PubMed Health⌕ Search

Biomedical subjects

David D'Cruz

Publications and source records attributed to David D'Cruz.

12 recordsLinked to original sources
PubMed2006

Revised British Isles Lupus Assessment Group 2004 index: a reliable tool for assessment of systemic lupus erythematosus activity.

OBJECTIVE: To test the interrater reliability of the revised British Isles Lupus Assessment Group 2004 (BILAG-2004) index for the assessment of systemic lupus erythematosus (SLE) activity. METHODS: Patients with SLE were recruited from 11 centers. Two physician raters separately assessed the patients' disease activity using the BILAG-2004 index in routine clinical practice. Scores ranged from A (for very active disease) to E (for inactivity). Two reliability exercises were performed. Changes were made to the index after the first exercise (E1), and additional training was provided to the raters before the second exercise (E2). E1 and E2 involved 12 and 14 raters, respectively. Interrater reliability was assessed using kappa statistics and intraclass correlation coefficients. Levels of agreement and the extent of major disagreement were also examined. Major disagreement was defined as a score difference between raters of A versus C, D, or E or B versus D or E. RESULTS: For each exercise, 97 patients were recruited. In E1, the mean age of the patients was 42.3 years (range 18.5-82.2 years), 89.7% were women, and 74.2% were white, 8.2% were Afro-Caribbean, and 13.4% were South Asian, and in E2, the mean age was 43.7 years (range 17.7-75 years), 90.7% were women, and 68% were white, 15.5% were Afro-Caribbean, and 11.3% were South Asian. The mean disease duration was 9.4 years (range 0-32.1 years) for patients in E1 and 10 years (range 0-34.8 years) in E2. There was improvement in the interrater reliability and the level of agreement from E1 to E2. Further improvement was achieved after removal of poorly performing items. CONCLUSION: The BILAG-2004 index is a reliable tool to assess SLE activity. The use of a well-defined glossary and training of raters are essential to ensure the optimal performance of the index.

Activities of Daily Living↗
PubMed2006

Cerebral manifestations in the antiphospholipid (Hughes) syndrome.

The importance of cerebral disease in patients with the Hughes syndrome is now becoming more widely recognized. The range of neuropsychiatric manifestations of APS is comprehensive, and includes focal symptoms attributable to lesions in a specific area of the brain as well as diffuse or global dysfunction. Patients with APS frequently present with strokes and TIA, but a wide spectrum of other neurologic features-also including non thrombotic neurologic syndromes-has been described in association with the presence of aPL. The recognition of APS has had a profound impact on the understanding and management of the treatment of CNS manifestations associated with connective tissue diseases, in particular, SLE. Many patients with focal neurologic manifestations and aPL, who a few years ago would have received high-dose corticosteroids or immunosuppression, are often successfully treated with anticoagulation. In our opinion, testing for aPL may have a major diagnostic and therapeutic impact not only in patients with autoimmune diseases and neuropsychiatric manifestations, but also in young individuals who develop cerebral ischemia, in those with atypical multiple sclerosis, transverse myelitis, and atypical seizures. We would also recommend testing for aPL for young individuals found with multiple hyperintensity lesions on brain MRI in the absence of other possible causes,especially when under the age of 40 years. It is our practice to anticoagulate patients with aPL suffering from cerebral ischemia with a target INR of 3.0 to prevent recurrences. Low-dose aspirin alone (with occasional exceptions)does not seem helpful to prevent recurrent thrombosis in these patients. Our recommendation, once the patient has had a proven thrombosis associated with aPL, is long-term (possibly life-long) warfarin therapy. Oral anti coagulation carries a risk of hemorrhage, but in our experience the risk of serious bleeding in patients with APS and previous thrombosis treated with oral anticoagulation to a target INR of 3.5 was similar to that in groups of patients treated with lower target ratios. Although a double-blind crossover trial comparing low molecular weight heparin with placebo in patients with aPL and chronic headaches did not show a significant difference in the beneficial effect of low molecular weight heparin versus placebo, in our experience selected patients with aPL and neuropsychiatric manifestations such as seizures, severe cognitive dys-function, and intractable headaches unresponsive to conventional treatment may respond to anticoagulant treatment. The neurologic ramifications of Hughes syndrome are extensive, and it behoves clinicians in all specialties to be aware of this syndrome because treatment with anticoagulation may profoundly change the outlook for these patients.

Anticoagulants↗
PubMed2004

Why do we need a new journal in autoimmunity?

A new online Journal of Autoimmune Diseases is created as an independent open access journal. In addition to the obvious advantages of the open access, the Journal will practice a double-blind reviewing of the manuscripts, which means that both the reviewers and the authors remain anonymous to each other. We believe that such a policy will reduce the influence of personal and other non-scientific factors on the reviewer's decision making.

Journal Article↗
PubMed2004

Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial.

OBJECTIVE: In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors. METHODS: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method. RESULTS: After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome. CONCLUSION: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.

Adolescent↗
PubMed2004

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus.

Animals↗
PubMed2003

Autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

BACKGROUND: Lichen sclerosus is a common acquired inflammatory disorder of skin and mucous membranes. The aetiology is unknown, although HLA-subtype susceptibility and high rates of other autoimmune disorders suggest that autoantibodies to specific mucocutaneous antigens are involved. The clinicopathological similarities between lichen sclerosus and lipoid proteinosis, which results from mutations in extracellular matrix protein 1 (ECM1), suggest this protein as an autoantigen. METHODS: We analysed serum autoantibody profiles in 171 individuals (86 with lichen sclerosus, 85 healthy controls) by immunoblotting of extracts from normal human skin and lipoid proteinosis skin (lacking ECM1). We generated a full-length glutathione-S-transferase fusion protein for ECM1 to confirm specific immunoreactivity. We affinity-purified serum from patients with lichen sclerosus and did indirect immunofluorescence microscopy on normal skin with or without preabsorption with recombinant ECM1. FINDINGS: By immunoblotting, IgG autoantibodies were found in 20 (67% [95% CI 45-84]) of 30 lichen sclerosus serum samples. The highest titre was 1 in 20. The bands were not detected in ECM1-deficient substrate. These samples, and those from 56 other patients with lichen sclerosus, showed immunoreactivity to the recombinant ECM1 protein (64 of 86 positive; 74% [65-84]). Only six (7% [2-13]) of 85 control serum samples were positive. Affinity-purified IgG from serum of patients with lichen sclerosus labelled skin similarly to a polyclonal antibody to ECM1. The positive staining was blocked by preabsorption with excess recombinant ECM1 protein. INTERPRETATION: These findings provide evidence for a specific humoral immune response to ECM1 in lichen sclerosus and offer insight into disease diagnosis, monitoring, and approaches to treatment.

Adult↗
PubMed2002

Testing for autoimmunity in humans.

A number of the autoimmune rheumatic diseases are associated with environmental factors, drugs and chemicals. The often non-specific presentation of these diseases makes early diagnosis difficult. The availability of serological markers such as autoantibodies improves diagnostic ability when taken in context with the presenting clinical features. This review focuses on some of the major autoimmune rheumatic diseases and their associated autoantibody markers.

Antibodies, Antinuclear↗
PubMed2002

Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.

OBJECTIVE: Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment. METHODS: In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed. RESULTS: Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant. CONCLUSION: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.

Adolescent↗
PubMed2002

Aerobic fitness, fatigue, and physical disability in systemic lupus erythematosus.

OBJECTIVE: To measure aerobic fitness, muscle strength, fatigue, and physical disability in patients with systemic lupus erythematosus (SLE). METHODS: Ninety-three patients with SLE and 41 sedentary controls were recruited into the study. Aerobic fitness was assessed by monitoring peak and submaximal oxygen uptake, heart rate, duration of exercise, and perceived exertion during a treadmill-walking test. Strength was measured using voluntary isometric quadriceps contraction. Symptomatic measures included physical and mental fatigue, mood, sleep, and functional incapacity. RESULTS: Compared to sedentary controls patients with SLE had significantly reduced levels of aerobic fitness (mean VO2peak SLE patients, 23.2 ml/kg/min vs controls, 29.6 ml/kg/min; p < 0.001) and reduced exercise capacity (mean exercise duration SLE patients, 10.4 min vs controls, 13.1 min; p < 0.001). The SLE patients also had reduced muscle strength (mean maximum voluntary quadriceps contraction SLE patients, 298 N vs controls, 376 N; p = 0.003). Resting lung function was also significantly worse in the SLE patients (mean FEV, SLE patients, 2.6 l vs controls, 2.9 l; p = 0.002). Fatigue (p < 0.001), depressed mood (p < 0.001), poor sleep quality (p < 0.001), and functional incapacity (p < 0.001) were all significantly greater in the SLE patients. Linear regression models suggested that physical disability correlated with aerobic fitness (p < 0.001), fatigue (p = 0.005), body mass index (p = 0.01), and depression (p = 0.05) and that fatigue correlated with depression (p < 0.001). CONCLUSION: Patients with SLE were less fit with reduced exercise capacity, reduced muscle strength, more fatigue, and greater disability compared to sedentary controls. Treatments developed to manage depression and improve aerobic fitness should be considered in the overall treatment of fatigue and disability in SLE.

Adult↗