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OBJECTIVE: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. DESIGN: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. RESULTS: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR = 1.55 [0.56.4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 [0.01.0.89] and 0.15 [0.01.0.29], respectively). HBM individuals had higher WOMAC knee pain scores (ß = 7.42 [1.17.13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. CONCLUSIONS: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.
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Densidad Ósea , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteofito/diagnóstico por imagen , Absorciometría de Fotón , Actividades Cotidianas , Tejido Adiposo , Anciano , Artralgia/fisiopatología , Peso Corporal , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/fisiopatología , Osteofito/fisiopatología , RadiografíaRESUMEN
El arco aórtico derecho es una entidad rara (prevalencia del 0,1%) que se adscribe a un grupo de malformaciones poco frecuentes y escasamente descritas en la bibliografía en su forma prenatal; sin embargo, no es infrecuente hallarlas como causa de enfermedad respiratoria o digestiva (refractarias a tratamiento) en pacientes adultos, e incluso como procesos vasculares severos con morbimortalidad elevada. Sus variantes pueden condicionar sintomatología compresiva y estar relacionadas con anomalías cardíacas (hasta 90%) y/o con la microdeleción 22q11 (hasta un 46%). El corte ecográfico de 3 vasos-tráquea es fundamental para su diagnóstico prenatal, y tras su detección está indicada una evaluación exhaustiva del corazón fetal, distinguir sus variantes y/o un estudio cromosómico-genético específico. En presencia de otras anomalías el pronóstico es pobre; los casos aislados suelen tener una evolución posnatal oligo o asintomática
Right aortic arch, which belongs to a group of rare malformations, is an uncommon finding (incidence of 0.1%) and few cases of prenatal forms have been described in the literature. Nevertheless, it is not unusual to find these anomalies as the cause of respiratory or digestive disease (refractory to treatment) in adult patients and even as severe vascular processes with high morbidity and mortality. Its variants may cause compressive symptoms and be associated with heart defects (up to 90%) and/or 22q11 microdeletion (up to 46%). The 3 vessels and trachea view is essential for the prenatal diagnosis of right aortic arch. Detection of this condition must be considered an indication for foetal echocardiography, to distinguish its variants, and/or specific chromosome/genetic testing. Isolated right aortic arch is usually asymptomatic, although the outcome of right aortic arch associated with other abnormalities is poor
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Humanos , Femenino , Embarazo , Adulto , Diagnóstico Prenatal/métodos , Aorta Torácica/diagnóstico por imagen , Pronóstico , Complicaciones del Embarazo/diagnóstico por imagen , Trastornos de los Cromosomas/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Desarrollo Fetal/efectos de la radiación , Ecocardiografía/métodosRESUMEN
La artrogriposis es un síndrome complejo, que responde etiológicamente a numerosas causas congénitas y adquiridas. Presentamos un caso familiar de artrogriposis. La necropsia aportó el hallazgo de inclusiones rojo-púrpura en el sarcoplasma del tejido muscular, sugestiva de miopatía por nemalinas
Arthrogryposis is a complex syndrome, the aetiology of which can be traced to numerous congenital and acquired causes. We present a case of familiar arthrogryposis. Necropsy revealed red-purple rod-like structures in the sarcoplasm of the muscle tissue, suggestive of nemaline myopathy
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Humanos , Femenino , Embarazo , Adulto , Miopatías Nemalínicas/complicaciones , Miopatías Nemalínicas/diagnóstico por imagen , Artrogriposis/etiología , Artrogriposis/genética , Amniocentesis/métodos , Atrofia Muscular Espinal/diagnóstico por imagen , Músculos/diagnóstico por imagen , Músculos/patología , Atrofia Muscular Espinal/complicaciones , Enfermedad de Gaucher/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo II/complicaciones , Mucopolisacaridosis VII/complicaciones , Mucopolisacaridosis VII/diagnóstico por imagenRESUMEN
BACKGROUND: Genomewide association studies (GWASs) of asthma have identified single-nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR. METHODS: A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. RESULTS: A total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta-analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma-associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. CONCLUSIONS: Combining GWAS with subsequent lung eQTL analysis revealed disease-associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma.
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Asma/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Pulmón/metabolismo , Sitios de Carácter Cuantitativo , Alelos , Asma/epidemiología , Estudios de Casos y Controles , Mapeo Cromosómico , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Pulmón/inmunología , Masculino , Metaanálisis como Asunto , Países Bajos/epidemiología , Fenotipo , Polimorfismo de Nucleótido Simple , Vigilancia de la PoblaciónRESUMEN
AIM: To assess the effectiveness of cardiac resynchronisation therapy (CRT), implantable cardioverter defibrillator (ICD) therapy, and the combination of these devices (CRT+ICD) in adult patients with left ventricular dysfunction and symptomatic heart failure. METHODS: A comprehensive systematic review of randomised clinical trials was conducted. Several electronic databases (PubMed, Embase, Ovid, Cochrane, ClinicalTrials.gov) were reviewed. The mortality rates between treatments were compared. A network was established comparing the various options, and direct, indirect and mixed comparisons were made using multivariate meta-regression. The degree of clinical and statistical homogeneity was assessed. RESULTS: 43 trials involving 13â 017 patients were reviewed. Resynchronisation therapy, defibrillators, and combined devices (CRT+ICD) are clearly beneficial compared to optimal medical treatment, showing clear benefit in all of these cases. In a theoretical order of efficiency, the first option is combined therapy (CRT+ICD), the second is CRT, and the third is defibrillator implantation (ICD). Given the observational nature of these comparisons, and the importance of the overlapping CIs, we cannot state that the combined option (CRT+ICD) offers superior survival benefit compared to the other two options. CONCLUSIONS: The combined option of CRT+ICD seems to be better than the option of CRT alone, although no clear improvement in survival was found for the combined option. It would be advisable to perform a direct comparative study of these two options.
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Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2â years.Individual data of 27â993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2â years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2â years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.
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Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/epidemiología , Ruidos Respiratorios/etiología , Fumar/efectos adversos , Contaminación por Humo de Tabaco/efectos adversos , Preescolar , Europa (Continente) , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Embarazo , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Studies have shown an inverse association of pet ownership with allergy but inconclusive findings for asthma. OBJECTIVE: To investigate whether pet ownership during pregnancy and childhood was associated with asthma and atopy at the age of 7 in a UK population-based birth cohort. METHODS: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time points from pregnancy to the age of 7 with asthma, atopy (grass, house dust mite, and cat skin prick test) and atopic vs. non-atopic asthma at the age of 7 using logistic regression models adjusted for child's sex, maternal history of asthma/atopy, maternal smoking during pregnancy, and family adversity. RESULTS: A total of 3768 children had complete data on pet ownership, asthma, and atopy. Compared with non-ownership, continuous ownership of any pet (before and after the age of 3) was associated with 52% lower odds of atopic asthma [odds ratio (OR) 0.48, 95% CI 0.34-0.68]. Pet ownership tended to be associated with increased risk of non-atopic asthma, particularly rabbits (OR 1.61, 1.04-2.51) and rodents (OR 1.86, 1.15-3.01), comparing continuous vs. non-ownership. Pet ownership was consistently associated with lower odds of sensitization to grass, house dust mite, and cat allergens, but rodent ownership was associated with higher odds of sensitization to rodent allergen. Differential effects of pet ownership on atopic vs. non-atopic asthma were evident for all pet types. CONCLUSIONS AND CLINICAL RELEVANCE: Pet ownership during pregnancy and childhood in this birth cohort was consistently associated with a reduced risk of aeroallergen sensitization and atopic asthma at the age of 7, but tended to be associated (particularly for rabbits and rodents) with an increased risk of non-atopic asthma. The opposing effects on atopy vs. non-atopic asthma might be considered by parents when they are deciding whether to acquire a pet.
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Asma/epidemiología , Exposición Materna , Mascotas , Adulto , Factores de Edad , Animales , Asma/etiología , Gatos , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Conejos , Sistema de Registros , Factores de Riesgo , Roedores , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: It has been suggested that maternal vitamin D status in pregnancy influences the risk of asthma and atopy in the offspring. The epidemiological evidence to support these claims is conflicting and may reflect chance findings and differences in how vitamin D was assessed. OBJECTIVE: To examine the association between blood total maternal 25-hydroxy vitamin D (25(OH)D) concentrations in pregnancy and offspring asthma, atopy and lung function in the largest birth cohort study to date. METHODS: Participants were largely of white European origin and resident in the South West of England. We examined the associations of maternal 25(OH)D concentrations in pregnancy with the following outcomes in the offspring: wheeze, asthma, atopy, eczema, hayfever, at mean age 7.5 years (n = 3652-4696 depending on outcome), IgE at 7 years (n = 2915) and lung function and bronchial responsiveness at mean age 8.7 years (n = 3728-3784). RESULTS: Sixty-eight per cent of mothers had sufficient (> 50 nmol/L) concentrations of 25(OH)D, 27% were insufficient (27.5-49.99 nmol/L) and 5% were deficient (< 27.5 nmol/L). There was no evidence to suggest that maternal 25(OH)D concentration in pregnancy was associated with any respiratory or atopic outcome in the offspring. These findings remained after adjustment for season of measurement and for potential confounders. There was also no evidence that these relationships followed a non-linear form and no evidence that either deficient or high concentrations of maternal 25(OH)D were associated with atopic or respiratory outcomes. CONCLUSIONS: We found no evidence that maternal blood 25(OH)D concentration in pregnancy is associated with childhood atopic or respiratory outcomes.
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Asma/epidemiología , Asma/etiología , Hipersensibilidad Inmediata/epidemiología , Hipersensibilidad Inmediata/etiología , Exposición Materna , Efectos Tardíos de la Exposición Prenatal , Vitamina D/análogos & derivados , Adulto , Asma/fisiopatología , Niño , Femenino , Humanos , Hipersensibilidad Inmediata/fisiopatología , Vigilancia de la Población , Embarazo , Estudios Prospectivos , Pruebas de Función Respiratoria , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
BACKGROUND: Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological findings of co-morbidity between these conditions. OBJECTIVE: To identify genetic variants that are associated with body mass index (BMI) in asthmatic children and adults, and to evaluate if there are differences between the genetics of BMI in asthmatics and healthy individuals. METHODS: In total, 19 studies contributed with genome-wide analysis study (GWAS) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. RESULTS: We report associations between several DENND1B variants (P = 2.2 × 10(-7) for rs4915551) on chromosome 1q31 and BMI from a meta-analysis of GWAS data using 2691 asthmatic children (screening data). The top DENND1B single nucleotide polymorphisms(SNPs) were next evaluated in seven independent replication data sets comprising 2014 asthmatics, and rs4915551 was nominally replicated (P < 0.05) in two of the seven studies and of borderline significance in one (P = 0.059). However, strong evidence of effect heterogeneity was observed and overall, the association between rs4915551 and BMI was not significant in the total replication data set, P = 0.71. Using a random effects model, BMI was overall estimated to increase by 0.30 kg/m(2) (P = 0.01 for combined screening and replication data sets, N = 4705) per additional G allele of this DENND1BSNP. FTO was confirmed as an important gene for adult and childhood BMI regardless of asthma status. CONCLUSIONS AND CLINICAL RELEVANCE: DENND1B was recently identified as an asthma susceptibility gene in a GWAS on children, and here, we find evidence that DENND1B variants may also be associated with BMI in asthmatic children. However, the association was overall not replicated in the independent data sets and the heterogeneous effect of DENND1B points to complex associations with the studied diseases that deserve further study.
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Índice de Masa Corporal , Estudio de Asociación del Genoma Completo , Adolescente , Adulto , Anciano , Alelos , Asma/complicaciones , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/genética , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
BACKGROUND: There are conflicting study results regarding the association of exposure to visible mould and fungal components in house dust with respiratory and allergic diseases in children. It has been suggested that functional polymorphisms of the GSTP1 gene may influence the risk for allergic disorders through an impaired defence against oxidant injury. METHODS: We examined in six birth cohorts of over 14 000 children whether the association between early exposure to reported mould at home in relation to respiratory and allergic diseases is modified by a single nucleotide polymorphism of the GSTP1 gene. RESULTS: We observed a positive association of mould exposure with nasal symptoms (2-10 year) aOR: 1.19 (1.02-11.38). Further, there was a borderline significant increased risk of rhinoconjunctivitis (6-8 year) in children homozygous for the minor allele Val/Val, aOR: 1.25 (0.98-1.60). In stratified analyses, subjects homozygous for the minor allele and exposed to mould at home were at increased risk for early wheezing aOR: 1.34 (1.03-1.75), whereas the major allele may confer susceptibility for later nasal outcomes, (6-8 year) aOR: 1.20 (1.00-1.45) and (2-10 year) aOR: 1.30 (1.04-1.61), respectively. For none of the health outcomes studied, we found gene by environment interactions. CONCLUSION: A genetic influence of the GSTP1 gene cannot be ruled out, but the magnitude of the effect is a matter of further research. In conclusion, the interplay between gene and environments is complex and remains subject of further study.
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Polvo/inmunología , Hongos/inmunología , Gutatión-S-Transferasa pi/genética , Hipersensibilidad/genética , Hipersensibilidad/inmunología , Microbiología del Aire , Niño , Preescolar , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Recién Nacido , Oportunidad Relativa , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Several cross-sectional studies during the past 10 years have observed an increased risk of allergic outcomes for children living in damp or mouldy environments. OBJECTIVE: The objective of this study was to investigate whether reported mould or dampness exposure in early life is associated with the development of allergic disorders in children from eight European birth cohorts. METHODS: We analysed data from 31 742 children from eight ongoing European birth cohorts. Exposure to mould and allergic health outcomes were assessed by parental questionnaires at different time points. Meta-analyses with fixed- and random-effect models were applied. The number of the studies included in each analysis varied based on the outcome data available for each cohort. RESULTS: Exposure to visible mould and/or dampness during first 2 years of life was associated with an increased risk of developing asthma: there was a significant association with early asthma symptoms in meta-analyses of four cohorts [0-2 years: adjusted odds ratios (aOR), 1.39 (95% CI, 1.05-1.84)] and with asthma later in childhood in six cohorts [6-8 years: aOR, 1.09 (95% CI, 0.90-1.32) and 3-10 years: aOR, 1.10 (95% CI, 0.90-1.34)]. A statistically significant association was observed in six cohorts with symptoms of allergic rhinitis at school age [6-8 years: aOR, 1.12 (1.02-1.23)] and at any time point between 3 and 10 years [aOR, 1.18 (1.09-1.28)]. CONCLUSION: These findings suggest that a mouldy home environment in early life is associated with an increased risk of asthma particularly in young children and allergic rhinitis symptoms in school-age children.
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Asma/epidemiología , Exposición a Riesgos Ambientales , Hongos/inmunología , Hipersensibilidad/epidemiología , Alérgenos/inmunología , Antígenos Fúngicos/inmunología , Asma/etiología , Asma/inmunología , Niño , Preescolar , Femenino , Humanos , Hipersensibilidad/etiología , Hipersensibilidad/inmunología , Lactante , Recién Nacido , Masculino , Rinitis/epidemiología , Rinitis/etiología , Rinitis/inmunología , Factores de RiesgoAsunto(s)
Asma/genética , Ligamiento Genético/genética , Predisposición Genética a la Enfermedad/genética , Fenotipo , Edad de Inicio , Asma/diagnóstico , Niño , Preescolar , Femenino , Investigación Genética , Humanos , Lactante , Masculino , Pruebas de Función Respiratoria , Ruidos Respiratorios/diagnóstico , Factores de RiesgoRESUMEN
BACKGROUND: Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals. METHODS: Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV(1)), mid forced expiratory flow (FEF(25-75))) and bronchial responsiveness were made at 7-9 years of age. RESULTS: Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV(1) per mumol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV(1) per mumol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes. CONCLUSIONS: The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.
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Asma/etiología , Hiperreactividad Bronquial/fisiopatología , Hipersensibilidad Inmediata/fisiopatología , Complicaciones del Embarazo , Ruidos Respiratorios/fisiopatología , Asma/fisiopatología , Niño , Preescolar , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Lactante , Masculino , Ápice del Flujo Espiratorio/fisiología , Fenotipo , EmbarazoRESUMEN
BACKGROUND: A recent study suggested a link between folate metabolism and atopy, based on a positive association between a common polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and allergic sensitization in Danish adults. OBJECTIVE: We investigated the associations between MTHFR C677T and allergy or atopy in a large, population-based birth cohort of children and their mothers, the Avon Longitudinal Study of Parents and Children (ALSPAC). We also looked for evidence of a pre-natal effect of maternal folate metabolism on subsequent atopic disease in the offspring. METHODS: Mothers were recruited in pregnancy and the children followed from birth. Atopy in the child was assessed at 7-8 years of age by skin prick tests to common allergens. Asthma was defined as a physician diagnosis and current symptoms at 71/2 years of age. Asthma and allergy status of the mothers were obtained from self-completion questionnaires. RESULTS: Data on MTHFR C677T genotype and allergy were available for 5364 children and on allergy and/or asthma for 7356 mothers. In children, the prevalence of atopy was 20.0% and asthma 10.0% whereas in mothers, the prevalence of self-reported allergy was 42.7% and asthma 11.5%. Atopy in the child was associated with male gender (P<0.001), less tobacco smoke exposure and higher maternal education. MTHFR C677T genotype was not associated with social factors or dietary folate intake. We found no evidence of associations between the MTHFR C677T variant allele and atopy, allergy or asthma in mothers or children. There was no evidence to support an effect of maternal MTHFR C677T genotype on atopy in the offspring. CONCLUSION: The results of this study do not support the hypothesis that impaired folate metabolism is associated with allergy in adults or children in this population.
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Dieta , Ácido Fólico/metabolismo , Hipersensibilidad Inmediata/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Adulto , Niño , Estudios de Cohortes , Femenino , Ácido Fólico/administración & dosificación , Humanos , MasculinoRESUMEN
OBJECTIVE: Osteoarthritis (OA) is a complex heterogeneous joint disease affecting more than 35 million people worldwide. The current gold standard diagnostic investigation is the plain radiograph, which lacks sensitivity. Biochemical markers have the potential to act as adjunct markers for imaging in the assessment of knee OA. We undertook this study to determine the association between individual biochemical markers and radiographic features, and to establish whether the association is strengthened when selected biochemical markers are combined into a single factor (a theoretical marker). METHODS: Twenty serum and urinary biochemical markers were analyzed in 119 patients with predominantly tibiofemoral knee OA. Pearson's correlation was performed, and corresponding coefficients of determination (R(2)) were calculated to determine the association between biochemical markers and a range of imaging features from radiographs and dual x-ray absorptiometry of the knee. Biochemical markers demonstrating a significant association (P < 0.05) with a specific imaging feature were combined by principal components analysis (PCA). Pearson's correlation was repeated to establish whether the combined panel of biochemical markers showed a stronger association with imaging than the best single marker. RESULTS: Fourteen biochemical markers showed significant associations with one or more imaging features. By combining specific panels of biochemical markers to form factors, the association of markers with imaging features (R(2)) increased from 11.9% to 22.7% for the Kellgren/Lawrence (K/L) score, from 5.9% to 9.2% for joint space width (JSW), from 6.6% to 10.8% for sclerosis, from 13.5% to 22.6% for osteophytes, and from 12.0% to 14.2% for bone mineral density (BMD). Biochemical markers identifying patients with osteophytes overlapped with those correlated with a high K/L score, while markers of subchondral BMD formed a completely separate group. Biochemical markers of JSW included markers associated with both osteophytes and BMD. CONCLUSION: The PCA results suggest that biochemical marker combinations may be more sensitive than individual biochemical markers for reflecting structural damage in patients with knee OA. The differences in biochemical marker profiles associated with osteophytes compared with those associated with subchondral BMD raise the possibility that these 2 processes, commonly seen in bone in knee OA, have underlying biologic differences.
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Biomarcadores/metabolismo , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/orina , Absorciometría de Fotón , Anciano , Densidad Ósea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadAsunto(s)
Neoplasias de Cabeza y Cuello/complicaciones , Síncope/etiología , Progresión de la Enfermedad , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Síncope/diagnóstico , Síncope/patologíaRESUMEN
No disponible
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Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/complicaciones , Síncope/etiología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/diagnóstico , Progresión de la Enfermedad , Invasividad Neoplásica , Síncope/patologíaRESUMEN
OBJECTIVES: There is some evidence that tibiofemoral osteoarthritis (TFJ OA) and patellofemoral osteoarthritis (PFJ OA) may have different risk factors. To investigate the possibility that these conditions are separate disease entities, we compared biomarker profiles of patients with each disease. METHODS: Serum samples were taken from 222 patients who had knee pain and X-ray signs of knee OA. Eighty-two had only medial TFJ OA and 38 only PFJ OA in one or both knees. The remaining patients had either mixed disease or equivocal radiographic evidence of OA. The following biomarkers were measured in serum samples from baseline and follow-up visits: cartilage oligomeric matrix protein (COMP), glycosaminoglycan, keratan sulphate epitope 5D4, YKL-40, osteocalcin, C-telopeptide of type I collagen, hyaluronan and C-reactive protein. RESULTS: The two subsets of OA (TFJ and PFJ) had similar radiographic disease severity and there were no significant differences in the presence and patterns of pain scores (visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index). No difference was found for the biomarkers between the two groups, with one exception. Both baseline and area under the curve per month COMP concentrations were significantly higher in the TFJ than the PFJ group (P<0.01). CONCLUSIONS: The reduced serum COMP in PFJ disease compared with TFJ OA could be due to small articular cartilage volume in the latter or to a qualitative difference in cartilage metabolism.
Asunto(s)
Proteínas de la Matriz Extracelular/sangre , Glicoproteínas/sangre , Osteoartritis de la Rodilla/sangre , Anciano , Biomarcadores/sangre , Proteína de la Matriz Oligomérica del Cartílago , Femenino , Fémur/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Masculino , Proteínas Matrilinas , Persona de Mediana Edad , Osteoartritis de la Rodilla/clasificación , Osteoartritis de la Rodilla/diagnóstico por imagen , Dimensión del Dolor , Rótula/diagnóstico por imagen , Radiografía , Índice de Severidad de la Enfermedad , Tibia/diagnóstico por imagenRESUMEN
OBJECTIVE: To compare the reproducibility of the standing extended view (SEV) (also known as the standing anteroposterior view) with the semiflexed, postero-anterior view [the 'metatarsophalangeal' (MTP)] view for assessing joint space width (JSW) and osteophytes in osteoarthritis of the knee when used in a busy routine X-ray department. METHODS: Forty-seven patients (24 men) had both SEV and MTP views taken on the same day in a busy National Health Service radiography department. Repeat views were taken as entirely separate procedures some time over the following 2 weeks, in the same department and with no special arrangements for the selection of radiographers, time of day, or X-ray machine. The first 24 patients had second views in the SEV position whilst the remaining 23 had second MTP views. Radiographs were read independently by two experienced observers who measured JSW with a transparent ruler to the nearest 0.5 mm at the narrowest point in both medial and lateral compartments of the tibiofemoral joint in both knees. Osteophytes were graded 0-2 according to a standard atlas. Ten SEV and 10 MTP radiographs selected randomly were re-read by one observer. RESULTS: Mean (95% confidence interval) JSW in the medial compartment measured on SEV radiographs was 3.54 mm (3.08, 3.99) and on MTP radiographs it was 2.80 mm (2.37, 3.23); in the lateral compartment it was 6.04 mm (5.71, 6.37) when measured on SEV radiographs and 5.47 mm (5.09, 5.85) on MTP radiographs. The estimated variances for the medial compartment were 2.0 mm2 for SEV and 0.2 mm2 for MTP (P < 0.001) and for the lateral compartment 1.4 mm2 for SEV and 0.5 mm2 for MTP (P < 0.001). The proportion of radiographs for which there was disagreement between observers regarding osteophyte grade was not statistically different between SEV and MTP views (SEV, medial 40%, lateral 44%; MTP, medial 39%, lateral 39%). CONCLUSIONS: Even when radiographs are taken in a busy National Health Service radiography department, measurement of JSW from the MTP view is more reproducible than from the SEV view, the MTP view gives a slightly lower measurement of JSW, and there is no advantage in using either view in recording osteophyte grade. We recommend the wider adoption of the MTP method.
Asunto(s)
Articulación de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/diagnóstico por imagen , Artrografía/métodos , Femenino , Humanos , Articulación de la Rodilla/patología , Masculino , Osteoartritis de la Rodilla/patología , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION AND OBJECTIVES: To assess the diagnostic capacity of a protocol to study syncope of unknown cause in which electrophysiological studies and tilting table tests are selectively used. PATIENTS AND METHODS: The study was performed in 137 consecutive patients (94 men and 43 women, with a mean age of 57.6+/-18.3 years) with syncope of unknown cause after the initial clinical evaluation, who were divided into two groups. Group A consisted of 77 patients meeting any of the following criteria: a) presence of structural heart disease; b) abnormal ECG; c) presence of significant non-symptomatic arrhythmia in the Holter recording, and d) presence of paroxysmal palpitations. These patients initially underwent an electrophysiological study. Group B consisted of 60 patients not meeting any of the above criteria, who were initially submitted to tilting table tests.Results. In group A, the electrophysiological study was positive in 43 patients (55%). In group B, the tilting test was positive in 41 patients (68%). Among patients in group A with a negative study, 20 (59%) were submitted to the tilting table test, with positive results in 7 cases (35%). Five patients from group B with a negative tilting test underwent the electrophysiological study, which was negative in all of them. Overall, a positive diagnosis was achieved in 91 of 137 patients (66%). CONCLUSIONS: In patients with syncope of a non-apparent cause in the initial assessment, selective use of electrophysiological studies or tilting table tests, guided by clinical criteria, allows for a positive diagnosis in over 60% of the cases. Our results suggest that the tilting table test should be performed in cases of group A with a negative electrophysiological study.