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Biomedical subjects

D D'Cruz

Publications and source records attributed to D D'Cruz.

At least 37 records · Page 2Linked to original sources
PubMed2001

Optimising testing for phospholipid antibodies.

AIM: To compare anticardiolipin (ACL) and anti-beta2 glycoprotein 1 (beta2gp1) enzyme linked immunosorbent assays (ELISAs) in the diagnosis of antiphospholipid syndrome (APS) and to incorporate these results into a meta-analysis of published data. METHOD: Three representative commercial ACL ELISAs and an in house beta2gp1 assay were optimised and then assessed on 124 sera from normal donors, patients with infection, or patients with APS. A Medline search was screened for papers meeting defined criteria to conduct a meta-analysis. The performance of the assays used in this study was included. RESULTS: A non-quantitative ACL assay performed at least as well as the anti-beta2gp1 assay in the diagnosis of APS. Meta-analysis confirmed that neither assay is perfect, although the anti-beta2gp1 assay had a higher specificity and lower sensitivity than the ACL assay. CONCLUSIONS: The pooled data suggest that the ACL assay is used to investigate thrombosis without overt underlying pathology and that the improved specificity of the anti-beta2gp1 assay is exploited where infection, connective tissue disease, or atheroma are present.

Antibodies, Anticardiolipin↗
PubMed2001

Antimalarial therapy: a panacea for mild lupus?

Antimalarial therapy has a long and successful track record in the management of patients with mild SLE. Medium to long term use of hydroxychloroquine, alone or in combination with mepacrine, ameliorates lupus and may reduce the relapse rate. Recent guidelines for monitoring hydroxychloroquine have reduced the need for frequent visual checks. Antimalarials have other beneficial effects on lipid and glucose metabolism as well as having weak anticoagulant activity. They should be considered for most patients with mild lupus.

Antimalarials↗
PubMed2000

Autoimmune diseases associated with drugs, chemicals and environmental factors.

Autoimmune connective tissue diseases are complex multisystems and may be life threatening. Their aetiology is unknown but genetic, hormonal and environmental factors are important. In systemic lupus erythematosus (SLE), factors such as UV light and drugs, including oestrogen, may trigger the disease; silica exposure may also be important. Scleroderma is associated with silica exposure and drugs such as bleomycin and pentazocine may induce scleroderma-like diseases. Organic solvents such as vinyl chloride and epoxy resins may also be associated with scleroderma-like illnesses. The toxic oil syndrome and eosinophila-myalgia syndrome are best known examples of connective tissue diseases induced by chemical exposure. The systemic vasculitides and in particular cutaneous vasculitis may be induced by drugs and possibly environmental factors. A number of autoimmune connective tissue diseases may therefore be associated with exposure to drugs, chemicals and environmental factors and the risks associated with these should be minimised where possible.

Autoimmune Diseases↗
PubMed2000

Antiendothelial cell antibodies in inflammatory myopathies: distribution among clinical and serologic groups and association with interstitial lung disease.

OBJECTIVE: To determine the prevalence and associations of antiendothelial cell antibodies (AECA) in a well characterized cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Clinical characteristics, AECA, and myositis-specific autoantibodies were assessed by standard methods in 56 subjects with IIM. RESULTS: AECA were found in 20/56 patients with IIM, were seen in all the major clinical and serologic IIM groups, and were found in 10/15 patients with interstitial lung disease (ILD) (chi squared 6.5, p<0.01 with Yates' correction, relative risk 2.7, specificity 86% and sensitivity 50%). Antisynthetase antibodies, also associated with ILD as described (chi squared = 26.5, p<0.001 with Yates' correction, relative risk 8.7, specificity 95%, sensitivity 77%), did not correlate with the presence of AECA. CONCLUSION: AECA appear to be present in all forms of IIM and are markers for ILD that are independent of anti-synthetase autoantibodies. AECA may be a useful serologic marker for ILD in IIM.

Adult↗
PubMed2000

Localized monocyte chemotactic protein-1 production correlates with T cell infiltration of synovium in patients with psoriatic arthritis.

OBJECTIVE: To examine normal and psoriatic skin and synovial tissue from patients with psoriatic arthritis (PsA) for evidence of monocyte chemotactic protein-1 (MCP-1) mediated T cell chemotaxis. METHODS: Peripheral blood (PB), synovial fluid (SF), normal and psoriatic skin, and synovial biopsies were obtained from patients with PsA (n = 19) and compared to samples from normal (n = 5) and disease (n = 5) controls (NC, DC). Immune cell populations in PB and SF samples were assessed by immunofluorescent labeling and flow cytometry, levels of soluble MCP-1 were determined by quantitative ELISA, and immunohistochemistry was used to detect T cell subsets and macrophages and MCP-1 protein in frozen skin and synovial tissue sections. RESULTS: CD8+ but not CD4+ T cells were elevated in SF compared to PB, and the majority of these cells expressed CD45RO. Plasma MCP-1 levels in PsA were elevated relative to NC. MCP-1 levels were significantly higher than paired plasma samples in patients with recent onset (< 6 mo) synovitis (n = 10). A positive correlation was observed between synovial T cell numbers and MCP-1 levels in SF. MCP-1 protein was present in all tissues examined, but most intense expression was observed in synovium. CONCLUSION: Elevated concentrations of MCP-1 concomitant with memory T cell infiltration in PsA SF suggests that MCP-1 mediated chemotaxis is involved in the recruitment of T lymphocytes into the synovial compartment of patients with PsA.

Arthritis, Psoriatic↗
PubMed1999

Destruction of articular cartilage by alpha 2 macroglobulin elastase complexes: role in rheumatoid arthritis.

OBJECTIVE: Neutrophil elastase accounts for the ability of some fresh rheumatoid synovial fluids to degrade cartilage matrix in vitro. The aim of this study was to determine if enzyme activity could result from depletion of synovial fluid inhibitors or protection of the enzyme from inhibition. METHODS: The ability of synovial fluids to inhibit porcine pancreatic elastase was investigated together with chemical pretreatments capable of inactivating alpha 1 protease inhibitor (alpha 1PI) or preventing formation of alpha 2 macroglobulin (alpha 2M) elastase complexes. Subsequently, complexes of human neutrophil elastase with alpha 2M were prepared and applied to frozen sections of cartilage. Proteoglycan loss was quantified by alcian blue staining and scanning and integrating microdensitometry. Parallel studies were carried out using a low molecular weight chromogenic elastase substrate. The effects of alpha 1PI and SF on these systems were investigated. Finally, synovial fluids were subjected to gel filtration and the fractions assayed for elastase activity. High molecular weight fractions were pooled, concentrated, and tested for their ability to degrade cartilage sections. RESULTS: All synovial fluids reduced the activity of porcine pancreatic elastase, the inhibition mainly being attributable to alpha 1PI, whereas remaining activity resulted from complexes of elastase with alpha 2M. Complexes of human neutrophil elastase with alpha 2M were shown to cause proteoglycan degradation in frozen sections of human articular cartilage. Alpha 1PI prevented alpha 2M elastase complexes from degrading cartilage but not the chromogenic substrate. The data suggested that alpha 1PI does not inhibit elastase bound to alpha 2M but sterically hinders the complex. However, only one of five synovial fluids was able to completely block the actions of alpha 2M elastase complexes against cartilage. Gel filtration of rheumatoid synovial fluids showed elastase and cartilage degrading activity to be associated with fractions that contained alpha 2M, and not with fractions expected to contain free enzyme. CONCLUSIONS: The data suggest that synovial fluid alpha 2M elastase complexes can degrade cartilage matrix in rheumatoid arthritis.

Adult↗
PubMed1999

Integrin signalling defects in T-lymphocytes in systemic lupus erythematosus.

OBJECTIVE: To establish the relationship between T cell responses to integrin coreceptor stimulation and B cell hyperreactivity as measured by pathologic autoantibody production. METHODS: Peripheral blood mononuclear cells from 42 patients with SLE according to the American Rheumatism Association criteria were examined for their ability to adhere to plate-immobilised fibronectin. Co-stimulation assays were performed on the same cells using anti-CD3 antibody alone or co-immobilised with an anti-beta1-integrin antibody. Proliferative responses were measured by 3[H]thymidine pulsing on day 3 and activation was determined using a commercial protein kinase C assay, the protocol being established by our group in association with Promega. Beta-integrin expression was established by FACS analysis. RESULTS: An impaired PKC response to integrin-mediated activation was found in T-lymphocytes from 6/21 (29%) SLE patients, which correlated significantly with an absence of anti-dsDNA antibody in patient sera, irrespective of prednisolone treatment. Integrin co-stimulation of TcR/CD3-induced proliferation and T cell adhesion to fibronectin were also impaired among 5/21 (24%) and 6/15 (40%) patients studied, respectively. CONCLUSION: We hypothesise that the integrity of beta1-integrin signalling pathways may influence pathological antibody production in SLE by affecting T-lymphocyte activation and interactions between T- and B-lymphocytes.

Adolescent↗
PubMed1999

Lymphocyte activation markers and von Willebrand factor antigen in Wegener's granulomatosis: potential markers for disease activity.

OBJECTIVE: To examine 3 soluble circulating T cell antigens: interleukin 2 receptors (sIL-2r), CD4 (sCD4), and CD8 (sCD8) with von Willebrand factor antigen levels (vWF:Ag) and antiendothelial cell antibodies (AECA) as indices of endothelial involvement in patients with Wegener's granulomatosis (WG). METHODS: We studied 23 patients with WG, of whom 11 had active disease with renal involvement, and 20 healthy controls. sIL-2r, sCD4, sCD8, vWF:Ag, and AECA were measured by ELISA. RESULTS: Median sIL-2r levels in patients were higher than controls (789.5 vs. 551 U/ml, p<0.01). sCD4 levels were higher in patients: 17.0 vs. 15.2 U/ml (p<0.005) and correlated with sIL-2r levels. sIL-2r and sCD4 levels correlated with disease activity scores, antineutrophil cytoplasmic antibodies (ANCA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil counts. sCD8 levels were also higher: 260.5 vs. 127 U/ml (p<0.001) and correlated with CRP levels but not with disease activity. vWF:Ag levels were elevated in patients (median 296% vs. controls 109%; p<0.001) and correlated with disease activity, ESR, CRP, ANCA titers, and serum creatinine levels. AECA levels did not differ from controls (5% vs. 7%). CONCLUSION: Circulating levels of sIL-2r, sCD4, sCD8, and vWF:Ag are elevated in active WG, indicating T cell and endothelial activation. sIL-2r, sCD4, and vWF:Ag are potentially useful disease activity markers.

Adult↗
PubMed1998

Vasculitis in systemic lupus erythematosus.

Vasculitis frequently complicates SLE, is associated with significant morbidity and mortality, and its pathophysiology is poorly understood. In seriously ill lupus patients with vasculitis, immunosuppression should almost always be considered.

Autoantibodies↗
PubMed1998

Pathogenic mechanisms in psoriatic arthritis.

Psoriatic arthritis is an inflammatory arthritis which can develop in some psoriasis patients. The absence of a serological test means that diagnosis must be based on consideration of clinical indices. This article summarizes the inflammatory mediators and immunological events which characterize psoriatic arthritis and examines evidence for involvement of an infectious agent in its aetiology.

Arthritis, Psoriatic↗
PubMed1998

Antibodies to beta2-glycoprotein I: a potential marker for clinical features of antiphospholipid antibody syndrome in patients with systemic lupus erythematosus.

OBJECTIVE: To clarify risk factors for the development of clinical features of antiphospholipid syndrome (APS) in patients with anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). METHODS: We studied 65 SLE patients, all with positive IgG and/or IgM aCL. Patients were divided into 2 groups; I: 29 SLE patients with features of APS (SLE/APS) and II: 36 aCL positive SLE patients without any feature of APS (SLE/aCL). Serum samples were collected from our serum bank. Anti-beta2-glycoprotein I (anti-beta2-GPI) were tested by ELISA using irradiated plates in the absence of cardiolipin. Anti-dsDNA antibodies were tested by standard Farr assay. RESULTS: There were no major differences between SLE clinical manifestations in both groups. However, the frequency of IgG anti-beta2-GPI was markedly increased in SLE/APS (18/29, 62%) than in SLE/aCL (4/36, 11%) (chi-squared 18.6, p=0.0001). The levels of anti-dsDNA antibodies in the same samples were slightly lower in SLE/APS. CONCLUSION: Our data suggest that increased levels of IgG anti-beta2-GPI may be a specific feature of SLE/APS patients rather than reflecting a polyclonal B cell activation.

Adult↗
PubMed1997

Systemic lupus erythematosus. Part 2: The role of the nurse.

The second article in this series of two describes the aims of patient education, and gives an overview of the implementation and evaluation of the patient education programme in the authors' department. It focuses on what patients can do to help prevent lupus flares and how they can develop coping skills in dealing with the day-to-day problems which often face these patients. It highlights the fundamental role of the nurse specialist as a resource in providing patient education and reflects a combined approach in the overall management of patients suffering with systemic lupus erythematosus.

Humans↗
PubMed1997

Management of systemic lupus erythematosus: Part 1.

This is the first of two articles examining the management of systemic lupus erythematosus. This week's article explores the history, aetiology, symptoms and treatment of the disease and next week, the importance of patient education programmes is described.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide.

OBJECTIVE: To review our experience with low dose intravenous pulse cyclophosphamide in the treatment of patients with severe connective tissue diseases. PATIENTS: Ninety patients (68F:22M) with severe connective tissue diseases received a total of 883 cyclophosphamide pulses with 78 of 90 patients initially having weekly 500 mg pulses for a median of three (2-10) weeks. Diagnoses included: systemic lupus erythematosus (SLE) (n = 43); systemic vasculitides (n = 42); idiopathic inflammatory myopathies (n = 4); mixed essential cryoglobulinaemic vasculitis (n = 1). The median age was 48 (range 22-76) years with a median disease duration of 94 (18-250) months. RESULTS: Complete or partial remission was noted in 68 of 90 patients (75.5%) after a median follow up of 56 (5-213) months. At follow up significant median changes were noted in SLE patients: erythrocyte sedimentation rate (ESR) from 44 to 22 mm 1st hour; anti-dsDNA antibody concentrations from 81 to 48 IU/ml; proteinuria from 2.5 to 1.5 g/day; serum albumin from 36 to 40 g/l; complement C3 from 0.88 to 0.90 g/l, and C4 from 0.18 to 0.22 g/l. In the vasculitis patients significant median changes were seen in: ESR from 44 to 15 mm 1st hour; C reactive protein (CRP) from 16 to 5 g/dl; neutrophils from 8.55 to 4.3 x 10(9)/l; platelets from 340 to 261 x 10(3)/l, and haemoglobin from 12.6 to 13.2 g/dl. Patients with Churg-Strauss syndrome, Wegener's granulomatosis, and neuropsychiatric lupus showed the best initial response but 58% of Wegener's patients relapsed. Median corticosteroid doses were significantly reduced from 15 (5-60) mg to 10 (3-35) mg daily. Adverse events: infections (7 patients), neutropenia (5), lymphopenia (18), and haemorrhagic cystitis (1 intravenous and 2 oral cyclophosphamide), allergies to mesna (2). None of the women at risk had prolonged amenorrhoea. Five patients doubled their serum creatinine and five died from sepsis (2) or severe disease (3). CONCLUSION: Treatment of severe connective tissue diseases with 'low dose' intravenous cyclophosphamide pulses compares in efficacy with the higher monthly doses previously advocated. Treatment was well tolerated with fewer adverse effects and most significantly, there were no cases of premature ovarian failure.

Adult↗