[Likelihood ratio as a measure of indirect immunofluorescence antinuclear antibodies. Application of clinical research results to patients].
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Biomedical subjects
Publications and source records attributed to M T Camps García.
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We document a 30 y old man with Primary Antiphospholipid Syndrome (PAPS) and thrombosis of the common femoral vein and both the external and common iliac veins, extending to the lower vena cava, which failed to respond to high dose heparin. After three days of fibrinolytic treatment with urokinase there was complete venous recanalization.
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BACKGROUND: To establish the relation between class I and II HLA antigens, systemic lupus erythematosus (SLE), autoantibodies production, and clinical manifestations in the south of Spain (Málaga). METHODS: In a regional hospital we undertook a case-control study with a consecutive sample of 104 patients with SLE who fulfilled at least 4 criteria of ARA. Three hundred and twenty-eight local controls with no apparent pathology were included for comparison. We evaluated clinical and analytical aspects about multisystem autoimmune disease. HLA typing was serologically determined. RESULTS: Univariate analysis showed a relation between SLE and the specificities B8 (21% of patients vs 10% of controls, p = 0.005; RR = 2.3), DR3 (36% vs 20%, p = 0.0006; RR = 2.5), DRw52 (69% vs 49%, p = 0.001; RR = 2.3), and DQ2 (49% vs 36%, p = 0.0150; RR = 1.7). However, in logistic regression multivariate analysis, there was a confounding effect between DR3 and DRw52, and it could be that only this specificity, HLA-DRw52 (RR = 2.0; 95% CI: 1.1-4.0), and of lesser degree B8 (RR = 1.9; 95% CI: 0.9-4.4), are really associated with SLE. Also, in multivariate analysis, DR6 showed a negative association (5% vs 25%, p = 0.011; RR = 4.2; 95% CI: 1.5-17.2) with anti-U1RNP, while DRw52 showed a negative association with IgG-aCL (50% vs 85%, p = 0.019; RR = 0.21; 95% CI: 0.06-0.76). Furthermore, DQ2/DQ6 showed positive association with anti-SSA/Ro antibodies (50% vs 24%; p = 0.046; RR = 3.0; 95% CI: 1.0-9.0). There were also several associations between clinical manifestations and HLA. The specificities DR and DRw53 were almost always risk factors, but only DR5 was a protector for renal lesion. DRw52 and DQ specificities were always protectors when they were associated with some clinical manifestations. Isolated DR3 antigen, is not associated with any of the above-mentioned manifestations. CONCLUSIONS: The previously described relation between SLE and the antigen DR3 is confirmed, but this association could be a result of the presence of DRw52 specificity in patients, that is in linkage disequilibrium with DR3.
To establish the relation between HLA antigens, Primary Sjögren Syndrome (PSS) and autoantibodies production, in our geographical area, we undertook a case-control study with a consecutive sample of 30 patients with PSS (Fox's criteria) attending in a reference hospital. Two hundred and sixty-four local controls with no apparent pathology were included for comparison. In patients we evaluated clinical and analytical aspects about multisystem autoimmune disease. Anti-SSA/Ro and -SSB/La autoantibodies were determined by double immunodiffusion. HLA typing was serologically determined. In logistic regression multivariate analysis, there were significant association between PSS and specificities HLA-Cw7 (73% in cases, versus 35% in controls; RR = 8.0; 95% CI: 23.2-2.7), HLA-DR3 (63% vs 20%; RR = 3.4; 95% CI: 9.5-1.4) and HL-DR11 (43% vs 13%; RR = 4.1; 95% CI: 12.0-1.4). In patients, the anti-SSA/Ro autoantibodies production were associated with HLA-DR3 antigen (83% vs 25%; RR = 6./; 95% CI: 1.3-34.2). All HLA-DQ2/DQ6 heterozygotes patients (8 cases) had anti-SSA/Ro autoantibodies, versus only one half of the remainder (p = 0.029; RR = 6.3). In anti-SSA/Ro negative patients there weren't association with HLA-DR3 antigen (33% vs 20%). HLA-DR3 were associated with the presence of anti-SSB/La autoantibodies, but there wasn't signification (p = 0.081). We conclude that our patients with PSS present association with HLA-DR11 specificity, that it's a risk factor for the disease development. HLA-DR3 would determined the anti-SSA/Ro autoantibodies, and maybe also anti-SSB/La autoantibodies, production. Furthermore, HLA-DQ2/DQ6 heterozygosity would determined immune response to SSA/Ro autoantigen.
BACKGROUND: To evaluate the efficacy of methotrexate in patients with systemic lupus erythematosus (SLE) without major organ involvement resistant to medium-high doses of prednisone. METHODS: Crossover, open clinical trial with two treatment periods, the first of 3 months and the second of 6 months, an intermediate control period of 3 months and another at the end of 6 months. A sample of 15 consecutive patients with SLE who, with no major organ damage, had active disease in spite of receiving more than 10 mg/day of prednisone or who relapsed on reduction of this doses during a period of at least 3 months. 7.5 mg/week of methotrexate were administered orally, divided into three doses of 2.5 mg/12 hours. Statistical significance was evaluated by Student's paired t test and chi 2; the strength of association by the Mantel-Haenzel odds ratio (OR) method and the precision, by Miettinen's confidence interval (CI). A p value of less than 0.05 was considered significant. RESULTS: Two patients failed to finish the study; one for worsening of cutaneous lesions of necrotizing vasculitis which she already had previously, and the other for an increase in her transaminase levels. In the remaining 13 there were 10 flares of disease activity during the control phases, 2 severe, versus 2 flares during the periods of methotrexate use (OR 7.69 (95% confidence interval, 1.67 to 33.33; p = 0.021). There were no significant changes in analytical results or prednisone requirements. During treatment six patients had oral aphthae and five had dyspepsia; three had an increase in transaminase levels, which in one caused the treatment to be stopped. There were two urinary infections, one community acquired pneumonia and one upper airway symptoms requiring antibiotic treatment; one female patient had acute cholecystitis with cholelithiasis necessitating surgical intervention. CONCLUSIONS: Weekly low doses of methotrexate may prevent flares of activity of SLE in this type of patients, but it does not reduce the requirements of prednisone, nor modify analytical data. Toxic effects are rare and reversible upon interrupting medication.
STUDY OBJECTIVE: Description of the clinical and analytical manifestations of 8 patients with Primary Antiphospholipid Syndrome (PAPS). DESIGN: Series of cases. SETTING: Patients seen in the Internal Medicine Department of a third level Medical Center in Malaga Province. PATIENTS AND INTERVENTIONS: We describe the symptoms and signs, as well as the analytical determinations that may be related with autoimmunity in 8 patients diagnosed of PAPS (Harris' Criteria). The antiphospholipid antibodies were determined by a) Biologic false-positive Venereal Disease Research Laboratory (BFP-VDRL), b) Lupus Anticoagulant (LAC): Enlargement of the activated thromboplastin partial time > 6" and Exner test, c) Anticardiolipin antibodies (aCL), IgG (UGPL/ml), IgM (UMPL/ml) by enzyme-linked immunosorbent assay (ELISA). RESULTS: Four patients were females and four males. The mean age was 35.1 +/- 13.6. None of the patients had criteria of systemic lupus erythematous. The principal clinical manifestations of the PAPS were the venous and arterial thrombotic events in different areas (7 patients); The female patient that didn't have thrombotic event presented thrombocytopenia. Only one patient had 1 abortion. The four females had livedo reticularis (LVR), associated in two of them with arterial hypertension and stroke (Sneddon syndrome). Others manifestations seen, have been, Raynaud's phenomenon, acrocyanosis, migraine, arthritis and myositis. All the patients had IgG aCL, 3 IgM aCL, 7 enlargement of the activated thromboplastin partial time and none presented VRL. Five patient had positive antinuclear antibodies (ANA), but none of them had anti- DNA, hypocomplementemia nor lymphopenia. As far as treatment goes three of the patients are anticoagulated with continuous dicoumarins . The remaining patients keep treatment with platelet antiaggregant, had a satisfactory evolution. CONCLUSIONS: This group of patients presented venous and arterial thrombotic events such as principal manifestation of the PAPS. The most sensitive test to detect antiphospholipid antibodies were the enlargement of the activated thromboplastin partial time and the aCL. It could be interest the determination of aCL in young people the present thrombotic events without another apparent cause.
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According to case and control studies we determine the prevalence of anticardiolipin antibodies (ACA) and autoimmune phenomena in 23 women with recurrent abortions (two or more) without apparent cause after study, using as pattern a sample of 86 patients belonging to different subgroups: 21 women with only one abortion, 15 with toxemia, 30 healthy pregnants and 20 healthy non-pregnants. We found that 6 (26%) of the cases with recurrent abortions showed high ACA-IgG versus 6 (7%) of the control group (p = 0.009), with an odds ratio (OR) of 4.7 (Confidence Interval [CI] 95%, 1.4-15). We didn't find a relation with ACA-IgM, OR or 2.2 (CI 95%, 0.72-6.50; p = 0.160). Our patients only showed as manifestation of antiphospholipid antibodies syndrome, recurrent abortions, finding neither association with thrombotic phenomena, nor thrombocytopenia. They didn't show either clinical or analytical manifestations of autoimmune disease. We concluded that the ACA-IgG can be associated to the fetal loss in these kind of patients.
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