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Although transmission of rubella virus within the United States is rare, the risk for imported cases persists. We describe a rubella case in a newborn, conceived in Saudi Arabia, in Texas during 2017, highlighting the importance of active surveillance and early diagnosis of this disease.
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Síndrome de Rubéola Congénita/epidemiología , Síndrome de Rubéola Congénita/transmisión , Enfermedad Relacionada con los Viajes , Historia del Siglo XXI , Humanos , Lactante , Masculino , Síndrome de Rubéola Congénita/historia , Síndrome de Rubéola Congénita/virología , Arabia Saudita , Texas/epidemiologíaRESUMEN
Infection with Angiostrongylus cantonensis roundworms is endemic in Southeast Asia and the Pacific Basin. A. cantonensis meningitis and myelitis occurred in summer 2013 in a child with no history of travel outside of Texas, USA. Angiostrongyliasis is an emerging neurotropic helminthic disease in Texas and warrants increased awareness among healthcare providers.
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Angiostrongylus cantonensis/patogenicidad , Anticuerpos Antihelmínticos/sangre , Inmunoglobulina G/sangre , Meningitis/diagnóstico , Mielitis/diagnóstico , Infecciones por Strongylida/diagnóstico , Albendazol/uso terapéutico , Angiostrongylus cantonensis/fisiología , Animales , Antihelmínticos/uso terapéutico , Niño , Femenino , Humanos , Meningitis/líquido cefalorraquídeo , Meningitis/tratamiento farmacológico , Meningitis/parasitología , Mielitis/líquido cefalorraquídeo , Mielitis/tratamiento farmacológico , Mielitis/parasitología , Infecciones por Strongylida/líquido cefalorraquídeo , Infecciones por Strongylida/tratamiento farmacológico , Infecciones por Strongylida/parasitología , Texas , Resultado del TratamientoRESUMEN
BACKGROUND: Robust immune restoration in human immunodeficiency virus (HIV)-positive patients is dependent on thymic function. However, few studies have investigated thymic function and its correlation with disease progression over time in HIV-positive patients. METHODS: In this longitudinal prospective study, we followed 69 HIV-positive patients who were perinatally infected. Peripheral blood mononuclear cells were stained with monoclonal anti-CD4 and anti-CD31 and recent thymic emigrants (CD4+recently emigrated from the thymus (RTE), CD4+CD31+) quantified by flow cytometry. Statistical analysis used Wilcoxon rank sum test, Kruskal-Wallis, Spearman correlation, and Kaplan-Meier estimates; Cox regression models were performed for the longitudinal analysis. RESULTS: Median age of HIV positive patients enrolled was 13 years (interquartile range [IQR], 8.6). CD4+RTE% decreased with age and was higher in females. Median CD4+RTE% was 53.5%, IQR, 22.9. CD4+RTE% was closely related to CD4+% and absolute counts but independent of viral load and CD8+CD38+%. Antiretroviral compliance as well as higher nadir CD4+% were associated with higher CD4+RTE%. Low CD4+RTE% predicted poor progression of VL and CD4+% over time. CONCLUSIONS: CD4+RTE% predicts disease progression and may reflect history of disease in HIV-positive patients and adolescents. They are easy to measure in the clinical setting and may be helpful markers in guiding treatment decisions.
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Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos , Progresión de la Enfermedad , Infecciones por VIH/inmunología , Timo/inmunología , Adolescente , Niño , Preescolar , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/inmunología , VIH-1/fisiología , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Estudios Longitudinales , Masculino , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/inmunología , Embarazo , Estudios Prospectivos , Texas/epidemiología , Timo/citología , Carga Viral , Adulto JovenRESUMEN
INTRODUCTION: Smoking is a major risk factor for both cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). More individuals with COPD die from CVD than respiratory causes and the risk of developing CVD appears to be independent of smoking burden. Although CVD is a common comorbid condition within COPD, the nature of its relationships to COPD affection status and severity, and functional status is not well understood. METHODS: The first 2,500 members of the COPDGene cohort were evaluated. Subjects were current and former smokers with a minimum 10 pack-year history of cigarette smoking. COPD was defined by spirometry as an FEV1/FVC < lower limit of normal (LLN) with further identification of severity by FEV1 percent of predicted (GOLD stages 2, 3, and 4) for the main analysis. The presence of physician-diagnosed self-reported CVD was determined from a medical history questionnaire administered by a trained staff member. RESULTS: A total of 384 (15%) had pre-existing CVD. Self-reported CVD was independently related to COPD (Odds Ratio = 1.61, 95% CI = 1.18-2.20, p = 0.01) after adjustment for covariates with CHF having the greatest association with COPD. Within subjects with COPD, pre-existing self-reported CVD placed subjects at greater risk of hospitalization due to exacerbation, higher BODE index, and greater St. George's questionnaire score. The presence of self-reported CVD was associated with a shorter six-minute walk distance in those with COPD (p < 0.05). CONCLUSIONS: Self-reported CVD was independently related to COPD with presence of both self-reported CVD and COPD associated with a markedly reduced functional status and reduced quality of life. Identification of CVD in those with COPD is an important consideration in determining functional status.
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Enfermedades Cardiovasculares/epidemiología , Estado de Salud , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Calidad de Vida , Fumar/epidemiología , Anciano , Enfermedades Cardiovasculares/fisiopatología , Estudios de Casos y Controles , Estudios de Cohortes , Comorbilidad , Prueba de Esfuerzo , Femenino , Volumen Espiratorio Forzado , Hospitalización/estadística & datos numéricos , Humanos , Hipercolesterolemia/epidemiología , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Índice de Severidad de la Enfermedad , Capacidad VitalRESUMEN
BACKGROUND: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs. Because many perinatally HIV-infected patients have been treated with first-generation NNRTIs, they may have acquired resistance-associated mutations to etravirine (RAMe). METHODS: We determined for the interval 1998-2009 the prevalence and factors associated with the presence of RAMe. RESULTS: Twenty-three of 66 (34.8%) children had RAMe; the most common were 181C (19.6%), 190A (7.5%), 98G (6%), 106I (4.5%), 179D (4.5%), 100I (3%), 181I (1.5%), 138A (1.5%) and 179T (1.5%). Eleven children with RAMe (17%) had a mutation score between 2.5 and 3.5 and 1 (1.5%) a score ≥4, indicating an intermediate and reduced response to etravirine. For each 1% increase in CD4% there is a 7% decrease in the odds of RAMe (OR 0.93; 95% CI 0.88-0.97; P < 0.01). History of nevirapine use (OR 8.95; 95% CI 2.31-34.73; P < 0.01) and Hispanic ethnicity (OR 4.76; 95% CI 1.03-21.87; P = 0.04) are significantly associated with risk of RAMe. CONCLUSIONS: RAMe are present and common among antiretroviral-experienced perinatally HIV-infected children without previous exposure to etravirine. This could limit the efficacy of etravirine-based regimens. In addition, our results underscore the importance of taking previous history of nevirapine into account for combined antiretroviral therapy regimens that contain etravirine.
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Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , VIH/efectos de los fármacos , Piridazinas/administración & dosificación , Piridazinas/farmacología , Niño , Preescolar , Estudios de Cohortes , Femenino , VIH/genética , VIH/aislamiento & purificación , Infecciones por VIH/virología , Humanos , Masculino , Mutación Missense , Nitrilos , Prevalencia , Pirimidinas , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Severe oropharyngeal infection can result in Lemierre's disease, a syndrome with high mortality secondary to inflammation and thrombosis of cervical and intracranial veins with involvement of contiguous structures; however arterial involvement is rare. We report a case of Lemierre's disease in a 12 year old boy with severe narrowing of the left cavernous carotid artery.
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Arteria Carótida Interna , Estenosis Carotídea/microbiología , Infecciones por Fusobacterium/microbiología , Fusobacterium necrophorum/aislamiento & purificación , Síndrome de Lemierre/complicaciones , Niño , Infecciones por Fusobacterium/diagnóstico , Humanos , MasculinoRESUMEN
Background: The kidney is a common target for human immunodeficiency virus (HIV), making renal disease a common noninfectious complication of HIV. Microalbuminuria is an important marker that can detect early renal damage. Timely detection of microalbuminuria is important to initiate renal management and stop the progression of renal dysfunction in people with HIV. Limited data are available about renal abnormalities in people with perinatal HIV infection. The objective of this study was to determine the prevalence of microalbuminuria in a cohort of perinatally HIV-infected children and young adults receiving combination antiretroviral therapy and investigate correlations between microalbuminuria and clinical and laboratory findings. Methods: This was a retrospective study of 71 patients with HIV followed in an urban pediatric HIV clinic in Houston, Texas, between October 2007 and August 2016. Demographic, clinical, and laboratory data were compared between subjects with persistent microalbuminuria (PM) and those without. PM is defined as a microalbumin-to-creatinine ratio ≥30â mg/g on at least 2 occasions separated by at least 1 month. Results: Sixteen of 71 patients (23%) met the definition of PM. In univariate analysis, patients with PM had significantly higher CD8+ T-cell activation and lower CD4+ T-cell nadir. Multivariate analysis demonstrated increased microalbuminuria to be independently associated with older age and CD8+ T-cell activation measured as CD8+HLA-DR+ T-cell percentage. Conclusions: Older age and increased activation of CD8+HLA-DR+ on T cells correlate with presence of microalbuminuria in this cohort of HIV-infected patients.
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OBJECTIVE: We hypothesized that women who are obese before they become pregnant and also have elevations of complement Bb and C3a in the top quartile in early pregnancy would have the highest risk of preeclampsia compared with a referent group of women who were not obese and had levels of complement less than the top quartile. STUDY DESIGN: This was a prospective study of 1013 women recruited at less than 20 weeks' gestation. An EDTA-plasma sample was obtained, and complement fragments were measured using enzyme-linked immunosorbent assays. The data were analyzed using univariable and multivariable logistic regression analysis. RESULTS: Women who were obese with levels of Bb or C3a in the top quartile were 10.0 (95% confidence interval, 3.3-30) and 8.8 (95% confidence interval, 3-24) times, respectively, more likely to develop preeclampsia compared with the referent group. CONCLUSION: We demonstrate a combined impact of obesity and elevated complement on the development of preeclampsia.
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Activación de Complemento , Complemento C3a/metabolismo , Factor B del Complemento/metabolismo , Obesidad/complicaciones , Preeclampsia/etiología , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Modelos Logísticos , Análisis Multivariante , Obesidad/sangre , Obesidad/inmunología , Preeclampsia/sangre , Preeclampsia/inmunología , Embarazo , Estudios ProspectivosRESUMEN
RATIONALE: A significant proportion of smokers have lung function impairment characterized by a reduced FEV(1) with a preserved FEV(1)/FVC ratio. These smokers are a poorly characterized group due to their systematic exclusion from chronic obstructive pulmonary disease (COPD) studies. OBJECTIVES: To characterize the clinical, functional, and radiographic features of Global Initiative for Chronic Obstructive Lung Disease (GOLD)-Unclassified (FEV(1)/FVC ≥ 0.7 and FEV(1) < 80% predicted) and lower limits of normal (LLN)-unclassified (FEV(1)/FVC ≥ LLN and FEV(1) < LLN) subjects compared to smokers with normal lung function and subjects with COPD. METHODS: Data from the first 2,500 subjects enrolled in the COPDGene study were analyzed. All subjects had 10 or more pack-years of smoking and were between the ages of 45 and 80 years. Multivariate regression models were constructed to determine the clinical and radiological variables associated with GOLD-Unclassified (GOLD-U) and LLN-Unclassified status. Separate multivariate regressions were performed in the subgroups of subjects with complete radiologic measurement variables available. MEASUREMENTS AND MAIN RESULTS: GOLD-U smokers account for 9% of smokers in COPDGene and have increased body mass index (BMI), a disproportionately reduced total lung capacity, and a higher proportion of nonwhite subjects and subjects with diabetes. GOLD-U subjects exhibit increased airway wall thickness compared to smoking control subjects and decreased gas trapping and bronchodilator responsiveness compared to subjects with COPD. When LLN criteria were used to define the "unclassified" group, African American subjects were no longer overrepresented. Both GOLD-U and LLN-Unclassified subjects demonstrated a wide range of lung function impairment, BMI, and percentage of total lung emphysema. CONCLUSIONS: Subjects with reduced FEV(1) and a preserved FEV(1)/FVC ratio are a heterogeneous group with significant symptoms and functional limitation who likely have a variety of underlying etiologies beyond increased BMI. Clinical trial registered with www.clinicaltrials.gov (NCT000608764).
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Volumen Espiratorio Forzado , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Fumar/fisiopatología , Capacidad Vital , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Espirometría , Tomografía Computarizada por Rayos X , Capacidad Pulmonar TotalRESUMEN
Long-term therapy with systemic corticosteroids is not recommended in the treatment of chronic obstructive pulmonary disease (COPD). However, experience demonstrates that some patients receive low dose therapy. Our objective was to describe the demographic, physiologic and radiologic characteristics of COPD patients treated with chronic systemic corticosteroids. We analyzed COPD subjects with GOLD I-IV disease in the COPDGene® study. Subjects were divided into 2 groups based on whether they reported using chronic oral steroids or not; 1264 subjects were included. Fifty-eight (4.5%) reported chronic systemic corticosteroid use. There were no differences in age, race, co-morbid conditions (other than asthma), or body mass index between the groups. There was a greater proportion of GOLD III (41% vs. 26%) and IV (41% vs. 13%) subjects in the group using chronic systemic corticosteroids. This group used more respiratory medications, required more oxygen (2.31 ± 0.21 vs. 0.59 ± 0.05 L/min; p < 0.0001), and walked less distance (245.4 ± 17.4 vs. 367.2 ± 3.9 meters; p < 0.0001). They reported more total (1.7 ± 0.16 vs. 0.62 ± 0.03; p < 0.0001) and severe exacerbations per year (0.41 ± 0.05 vs. 0.18 ± 0.01; p < 0.0001). BODE (5.0 ± 0.3 vs. 2.6 ± 0.1; p < 0.0001), MMRC (3.31 ± 0.19 vs. 1.90 ± 0.04; p < 0.0001) and SGRQ scores (54.9 ± 2.9 vs 53.3 ± 0.6; p < 0.0001) were higher. They also had a higher percentage of emphysema (22.4 ± 1.9 vs. 14.0 ± 0.4;%, p = <0.0001) on CT scan. COPD patients that report using chronic systemic corticosteroids have more severe clinical, physiologic, and radiographic disease.
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Glucocorticoides/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Administración Oral , Agonistas Adrenérgicos beta/uso terapéutico , Asma/epidemiología , Broncodilatadores/uso terapéutico , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Hipersensibilidad/epidemiología , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Nebulizadores y Vaporizadores , Oxígeno/sangre , Terapia por Inhalación de Oxígeno , Prednisona/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Calidad de Vida , Derivados de Escopolamina/uso terapéutico , Índice de Severidad de la Enfermedad , Fumar/epidemiología , Espirometría , Teofilina/uso terapéutico , Bromuro de Tiotropio , Estados Unidos/epidemiología , Caminata/fisiologíaRESUMEN
UNLABELLED: The purposes of this study were: to describe chest CT findings in normal non-smoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring. METHODS: Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9-11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements. RESULTS: Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75%, 87% and 65%, respectively. CONCLUSIONS: Despite substantial inter-observer variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.
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Enfisema/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Estudios de Casos y Controles , Educación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Prevalencia , Proyectos de Investigación , FumarRESUMEN
Objective: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy. Background: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis. Methods: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy for appendicitis. Of 34 independent variables initially, 12 variables with the highest influence on the outcome selected for the final dataset for ANN model training and testing. Results: A total of 1574 patients were used for training and test sets (80%/20% split). Model 1 achieved accuracy of 89.84%, sensitivity of 70%, and specificity of 93.61% on the test set. Model 2 achieved accuracy of 84.13%, sensitivity of 81.63%, and specificity of 84.6%. Conclusions: ANN applied to selected variables can accurately predict patients who will have IAA post-appendectomy. Our reproducible and explainable ANNs potentially represent a state-of-the-art method for optimizing post-appendectomy care.
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Cachexia, whether assessed by body mass index (BMI) or fat-free mass index (FFMI), affects a significant proportion of patients with chronic obstructive pulmonary disease (COPD), and is an independent risk factor for increased mortality, increased emphysema, and more severe airflow obstruction. The variable development of cachexia among patients with COPD suggests a role for genetic susceptibility. The objective of the present study was to determine genetic susceptibility loci involved in the development of low BMI and FFMI in subjects with COPD. A genome-wide association study (GWAS) of BMI was conducted in three independent cohorts of European descent with Global Initiative for Chronic Obstructive Lung Disease stage II or higher COPD: Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-Points (ECLIPSE; n = 1,734); Norway-Bergen cohort (n = 851); and a subset of subjects from the National Emphysema Treatment Trial (NETT; n = 365). A genome-wide association of FFMI was conducted in two of the cohorts (ECLIPSE and Norway). In the combined analyses, a significant association was found between rs8050136, located in the first intron of the fat mass and obesity-associated (FTO) gene, and BMI (P = 4.97 × 10(-7)) and FFMI (P = 1.19 × 10(-7)). We replicated the association in a fourth, independent cohort consisting of 502 subjects with COPD from COPDGene (P = 6 × 10(-3)). Within the largest contributing cohort of our analysis, lung function, as assessed by forced expiratory volume at 1 second, varied significantly by FTO genotype. Our analysis suggests a potential role for the FTO locus in the determination of anthropomorphic measures associated with COPD.
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Índice de Masa Corporal , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Proteínas/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Adulto , Anciano , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Biomarcadores , Composición Corporal , Peso Corporal , Estudios de Cohortes , Femenino , Volumen Espiratorio Forzado , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Noruega , Pruebas de Función Respiratoria , Factores de RiesgoRESUMEN
OBJECTIVE: To assess the outcome of oral food challenges in patients placed on elimination diets based primarily on positive serum immunoglobulin E (IgE) immunoassay results. STUDY DESIGN: This is a retrospective chart review of 125 children aged 1-19 years (median age, 4 years) evaluated between January 2007 and August 2008 for IgE-mediated food allergy at National Jewish Health and who underwent an oral food challenge. Clinical history, prick skin test results, and serum allergen-specific IgE test results were obtained. RESULTS: The data were summarized for food avoidance and oral food challenge results. Depending on the reason for avoidance, 84%-93% of the foods being avoided were returned to the diet after an oral food challenge, indicating that the vast majority of foods that had been restricted could be tolerated at discharge. CONCLUSIONS: In the absence of anaphylaxis, the primary reliance on serum food-specific IgE testing to determine the need for a food elimination diet is not sufficient, especially in children with atopic dermatitis. In those circumstances, oral food challenges may be indicated to confirm food allergy status.
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Dermatitis Atópica/inmunología , Hipersensibilidad a los Alimentos/diagnóstico , Inmunoglobulina E/sangre , Adolescente , Alérgenos , Niño , Preescolar , Dermatitis Atópica/epidemiología , Femenino , Alimentos , Hipersensibilidad a los Alimentos/dietoterapia , Hipersensibilidad a los Alimentos/inmunología , Humanos , Inmunoensayo , Lactante , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers. METHODS: Current smokers with COPD (GOLD stage ≥ 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes. RESULTS: Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p < .0001) as well as in COPD cases (ρ = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers. CONCLUSIONS: Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.
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Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Receptores Nicotínicos/genética , Fumar/epidemiología , Tabaquismo/epidemiología , Tomografía Computarizada por Rayos X , Anciano , Análisis de Varianza , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Volumen Espiratorio Forzado , Predisposición Genética a la Enfermedad , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/epidemiología , Enfisema Pulmonar/genética , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Fumar/efectos adversos , Fumar/genética , Espirometría , Tabaquismo/genética , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Alloimmunization to red blood cell (RBC) blood group antigens is a major complication for patients with sickle cell disease (SCD), which limits the usefulness of RBC transfusion. Here, we report our experiences with extended RBC antigen matching for SCD patients. STUDY DESIGN AND METHODS: Records for 99 SCD patients transfused only with the extended matching protocol between 1993 and 2006 were reviewed. Patients and donors were phenotyped for 20 blood group antigens and RBC units that were negative for antigens not expressed by the recipient were provided. When necessary, mismatches were allowed at Le(a) , Le(b) , Fy(b) , and MNSs to meet requirements for antigens regarded as the most clinically significant. Matched RBC units (6946) were provided to 99 patients (mean, 70 units/patient; range, 1-519 units/patient). Eliminating mismatches, 90% of the transfusions matched all other negative antigens. RESULTS: Seven alloantibodies were detected in seven patients resulting in 7% alloimmunized at a rate of 0.1 antibodies per 100 units transfused. Three recipients who developed antibodies were D mosaic and would have been mistyped with serologic techniques. Alloimmunization was decreased compared to ABO and/or D matching at our institution and others. Twelve autoantibodies and no severe hemolytic transfusion reactions were reported. CONCLUSION: Exact matching for ABO, Rhesus, Kell, Kidd, and Fy(a) and extending this match whenever possible is an effective strategy to reduce alloimmunization to RBC antigens. Consideration should be given to exploring this conclusion further with a controlled, multi-institutional trial to determine efficacy, cost-benefit analysis, and reproducibility of this approach.
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Anemia de Células Falciformes/inmunología , Anemia de Células Falciformes/terapia , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , Transfusión de Eritrocitos , Eritrocitos/inmunología , Adolescente , Adulto , Anemia de Células Falciformes/sangre , Niño , Preescolar , Transfusión de Eritrocitos/métodos , Femenino , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
RATIONALE AND OBJECTIVES: There are limited data on, and controversies regarding gender differences in the airway dimensions of smokers. Multi-detector CT (MDCT) images were analyzed to examine whether gender could explain differences in airway dimensions of anatomically matched airways in smokers. MATERIALS AND METHODS: We used VIDA imaging software to analyze MDCT scans from 2047 smokers (M:F, 1021:1026) from the COPDGene® cohort. The airway dimensions were analyzed from segmental to subsubsegmental bronchi. We compared the differences of luminal area, inner diameter, wall thickness, wall area percentage (WA%) for each airway between men and women, and multiple linear regression including covariates (age, gender, body sizes, and other relevant confounding factors) was used to determine the predictors of each airway dimensions. RESULTS: Lumen area, internal diameter and wall thickness were smaller for women than men in all measured airway (18.4 vs 22.5 mm(2) for segmental bronchial lumen area, 10.4 vs 12.5 mm(2) for subsegmental bronchi, 6.5 vs 7.7 mm(2) for subsubsegmental bronchi, respectively p < 0.001). However, women had greater WA% in subsegmental and subsubsegmental bronchi. In multivariate regression, gender remained one of the most significant predictors of WA%, lumen area, inner diameter and wall thickness. CONCLUSION: Women smokers have higher WA%, but lower luminal area, internal diameter and airway thickness in anatomically matched airways as measured by CT scan than do male smokers. This difference may explain, in part, gender differences in the prevalence of COPD and airflow limitation.
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Broncografía/métodos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/patología , Interpretación de Imagen Radiográfica Asistida por Computador , Análisis de Regresión , Pruebas de Función Respiratoria , Factores Sexuales , Fumar/efectos adversos , Fumar/fisiopatologíaRESUMEN
BACKGROUND: There is little knowledge about clinical variables associated with vitamin D (VitD) insufficiency in asthmatic children. OBJECTIVE: We sought to investigate disease variables associated with VitD insufficiency in patients with childhood asthma and interaction of VitD with corticosteroid-mediated anti-inflammatory responses. METHODS: We analyzed 25-hydroxyvitamin D serum levels in 100 asthmatic children to investigate relationships between 25-hydroxyvitamin D levels and patients' characteristics. We determined VitD's effects on dexamethasone (DEX) induction of mitogen-activated protein kinase phosphatase 1 and IL-10 in PBMCs. RESULTS: The median 25-hydroxyvitamin D serum level was 31 ng/mL. Forty-seven percent of subjects had VitD levels in the insufficient range (<30 ng/mL), whereas 17% were VitD deficient (<20 ng/mL). Log(10) IgE (P = .01, rho = -0.25) and the number of positive aeroallergen skin prick test responses (P = .02, rho = -0.23) showed a significant inverse correlation with VitD levels, whereas FEV(1) percent predicted (P = .004, rho = 0.34) and FEV(1)/forced vital capacity ratio (P = .01, rho = 0.30) showed a significant positive correlation with VitD levels. The use of inhaled steroids (P = .0475), use of oral steroids (P = .02), and total steroid dose (P = .001) all showed significant inverse correlations with VitD levels. The amount of mitogen-activated protein kinase phosphatase 1 and IL10 mRNA induced by VitD plus DEX was significantly greater than that induced by DEX alone (P < .01). In an experimental model of steroid resistance in which DEX alone did not inhibit T-cell proliferation, addition of VitD to DEX resulted in significant dose-dependent suppression of cell proliferation. CONCLUSIONS: Corticosteroid use and worsening airflow limitation are associated with lower VitD serum levels in asthmatic patients. VitD enhances glucocorticoid action in PBMCs from asthmatic patients and enhances the immunosuppressive function of DEX in vitro.
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Asma/tratamiento farmacológico , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Deficiencia de Vitamina D/etiología , Vitamina D/análogos & derivados , Niño , Preescolar , Dexametasona/farmacología , Fosfatasa 1 de Especificidad Dual/metabolismo , Femenino , Glucocorticoides/farmacología , Humanos , Interleucina-10/metabolismo , Activación de Linfocitos , Masculino , Reacción en Cadena de la Polimerasa , Linfocitos T/inmunología , Linfocitos T/metabolismo , Vitamina D/sangreRESUMEN
Pulmonary infection due to Mycobacterium abscessus occurs in patients with cystic fibrosis, but rarely in immunocompetent children without underlying lung pathology. Treatment is complicated by frequent resistance to many antibiotics. We present a case report of a 4-month-old female infant with 2 months of cough, difficulty feeding, and failure to thrive, with extensive culture-confirmed M. abscessus pulmonary infection without identified immunodeficiency or underlying lung pathology following multidisciplinary evaluation. We describe our complete evaluation including immunodeficiency evaluation incorporating whole-exome sequencing, describe our antibiotic selection and treatment duration given complicated susceptibility pattern of the M. abscessus isolate, and review literature for nontuberculous mycobacterial pulmonary disease in immunocompetent children. A complete multidisciplinary evaluation for underlying lung disease and primary and acquired immunodeficiency should be undertaken in pediatric patients with M. abscessus pneumonia. Confirming macrolide susceptibility through erm(41) gene evaluation is clinically important for isolates with complicated susceptibility pattern.
RESUMEN
This study was designed to quantify and identify differences in protein levels between tumor and adjacent normal breast tissue from the same breast in 18 women with stage I/II ER positive/Her2/neu negative invasive breast cancer. Eighteen separate difference gel electrophoresis (DIGE) gels were run (1 gel per patient). Relative quantification was based on DIGE analysis. After excision and tryptic digestion, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass mapping were used to identify protein spots. Two hundred and forty-three spots were differentially abundant between normal and cancer tissues. Fifty spots were identified: 41 were over abundant and nine were less abundant in cancers than in normal breast tissue. Western blotting provided independent confirmation for three of the most biologically and statistically interesting proteins. All 18 gels were replicated by another technician and 32% of the differentially abundant proteins were verified by the duplicate analysis. Follow-up studies are now examining these proteins as biomarkers in blood.