RESUMEN
BACKGROUND: We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age. METHODS: 67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (â¼3 months, 1 year and 2 years) and at preschool (3-6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life. RESULTS: At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%. CONCLUSIONS: Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.
Asunto(s)
Fibrosis Quística , Lactante , Recién Nacido , Preescolar , Humanos , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Pseudomonas aeruginosa , Pulmón/diagnóstico por imagen , Pruebas de Función Respiratoria/métodos , Lavado BroncoalveolarRESUMEN
ß-Thalassemia (ß-thal) is a hemolytic anemia that is caused by point mutations in most cases. The Brazilian population is highly heterogeneous and knowledge of the mutations that make up the genotypic profile of individuals can contribute information about the formation of the population and clinical condition of patients. In this study, we evaluated the mutations present in homozygous ß-thal patients from Rio de Janeiro, Brazil. We analyzed 24 samples of peripheral blood of patients with homozygous ß-thal. To identify the mutations, we carried out allele-specific-polymerase chain reaction (AS-PCR) and DNA sequencing. We found 11 different mutations on the ß-globin gene. Among the most frequent mutations observed were HBB: c.92 + 6T>C, followed by HBB: c.93-21G>A, HBB: c.118C>T and HBB: c.92 + 1G>A. We also identified the rare mutation HBB: c.75T>A that was reported in an individual carrying Hb S (HBB: c.20A>T)/ß-thal (HBB: c.75T>A) but not in Brazilian thalassemic patients, thus, this is the first report of this mutation in Brazilian ß-thal patients. For its multiethnic character, Brazil has different mutations that cause ß-thal and that are distributed with different frequencies according to the regions of the country. Our findings contribute to the description of the mutational profile of Brazilian thalassemic patients, showing wide heterogeneity and genetic variability.
Asunto(s)
Mutación , Globinas beta/genética , Talasemia beta/genética , Adolescente , Adulto , Alelos , Brasil/epidemiología , Niño , Codón , Análisis Mutacional de ADN , Exones , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Intrones , Masculino , Persona de Mediana Edad , Fenotipo , Regiones Promotoras Genéticas , Adulto Joven , Talasemia beta/diagnóstico , Talasemia beta/epidemiología , Talasemia beta/terapiaRESUMEN
The consistency approach for release testing of established vaccines promotes the use of in vitro, analytical, non-animal based systems allowing the monitoring of quality parameters during the whole production process. By using highly sensitive non-animal methods, the consistency approach has the potential to improve the quality of testing and to foster the 3Rs (replacement, refinement and reduction of animal use) for quality control of established vaccines. This concept offers an alternative to the current quality control strategy which often requires large numbers of laboratory animals. In order to facilitate the introduction of the consistency approach for established human and veterinary vaccine quality control, the European Partnership for Alternatives to Animal Testing (EPAA) initiated a project, the "Vaccines Consistency Approach Project", aiming at developing and validating the consistency approach with stakeholders from academia, regulators, OMCLs, EDQM, European Commission and industry. This report summarises progress since the project's inception.
Asunto(s)
Alternativas a las Pruebas en Animales/métodos , Alternativas a las Pruebas en Animales/normas , Vacunas/normas , Alternativas a las Pruebas en Animales/tendencias , Animales , Europa (Continente) , Humanos , Control de CalidadRESUMEN
More than 1900 different mutations in the CFTR gene have been reported. These are grouped into classes according to their effect on the synthesis and/or function of the CFTR protein. CFTR repair therapies that are mutation or mutation class specific are under development. To progress efficiently in the clinical phase of drug development, knowledge of the relative frequency of CFTR mutation classes in different populations is useful. Therefore, we describe the mutation class spectrum in 25,394 subjects with CF from 23 European countries. In 18/23 countries, 80% or more of the patients had at least one class II mutation, explained by F508del being by far the most frequent mutation. Overall 16.4% of European patients had at least one class I mutation but this varied from 3 countries with more than 30% to 4 countries with less than 10% of subjects. Overall only respectively 3.9, 3.3 and 3.0% of European subjects had at least one mutation of classes III, IV and V with again great variability: 14% of Irish patients had at least one class III mutation, 7% of Portuguese patients had at least one class IV mutation, and in 6 countries more than 5% of patients had at least one class V mutation.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/genética , ADN/genética , Mutación , Fibrosis Quística/epidemiología , Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Análisis Mutacional de ADN , Europa (Continente)/epidemiología , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Prevalencia , Estudios RetrospectivosRESUMEN
Recent data from our laboratory have shown that patients with the indeterminate form of Chagas' disease can have impairment of left ventricular contractility, as evaluated by the slope of the left ventricle end-systolic pressure-dimension relationship. We also showed that Chagas' disease patients with minimal baseline wall motion abnormalities detected by two-dimensional echocardiography have more intense contractility impairment when compared to patients with the indeterminate form of the disease without this abnormality. The prognostic implications of these findings have not been established. We evaluated 59 patients (37-76 years, mean = 55 years) with different clinical forms of Chagas' disease, who had normal left ventricular global systolic function at baseline (57.6 +/- 6.9%) and who had at least one additional echo during clinical follow-up (0.4-17.6; mean 4.6 years). Group 1 consisted of 14 patients with minor baseline left ventricle wall motion abnormalities and group 2 consisted of 45 patients without these abnormalities. During follow-up, global left ventricle systolic function deterioration was observed in 10 group 1 patients (71.4%) and in only 10 group 2 patients (22.2%; P < 0.005). Age and duration of follow-up were not independent determinants of left ventricular function deterioration in these patients. The present data indicate that mild segmental left ventricular wall motion abnormalities are associated with worsening of systolic function in Chagas' disease patients who have normal baseline global systolic performance.
Asunto(s)
Enfermedad de Chagas/fisiopatología , Contracción Miocárdica/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Adulto , Anciano , Cardiomiopatía Chagásica/diagnóstico por imagen , Cardiomiopatía Chagásica/fisiopatología , Enfermedad Crónica , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
Recent data from our laboratory have shown that patients with the indeterminate form of Chagas' disease can have impairment of left ventricular contractility, as evaluated by the slope of the left ventricle end-systolic pressure-dimension relationship. We also showed that Chagas' disease patients with minimal baseline wall motion abnormalities detected by two-dimensional echocardiography have more intense contractility impairment when compared to patients with the indeterminate form of the disease without this abnormality. The prognostic implications of these findings have not been established. We evaluated 59 patients (37-76 years, mean = 55 years) with different clinical forms of Chagas' disease, who had normal left ventricular global systolic function at baseline (57.6 ± 6.9 percent) and who had at least one additional echo during clinical follow-up (0.4-17.6; mean 4.6 years). Group 1 consisted of 14 patients with minor baseline left ventricle wall motion abnormalities and group 2 consisted of 45 patients without these abnormalities. During follow-up, global left ventricle systolic function deterioration was observed in 10 group 1 patients (71.4 percent) and in only 10 group 2 patients (22.2 percent; P < 0.005). Age and duration of follow-up were not independent determinants of left ventricular function deterioration in these patients. The present data indicate that mild segmental left ventricular wall motion abnormalities are associated with worsening of systolic function in Chagas' disease patients who have normal baseline global systolic performance.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Chagas/fisiopatología , Contracción Miocárdica/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Enfermedad Crónica , Cardiomiopatía Chagásica/fisiopatología , Cardiomiopatía Chagásica , Ecocardiografía , Estudios de Seguimiento , Pronóstico , Índice de Severidad de la Enfermedad , Disfunción Ventricular IzquierdaRESUMEN
PURPOSE: To assess the clinical, angiographic and early follow-up findings of young patients suffering an acute myocardial infarction, in comparison with older patients with infarction, in the thrombolytic era. METHODS: A retrospective analysis of the medical records of 46 patients < 40 years-old (group I) at the time of an acute myocardial infarction was compared with that of 46 older patients, randomly selected, presenting with this syndrome between february, 1991 and february, 1996 (group II). In both groups a comparison was conducted regarding the proportions of gender, risk factors, type of infarction (Q vs non-Q), left ventricular function, coronary anatomy and early mortality (1 month). The medical treatment was comparable for both groups, including the utilization of thrombolytics. RESULTS: The groups were discriminated only by: higher prevalence of smoking, of angiographically normal coronary arteries, and of non-critical (< 75% reduction of luminal diameter) coronary stenosis in group I; in the older group a higher proportion of patients had multivessel disease. Although not reaching statistical significance, a trend was observed to a more benign early course of the infarction in the patients less than < 40 years-old. CONCLUSION: The present findings are similar to those described in the pre-thrombolytic era, for young patients suffering an acute myocardial infarction.