Search PubMed⌕ Search

Biomedical subjects

C Fonseca

Publications and source records attributed to C Fonseca.

At least 19 recordsLinked to original sources
PubMed2006

A polymorphism in the promoter region of the CD86 (B7.2) gene is associated with systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease of unknown aetiology characterized by fibrosis of the skin and internal organs, vascular abnormalities and humoral autoimmunity. Strong T-cell-dependent autoantibody and HLA associations are found in SSc subsets. The co-stimulatory molecule, CD86, expressed by antigen-presenting cells, plays a crucial role in priming naïve lymphocytes. We hypothesized that SSc, or one of the disease subsets, could be associated with single-nucleotide polymorphisms of the CD86 gene. Using sequence specific primer-polymerase chain reaction (SSP-PCR) methodology, we assessed four CD86 polymorphisms in 221 patients with SSc and 227 healthy control subjects from the UK. Haplotypes were constructed by inference and confirmed using PHASE algorithm. We found a strong association between SSc and a specific haplotype (haplotype 5), which was more prevalent in patients than in controls (29% vs 15%, OR = 2.3, chi(2) = 12, P = 0.0005). This association could be attributed to the novel -3479 promoter polymorphism; a significant difference was observed in the distribution of the CD86 -3479 G allele in patients with SSc compared to controls (43.7% vs. 32.4%, OR = 1.7, chi(2) = 12.1, P = 0.0005). TRANSFAC analyses suggest that the CD86-3479T allele contains putative GATA and TBP sites, whereas G allele does not. We assessed the relative DNA protein-binding activity of the -3479 polymorphism in vitro using electromobility gel shift assays (EMSA), which showed that the -3479G allele has less binding affinity compared to the T allele for nuclear proteins. These findings highlight the importance of co-stimulatory pathways in SSc pathogenesis.

Algorithms↗
PubMed2005

Environmental tobacco smoke exposure in public places of European cities.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has important public health implications. The results of the first European multi-centre study that measured ETS exposure in a range of public places (transport, educational settings, and leisure facilities such as bars and restaurants) are presented. METHOD: Nicotine vapour phase was measured using ETS passive samplers containing a filter treated with sodium bisulfate. RESULTS: Bars and discos are the places with the highest concentrations of nicotine from ETS, median ranging from 19 to 122 microg/m(3). Restaurants had the next highest values. Concentrations of nicotine generally range from 0.1-5 microg/m(3) in airports, and from 0.5-10 microg/m(3) in train stations. Nicotine was also found in schools and universities, yet schools tended to have the lowest concentrations compared to all the other public places sampled. In hospitals levels were generally below 5 microg/m(3). CONCLUSIONS: Although there is some variability between cities, this study shows that tobacco smoke is present in most of the studied public places. The study also showed that in areas where smoking is prohibited, concentrations of nicotine are lower than in areas where smoking is allowed but they are not zero. The results of this study indicate that policies should be implemented that would effectively reduce levels of tobacco smoke in public areas.

Air Pollutants↗
PubMed2004

Single-nucleotide polymorphisms in the SPARC gene are not associated with susceptibility to scleroderma.

OBJECTIVE: SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that modulates cell-cell and cell-extracellular matrix interactions. SPARC expression is restricted mainly to sites of tissue remodelling and wound repair, and is prominent in fibrotic disorders. Single-nucleotide polymorphisms (SNPs) in the SPARC gene are reportedly linked to scleroderma in four ethnic groups: Choctaw Indians, Caucasians, African Americans and Mexican Americans. We set out to reproduce and to positionally clone these disease associations in a set of UK Caucasian scleroderma patients and ethnically matched controls. METHODS: One hundred and twenty-one scleroderma subjects and 200 controls were genotyped by polymerase chain reaction with sequence-specific primers differing only in the 3' nucleotide corresponding to each allele of the biallelic SNPs. Scleroderma patients were analysed against controls and on the basis of their fibrosing alveolitis status as judged by high-resolution computed tomography evaluation and the extent of cutaneous involvement. RESULTS: Eight biallelic SNPs were genotyped: three from the last untranslated exon, which had been described previously, and an additional five novel SNPs: two in the promoter region, one in exon three and two in the 3' untranslated region. Six major haplotypes were constructed across all eight SNP positions. No significant differences in genotype, allele or haplotype frequency were observed between scleroderma and controls or within scleroderma subgroups. CONCLUSIONS: SNPs in the SPARC gene are not associated with susceptibility to scleroderma. This research adds to the genetic knowledge of the SPARC gene by identifying five novel SNPs spanning the whole gene and inserting these within the context of clearly defined haplotypes.

Female↗
PubMed2003

Albumin adsorption on alkanethiols self-assembled monolayers on gold electrodes studied by chronopotentiometry.

Chronopotentiometry was used to study the adsorption of human serum albumin (HSA) to self-assembled monolayers with the following terminal functional groups: CH(3), COOH and OH. Surfaces were characterized by X-ray photoelectron spectroscopy, water contact angle measurements and cyclic voltammetry. HSA coverage of the different SAMs was investigated by chronopotentiometry and the total amount of adsorbed protein was determined using radiolabelled albumin. Both techniques have demonstrated that HSA adsorption to the different SAM-modified electrodes increases in the following order: OH<COOH<CH(3)-terminated SAMs. A good correlation between coverage and total amount of HSA adsorbed was observed for long adsorption times (900s).

Adsorption↗
PubMed2001

[Relationship between respiratory syncytial virus subtype and clinical severity in bronchiolitis].

BACKGROUND: Respiratory syncytial virus (RSV) is the most frequently implicated agent in bronchiolitis. The virus presents two antigenic subtypes (A and B). The results of studies on the relationship between viral subtype and clinical severity are conflicting. PURPOSE: To evaluate whether the subtype of this virus constitutes an independent variable in the severity of clinical expression of RSV infection. PATIENTS AND METHODS: We prospectively studied previously healthy children aged less than 2 years admitted for RSV infection during an epidemic season. Clinical presentation and evolution, laboratory and radiological aspects were compared in subsets of children infected with RSV subtype A or B. Clinical severity parameters included score and duration of respiratory distress, oxygen requirements, admission to the intensive care unit, mechanical ventilation and length of hospital stay. RESULTS: Eighty-five patients were enrolled in the study (50 boys and 35 girls; mean age 4.8,4.3 months). Fifty-nine children were infected with RSV subtype A. No differences were found in age, sex or antecedents but children with subtype B were less likely to have been breast-fed. Clinical presentation and laboratory and radiological findings were similar in both groups. No statistically significant differences in clinical severity parameters were found between subsets A and B. Age less than 3 months was associated with greater duration of respiratory distress and longer hospital stay. CONCLUSION: The results do not support the hypothesis that subtype A infection is associated with more severe respiratory syncytial virus disease.

Bronchiolitis↗
PubMed2001

Heart failure treatment in Portuguese hospitals: results of a survey.

The management of heart failure in Europe is largely conducted by primary care physicians in out-patient clinics and by cardiologists and internists in hospitals. Several reports suggest differences among these specialists regarding knowledge and actual practice, and indicate that the application of guidelines is far from optimal. In order to look for differences between cardiologists and internists in terms of implementation of guidelines a survey was carried out among the directors of 83 hospital departments of cardiology and internal medicine in Portugal. The survey included questions about diagnostic and treatment protocols, special areas for management, and suggestions to improve the quality of heart failure patient treatment. The answers suggest that in Portuguese hospitals at least half of the patients with HF are treated by internists. Treatment protocols exist in about 25% of the cardiology departments but are virtually non-existent in internal medicine. The use and availability of echocardiography are high in cardiology but no more than reasonable in internal medicine. There are neither special in-hospital areas nor specialized nurses for the treatment of HF. Cardiologists recognize the need for greater specialization in this field--doctors, nurses and clinics--but this is not a priority for internists. An effort should be made to improve in-hospital HF treatment.

Cardiology↗
PubMed2000

Autocrine overexpression of CTGF maintains fibrosis: RDA analysis of fibrosis genes in systemic sclerosis.

We have used representational difference analysis (RDA) to identify up-regulated genes in skin fibroblasts from fibrotic lesions obtained from patients with systemic sclerosis (scleroderma). RDA of cDNA libraries derived from fibroblasts from involved and uninvolved skin detected several differentially expressed genes. One such gene consistently up-regulated in scleroderma cells coded for human connective tissue growth factor (CTGF). Other studies described here show that the CTGF protein is readily detected in cultures of systemic sclerosis fibroblasts but was not detected in comparable normal cells. High levels of CTGF are also evident in biological fluids from patients with systemic sclerosis. TGFbeta stimulates CTGF production in both normal and systemic sclerosis fibroblasts with the latter found to be higher producers. Moreover, an analysis of constitutive and TGFbeta-induced CTGF gene activation showed altered and elevated transcriptional responses in systemic sclerosis cells compared with controls. CTGF stimulated a two- to threefold increase in proalpha1(I) collagen and fibronectin synthesis by both dermal and lung fibroblasts in culture and promoted significant matrix remodeling of fibroblast-populated three-dimensional collagen lattices. A direct relation between the overexpression of CTGF and elevated collagen synthesis was suggested by the observation that transfection of a CMV-CTGF cDNA construct and protein expression in fibroblasts increased the transcription of a Col 1alpha2 promoter-reporter construct to levels seen in systemic sclerosis fibroblasts. Using Col 1alpha2 promoter deletion constructs the CTGF responsive element was localized to the first 379 bp upstream of the transcriptional start site. These data indicate that there is an overexpression of CTGF in the systemic sclerosis cells, probably due to increased gene transcription, and suggest that the dysregulation of CTGF production is an important factor in fibroblast activation and the excessive deposition of collagen in systemic sclerosis.

3T3 Cells↗
PubMed2000

Tissue Doppler imaging in different locations of the mitral annulus: all different or all the same?

BACKGROUND: The assessment of the mitral annulus motion with tissue Doppler imaging is claimed to be an accurate method to quantify global left ventricular systolic and diastolic function. However, it is not yet perfectly defined which site of the annulus must be selected. Familial amyloidotic polyneuropathy of the Portuguese type (FAP) is an hereditary systemic disease in which diastolic dysfunction may occur. AIM: 1--To determine if in FAP patients the mitral annulus motion is independent of the selected site. 2--To compare pulsed wave Doppler parameters with tissue Doppler parameters in the different annular sites. METHODS: Of 24 FAP patients studied, 14 were included. In each patient we performed conventional transmitral pulsed wave Doppler and tissue Doppler in the 4 sites of the mitral annulus and measured the velocities of the rapid filling wave e, of the atrial contraction wave a and calculated e/a ratio. RESULTS: According to the transmitral inflow profile, patients were divided in 2 groups: Group I--normal global diastolic function and Group II--abnormal relaxation. Group I--33% of these patients showed e/a > 1 in the four sites and 67% showed e/a > 1 in at least 1, but not in all the sites. The rate of normal sites per patient was 3.1. Group II--25% of these patients showed e/a < 1 in the 4 sites of the annulus and 75% had e/a < 1 in at least 1, but not in all the sites analysed. The rate of abnormal sites/patient was 3.1. in this group. When conventional and tissue Doppler data were compared (bland and altman) the septal portion of the annulus was the one with the best correlation. CONCLUSIONS: 1--The assessment of the mitral annulus motion with tissue Doppler imaging is dependent on the site selected for study. 2--The septal site was the one that showed the highest correlation and concordance between pulsed wave Doppler and tissue Doppler. 3--The relative number of normal versus abnormal sites was determinant of the transmitral pattern. 4--Tissue Doppler imaging identified: a) among patients until now classified as normal diastolic function, a subgroup of patients with abnormal function in some sites of the annulus and b) among patients with abnormal relaxation, a subgroup with normal diastolic function in some sites of the annulus.

Adult↗
PubMed2000

[Diastolic dysfunction and left ventricular hypertrophy in familial amyloidotic polyneuropathy: a cause-effect relationship?].

UNLABELLED: TTR Met30 Familial Amyloidotic Polyneuropathy of the Portuguese type (FAP) is an incapacitating and lethal hereditary disorder that affects predominantly young adults of both genders. Portuguese type FAP patients have sensory, motor and autonomic polyneuropathy. The generalised systemic amyloid infiltration involves the heart, leading to the characteristic granular bright sparkling echocardiographic pattern. LV wall thickening occurs in the late phases of the disease. LV diastolic dysfunction has been reported in the absence of systolic dysfunction; an abnormal diastolic transmitral flow pattern assessed by pulsed wave Doppler (PW) was described. PW is very much dependent on load conditions. Tissue Doppler imaging (TDI) has been used as a more reliable method to assess long axis diastolic function. OBJECTIVE: 1--To identify the incremental value of TDI in the assessment of diastolic function in FAP. 2--To correlate diastolic pattern abnormalities and left ventricular mass index (LVMI) in FAP patients. METHODS: We performed a prospective evaluation of 24 consecutive FAP patients and selected 14 (sinus rhythm, age < 45 years). Diastolic function was assessed by PW and classified as normal (GI-E/A > 1) or abnormal (GII-E/A < 1). TDI was performed in 4 sites of the mitral annulus (septum, lateral, inferior, anterior). Velocities of the rapid filling wave (E') and atrial contraction wave (A') were measured and E'/A' calculated. In each site we considered the TDI as normal (E'/A' > 1) or abnormal (E'/A' < 1). The LVMI was calculated by Devereux's formula. RESULTS: Age, gender and heart rate were similar in both groups. TDI at the septal mitral annulus was normal in all of the GI patients (E'/A': 1.29 +/- 0.19) and suggestive of abnormal LV relaxation in all of the GII patients (E'/A': 0.82 +/- 0.11, p < 0.0001). TDI revealed abnormal diastolic pattern when a restricted number of sites of the mitral annulus were assessed, even in GI patients and before PW abnormalities occurred. Fractional shortening (FS) and LVMI were similar in GI and GII (FS-GI: 45.5 +/- 5.3, GII 43.5 +/- 8.1%, p: NS; LVMI--GI: 66 +/- 9.3, GII: 67 +/- 3.0 g/m2 p: NS). CONCLUSION: The assessment of mitral annulus motion has introduced new data in the study of diastolic function of FAP patients. An abnormal LV relaxation pattern occurred early in the evolution of the disease in patients with normal LVMI and systolic function.

Adult↗
PubMed1999

Lung fibrosis.

Explore the source record for details and available documents.

Animals↗
PubMed1999

[Prevalence of heart failure in Portugal].

UNLABELLED: The incidence and prevalence of heart failure are increasing, which presents an enormous problem for health care systems. In Portugal, there are no studies assessing this issue. The EPICA study was designed to estimate the prevalence of chronic heart failure in Portugal in 1998. This is a community-based epidemiological survey involving 13,000 primary care recipients, selected through a two-stage sampling procedure: each GP, from a random sample of 500, with proportionality to district population, will include 26 primary care recipients recruited sequentially within each age group. The cases will be identified according to ESC Guidelines: symptoms and signs of heart failure and echocardiographic evidence of cardiac dysfunction. The individuals will be screened for echo examination on the basis of a structured questionnaire (EPICA questionnaire) that was drafted from seven questionnaires previously used in epidemiological surveys for heart failure. Age and gender adjusted estimates of the prevalence of chronic heart failure will be obtained as well as a prevalence estimate for the whole population. The study will also estimate the test statistics (sensitivity, specificity and predictive values) for the EPICA questionnaire compared to echo data, as well as the seven other questionnaires used for the diagnosis of chronic heart failure. Their agreement will also be evaluated. PRELIMINARY RESULTS: 93% of the GPs recruited have participated. The final data will be available in early 2000.

Adult↗
PubMed1998

The natural history of asymptomatic moderate internal carotid artery stenosis by duplex ultrasound.

The purpose of this study was to determine the rate of progression of the degree of carotid stenosis and to determine the risk of continued observation in a group of asymptomatic patients with moderate stenosis of at least one internal carotid artery. Between 1989 and 1994, 2130 patients were found to have 60-79% stenosis of at least one internal carotid artery following a duplex ultrasound examination in the authors' vascular laboratory. Of these, 465 patients (255 men, 210 women) were asymptomatic and had more than one ultrasound examination, and they form the basis of this retrospective review. The mean +/- SD age was 68.8 +/- 9.0 years. The mean +/- SD number of ultrasound examinations was 3.1 +/- 1.4 (range 2-11). The mean +/- SD follow-up was 24.4 +/- 17.6 months (range 2-79 months). Over the period of follow-up 72 patients (15.5%) progressed to 80-99% stenosis (n = 71) or to occlusion (n = 1). The estimated percentage of patients who progressed by life table methods were 5 +/- 1% at 1 year, 11 +/- 2% at 2 years and 20 +/- 3% at 3 years. There was no statistically significant difference in the rate of progression in men compared with women. Twenty-one patients had a late ipsilateral TIA or stroke. Five out of 72 patients (6.9%) who progressed had a late ipsilateral TIA compared with nine out of 393 patients (2.3%) who did not progress (estimated risk ratio 16.1, P = 0.0001). Four out of 72 patients (5.6%) who progressed had a late ipsilateral stroke compared with three out of 393 patients (0.76%) who did not progress (estimated risk ratio 23.6, p = 0.0002). The cumulative ipsilateral stroke rate using life table methods was 0.22% at 1 year, 1% at 2 years and 2.4% at 3 years. In a large cohort of asymptomatic patients, the frequency of progression of 60-79% internal carotid artery stenosis was 5% at 1 year, 11% at 2 years and 20% at 3 years. Patients who progressed were more likely to have symptoms, but the rate of unheralded stroke was relatively low over a 3-year time period. Surveillance carotid ultrasound examinations should be performed in patients with moderate carotid stenosis. Because of the lack of clear benefit, carotid endarterectomy for asymptomatic 60-79% internal carotid artery stenosis cannot be justified.

Aged↗
PubMed1998

[Pulmonary embolism: a clinical case documented, in acute setting, using pulmonary scintigraphic perfusion].

The acute clinical evolution is presented of a patient with previous myocardial infarction who was admitted for dyspnea and chest pain. Acknowledging the possibility of a new ischemic event, confronted with aortic dissection or pulmonary embolism, the clinical investigation is described up to the scintigraphic diagnosis of pulmonary embolism. The clinical presentation, diagnostic investigation and therapeutic decisions are discussed, with emphasis on the usefulness of pulmonary scintigraphy.

Adult↗