathies is largely not known. Genetic loci and clinical features of familial episodic ataxias have been defined in linkage disequilibrium studies with mutations in neuronal genes KCNA1 and CACNA1A.

MICA-STR A.4 is associated with slower hearing loss progression in patients with Ménière's disease.

Hypothesis: Immune response may influence hearing outcome in Ménière's disease (MD).

Background: Major histocompatibility complex class I chain-related A (MICA) encodes a highly polymorphic stress-inducible protein, which interacts with NKGD2 receptor on the surface of NK, γδ T cells and T CD8 lymphocytes. We investigated the association of MICA gene with hearing outcome in MD and its linkage disequilibrium (LD) with human leukocyte antigen (HLA)-B.

High prevalence of systemic autoimmune diseases in patients with Menière's disease.

Background: Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL).

Methods And Findings: We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ).

Functional variants in NOS1 and NOS2A are not associated with progressive hearing loss in Ménière's disease in a European Caucasian population.

Hearing loss in Ménière's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are associated with MD, we genotyped three functional variants of NOS1 (rs41279104, rs2682826, and a cytosine-adenosine microsatellite repeat in exon 1f) and the CCTTT repeat in the promoter of NOS2A gene (rs3833912) in two independent MD sets (273 patients in total) and 550 controls.

Polymorphisms of CD16A and CD32 Fcγ receptors and circulating immune complexes in Ménière's disease: a case-control study.

Background: Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC.

Association of a functional polymorphism of PTPN22 encoding a lymphoid protein phosphatase in bilateral Meniere's disease.

Objectives/hypothesis: Bilateral Meniere's disease (BMD) is a severe disease that usually results in bilateral severe or profound sensorineural hearing loss and chronic disequilibrium with loss of vestibular function. We examined single nucleotide polymorphisms (SNPs) in the PTPN22 and CTLA4 genes in Caucasian patients with BMD to assess the possible association between these polymorphism and the predisposition and clinical expression of this disease.

Study Design: A case control study.

Prospective, randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia.

Background: Recommendations for diagnostic testing in hospitalised patients with community-acquired pneumonia remain controversial. The aim of the present study was to evaluate the impact of a therapeutic strategy based on the microbiological results provided by urinary antigen tests for Streptococcus pneumoniae and Legionella pneumophila.

Methods: For a 2-year period, hospitalised patients with community-acquired pneumonia were randomly assigned to receive either empirical treatment, according to international guidelines, or targeted treatment, on the basis of the results from antigen tests.

Risk factors and outcome of community-acquired pneumonia due to Gram-negative bacilli.

Background And Objective: Several sets of guidelines have advocated initial antibiotic treatment for community-acquired pneumonia due to Gram-negative bacilli in patients with specific risk factors. However, evidence to support this recommendation is scarce. We sought to identify risk factors for community-acquired pneumonia due to Gram-negative bacilli, including Pseudomonas aeruginosa, and to assess outcomes.

Diagnosis of tuberculous pleuritis by the measurement of soluble interleukin 2 receptor in pleural fluid.

Objective: As soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation, we sought to determine whether its measurement in pleural fluid is diagnostically useful in tuberculous pleurisy.

Design: We compared the concentrations of sIL-2R in pleural samples of 23 patients with tuberculous pleurisy and 109 patients with non-tuberculous effusions (34 malignant, 34 parapneumonic, 27 transudates and 14 miscellaneous). sIL-2R was measured by a commercial ELISA test and its performance was evaluated using receiver operating characteristic (ROC) analysis.

Pleural SC5b-9: a test for identifying complicated parapneumonic effusions.

Unlabelled: BACKGROUND AND OBJECTIVES We have tested whether the complement activation products SC5b-9 and C3a-desArg are useful to distinguish complicated (CPE) from uncomplicated parapneumonic effusions (UPE).

Design: A total of 66 patients were enrolled in the study: 5 with empyema, 19 with CPE, 12 with UPE, and 30 transudates who served as controls. SC5b-9 and C3a-desArg were measured by commercial ELISA tests, and their performances were evaluated using receiver operating characteristic (ROC) analysis.

Usefulness of pleural complement activation products in differentiating tuberculosis and malignant effusions.

Objective: To determine whether measurement of the complement activation products SC5b-9 and C3a-desArg in pleural fluid can reliably differentiate tuberculous from malignant pleural effusions.

Design: Twenty-four patients with tuberculous pleuritis, 29 with malignant pleural effusion, and 30 control subjects with transudates were enrolled in the study. SCSb-9 and C3a-desArg were measured in pleural fluid using commercial ELISA tests, and their performances were evaluated using receiver operating characteristic (ROC) analysis.

Comparative analysis of Light's criteria and other biochemical parameters for distinguishing transudates from exudates.

Objectives: To compare the accuracy of Light's criteria for categorizing a pleural effusion as an exudate with several alternative criteria.

Design: Prospective evaluation of patients who underwent a diagnostic thoracocentesis.

Setting: Community teaching hospital in Lleida, Spain.

[Epidemiologic and clinical characteristics and clinical course of the HIV positive patient infected by heterosexual transmission].

We reviewed the features of patients with human immunodeficiency virus (HIV) infection, whose only way of acquisition was heterosexual contacts, analyzing differences with others risk groups. Epidemiological features (age, gender, family situation, socioeconomic status and sexual behavior), clinical manifestations immunological status, and evolution of 40 patients with HIV infection through heterosexual contact are studied, and compared with others risk groups. All were attended in our center from 1985 to October 1991; 15 were in stage IV.