Biomedical subjects

Javier Llorca

Publications and source records attributed to Javier Llorca.

At least 73 records · Page 4Linked to original sources

PubMed2003

Effect of transdermal nitroglycerin on inflammatory mediators in patients with peripheral atherosclerotic vascular disease.

OBJECTIVE: To demonstrate that nitroglycerin improves biological markers of arterial inflammation in patients with peripheral vascular disease. BACKGROUND: Atherosclerosis is an inflammatory disease in which there is an increase in active inflammation markers such as C-reactive protein and other factors released by endothelial cells. Nitroglycerin acts by a chemical liberation of nitric oxide. We have previously published the results from several controlled clinical trials confirming an anti-inflammatory action of nitroglycerin. METHODS: Forty patients with peripheral vascular disease entered a randomized, double-blind, placebo-controlled pilot study for 6 weeks. Twenty-one patients were treated with continuous application of a transdermal nitroglycerin patch (15 mg/24 hours) on the anterior face of the thigh. Venous blood samples were obtained before treatment and 2 and 6 weeks after. We measured plasma levels of C-reactive protein, cGMP (also intraplatelet cGMP), E-selectin, ICAM, VCAM-1, IL-6, and nitrites/nitrates. RESULTS: No biological parameter was modified in the placebo group. On the contrary, nitroglycerin significantly reduced plasma levels of C-reactive protein and sE-selectin and increased the levels of intraplatelet cGMP. CONCLUSIONS: The results of this preliminary study show that nitroglycerin has an anti-inflammatory action in patients with peripheral vascular disease. This may provide a new therapeutic approach to understanding the efficacy of nitrovasodilators in the improvement of atherosclerotic syndromes.

Administration, Cutaneous↗

PubMed2003

Quality of published clinical trials on asthma.

The quality of 287 clinical trials on asthma treatment published between 1984 and 1997 is described in this article, using a scale adding to a maximum of 14 points. The mean quality score was 8.60 (standard deviation 1.55). Quality improved throughout time from 8.17 +/- 1.40 before 1989 until 9.55 +/- 1.66 after 1992. Several methodological issues were associated with higher quality, namely parallel design, longer length of the follow-up, complete description of the exclusion criteria, description of the initial and ending recruitment dates, higher sample size, explicit sample size calculation, blinding, full description of randomization, intention-to-treat analysis, full description of the intervention, and evaluation of bias. The higher statistical significance, however, was not associated with higher clinical trial quality.

Asthma↗

PubMed2003

Audiovestibular manifestations in giant cell arteritis: a prospective study.

Giant cell arteritis (GCA) is a multisystemic vasculitis of elderly people that involves large and medium-sized blood vessels with predisposition to the cranial arteries. Some cranial ischemic manifestations, in particular permanent visual loss, have been widely described. Audiovestibular manifestations have been less commonly reported. In the present study we assessed the frequency and outcome of audiovestibular manifestations in a series of GCA and isolated polymyalgia rheumatica (PMR) patients examined prospectively between June 1999 and May 2001 at the single hospital for a defined population. Patients were included in the study if a temporal artery biopsy had been performed and they were examined within a week after beginning corticosteroid treatment. Patients with abnormal otoscopy or tympanogram, history of cerebrovascular complications, syphilis, Ménière and other vestibular syndromes, infections involving the inner ear, barotrauma, or being treated with ototoxic drugs were excluded. During the study period 44 patients with GCA and 10 patients with biopsy-negative isolated PMR were examined. Patients with isolated PMR were younger. Audiovestibular dysfunction was significantly more frequent in GCA patients than in those with isolated PMR and matched controls. Almost 90% of the GCA patients had vestibular dysfunction, which was generally reversible after several days of steroid treatment; after 3 months of treatment, vestibular dysfunction was observed in only 13 (29.6%) of the 44 GCA patients. These patients with persistent vestibular dysfunction were more likely to have persistent head-shaking nystagmus. Twelve (27.3%) of the 44 GCA patients had hearing improvement after 3 months of therapy. After 6 months of therapy, only 1 of the 44 GCA patients had abnormal vestibular tests. However, no additional improvement in hearing function was observed. The present study confirms a high frequency of audiovestibular manifestations in GCA. It also suggests that audiovestibular damage may be reversible in some patients with GCA.

Adrenal Cortex Hormones↗

PubMed2003

Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease.

We conducted the current study to search for subclinical atherosclerosis in patients with rheumatoid arthritis (RA) without clinically evident atherosclerosis or its complications who had been treated for a long duration, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with 1 or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, hypertension, cardiovascular or cerebrovascular disease, and smokers were excluded. Forty-seven matched controls were also studied. Carotid intima-media wall thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound. Patients had greater carotid IMT (0.779 +/- 0.164 mm) than did controls (0.699 +/- 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid plaques compared with only 7 (15%) controls (p = 0.031). There was a positive correlation between the age at the time of study and the carotid IMT. Patients with carotid plaques had significantly greater carotid IMT (0.859 +/- 0.116 mm) than those without plaques (0.739 +/- 0.171 mm) (p = 0.014). Also, RA patients with carotid plaques had a significantly longer disease duration (mean, 21.0 yr) and more extraarticular manifestations (63%) than those without plaques (mean, 12.7 yr and 26%, respectively). Age at the time of the study and disease duration were the best predictive factors for the development of severe morphologic expression of atherosclerotic disease. The present study confirms an increased frequency of severe subclinical atherosclerotic findings in long-term actively treated RA patients from northwest Spain.

Age Factors↗

PubMed2003

Interaction of the H63D mutation in the hemochromatosis gene with the apolipoprotein E epsilon 4 allele modulates age at onset of Alzheimer's disease.

The H63D mutation in the hemochromatosis gene (HFE) has recently been considered as a risk factor in Alzheimer's disease (AD) with advancing age at onset of the disease, independently of the apolipoprotein E (ApoE) epsilon4 allele effect. We examined the distribution of the H63D mutation and ApoE genotypes as a function of age at AD onset in 328 patients with sporadic AD. Our data show that the mutant H63D allele potentially interacts with the ApoE epsilon4 allele to significantly reduce age at onset of AD compared to ApoE epsilon4 carriers alone, but has no effect on age at onset in ApoE epsilon4 non-carriers.

Age of Onset↗

PubMed2003

Age-dependent association between the Q7R polymorphism in the Saitohin gene and sporadic Alzheimer's disease.

A vigorous controversy exists over whether tau tangles or amyloid-beta plaques are the primary cause of neurodegeneration in Alzheimer's disease (AD), and it is not well established whether genetic variation in tau is associated with AD. A recently identified novel protein, named Saitohin (STH), shares tissue expression pattern with tau, and preliminary evidence in a North American population indicates that a polymorphism at codon 7 (Q7R) of the STH gene is a predisposing factor for sporadic AD. A case-control study utilizing a clinically well-defined group of 315 sporadic AD patients and 307 control subjects was performed to test this association. The current study reveals that increased risk of AD associated with the STH RR genotype (OR 2.17, p = 0.04) is limited to late-onset (after the age of 72 years) AD cases.

Age of Onset↗

PubMed2003

Corticotropin-releasing hormone promoter polymorphisms in patients with rheumatoid arthritis from northwest Spain.

OBJECTIVE: To investigate the possible implications of polymorphism in the CRH promoter in rheumatoid arthritis (RA) susceptibility, we examined a series of patients with RA from a defined area of Northwest Spain. METHODS: A total of 177 patients with RA and 147 ethnically matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for CRH polymorphisms in the 5' regulatory region of the gene at position 1273 (alleles A1 and A2) and at position 225 (alleles B1 and B2) by PCR-restriction fragment length polymorphism. Patients were stratified for age at onset of disease and rheumatoid factor status. RESULTS: When the whole group of patients was examined, no significant differences in CRH allele or genotype frequency were found compared with controls. However, the CRH allele A2 was significantly increased in patients with late onset seronegative RA compared with the seronegative group with younger age of disease onset (p = 0.03). In addition, 4 (36.4%) of the 11 patients with late onset seronegative RA carried the CRH-A2 allele versus only 2 (6.6%) of 31 patients with seronegative RA beginning before age 61 (OR 8.3, 95% CI 1.4-47.0; p = 0.015). CONCLUSION: In Northwest Spain, polymorphism in the CRH gene regulatory region may play a role as a disease susceptibility marker for late onset seronegative RA.

Age of Onset↗

PubMed2003

Influence of age, sex, and place of residence on clinical expression of giant cell arteritis in northwest Spain.

OBJECTIVE: To investigate the epidemiology of giant cell arteritis (GCA), we examined whether differences in clinical and laboratory features exist in patients with biopsy-proven GCA from Northwest Spain according to sex, place of residence, and age at disease onset. METHODS: Retrospective study of biopsy-proven GCA diagnosed from January 1, 1981, to December 31, 2001, at the single hospital for a well defined population of 250,000. A comparative analysis was conducted of clinical and laboratory features according to sex, place of residence (rural or urban), and age at the onset of symptoms (< 70 yrs; >or= 70 yrs). RESULTS: Between 1981 and 2001, 210 patients from the Lugo region were diagnosed with biopsy-proven GCA. In urban areas GCA was significantly more common in women (rate ratio 1.58, 95% CI 1.00-2.53, p = 0.05). Women presented manifestations of polymyalgia rheumatica (PMR) more commonly than men. However, no statistically significant difference in the frequency of visual manifestations or permanent visual loss were observed between the sexes. GCA was slightly more common in rural than in urban areas (annual adjusted incidence rate in rural areas 10.4/100,000 in people age >or= 50 years vs 9.1/100,000 in urban areas; p = 0.34). GCA was more common among men in rural areas (rate ratio 1.73, 95% CI 1.10-2.70, p = 0.02). Patients younger than 70 years at the time of diagnosis (20%) had a trend to a longer delay to diagnosis and a marginal increase in the frequency of PMR compared with those with disease onset at age >or= 70 years. A higher inflammatory response was observed in the patients younger than 70 years. CONCLUSION: In patients with biopsy-proven GCA from Northwest Spain PMR manifestations are more commonly observed in women. The higher inflammatory response and the longer delay to diagnosis in younger patients call for a higher physician awareness of this vasculitis among individuals younger than 70 years.

Age of Onset↗

PubMed2003

Endothelial nitric oxide synthase haplotype associations in biopsy-proven giant cell arteritis.

OBJECTIVE: To assess the influence of endothelial nitric oxide synthase (eNOS) polymorphisms in the susceptibility to giant cell arteritis (GCA). METHODS: We studied 57 patients with biopsy-proven GCA diagnosed at the Rheumatology Division of Hospital Xeral-Calde and 117 ethnically matched controls. Patients and controls were genotyped by PCR for a variable number tandem repeat polymorphism in intron 4, a T/C polymorphism at position -786 in the promoter region, and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. RESULTS: No differences in allele or genotype frequencies for individual polymorphisms were observed between patients with GCA and controls. However, when haplotype frequencies for the combination of the 3 eNOS polymorphisms were estimated, a significant increase in the frequency of haplotype C/1/T and a significant decrease in the frequency of haplotype C/1/G were observed in GCA patients compared to controls (p = 0.04, OR 1.8, 95% CI 1.0-3.3; p = 0.02, OR 0.3, 95% CI 0.1-0.8, respectively). CONCLUSION: Significant differences in eNOS haplotype frequencies between GCA patients and controls may indicate a role for these polymorphisms in the susceptibility to this condition.

Base Sequence↗

PubMed2003

Infective endocarditis due to Streptococcus bovis in a series of nonaddict patients: clinical and morphological characteristics of 20 cases and review of the literature.

BACKGROUND AND OBJECTIVES: Controversy frequently exists about the actual frequency of Streptococcus bovis infective endocarditis (IE), its incidence of malignancy and its outcome. Consequently, the characteristics of S bovis IE were examined in an unselected population of nondrug-addicted patients. The literature was also reviewed. METHODS: Nondrug-addicted patients with S bovis IE were retrospectively reviewed. Clinically definite IE was diagnosed according to the Duke classification criteria at the single reference hospital for a defined population in northwestern Spain over a 13-year period. The clinical features, need for surgery and mortality rate of these patients were compared with those of other nondrug-addicted patients with IE examined during the same time period. RESULTS: Between 1987 and 1999, S bovis IE was diagnosed in 20 consecutive patients. This pathogen was responsible for 16.8% of the cases of definite IE in nondrug-addicted patients. Underlying conditions and embolic septic events were common. The aortic valve was the most common site of IE. Simultaneous involvement of two cardiac valves and moderate to severe regurgitation were more common in patients with S bovis IE. Colonic neoplasms were observed in 77% of patients. However, in-hospital mortality rate, need for in-hospital surgery and surgery during follow-up did not differ between patients with S bovis IE and the other nondrug-addicted patients with IE. CONCLUSIONS: In unselected patients, the rate of mortality due to S bovis IE is similar to that observed in IE due to other microorganisms. However, colonoscopic evaluation during admission and follow-up is required.

Aged↗

PubMed2002

Polymorphism at codon 174 of the prion-like protein gene is not associated with sporadic Alzheimer's disease.

Alzheimer's disease (AD) and prion diseases are associated with the occurrence of protein aggregates called amyloid fibrils, containing the amyloid-beta peptide in AD, and a modified form (PrP(Sc)) of the normal cellular prion protein (PrP(c)) in prion diseases. PrP(c) is encoded by the prion protein gene, and a common polymorphism at codon 129 of this gene is a determinant of susceptibility to acquired and sporadic prion diseases but not for sporadic AD. A recently identified novel protein, named Doppel, shares biochemical and structural homology with PrP(c). Preliminary evidence in a German population indicates that a polymorphism at codon 174 of the prion-like protein (PRND) gene encoding for Doppel protein is a predisposing factor for both prion diseases and sporadic AD. A case-control study utilizing a clinically well-defined group of 283 sporadic AD patients and 288 control subjects was performed to test this association. The current study does not demonstrate any significant difference in T174M PRND genotype or allele frequencies between AD patients and controls. Our study in the Spanish population argues against the hypothesis that the PRND gene is causally related to AD.

Aged↗

PubMed2002

No synergistic effect between -850 tumor necrosis factor-alpha promoter polymorphism and apolipoprotein E epsilon 4 allele in Alzheimer's disease.

In the brains of Alzheimer's disease (AD) patients, microglia cells are activated and produce inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha). A recent study conducted in Northern Ireland showed that a polymorphism in the promotor region (-850) of the TNF-alpha gene increased the risk of AD associated with carriage of the apolipoprotein E (APOE) epsilon 4 allele. In a case-control study restricted to a population from Northern Spain and utilizing 321 sporadic AD patients and 312 control subjects, we have found that the -850 TNF-alpha polymorphism does not interact with the APOE gene to increase the risk associated with the epsilon 4 allele.

Age of Onset↗

PubMed2002

The myeloperoxidase gene in Alzheimer's disease: a case-control study and meta-analysis.

Myeloperoxidase (MPO) presence has been demonstrated in microglia associated with senile plaques, and contributes to Alzheimer's disease (AD) pathology through oxidation-induced damage. Recently, a functional biallelic (G/A) polymorphism in the promotor region (-463) of the MPO gene has been associated with susceptibility to AD, but the reports of this association have been inconsistent. A case-control study utilizing a clinically well-defined group of 315 sporadic AD patients and 327 control subjects was performed to test this association. The current study does not demonstrate any significant difference in MPO genotype or allele frequencies between AD patients and controls. A meta-analysis of all studies available gave a non-significant (P=0.83) odds ratio of 1.02 for the MPO GG genotype. Our study in the Spanish population as well as the meta-analysis argue against the hypothesis that the MPO gene is causally related to AD.

Aged↗

PubMed2002

A new prognostic scoring system for meningococcal septic shock in children. Comparison with three other scoring systems.

OBJECTIVE: To develop a quick and sensitive method for identification of children with presumed meningococcal septic shock at risk of death at admission to the pediatric intensive care unit (PICU) and to compare its performance with three other prognostic systems: Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS), Malley score and the Paediatric Index of Mortality (PIM). DESIGN: Multicenter retrospective cohort study. SETTING: PICUs of 14 tertiary hospitals. PATIENTS: The developmental sample included 192 children consecutively admitted to the PICUs with presumed or confirmed meningococcal septic shock from 1983 to 1995. The validation sample included 158 children consecutively admitted from 1996 to 1998. INTERVENTIONS: Clinical and laboratory data gathered during the first 2 h after admission were used to develop the new score and to compute the other scoring systems. Logistic regression was applied to identify the independent predictors of death. MEASUREMENTS AND RESULTS: Overall mortality was 31.5%. The new score included seven variables: cyanosis (2 points), Glasgow coma scale less than 8 (2 points), refractory hypotension (2 points), oliguria (1 point), leukocytes less than 4000/mm(3) (1 point), partial thromboplastin time more than 150% of control value (1 point) and base deficit more than 10 mmol/l (1 point). The new score provided the best discriminative capability, as measured by the area under the ROC curve (SEM) in the validation sample =0.88 (0.03), PIM =0.82 (0.04), Malley I =0.80 (0.04), GMSPS =0.79 (0.04) and Malley II =0.76 (0.04). CONCLUSIONS: A new prognostic score is proposed for therapeutic stratification of children with presumed meningococcal septic shock.

Adolescent↗

PubMed2002

Lack of association between cathepsin D genetic polymorphism and Alzheimer disease in a Spanish sample.

Cathepsin D (catD) is an intracellular aspartyl protease that exhibits beta and gamma secretase-like activity to cleave amyloid precursor protein into beta amyloid peptide. The T-allele of a biallelic (alleles C and T) polymorphism in the exon 2 of the catD gene has been found to be associated with increased risk of Alzheimer disease (AD) in two independent German populations. Other groups have been unable to replicate this association in Caucasian American and Northern Ireland populations. Moreover, a small and no significant tendency for the T-allele to be protective for AD has been demonstrated in Caribbean Hispanics. A case control study utilizing a clinically well-defined group of 311 sporadic AD patients and 346 control subjects was performed to test this association in an ethnically homogeneous population from Spain. We did not observe any association between the T-allele of the catD gene and the disease. Furthermore, catD was not predictive of AD in an interactive fashion when considering apolipoprotein E, age, or gender.

Aged↗

PubMed2002

Gene dose-dependent association of interleukin-1A [-889] allele 2 polymorphism with Alzheimer's disease.

Interleukin (IL)-1 is a potent proinflammatory cytokine that is markedly overexpressed in the brains of patients with Alzheimer's disease (AD). The IL-1A [-889] allele 2 has been shown to increase AD risk, probably by upregulating the inflammatory cascade in the disease process. A case-control study utilizing a clinically well-defined group of 298 sporadic AD patients and 306 control subjects was performed to test this association. Our data show that the IL-1A allele 2 is a risk factor in a dose-dependent manner, the risk of developing AD with two copies of the IL-1A allele 2 (odds ratio 3.1, 95 % CI 1.30-7.45) being approximately double that of one copy of the IL-1A allele 2 (odds ratio 1.4, 95 % CI 0.99-1.94, P for trend = 0.0004). Furthermore, the risk associated with the IL-1A allele 2 was not restricted to AD patients of a particular age, and we could confirm this association in our early-onset and late-onset AD patients.

Aged↗

PubMed2002

[Reproducibility of C-reactive protein analyses].

The aim of this study was to measure the reliability of different nephelometric techniques for measuring C-reactive protein (CRP). One hundred and twenty samples were obtained from 40 patients. All 120 samples were divided in three parts to measure CRP using three different methods. Reliability was determined by the kappa index and intraclass correlation coefficient. The intraclass correlation coefficient ranged from 0.78 to 0.94. When CRP values were categorized in four groups, the kappa index reached 75-86% and percentage of agreement varied from 95% to 97%. When CRP values were divided into two groups, the kappa index was 73% to 78% and the percentage of agreement was 86% to 89%. We found that CRP determinations with different nephelometric methods were highly reproducible, even when different analysts were involved. Ultrasensitive techniques are needed only if the clinical objective is to obtain a CRP measurement under 0.3 mg/dl.

Adult↗

PubMed2002

Henoch-Schönlein purpura in children and adults: clinical differences in a defined population.

OBJECTIVE: To examine epidemiologic, clinical, and outcome differences between children and adults with Henoch-Schönlein purpura (HSP) in a well-defined population. PATIENTS AND METHODS: Retrospective study of unselected patients with HSP seen at the only referral hospital for the Lugo region of Northwest Spain between 1980 and 2000. Patients were classified according to the criteria proposed by Michel et al. Two well-differentiated age groups were established for comparison: children (under 14 years of age) and adults (over 20 years of age). Also, to assess possible differences in the outcome, only those patients with at least 1 year of follow-up were included in the study. RESULTS: Seventy-three children and 31 adults fulfilled the inclusion criteria described above. Unlike in children, HSP in adults was more common in males. While in children, HSP manifested more commonly in fall and winter, summer and winter were the most common seasons of onset in adults. The frequency of gastrointestinal manifestations was similar in both groups. However, during the course of the disease, 6 of the 31 adults (19%) had severe renal manifestations and another 4 (13%) renal insufficiency. In children, by contrast, the frequency of severe renal manifestations or renal insufficiency during the course of the disease was significantly reduced compared with adults. After 6 years' median follow-up in children, complete recovery was observed in most cases. However, after 5 years' median follow-up, almost 40% of adults had persistent hematuria and 3 of them (10%) renal insufficiency that required hemodialysis in 2 cases. CONCLUSIONS: HSP is generally benign and self-limited in children and more severe in adults.

Adolescent↗