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AIMS: X-linked adrenoleukodystrophy (X-ALD) is a genetic white matter disorder in which demyelination occurs due to accumulation of very long-chain fatty acids. Inflammation in the brain white matter is a hallmark of the pathology of cerebral X-ALD, but the underlying pathogenic mechanisms are still largely unknown. In other inflammatory demyelinating disorders, such as multiple sclerosis, the expression of heat shock proteins (HSPs) in combination with interferon-γ (IFN-γ) has been suggested to play a prominent role in the initiation of demyelination and inflammation. We therefore investigated these pathways in X-ALD lesions. METHODS: By immunohistochemistry, we examined the expression of small HSPs (HSPB1, HSPB5, HSPB6, HSPB8) and higher molecular weight HSPs (HSPA, HSPD1), and the expression of elements of the IFN-γ pathway on autopsy material of five patients with X-ALD. RESULTS: The expression of the larger HSPs, HSPA and HSPD1, as well as small HSPs is increased in X-ALD lesions compared with normal-appearing white matter. Such upregulation can already be detected before demyelination and inflammation occur, and it is predominant in astrocytes. The IFN-γ pathway does not seem to play a leading role in the observed inflammation. CONCLUSIONS: The finding that astrocytes show signs of cellular stress before demyelination suggests that they play a major role early in the pathogenesis of cerebral X-ALD, and may therefore be involved in the initiation of inflammation and demyelination.
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Adrenoleucodistrofia/metabolismo , Astrocitos/metabolismo , Corteza Cerebral/metabolismo , Proteínas de Choque Térmico/metabolismo , Adolescente , Adrenoleucodistrofia/patología , Adulto , Astrocitos/patología , Corteza Cerebral/patología , Niño , Enfermedades Desmielinizantes/metabolismo , Enfermedades Desmielinizantes/patología , Humanos , Masculino , Persona de Mediana Edad , Vaina de Mielina/metabolismo , Vaina de Mielina/patología , Sustancia Blanca/metabolismo , Sustancia Blanca/patologíaRESUMEN
AIM: Vanishing White Matter (VWM) is a devastating leucoencephalopathy without effective treatment options. Patients have mutations in the EIF2B1-5 genes, encoding the five subunits of eIF2B, a guanine exchange factor that is an important regulator of protein translation. We recently developed mouse models for VWM that replicate the human disease. To study disease improvement after treatment in these mice, it is essential to have sensitive biomarkers related to disease stage. The Bergmann glia of the cerebellum, an astrocytic subpopulation, translocate into the molecular layer in symptomatic VWM mice and patients. This study looked at the prospects of using Bergmann glia pathology as an objective disease marker for VWM. METHODS: We defined a new quantitative measurement of Bergmann glia pathology in the cerebellum of VWM mice and patients. To test the sensitivity of this new marker for improvement, VWM mutant mice received long-term treatment with Guanabenz, an FDA-approved anti-hypertensive agent affecting eIF2B activity. RESULTS: Bergmann glia translocation was significantly higher in symptomatic VWM mice and VWM patients than in controls and worsened over the disease course. Both Bergmann glia pathology and cerebellar myelin pathology improved with Guanabenz treatment in mice, showing that Bergmann glia translocation is a sensitive measurement for improvement. CONCLUSIONS: Bergmann glia translocation can be used to objectively assess effects of treatment in VWM mice. Future treatment strategies involving compounds regulating eIF2 phosphorylation might benefit VWM patients.
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Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Astrocitos/patología , Guanabenzo/uso terapéutico , Leucoencefalopatías/patología , Animales , Biomarcadores , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Leucoencefalopatías/tratamiento farmacológico , Ratones , Fosforilación , Resultado del TratamientoRESUMEN
AIMS: Diffuse intrinsic pontine glioma (DIPG) is a fatal paediatric malignancy. Tumour resection is not possible without serious morbidity and biopsies are rarely performed. The resulting lack of primary DIPG material has made preclinical research practically impossible and has hindered the development of new therapies for this disease. The aim of the current study was to address the lack of primary DIPG material and preclinical models by developing a multi-institutional autopsy protocol. METHODS: An autopsy protocol was implemented in the Netherlands to obtain tumour material within a brief post mortem interval. A team of neuropathologists and researchers was available at any time to perform the autopsy and process the material harvested. Whole brain autopsy was performed and primary DIPG material and healthy tissue were collected from all affected brain areas. Finally, the study included systematic evaluation by parents. RESULTS: Five autopsies were performed. The mean time interval between death and time of autopsy was 3 h (range 2-4). All tumours were graded as glioblastoma. None of the parents regretted their choice to participate, and they all derived comfort in donating tissue of their child in the hope to help future DIPG patients. In addition, we developed and characterized one of the first DIPG cell cultures from post mortem material. CONCLUSION: Here we show that obtaining post mortem DIPG tumour tissue for research purposes is feasible with short delay, and that the autopsy procedure is satisfying for participating parents and can be suitable for the development of preclinical DIPG models.
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Autopsia/normas , Neoplasias del Tronco Encefálico/patología , Glioma/patología , Cultivo Primario de Células/normas , Animales , Niño , Preescolar , ADN de Neoplasias/biosíntesis , ADN de Neoplasias/genética , Femenino , Humanos , Lactante , Masculino , Ratones , Ratones Desnudos , Padres , Puente/patología , ARN Neoplásico/biosíntesis , ARN Neoplásico/genéticaRESUMEN
Pulmonary hypoplasia and respiratory failure are primary causes of death in patients with osteogenesis imperfecta (OI) type II. OI is a genetic skeletal disorder caused by pathogenic variants in genes encoding collagen type I. It is still unknown if the collagen defect also affects lung development and structure, causing lung hypoplasia in OI type II. The aim of this study was to investigate the intrinsic characteristics of OI embryonic lung parenchyma and to determine whether altered collagen type I may compromise airway development and lung structure. Lung tissue from nine fetuses with OI type II and six control fetuses, matched by gestational age, was analyzed for TTF-1 and collagen type I expression by immunohistochemistry, to evaluate the state of lung development and amount of collagen. The differentiation of epithelium into type 2 pneumocytes during embryonic development was premature in OI type II fetuses compared to controls (p < 0.05). Collagen type I showed no significant differences between the two groups. However, the amount of alpha2(I) chains was higher in fetuses with OI and the ratio of alpha1(I) to alpha2(I) lower in OI compared to controls. Cell differentiation during lung embryonic development in patients with OI type II is premature and impaired. This may be the underlying cause of pulmonary hypoplasia. Altered cell differentiation can be secondary to mechanical chest factors or a consequence of disrupted type I collagen synthesis. Our findings suggest that collagen type I is a biochemical regulator of pulmonary cell differentiation, influencing lung development.
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Colágeno Tipo I , Osteogénesis Imperfecta , Humanos , Colágeno Tipo I/genética , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Colágeno/metabolismo , Diferenciación CelularRESUMEN
The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20-44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991-1993; n = 6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998-2000; n = 18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007-2010; n = 10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19-1.59) from 1998-2000 to 2007-2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.
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Asma/epidemiología , Rinitis Alérgica Perenne/epidemiología , Rinitis Alérgica Estacional/epidemiología , Adulto , Estudios Transversales , Femenino , Humanos , Italia/epidemiología , Masculino , Prevalencia , Ruidos Respiratorios , Fumar/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
AIMS: Chronic cough is more frequent and severe in women than in men. Women often have decreased iron stores, because of menses and pregnancies. We investigated if iron deficiency has a role in chronic cough by increasing airway sensitivity to inhaled irritants. METHODS: Twenty-two non-smoking women with chronic unexplained cough and iron deficiency (serum ferritin below 15 ng/ml) were examined in baseline, after 2 months empiric treatment with anti H1-histaminic drug and proton pump inhibitor, and after iron supplementation (330-660 mg iron sulphate tablets daily) for 2 months. Outcome measures were cough visual analogue scale (VAS), and histamine thresholds of the larynx (PC25MIF50, concentration causing 25% in MIF50), bronchi (PC20FEV1) and cough (PC5cough). RESULTS: Mean serum ferritin was 9.3 ng/ml (95% CI 7.7-10.9), 13 patients had mild anaemia. All the patients had laryngeal and cough hyperresponsiveness,12 had also bronchial hyperresponsiveness. Empiric treatment produced no significant effect, whereas iron supplementation improved cough VAS from 4.03 (3.6-4.47) to 2.6 (1.9-3.27), p < 0.0001, PC20FEV1 from 10.04 mg/ml (5.37-18.77) to 22.2 (11.7-41.8), p < 0.001, PC25MIF50 from 3.09 mg/ml (1.9-4.9) to 11.9 (7.3-19.4), p < 0.001 and PC5cough from 2.1 mg/ml (1.2-3.6) to 8.8 (5.2-15.1), p < 0.001. CONCLUSION: In women with unexplained chronic cough unresponsive to targeted treatment, airway and cough hyperresponsiveness may be sustained by iron deficiency. Healthy women with chronic cough should be checked for iron deficiency as iron repletion may resolve such disturbing symptom.
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Anemia Ferropénica/dietoterapia , Tos/dietoterapia , Suplementos Dietéticos , Deficiencias de Hierro , Adulto , Anemia Ferropénica/complicaciones , Anemia Ferropénica/fisiopatología , Enfermedad Crónica , Tos/etiología , Tos/fisiopatología , Femenino , Ferritinas/deficiencia , Humanos , Hierro/administración & dosificación , Óxido Nítrico/análisis , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND AND AIM: Monitoring the efficacy of antituberculosis therapy is crucial. The aim of this work is to investigate the effect of tuberculosis treatment on interferon-gamma response using Quanti-FERON-TB Gold in tube (QFT-GIT). METHODS: A total of 216 new pulmonary tuberculosis (TB) cases were tested with QFT-GIT at the start of the treatment and, randomly, once or twice between 90 and 180 days afterwards. Data was analysed using the random effect regression model analysis. RESULTS: 63.4% of patients were positive at the QFT-GIT (> .35 UI cut-off). TB cases showed a significant log-linear increase in interferon-gamma (IFN-gamma) concentration, over time of treatment: IFN-gamma concentration increased by 78% after 6 months of treatment in acid-fast bacilli positive (A) and culture negative cases in culture confirmed cases the increase was 43% if A+ and 20% in A-. CONCLUSIONS: Effective therapy seems to restore cellular responses to Mycobacterium tuberculosis antigens. The potential use of interferon gamma release assay (IGRA) in monitoring response to TB treatment is hampered by the presence of active mycobacterial replication at baseline and needs further evaluation.
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Antituberculosos/farmacología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Mycobacterium tuberculosis/inmunología , Adulto , Antígenos Bacterianos/inmunología , Técnicas Bacteriológicas/métodos , Femenino , Humanos , Inmunidad Celular/inmunología , Inmunoensayo/métodos , Modelos Lineales , Masculino , Monitoreo FisiológicoRESUMEN
It is uncertain the Forced Expiratory Time (FET) acceptable during spirometry of young people (16-20 years old) because they are not children nor adults. We studied 235 boys and 187 girls of this age and, comparing spirometries with FET > 3 s and > 6 s, we found no significative difference (t test) between Vext, DtPEF, FVC and FEV1 repeatibility, while for wheight in males (p =0.0022) and plateau time (p < 0.00001) in males and females. We conclude that blows with FET < 6s but > 3s can be acceptable in young people when other criteria are respected.
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Salud Laboral , Espirometría/normas , Adolescente , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
INTRODUCTION: Respiratory failure is a major cause of death in patients with Osteogenesis Imperfecta. Moreover, respiratory symptoms seem to have a dramatic impact on their quality of life. It has long been thought that lung function disorders in OI are mainly due to changes in the thoracic wall, caused by bone deformities. However, recent studies indicate that alterations in the lung itself can also undermine respiratory health. OBJECTIVES: Is there any intrapulmonary alteration in Osteogenesis Imperfecta that can explain decreased pulmonary function? The aim of this systematic literature review is to investigate to what extent intrapulmonary or extrapulmonary thoracic changes contribute to respiratory dysfunction in Osteogenesis Imperfecta. METHODS: A literature search (in PubMed, Embase, Web of Science, and Cochrane), which included articles from inception to December 2020, was performed in accordance with the PRISMA guidelines. RESULTS: Pulmonary function disorders have been described in many studies as secondary to scoliosis or to thoracic skeletal deformities. The findings of this systematic review suggest that reduced pulmonary function can also be caused by a primary pulmonary problem due to intrinsic collagen alterations. CONCLUSIONS: Based on the most recent studies, the review indicates that pulmonary defects may be a consequence of abnormal collagen type I distorting the intrapulmonary structure of the lung. Lung function deteriorates further when intrapulmonary defects are combined with severe thoracic abnormalities. This systematic review reveals novel findings of the underlying pathological mechanism which have clinical and diagnostic implications for the assessment and treatment of pulmonary function disorders in Osteogenesis Imperfecta.KEY MESSAGESDecreased pulmonary function in Osteogenesis Imperfecta can be attributed to primary pulmonary defects due to intrapulmonary collagen alterations and not solely to secondary problems arising from thoracic skeletal dysplasia.Type I collagen defects play a crucial role in the development of the lung parenchyma and defects, therefore, affect pulmonary function. More awareness is needed among physicians about pulmonary complications in Osteogenesis Imperfecta to develop novel concepts on clinical and diagnostic assessment of pulmonary functional disorders.
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Osteogénesis Imperfecta/complicaciones , Insuficiencia Respiratoria/fisiopatología , Humanos , Pulmón , Osteogénesis Imperfecta/patología , Calidad de Vida , Pruebas de Función Respiratoria , Insuficiencia Respiratoria/etiología , EscoliosisRESUMEN
BACKGROUND: Allergen exposure may increase airway oxidative stress, which causes lipid membrane peroxidation and an increased formation of 8-isoprostane. OBJECTIVE: The aim of the study was to investigate oxidative stress induced by allergen challenge in mild asthmatics, by measuring 8-isoprostane in exhaled breath condensate (EBC), and to examine their relationship with mediators derived from arachidonic acid. Methods 8-isoprostane, cysteinyl leukotrienes (cys-LTs) and prostaglandin E2 (PGE(2) ) concentrations in EBC were measured at baseline and after allergen challenge in 12 patients with mild allergic asthma sensitized to cat allergen. RESULTS: At 24 h after allergen challenge, compared with baseline values, EBC 8-isoprostane increased [48.64 pg/mL (44.14-53.61) vs. 21.56 pg/mL (19.92, 23.35), P<0.001], cys-LTs increased [27.37 pg/mL (24.09-31.10) vs. 13.28 pg/mL (11.32, 15.57), P<0.001] and PGE(2) decreased [18.69 pg/mL (12.26, 28.50) vs. 39.95 pg/mL (34.37, 46.43), P<0.001]. The trend of increasing 8-isoprostane after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.85, P<0.001) whereas the trend of decreasing PGE(2) after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.52, P=0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The increase in EBC 8-isoprostane observed after allergen challenge indicates that allergen exposure increases airway oxidative stress in allergic asthma. The strict correlation between cys-LTs and 8-isoprostane underlines the relationship between allergic inflammation and oxidative stress. A shift of arachidonic acid metabolism towards lipoxygenase pathway is induced by the allergen challenge. Airway oxidative stress occurs after allergen challenge even in patients with mild intermittent allergic asthma.
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Alérgenos/administración & dosificación , Asma/metabolismo , Pruebas Respiratorias , Espiración , Peroxidación de Lípido , Pulmón/metabolismo , Estrés Oxidativo , Administración por Inhalación , Adulto , Animales , Asma/diagnóstico , Asma/inmunología , Asma/fisiopatología , Biomarcadores/metabolismo , Estudios de Casos y Controles , Gatos , Dinoprost/análogos & derivados , Dinoprost/metabolismo , Dinoprostona/metabolismo , Femenino , Volumen Espiratorio Forzado , Humanos , Leucotrienos/metabolismo , Pulmón/inmunología , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto JovenRESUMEN
The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.
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Ambiente , Diseño de Investigaciones Epidemiológicas , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/genética , Asma/epidemiología , Asma/genética , Sesgo , Estudios de Casos y Controles , Recolección de Datos , Interpretación Estadística de Datos , Bases de Datos Factuales , Contaminación Ambiental , Femenino , Vivienda , Humanos , Italia/epidemiología , Estudios Longitudinales , Masculino , Encuestas Nutricionales , Fenotipo , Sector Público , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/genética , Rinitis Alérgica Perenne/epidemiología , Rinitis Alérgica Perenne/genética , Rinitis Alérgica Estacional/epidemiología , Rinitis Alérgica Estacional/genética , Encuestas y CuestionariosRESUMEN
Prion diseases are transmissible neurodegenerative conditions characterized by the accumulation of protease-resistant forms of the prion protein (PrP), termed PrPres, in the brain. Insoluble PrPres tends to aggregate into amyloid fibrils. The anthracycline 4'-iodo-4'-deoxy-doxorubicin (IDX) binds to amyloid fibrils and induces amyloid resorption in patients with systemic amyloidosis. To test IDX in an experimental model of prion disease, Syrian hamsters were inoculated intracerebrally either with scrapie-infected brain homogenate or with infected homogenate coincubated with IDX. In IDX-treated hamsters, clinical signs of disease were delayed and survival time was prolonged. Neuropathological examination showed a parallel delay in the appearance of brain changes and in the accumulation of PrPres and PrP amyloid.
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Doxorrubicina/análogos & derivados , Priones/metabolismo , Scrapie/tratamiento farmacológico , Amiloide/metabolismo , Animales , Conducta Animal , Encéfalo/metabolismo , Encéfalo/patología , Síndrome de Creutzfeldt-Jakob/metabolismo , Cricetinae , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Humanos , Mesocricetus , ARN Mensajero/genética , ARN Mensajero/metabolismo , Scrapie/metabolismo , Scrapie/patología , Tubulina (Proteína)/análisisRESUMEN
BACKGROUND: There is no agreement about exhaled nitric oxide (FE(NO)) and its change after haemodialysis (HD) in end-stage renal disease (ESRD) patients. To comprehensively assess NO production in the respiratory system, NO metabolites in exhaled breath condensate (EBC) needs to be measured in addition to FE(NO), taking into account the influence on these markers of airway pH, which may be regulated by ammonia (NH3+), present in large amounts in the breath of ESRD patients and removed by HD. STUDY DESIGN: FE(NO) and NO metabolites (NOx, NO2-,NO3- ), pH and NH3+ in EBC were measured in 12 ESRD patients, before and after HD. Twelve healthy subjects acted as controls. RESULTS: FE(NO )values of ESRD patients were similar to normals, while EBC-NOx, NO2-, NH3+ and pH were significantly higher in ESRD patients compared to normals (EBC-NOx 12.3, range 11.1-41.9 microm vs. 9.4, range 4.6-10.9 microm, P = 0.007; NO2- 4.70, range 1.17-8.22 microm vs. 0.90, range 0.72-1.17 microm, P = 0.023; NH3+ 2340, range 1325-3922 microm vs. 660, range 406-872 microm, P < 0.001; pH 7.16, range 6.82-7.44 vs. 6.60, range 6.42-6.76, P = 0.004, respectively). HD caused a mild significant decrease of FE(NO), and normalization of NH3+, NOx, NO2- and pH. A significant positive relationship between EBC-pH and EBC-NH3+ before and after HD (r(2) = 0.65, P = 0.000) was observed, explaining higher than normal EBC-pH before HD, while no relationship was found between EBC-pH and FE(NO) or NO metabolites. CONCLUSION: Oxidative stress, and not EBC-pH, is the most probable cause of increased NO metabolites in ESRD patients before HD.
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Pruebas Respiratorias , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Óxido Nítrico/análisis , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Amoníaco/análisis , Biomarcadores/análisis , Estudios de Casos y Controles , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Nitratos/análisis , Nitritos/análisis , Dióxido de Nitrógeno/análisis , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Health-related quality-of-life (HRQL) has been poorly studied in large samples of asthmatics from the general population. HRQL and its relationship to asthma-severity were assessed among 900 asthmatics enrolled in the European Community Respiratory Health Survey. METHODS: Among asthmatics, 864 completed the short form-36 (SF-36) questionnaire and 477 also completed the Asthma Quality-of-life Questionnaire (AQLQ). A 4-class asthma-severity scale, combining clinical items, forced expiratory volume in 1 s and the level of treatment and the different asthma-severity components (each of the clinical items and hospitalization) were studied in relation to HRQL. RESULTS: Mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (45.5 and 48.8 respectively) were lower than expected in a general population. The mean total AQLQ score was 5.8. The AQLQ score and to a lesser extent the PCS score were significantly related to the 4-class asthma-severity scale, although the risk of having a lower HRQL score did not vary proportionally across the levels of severity. Asthma-severity had no impact on the MCS score. Asthma attack frequency and hospitalization were associated with both total AQLQ and PCS scores, whereas nocturnal symptoms and lung function were more strongly related to the AQLQ and PCS score respectively. CONCLUSION: In population-based asthmatics, the specific AQLQ questionnaire, and also to a lesser extent the generic SF-36 questionnaire, were sensitive to asthma-severity. Frequencies of asthma attacks, of nocturnal symptoms and hospitalization for asthma have independent impact on HRQL.
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Asma , Calidad de Vida , Índice de Severidad de la Enfermedad , Adulto , Asma/fisiopatología , Asma/psicología , Europa (Continente) , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females.
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Asma/economía , Costo de Enfermedad , Servicios de Salud/economía , Calidad de Vida , Adulto , Asma/diagnóstico , Asma/terapia , Estudios Transversales , Europa (Continente) , Femenino , Gastos en Salud , Servicios de Salud/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Probabilidad , Medición de Riesgo , Perfil de Impacto de Enfermedad , Factores SocioeconómicosRESUMEN
SETTING: Based on the cohort of pulmonary tuberculosis (PTB) cases resident between 2001 and 2005 in the Piedmont region of Italy, this study estimated the effect of selected determinants on the success of standardised short-course chemotherapy (SSCC). OBJECTIVE: To identify predictors of unsuccessful treatment of PTB and to generate a nomogram to assist treating physicians and public health authorities with the identification of cases needing close follow-up. RESULTS: Overall, 1564 cases were identified. Among new cases, predictors of successful treatment outcome were sex (women vs. men, aOR 0.48, 95%CI 0.37-0.63), geographic origin (EU vs. non-EU countries, aOR 0.43, 95%CI 0.31-0.60) and treatment setting (out-patient vs. in-patient services and unknown setting, aOR 0.2, 95%CI 0.16-0.26). Predictors of unsuccessful outcome were long-term residency status (homeless vs. residential, aOR 9.91, 95%CI 4.38-22.38) and age (for each year, aOR 1.02, 95%CI 1.01-1.03). CONCLUSION: Using a limited number of predictors, the authors designed a nomogram predicting the individual probability of unfavourable SSCC. In principle, this approach is generalisable to other settings and the nomogram can be calibrated on local data to ensure appropriate case management and support targeted treatment follow-up.
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Tuberculosis Pulmonar/tratamiento farmacológico , Estudios de Cohortes , Atención a la Salud , Femenino , Humanos , Masculino , Factores Sexuales , Resultado del TratamientoRESUMEN
Toxicological potential of carbon monoxide (CO) on humans is well known. Nevertheless, CO is still considered as a useful marker to detect some environmental and occupational human risk factors typical of cities. The role played by traffic pollution, indoor air quality in offices and tobacco smoke on the expression of carboxyhemoglobin (COHb%) levels was investigated in a large group of traffic policemen in Torino city (North-Western Italy). At the end of the working shift, 228 policemen responded to a questionnaire, weight and height recorded, urine spot samples collected to measure cotinine as biomarker of tobacco smoke exposure, and an arterial blood sample was taken to measure COHb levels. Data of outdoor urban air-CO were collected and to each subject a "CO outdoor air measurement" was related to his/her COHb level. Considering the annual trend of air-CO pollution from 2002 to 2004, one can assume that a general improvement of air quality in Torino was evident. Taking into account the environments where policemen work (urban outdoor and indoor), and analyzing their COHb% content, the traffic-congested areas, and, in general, the outdoor urban environment were equally risky as offices. Furthermore, if compared to CO arising from traffic-congested areas or other outdoor environments, the traffic policemen in Torino city demonstrate COHb% levels largely due to smoking habits.
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Contaminantes Atmosféricos/análisis , Monóxido de Carbono/análisis , Carboxihemoglobina/metabolismo , Policia , Contaminación por Humo de Tabaco , Adulto , Contaminación del Aire Interior , Biomarcadores/sangre , Biomarcadores/orina , Ciudades , Cotinina/orina , Monitoreo del Ambiente , Humanos , Italia , Masculino , Exposición Profesional/análisis , Emisiones de VehículosRESUMEN
Mitochondrial diseases affect all age groups, but those with childhood onset often seem to experience the greatest burden of disability. In some paediatric patients this can be explained by a cumulative disability acquired over many years. In others, additional factors, including the nature and severity of the molecular defect, must be considered. To date, no large-scale studies have attempted to document the natural history of paediatric mitochondrial disease. This is in part at least, because no assessment tool has been available to plot the temporal course of a disease with such a diverse clinical spectrum. This paper describes how a practical and semi-quantitative rating scale has been devised for children with mitochondrial disease, the Newcastle paediatric mitochondrial disease scale (NPMDS). The scale is multi-dimensional and reproducible, offering a tool through which mitochondrial disease progression can be objectively monitored. We anticipate that use of this tool will facilitate both longitudinal natural history studies and the assessment of future therapeutic interventions.
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Evaluación de la Discapacidad , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/terapia , Encefalomiopatías Mitocondriales/diagnóstico , Encefalomiopatías Mitocondriales/terapia , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Neurología/métodos , Variaciones Dependientes del Observador , Pediatría/métodos , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Reino UnidoRESUMEN
SETTING: Under-ascertainment and under-reporting of tuberculosis (TB) hampers surveillance and control. Case detection is improved by record linkage of case registers and under-reporting can be estimated by capture-recapture (CR) analysis. OBJECTIVES: To assess the completeness of the TB registration systems and estimation of TB incidence and under-reporting in the Piedmont Region of Italy in 2001. METHODS: Record linkage of the 'physician notification system', the TB laboratory register and the hospital records register, and subsequent three-sample CR analysis. RESULTS: Record linkage identified 657 TB cases; CR analysis estimated 47 (95%CI 31-71) unrecorded cases. Under-reporting of the 'physician notification system' was estimated at 21% (95%CI 20-23). The overall estimated TB incidence rate was 16.7 cases per 100000 population (95%CI 16.3-17.3), varying according to the subset investigated: 12.7 for individuals from low TB prevalence countries and 214.1 for immigrants from high TB prevalence countries; 13.1 and 25.8 for persons aged < and > or = 60 years, respectively; and 32.1 in Turin, the regional capital and 10.8 in the rest of the region. CONCLUSIONS: When multiple recording systems are available, record linkage and CR analysis can be used to assess TB incidence and the completeness of different registers, contributing to a more accurate surveillance of local TB epidemiology.
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Tamizaje Masivo/métodos , Vigilancia de la Población , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Incidencia , Lactante , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Isolated cytochrome c oxidase (COX) deficiency is usually associated with mutations in several factors involved in the biogenesis of COX. METHODS: We describe a patient with atypical, long surviving Leigh syndrome carrying two novel mutations in the COX15 gene, which encodes an enzyme involved in the biosynthesis of heme A. RESULTS: Only two COX15 mutated patients, one with severe neonatal cardiomyopathy, the other with rapidly fatal Leigh syndrome, have been described to date. In contrast, our patient had a slowly progressive course with no heart involvement. COX deficiency was mild in muscle and a normal amount of fully assembled COX was present in cultured fibroblasts. CONCLUSIONS: The clinical and biochemical phenotypes in COX15 defects are more heterogeneous than in other conditions associated with COX deficiency, such as mutations in SURF1.