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Biomedical subjects

Javier Llorca

Publications and source records attributed to Javier Llorca.

At least 55 records · Page 3Linked to original sources
PubMed2004

No evidence for association of the monocyte chemoattractant protein-1 (-2518) gene polymorphism and Alzheimer's disease.

Activation of microglia is a central part of the chronic inflammatory process in Alzheimer disease (AD). The monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a role in microglial migration and accumulation at sites of beta-amyloid deposition in senile plaques in the AD brain. A polymorphism in the regulatory region (-2518) of the MCP-1 gene affects the level of MCP-1 expression, and has been associated with a stronger inflammatory response and higher peripheral tissue damage in chronic inflammatory diseases. We investigated whether the MCP-1 (-2518) polymorphism might be responsible for susceptibility to AD in a large Spanish population, utilizing a clinically well-defined group of 328 sporadic AD patients and 315 control subjects. We also examined the combined gene effects between MCP-1 and other proinflammatory cytokine genes such as interleukin-1A (IL-1A) and tumor necrosis factor-alpha (TNF-alpha), and the apolipoprotein E (APOE) gene. In the present study, neither the MCP-1 (-2518) G allele itself nor its interaction with the IL-1A (-889) allele 2, TNF-alpha (-850) allele T or APOE epsilon4 allele conferred increased risk for AD.

Aged↗
PubMed2004

Giant cell arteritis without clinically evident vascular involvement in a defined population.

OBJECTIVES: To examine the frequency and clinical presentation of biopsy-proven giant cell arteritis (GCA) patients who do not exhibit overt clinical vascular manifestations. To assess whether differences exist between this group of patients and the rest of biopsy-proven GCA patients. METHODS: Retrospective study of biopsy-proven GCA patients diagnosed from 1981 through 2001 at the single hospital for a well-defined population of almost 250,000 people. Patients were considered as having no evident vascular involvement if cranial ischemic manifestations or other vascular complications of GCA were not present at the time of diagnosis or during at least 12 months' followup. RESULTS: Between 1981 and 2001, 210 patients from the Lugo region of northwest Spain were diagnosed with biopsy-proven GCA. Eleven patients did not show overt vascular manifestations of GCA. Nine of them presented with polymyalgia rheumatica (PMR) and another 2 fulfilled criteria for fever of unknown origin. Patients without clinically evident vascular involvement had a significantly longer delay to diagnosis than those with vascular manifestations. Also, PMR manifestations were more frequently observed in this group of patients. CONCLUSIONS: Biopsy-proven GCA without clinically evident vascular involvement is not exceptional. Despite having a longer delay to diagnosis, these patients constitute a more benign subgroup of GCA.

Aged↗
PubMed2004

Polymorphism at codon 66 of the brain-derived neurotrophic factor gene is not associated with sporadic Alzheimer's disease.

Memory acquisition and consolidation are associated with an increase in brain-derived neurotrophic factor (BDNF) in synapses, particularly those innervating the hippocampus and cerebral cortex. A polymorphism producing an amino acid substitution (valine to methionine) at codon 66 of the BDNF gene could affect intracellular processing and secretion of BDNF and lead to impairments in hippocampal function. Preliminary evidence in an Italian population indicates that this polymorphism is a predisposing factor for sporadic Alzheimer's disease (AD). A case-control study utilizing a clinically well-defined group of 237 sporadic AD patients and 218 control subjects was performed to test this association. The current study does not demonstrate any significant difference in Val66Met BDNF genotype or allele frequencies between AD patients and controls. Our study in the Spanish population argues against the hypothesis that this polymorphism is causally related to AD.

Aged↗
PubMed2004

Polymorphism at codon 469 of the intercellular adhesion molecule-1 gene is not associated with sporadic Alzheimer's disease.

Activation of microglia is a central part of the chronic inflammatory response in Alzheimer's disease (AD). Intercellular adhesion molecule-1 (ICAM-1) is a cell surface receptor that may act in AD to adhere microglia to beta amyloid fibrils within senile plaques. Preliminary evidence in an Italian population indicates that a polymorphism at codon 469 of the ICAM-1 gene is a predisposing factor for sporadic AD. Another group has been unable to replicate this association in a Finnish population. A case-control study utilizing a clinically well-defined group of 283 sporadic AD patients and 283 control subjects was performed to test this association in an ethnically homogeneous population from Spain. The current study does not demonstrate any significant difference in E469K genotype or allele frequencies between AD patients and controls. Our study in the Spanish population argues against the hypothesis that polymorphism at codon 469 of the ICAM-1 gene is causally related to AD.

Aged↗
PubMed2004

Tricuspid valve repair: an old disease, a modern experience.

BACKGROUND: We review our experience in patients who required surgical correction of tricuspid valve disease with concomitant disease of the mitral or aortic valve, or both, operated on between 1987 and 1999. METHODS: We studied 232 consecutive patients (mean age, 59.8 years) followed for a mean of 6.8 years (range, 2 to 12 years). All patients were investigated by means of Doppler echocardiography, with hemodynamic studies in 135. Median tricuspid insufficiency was 3+. The cause was rheumatic heart disease in 186 patients and degenerative in 46. All patients underwent suture annuloplasty (De Vega or segmental) at the time of mitral or aortic valve surgery. Tricuspid lesions were functional in 128 patients and organic in 104. RESULTS: The hospital and late mortality rates were 8.1% and 23.3%, respectively. These figures were independent of the type of annuloplasty performed. Predictors of hospital mortality were biologic prosthesis, renal insufficiency, time of cardiopulmonary bypass, and use of inotropic drugs. Predictors of late mortality were age older than 60 years, left ventricular ejection fraction less than 0.50, and New York Heart Association functional class IV. At 12 years, the actuarial survival rate was 50.5% +/- 6.1%, and the actuarial curve free from reoperation 75.7% +/- 7.3%. The actuarial curve for freedom from valve-related complication was 39.0% +/- 6.3% at 11 years. CONCLUSIONS: Despite the use of modern technologic advances in the diagnosis and treatment of valvular hear disease, tricuspid insufficiency continues to be a poor prognostic factor in patients with concomitant disease of the mitral or aortic valve, or both.

Adult↗
PubMed2004

A new way to estimate the contribution of a risk factor in populations avoided nonadditivity.

OBJECTIVE: Attributable fraction in the exposed and (population) attributable fraction have been extensively used to determine the proportion of cases of a particular disease that can be attributable to any risk factor. Epidemiologists know that these measurements can add up to more than 100%; nevertheless, in a clinical context or in mass media, this characteristic is sometimes misinterpreted. This article provides a way to estimate the contribution of a risk factor in populations. STUDY DESIGN AND SETTING: McElduff et al. have suggested a method for estimating the contribution of a risk factor in a person with more than one risk factor. We extend their suggestion to populations where risk factors are mixed in different proportions. We illustrate the usage of this method by enlarging the example provided by them and compare it with the average attributable fraction suggested by Eide and Gefeller. RESULTS: Population attributable fraction can be modified to obtain additivity; therefore, the contribution of a risk factor in populations can be estimated, which would be of interest, for example, in clinical or in court settings. CONCLUSION: The suggested method and the average attributable fraction provide different results, and would be applicable under different assumptions.

Data Interpretation, Statistical↗
PubMed2004

Echocardiographic and Doppler findings in long-term treated rheumatoid arthritis patients without clinically evident cardiovascular disease.

OBJECTIVE: To assess the frequency of echocardiographic and Doppler abnormalities in long-term treated rheumatoid arthritis (RA) patients without clinically evident cardiovascular manifestations. METHODS: Forty-seven patients with RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years and to be on treatment with 1 or more disease-modifying antirheumatic drugs. Patients seen during the period of recruitment who had cardiovascular risk factors or had suffered cardiovascular or cerebrovascular events were excluded. Forty-seven healthy matched controls were also studied. Echocardiographic and Doppler studies were performed in all cases and controls. Patients were HLA-DRB1 genotyped by using molecular-based methods. RESULTS: In patients with RA, the prevalence of aortic regurgitation (17%) and tricuspid regurgitation (17%) was not higher than that seen in controls (15% and 6%). The pulmonary artery systolic pressure was higher in patients with RA (30.3 +/- 8.0 mm Hg) than in controls (26.2 +/- 4.8) (P =.004). Incidence of pulmonary artery systolic pressure >35 mm Hg was significantly higher in patients with RA (21% versus 4% in controls; P =.03). Diastolic dysfunction caused by impaired relaxation was also more common in patients with RA (66%) than in controls (43%) (P =.02). It was more frequent in the older patients. Extra-articular manifestations were more common in patients with RA with diastolic dysfunction (P =.05). The HLA-DRB1 genotype was not implicated in the risk of developing diastolic dysfunction. CONCLUSIONS: The present study confirms a high frequency of left ventricular diastolic dysfunction and pulmonary hypertension in patients with RA without evident cardiovascular disease.

Aged↗
PubMed2004

Breast-feeding and risk of hospitalization for all causes and fever of unknown origin.

BACKGROUND: Breast-feeding has shown to give a reduction in the risk of hospitalization due to respiratory tract infections and gastrointestinal conditions during the first two years of life. The association of breast-feeding with all admission causes and with fever of unknown origin (FUO) was analysed. METHODS: A case-reference study in Cantabria (northern Spain) was carried out. Cases (n=336) were hospitalized children aged less than 24 months at University of Cantabria Hospital; the reference was a 1:1 matched (by time from delivery to admission) sample of children from mothers delivering at the same hospital. Information on breast-feeding, socioeconomic variables and employment were obtained. Odds ratios (ORs), their 95% confidence intervals (CIs), and mean length of breast-feeding were estimated after adjusment for confounding variables. RESULTS: In the reference population, shorter duration of breast-feeding was associated with smoking, lower educational level, and less privileged social strata. The frequency of breast-feeding was higher in the reference than in the cases, 82.3% vs 75.6% (p=0.023). Significant negative trends were noted in univariate analyses between the length of breast-feeding and both all admission causes and FUO, although the statistical significance was lost after adjusting for confounding variables (educational level, social class, smoking, and use of incubator after delivery). The adjusted mean length of breast-feeding was shorter in hospitalized children < or = 6 months old for both all admission causes (40.6 +/- 5.4 vs 99.5 +/- 5.4, p < 0.001) and FUO (40.8 +/- 12.4 vs 91.7 +/- 12.4, p=0.006). CONCLUSION: Breast-feeding time is shorter in hospitalized children for both all admission causes and FUO.

Adult↗
PubMed2004

Giant cell arteritis: a new association with benign paroxysmal positional vertigo.

OBJECTIVE: To assess the incidence and characteristics of both benign paroxysmal positional vertigo (BPPV) and positional nystagmus in a series of patients with giant cell arteritis (GCA). STUDY DESIGN: Patients diagnosed with GCA between June 1999 and May 2001 at the single hospital for a defined population were examined prospectively. METHOD: Patients included in this study fulfilled the 1990 American College of Rheumatology classification criteria for GCA. Otologic and oculographic studies were performed. Type, frequency, and outcome of positional oculographic findings was assessed. Patients were required to have been examined within 1 week after the onset of corticosteroid therapy. Data found in GCA patients were compared with those observed in an age, sex, and ethnically matched control population. Further studies in patients and controls were performed 3 and 6 months later. RESULTS: Forty-four patients and 44 matched controls were included in this study. Nine (20.5%) GCA patients fulfilled diagnostic criteria of BPPV compared with only 1 (2.3%) of the controls (P =.007). In seven of these nine GCA patients, BPPV was related to the posterior and two to the horizontal semicircular canals, respectively. Horizontal nystagmus was found in seven GCA patients who developed nystagmus in the head hanging position test compared with none in the controls (P =.006). CONCLUSIONS: The present study shows a higher frequency of BPPV in GCA than in matched controls. Because most clinical manifestations in GCA are caused by ischemic complications, our results suggest an ischemic etiology as responsible for BPPV in these elderly patients. According to these results, GCA may constitute a new association with BPPV.

Giant Cell Arteritis↗
PubMed2004

Aortic aneurysm and dissection in patients with biopsy-proven giant cell arteritis from northwestern Spain: a population-based study.

Most classical manifestations of giant cell arteritis (GCA) are the result of occlusive vascular involvement. However, unlike ischemic manifestations, aortic aneurysmal disease in patients with GCA has been less well described. We assessed the incidence and predictors of aortic aneurysm and dissection in patients with biopsy-proven GCA from the Lugo region of northwestern Spain and compared the results with those in a 2003 report from Olmsted County, MN. We performed a retrospective study of biopsy-proven GCA patients diagnosed from 1981 to 2001 at the single hospital for a well-defined population of almost 250,000 people. Twenty (9.5%) of the 210 biopsy-proven GCA patients diagnosed during the study period developed aortic aneurysmal disease. Sixteen of the 20 patients had thoracic aneurysms and 6 had abdominal aneurysms. The incidence of aortic aneurysm and/or dissection in Lugo (18.9 per 1000 person years at risk) was similar to that reported in Olmsted County (18.7 per 1000 person years at risk). Hypertension (hazard ratio: 4.73) and polymyalgia rheumatica with a marked acute inflammatory response at the time of diagnosis of GCA (hazard ratio: 3.71) were the best predictors of aortic aneurysmal disease. Our present observations suggest that a severe inflammatory response associated with hypertension at the time of diagnosis of GCA may promote the development of aortic aneurysmal disease. GCA patients having these features should be monitored for the existence of aortic aneurysm and dissection.

Aged↗
PubMed2004

Influence of traditional risk factors of atherosclerosis in the development of severe ischemic complications in giant cell arteritis.

Because the prognosis of giant cell arteritis (GCA) is related to the development of ischemic complications, we sought to assess the possible influence of traditional risk factors of atherosclerosis in the development of severe ischemic complications of GCA. We conducted a retrospective study of patients with biopsy-proven GCA diagnosed from 1981 to 2001 at the single hospital for a well-defined population of almost 250,000 people. Patients were considered to have severe ischemic manifestations if they suffered visual manifestations, cerebrovascular accidents, jaw claudication, or signs of occlusive changes in large arteries of the extremities. Patients were assessed for the presence of hypercholesterolemia, hypertension, diabetes mellitus, and heavy smoking at the time of GCA diagnosis. The presence of traditional risk factors of atherosclerosis at the time of GCA diagnosis in this series of 210 patients increased significantly the risk of developing at least 1 of the severe ischemic complications (odds ratio [OR], 1.79; 95% confidence intervals [CI], 1.03-3.11; p = 0.04). Patients with traditional atherosclerosis risk factors had fever less commonly than the rest of GCA patients (5.2% vs. 16.0%; p = 0.01). GCA patients with hypertension exhibited a significantly increased risk of developing severe ischemic complications (OR, 1.80; 95% CI, 1.00-3.25; p = 0.05). The current study suggests that the presence of atherosclerosis risk factors at the time of diagnosis of GCA may influence the development of severe ischemic manifestations of the disease.

Aged↗
PubMed2004

Bias.

The concept of bias is the lack of internal validity or incorrect assessment of the association between an exposure and an effect in the target population in which the statistic estimated has an expectation that does not equal the true value. Biases can be classified by the research stage in which they occur or by the direction of change in a estimate. The most important biases are those produced in the definition and selection of the study population, data collection, and the association between different determinants of an effect in the population. A definition of the most common biases occurring in these stages is given.

Bias↗
PubMed2004

Interleukin 1beta gene polymorphism association with severe renal manifestations and renal sequelae in Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of the interleukin (IL)-1beta gene (-511 C/T) in the incidence of Henoch-Schönlein purpura (HSP) and determine its possible implication in severe systemic complications of HSP, in particular severe renal involvement and permanent renal dysfunction (renal sequelae). METHODS: Patients from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-1beta gene (-511 C/T) polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Forty-nine Caucasian patients (38 of them younger than 21 years) who fulfilled classification criteria for HSP and 148 controls were examined. No allele or genotype differences between the whole group of HSP and controls were observed. However, all 5 patients who developed severe nephropathy during the course of disease carried the rare T allele compared with only 16 of the remaining 44 patients (pcorr = 0.01). A significant association between carriage of the -511(IL-1beta) T allele and renal sequelae (pc = 0.02; OR: 3.6, 95% CI: 1.3-10.0) was also found. CONCLUSION: In unselected patients with cutaneous vasculitis who fulfill classification criteria for HSP, carriage of IL-1beta (-511) T allele appears to influence severity of renal involvement.

Adult↗
PubMed2003

The epidemiology of the primary systemic vasculitides in northwest Spain: implications of the Chapel Hill Consensus Conference definitions.

OBJECTIVE: To assess the epidemiology of the primary systemic vasculitides (PSV) in a well-defined population of southern Europe over a 14-year period using the Chapel Hill Consensus Conference (CHCC) definitions. METHODS: The case records of all patients 15 years or older with vasculitis diagnosed between January 1988 and December 2001 at a single reference hospital in the Lugo region of northwest Spain were reviewed. Incidence rates were age- and sex-adjusted to the European standard population. Patients were classified as having PSV according to the CHCC definitions. RESULTS: Fifty-four Lugo residents (29 men) fulfilled the CHCC definitions for PSV. The mean age was 60.7 +/- 13.5 years (men: 61.0 +/- 13.4; women: 60.4 +/- 13.8 years). The overall annual incidence of PSV was 13.07/million (95% confidence interval [95% CI] 8.89-19.22). PSV were slightly more common in men. The age-specific incidence showed a clear increase with age. A peak in the 55-64 year age group for the whole group of patients with PSV was observed (34.9/million; 95% CI 28.6-42.6). Nonrandom periodical peaks of incidence every 3 years were only observed when the group of PSV was considered as a whole (P = 0.040). The annual incidence was 2.95/million (95% CI 1.44-6.05) for Wegener's granulomatosis (WG) and 7.91/million (95% CI 4.74-13.20) for microscopic polyangiitis (MPA) (P = 0.035). None of the patients with Churg Strauss syndrome (n = 4) lived in a rural area. CONCLUSION: Our observations support an increasing incidence of PSV with age. In patients from northwest Spain defined by the CHCC definitions, MPA is more common than WG.

Age Distribution↗
PubMed2003

HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis.

PURPOSE: To examine endothelial function in rheumatoid arthritis patients and to assess whether clinical or genetic factors affect the development of endothelial dysfunction. METHODS: Fifty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with one or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, or cardiovascular disease were excluded. Thirty-one age-, sex-, and ethnically matched controls were also studied. Endothelium-dependent (postischemia) and -independent (postnitroglycerin) vasodilatation were measured by brachial ultrasonography. Patients were genotyped for human leukocyte antigen (HLA)-DRB1. RESULTS: Patients had decreased endothelium-dependent vasodilatation (mean [+/- SD], 3.8% +/- 4.9%) compared with controls (8.0% +/- 4.5%; P <0.001). There were no differences in endothelium-independent vasodilatation. Clinical features were not associated with endothelial dysfunction. Endothelium-dependent vasodilatation was lower in the 30 rheumatoid arthritis patients with the HLA-DRB1*04 shared epitope alleles (2.4% +/- 4.1%) than in the remaining patients (5.5% +/- 5.3%; P = 0.01). Similar results were seen for patients with the HLA-DRB1*0404 shared epitope allele (-0.4% +/- 2.5%) compared with other patients (4.4% +/- 4.9%; P = 0.01). CONCLUSION: Patients with chronically treated rheumatoid arthritis had evidence of endothelial dysfunction, especially those with certain HLA-DRB1 genotypes. If confirmed, our results suggest that HLA-DRB1 status may be a predictor of cardiovascular risk in these patients.

Adult↗