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Biomedical subjects

M J Cuadrado

Publications and source records attributed to M J Cuadrado.

12 recordsLinked to original sources
PubMed1998

Lack of cross-reaction between antibodies to beta2-glycoprotein-I and oxidized low-density lipoprotein in patients with antiphospholipid syndrome.

Previous studies have shown a cross-reaction between anticardiolipin and anti-oxidized low-density lipoprotein (LDL) antibodies in patients with the antiphospholipid syndrome (APS). The aim was to investigate the existence of a cross-reaction between anti-beta2-glycoprotein-I (beta2-GP-I) and anti-oxidized LDL antibodies in a group of APS patients. Ninety-three patients with APS were included in the study; 47 of these patients were diagnosed as primary APS, while the rest (46 patients) fulfilled criteria for the classification of systemic lupus erythematosus (SLE). All patients were positive for the IgG isotype of anticardiolipin antibodies (aCL). Twelve (26%) SLE-associated APS and 14 (29.7%) primary APS patients had raised concentrations of IgG antibodies to oxidized LDL. There was no correlation between anti-beta2-GP-I and anti-oxidized LDL antibodies. Inhibition experiments showed no cross-reaction either between anti-beta2-GP-I and anti-oxidized LDL antibodies, or between anti-beta2-GP-I and anti-native LDL antibodies. Our study suggests that the presence of both anti-beta2-GP-I and anti-oxidized LDL antibodies in patients with APS is not due to the structural similarity and consequent cross-reaction, and that they are two different populations of antibodies directed against different antigens.

Adolescent↗
PubMed1997

Thrombosis in primary antiphospholipid syndrome: a pivotal role for monocyte tissue factor expression.

OBJECTIVE: The antiphospholipid syndrome (APS) is a disorder of recurrent thrombosis, pregnancy loss, and thrombocytopenia associated with the production of anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). The mechanisms of thrombus formation remain unknown. Tissue factor (TF), an inducible cell glycoprotein, is a major initiator of coagulation in vivo. The present study was therefore undertaken to investigate TF expression and procoagulant activity on monocytes from patients with primary APS and its correlation with thrombotic events. METHODS: Three groups of patients were studied: group 1 comprised 23 primary APS patients with thrombosis, group 2 consisted of 10 primary APS patients without thrombosis, and group 3 contained 20 patients with thrombosis but without antiphospholipid antibodies. Twenty age- and sex-matched healthy blood donors were used as controls (group 4). Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay (ELISA) and LAC by standard methodology. Cell surface expression of TF on monocytes was assessed by flow cytometry. The amount of TF in cell lysates (TF(Ag)) and soluble TF(Ag) plasma levels were analyzed by ELISA, and the TF-related procoagulant activity (PCA-TF) on intact cells and cell lysates by a chromogenic assay. Levels of the cytokines that influence TF production, i.e., tumor necrosis factor alpha (TNF alpha) and interleukin-1beta (IL-1beta), were determined by ELISA. RESULTS: Cell surface expression of TF was increased in group 1 (mean +/- SEM 50.2 +/- 4% positive cells) compared with group 2 (14.6 +/- 1.6%), group 3 (16.8 +/- 3.7%), and group 4 (14.1 +/- 1.6%). TF(Ag) levels were also elevated in group 1 (215.8 +/- 11.2 pg/10(6)) compared with group 2 (150.8 +/- 15.2), group 3 (101.4 +/- 14.8), and group 4 (80.32 +/- 5.5). PCA-TF on intact cells and cell lysates was significantly increased in group 1 (148.8 +/- 16.3 units/10(5) lysate cells, compared with 54.5 +/- 11.5, 38.6 +/- 9.7, and 22.5 +/- 3.1 in groups 2, 3, and 4, respectively). Among group 1 patients, there was a significant increase in the degree of TF expression in those positive for IgG aCL, but not in those positive for IgM aCL or LAC. TNF alpha and IL-1beta plasma levels did not differ significantly between any of the groups. CONCLUSION: These results suggest that monocyte TF expression is directly involved in the pathogenesis of thrombotic complications in patients with the primary APS.

Adult↗
PubMed1997

Thrombocytopenia in the antiphospholipid syndrome.

OBJECTIVE: To determine the prevalence of thrombocytopenia in a group of patients suffering from the antiphospholipid syndrome (APS) and to investigate whether these patients may have any particular clinical or serological features. METHODS: Retrospective analysis. A group of 171 APS patients seen in our department were studied for the presence of thrombocytopenia. Clinical and serological features of these patients were analysed by standard methods and each of them was correlated to the presence of thrombocytopenia and compared with those found in the group without thrombocytopenia. RESULTS: Each of the patients studied had a minimum of three platelet counts during the follow up period. Forty (23.4%) were found to have thrombocytopenia; 13 with persistently low and 27 patients with intermittently low platelet counts. There were no statistically significant differences in sex, age, disease duration or diagnosis when compared with the group of APS patients without thrombocytopenia. Thrombocytopenia was associated with thrombosis in 18, with miscarriages in five, and with both of these features in 13 patients. It was the only manifestation of the APS in four patients. All patients had persistently positive tests for antiphospholipid antibodies concomitantly with the low platelet counts. No significant association was found between the presence of thrombocytopenia and clinical or serological manifestations in APS patients. CONCLUSION: This study showed a prevalence of thrombocytopenia of 23.4% in APS. These patients did not present any significant clinical or serological features that distinguish them from those patients without thrombocytopenia.

Adult↗
PubMed1996

Defective B7 expression on antigen-presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients.

Defective T cell functions, including IL-2 production and proliferation, have been shown in SLE patients. After T cell stimulation (first signal), a costimulatory signal (second signal) is required to achieve complete T cell activation. Main costimulatory signals are provided to T cells by B7 antigens (CD80 and CD86, expressed on antigen-presenting cells (APC)) upon interaction with its receptor, the CD28 molecule expressed on T cells. The aim of this study was to investigate the role of CD28/B7 interactions in the impaired T cell responses of SLE patients. We show that stimulation of T cells with phytohaemagglutinin (PHA) in the presence, but not in the absence, of anti-CD28 MoAb or B7+ cells results in tyrosine phosphorylation of specific substrates, transcription of mRNA and production of IL-2 that is indistinguishable in SLE patients and healthy controls. Moreover, proliferation of costimulated T cells from SLE and controls was specifically abrogated by blocking the CD28/B7 interactions by means of addition to the culture of the CTLA4-Ig fusion protein. However, in most patients activated APC failed to up-regulate B7 molecules, giving rise to ineffective costimulatory signalling to T cells. These results indicate that the CD28/B7 costimulatory pathway is defective in SLE patients.

Abatacept↗
PubMed1995

The management of thrombosis in the antiphospholipid-antibody syndrome.

BACKGROUND: The antiphospholipid-antibody syndrome is a thrombophilic disorder in which venous or arterial thrombosis, or both, may occur in patients with antiphospholipid antibodies. The optimal treatment of these patients is unclear. We assessed the efficacy of warfarin, low-dose aspirin, or both in the secondary prevention of thrombosis in patients with the syndrome. METHODS: One hundred forty-seven patients (124 [84 percent] of whom were female) with the antiphospholipid-antibody syndrome and a history of thrombosis were studied retrospectively. The syndrome was primary in 62 patients and was associated with systemic lupus erythematosus in 66 patients and lupus-like disease in 19. Each patient's history was reviewed. RESULTS: One hundred one patients (69 percent) had a total of 186 recurrences of thrombosis. The median time between the initial thrombosis and the first recurrence was 12 months (range, 0.5 to 144 months). Treatment with high-intensity warfarin (producing an international normalized ratio of > or = 3) with or without low-dose aspirin (75 mg per day) was significantly more effective (P < 0.001 by the log-rank test) than treatment with low-intensity warfarin (producing an international normalized ratio of < 3) with or without low-dose aspirin or treatment with aspirin alone in preventing further thrombotic events (recurrence rates per patient-year, 0.013, 0.23, and 0.18, respectively). The rate of recurrence of thrombosis was highest (1.30 per patient-year) during the first six months after the cessation of warfarin therapy. Complications involving bleeding occurred in 29 patients during warfarin therapy and were severe in 7 (0.071 and 0.017 occurrence per patient-year, respectively). CONCLUSIONS: The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high. Long-term anticoagulation therapy in which the international normalized ratio is maintained at or above 3 is advisable in these patients.

Adolescent↗
PubMed1995

Association between HLA class II antigens and primary antiphospholipid syndrome from the south of Spain.

Recent studies have suggested an association between primary antiphospholipid syndrome (PAPS), antiphospholipid antibodies and some major histocompatibility complex (MHC) antigens. We have studied the relationship between MHC class II antigens and PAPS in 19 patients from the south of Spain. Univariant analysis showed an association between PAPS and HLA-DQ7 (47% vs 25%l P = 0.3), DR4 (32% vs 16%; P = 0.08) and DQ3 (63% vs 39%; P = 0.04). However, multivariant analysis confirmed the association with DQ7 (RR = 2.5; CI 80%: 1.3-4.7) and DR4 (RR = 2.2; CI 80%: 1.1-4.4) but not with DQ3. When we introduced DRw53 into this analysis, we noticed a DR4 confounding effect, with DQ7 (RR = 3.1; CI 80%: 1.7-5.8) and Drw53 (RR = 2.3; CI 80%: 1.2-4.4) remaining as the most important HLA antigens related to PAPS. In conclusion, in PAPS patients from the South of Spain, HLA-DQ7 antigen showed the highest relative risk for PAPS, followed by DRw53.

Abortion, Spontaneous↗
PubMed1995

Primary antiphospholipid syndrome evolving into systemic lupus erythematosus.

Since 1983 we have followed a total of 165 patients with antiphospholipid syndrome (APS). During the median followup period of 78 mo (range 12-336 mo), 3 of 80 patients with primary APS subsequently developed features of systemic lupus erythematosus (SLE) or lupus-like disease. One patient developed lupus-like disease 4 yrs and the other 2 developed full blown SLE more than 10 yrs after initial presentation of primary APS. Tissue typing in patients who developed SLE showed HLA antigens A2, A3, B35, Bw6, Cw4, DR7, DRw53, and DQ2 (Case 2); and A1, A3, B7, B8, Bw6, Cw7, DR4, DR15, DR51, DRw53, and DQ1 (Case 3). We report clinical features and genetic associations of these 3 patients.

Adolescent↗
PubMed1994

Allergic disorders in systemic vasculitis: a case-controlled study.

A number of the systemic vasculitides (SV) may have an allergic component although specific allergens remain unknown. We evaluated the prevalence of several types of allergy in 60 consecutive patients with SV and their families. Two control groups were studied. One included 60 healthy people and the other 60 unselected patients attending a general rheumatology clinic who did not have SV. Forty-four of the 60 patients (73%) had a history of at least one type of allergy. This was significantly higher than in either control group (P = 0.0001 and P = 0.0002). There was also a significantly higher prevalence of allergies among the families of the SV patients compared to the controls. This data supports the idea that an allergic response to an external allergen may play an important part in the aetiology of these diseases.

Adult↗
PubMed1993

Relationship of IL-2, IL-2R (CD25+), soluble IL-2R and IL-4 with disease activity in SLE patients.

The plasma levels of interleukin-4 (IL-4), interleukin-2 (IL-2), soluble receptor of IL-2 (IL-2R) and T cell expression of IL-2 receptor chain (CD25+) were determined in an attempt to relate these parameters with disease activity in systemic lupus erythematosus (SLE). IL-4, IL-2 and sIL-2R plasma levels of SLE patients were significantly higher than those of the control group (P < 0.05) while CD25+ expression was similar in both groups. Only sIL-2R levels were significantly higher (P < 0.05) in active than in inactive patients.

Adolescent↗
PubMedDate not supplied

Prevalence and clinical significance of subungual splinter haemorrhages in patients with the antiphospholipid syndrome.

OBJECTIVE: To assess the prevalence and clinical significance of subungual splinter haemorrhages in patients with the antiphospholipid syndrome. METHODS: A group of 147 patients with the antiphospholipid syndrome (124 female, 23 male) were studied. All patient histories were carefully reviewed and each patient was interviewed at least once. Particular attention was paid to clinical manifestations of the antiphospholipid syndrome at the time of subungual splinter haemorrhages. Patients who had evidence of infective endocarditis confirmed by echocardiogram and a positive blood culture were excluded from the study. RESULTS: Six out of 147 patients developed subungual splinter haemorrhages. Amongst 80 patients (54%) with a history of venous thrombosis, only one developed subungual splinter haemorrhages during a lupus flare in the post-partum period. This sign was found in 4 out of 67 patients with arterial occlusions; in 2 of these the occlusion manifested as a cerebrovascular accident. Another patient with a history of lupus and recurrent miscarriages developed subungual splinter haemorrhages during a lupus flare. CONCLUSION: Subungual splinter haemorrhages appeared to be relatively uncommon in our group of patients with the antiphospholipid syndrome. The differences in clinical setting and response to different treatment regimes in these cases suggest varied aetiopathologies and may reflect a number of different types of vascular insult.

Adolescent↗
PubMedDate not supplied

Immunosuppressive therapy in lupus nephritis.

OBJECTIVE: To evaluate the outcomes and side effects of immunosuppressive therapy in patients with lupus nephritis. PATIENTS AND METHODS: Thirty-nine patients with lupus nephritis assessed between 1988 and 1993 with a median follow-up of 46 months (range 12-60 months) were studied. Lupus nephritis was biopsy-proven in 37 patients. Patients received a median of 3 (500 mg) weekly pulses of intravenous cyclophosphamide followed either by azathioprine (n = 32) or oral cyclophosphamide (n = 7). All patients received oral prednisolone. The time from biopsy to renal insufficiency, defined by doubled serum creatinine and/or end stage renal failure, was used to assess outcome. RESULTS: There were significant improvements in the median changes of all major laboratory parameters. Serum creatinine levels did not change significantly. The prednisolone dose was significantly reduced during the follow-up period. OUTCOME: renal function remained stable in 26 (67%) and deteriorated despite therapy in 13 (33%) patients. 6/13 (42%) of these patients had impaired renal function at the time of biopsy. The adverse effects of intravenous cyclophosphamide seen were Herpes zoster (1), transient leucopenia (2), rash (1) and fatal septicaemia (1); of azathioprine urinary infections (3), leucopenia (5), rash (1) and increased liver enzymes (1); and of oral cyclophosphamide ovarian failure (4), Herpes zoster (3), haemorrhagic cystitis (1), and fatal septicaemia (1). CONCLUSIONS: Therapy with weekly low dose intravenous pulse cyclophosphamide to induce remission, followed by azathioprine appears to be useful in preserving renal function in patients with diffuse proliferative lupus nephritis. In comparison to other studies, the reduced incidence of ovarian failure using this regimen was striking.

Administration, Oral↗