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Query: UMLS:C0409974 (lupus)
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The ability of outcome measures to detect change over time is critical for their usefulness in clinical trials. Two concepts are applied in the assessment of evaluative instruments: We endorse the recommendation that a distinction be made between sensitivity and responsiveness. Sensitivity to change refers to the capacity of instruments to measure change statistically. Sensitivity statistics relate the magnitude of observed change to some measure of variablity and are essentially signal-to-noise ratios. Responsiveness addresses the detection of clinically relevant change. The methodology is still evolving but a common approach has been to correlate the observed change in scores with external standards that are believed to indicate clinical relevance (e.g., physician- or patient-based transition scales). Sensitivity to change and responsiveness of SLE activity indices have been addressed in a small number of studies. These indicate that the most widely used systems (SLEDAI. SLAM, BILAG) are sensitive to change although the available evidence does not allow preference for one instrument over the others. Little research has been done on the responsiveness of these measures. This article reviews the methodological concepts in measuring clinical change and summarizes reports on sensitivity and responsiveness of lupus activity scores.
Lupus 1999
PMID:Responsiveness and sensitivity to change of SLE disease activity measures. 1056 3

The aim of this study was to evaluate morphological and functional abnormalities by cerebral imaging in a series of systemic lupus erythematosus (SLE) patients with and without overt central nervous system (CNS) manifestations, and to detect possible relationships with clinical parameters and a large panel of autoantibodies, including those reactive against neurotypic and gliotypic antigens. 68 patients with SLE were investigated in a cross-sectional study which included clinical evaluation of symptoms, cerebral magnetic resonance imaging (MRI) and brain single photon emission tomography (SPECT) analysis, electroencephalography (EEG), and serological tests for antibodies directed against nuclear, cytoplasmic neuronal and glial cell-related antigens. The results of this study showed: (1) a significant positive association of (a) anti-glial fibrillary acidic protein (GFAP) serum antibodies with neuropsychiatric (NP) manifestations and (b) anti-serin proteinase 3 (anti-PR3/c-ANCA) serum antibodies with pathological cerebral SPECT; (2) the presence of significantly higher values of (a) SLICC organ damage index in patients with abnormal MRI and (b) SLAM activity index in patients with abnormal SPECT; and (3) the association of (a) abnormal MRI with nonactive NP manifestations and (b) combined abnormality of brain SPECT and MRI with the occurrence of overall overt NP manifestations and with those of the organic/major type. Neuropsychiatric manifestations, namely those of the organic/major type, appeared to be significantly associated to the presence of a serum antibody against GFAP, a gliotypic antigen. There was also evidence of an association between SPECT abnormality and the presence of anti-PR3 (c-ANCA). Furthermore, brain imaging by MRI and SPECT applied to SLE patients appears to express CNS involvement significantly related to specific categories of NP manifestations. The abnormalities detected by the two tests seem to be preferentially associated with different activity phases of the NP disorder or of the lupus disease.
Lupus 2000
PMID:Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations. 1148 Aug 54

The aim of the present study was to assess the effects of disease severity and demonstrable organ damage as risk factors for the development of osteoporosis in systemic lupus erythematosus (SLE). Sixty-four SLE patients were included. Mean disease duration was 7.7 +/- 5.7 y. Thirty-two patients had persistent organ damage, defined as SLICC-ACR damage score > or = 1. Disease activity measured by SLAM-2 ranged from 3 to 27. Bone mineral density (BMD) measurements were performed with dual X-ray absorptiometry. In addition, biochemical markers of bone metabolism were studied. BMD was inversely correlated with disease duration, damage score and cumulative glucocorticoid intake, but no correlation was found for current glucocortioid use or with markers of bone metabolism. In a multivariate analysis, body weight, disease duration and damage index fitted best for the prediction of BMD at both lumbar spine and femoral neck. Seven out of 64 patients had osteoporosis according to WHO criteria. In conclusion, severe osteoporosis is uncommon in lupus patients. Disease activity and severity were no major risk factors for loss of BMD in this study, but persistent non-bone-related organ damage was significantly linked to the presence of osteoporosis measured as decreased BMD. Our data suggest that, in addition to patients receiving glucocorticoids, patients with an SLICC-ACR > or = 1 or a disease duration > or = 7 y might benefit from regular monitoring of BMD as secondary prevention of damage.
Lupus 2001
PMID:Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage. 1178 91

The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95% confidence limits (CL) = 1.07-6.87, P < 0.04) and African-American ethnicities (OR = 3.13, 95% CL = 1.21-8.09, P < 0.02), not married or living together (OR = 3.45, 95% CL = 1.69-7.69, P < 0.0003), higher SLAM score (OR = 1.11, 95% CL = 1.02-1.19, P < 0.007), anti-dsDNA (OR = 3.14, 95% CL = 1.50-6.57, P < 0.0001) and anti-RNP (OR = 4.24, CL = 1.98-9.07, P < 0.0001) antibodies were shown to be significant predictors of the occurrence of LN. Repeated analyses excluding the patients with missing HLA data showed that absence of HLA-DQB1*0201 was also a significant predictor for the occurrence of LN (OR = 2.34, CL = 1.13-5.26, P < 0.04). In conclusion, LN occurred significantly more often in Hispanics and African-Americans with SLE. Sociodemographic, clinical and immunologic/immunogenetic factors seem to be predictive of LN occurring after the diagnosis of SLE has been made.
Lupus 2002
PMID:Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. 1200 88

Both the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) are valid and reliable measures of disease activity in systemic lupus erythematosus (SLE). However, more study of their responsiveness is needed. The purpose of this study was to compare the responsiveness of SLAM-R and SLEDAI to disease activity changes relevant to physicians and patients. Patients were evaluated monthly for up to 12 months. At each visit, the physician completed SLAM-R and SLEDAI. Patients and physicians assessed whether relevant improvement or worsening of disease activity had occurred since the previous visit. Based on repeated measurements, effect size (ES), standardized response mean (SRM), and control-standardized response mean (CSRM) were calculated for each response category, with bootstrap-based 95% confidence intervals (CIs). Seventy-six patients contributed 471 score changes. For physicians' responses, the CSRMs for SLAM-R and SLEDAI were -0.47 versus -0.42 for improvement, 0.04 versus 0.003 for no change, and 0.65 versus 0.66 for deterioration. For patients, the CSRMs for SLAM-R and SLEDAI were -0.31 versus -0.18 for improvement, -0.08 versus 0.06 for no change, and 0.48 versus 0.05 for deterioration. Only for SLAM-R did the 95% CIs exclude zero when improvement or deterioration were detected. Similar results were found for ES and SRM. Both SLAM-R and SLEDAI are responsive to changes in SLE disease activity important to physicians. Only SLAM-R is responsive to changes important to patients. These differences may result from the inclusion of subjective SLE manifestations in SLAM-R.
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PMID:Comparison of the responsiveness of lupus disease activity measures to changes in systemic lupus erythematosus activity relevant to patients and physicians. 1200 52

Serum concentrations of three angiogenic cytokines: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-18 (IL-18) and antiangiogenic factor endostatin in the serum of 52 patients with systemic lupus erythematosus (SLE) and 20 healthy subjects were investigated. The possible association between serum levels of these proteins and SLE activity as well as correlation between the concentrations of angiogenic cytokines and the level of endostatin was also analyzed. VEGF and IL-18 were detectable in all SLE patients and healthy control group. bFGF was measurable in 71.2% of patients with SLE and 65% of healthy persons. Endostatin was detectable in 94.2% of SLE patients and 95% of normal subjects. The serum levels of endostatin and bFGF were not significantly different in SLE and healthy control (P > 0.05). The median concentration of VEGF was higher in active SLE (238.4 pg/ml) than in inactive disease (118.1 pg/ml, P < 0.05) or in control group (133.5 pg/ml, P < 0.04). The median serum level of IL-18 was higher in the SLE patients (595.2 pg/ml) than in the control group (252.7 pg/ml) (P < 0.001). The correlations between the levels of angiogenic cytokines and endostatin with clinical features, laboratory abnormalities and also with the type of treatment were analysed. We found a positive correlation between VEGF serum concentration and SLE activity according to SLAM score (p = 0.275, P < 0.05). The significant positive correlation was also found between IL-18 and endostatin (p = 0.289, P < 0.04). In contrast, the correlation between bFGF and endostatin was significantly negative (p = - 0.299, P < 0.04). In conclusion, serum levels of the angiogenic and antiangiogenic factors may play an important role in SLE pathogenesis.
Lupus 2002
PMID:Circulating angiogenesis inhibitor endostatin and positive endothelial growth regulators in patients with systemic lupus erythematosus. 1213 72

Cytotoxic therapy is a cornerstone for patients with severe systemic lupus erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete remission without the need for stem cell rescue in patients with autoimmune illnesses. Here we report on our first four patients treated for severe SLE with this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day, until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two consecutive days. Disease activity as evaluated by scores from the Systemic Lupus Activity Measure-2, the SLE Disease Activity Index and the Responder Index for Lupus Erythematosus were completed before and after high-dose therapy. Before high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5) years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5 (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12-39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI decreased to 6.25 and 7.75, respectively. All patients experienced febrile neutropenia. No long-term morbidities or mortalities were observed. High dose cyclophosphamide is a therapy capable of decreasing disease severity in poor prognosis SLE patients. Future study is warranted for both refractory patients as well as primary therapy for patients with moderate to severe disease presentations.
Lupus 2002
PMID:High-dose cyclophosphamide for severe systemic lupus erythematosus. 1219 80

Due to our increasing knowledge on the pathophysiological basis of autoimmunity and the development of combined medical-obstetric clinics, pregnancy is becoming common among women with systemic lupus erythematosus (SLE). However, whether lupus worsens during pregnancy continues to be a controversial issue. SLE assessment during pregnancy is sometimes difficult due to physiological changes during this period, and common tools for measuring lupus activity during pregnancy were not available until recently. Several lupus activity scales in common use have been adapted for pregnancy [systemic lupus erythematosus in pregnancy activity index (SLEPDAI), modified lupus activity measurement (m-SLAM) and lupus activity index in pregnancy (LAI-P)]. All of them take into account the influence of pregnancy on clinical manifestation and common biochemical tests. LAI-P also accounts for specific manifestations of antiphospholipid syndrome in order not to score them as due to SLE activity. LAI-P has recently been validated for use in SLE pregnancy and could be used in future studies. However, daily assessment and management of individual pregnant women with lupus still relies on the clinical skills of attending physicians.
Lupus 2004
PMID:Evaluation of systemic lupus erythematosus activity during pregnancy. 1548 2

The objective of this study was to examine factors predictive of a decline to low levels of disease activity in a cohort of systemic lupus erythematosus (SLE) patients. Patients with SLE of Hispanic (from Texas or Puerto Rico), African-American or Caucasian ethnicity from a multiethnic cohort were included. A decline to low levels of disease activity was defined as a score < or =5 as per the Systemic Lupus Activity Measure-Revised (SLAM-R) at any annual study visit if preceded by a SLAM-R > or =8. Using Generalized Estimating Equation (GEE), socioeconomic-demographic, behavioral, function, psychological, laboratory and clinical data [disease manifestations, number of ACR criteria accrued at diagnosis and damage accrual as per the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI)] from the visit preceding that meeting the definition were examined as predictors of decline to low levels of disease activity. Two-hundred and eighty-seven patients (67 Hispanics from Texas, 32 Hispanics form Puerto Rico, 120 African-Americans and 68 Caucasians), accounting for 632 visits were analyzed. In the GEE multivariable analysis, higher degrees of social support (OR = 1.208, 95% CI 1.059-1.379; P = 0.005) were predictive of a decline to low levels of disease activity, while the number of ACR criteria accrued at diagnosis (OR = 0.765, 95% CI 0.631-0.927; P = 0.006) and damage (OR = 0.850, 95% CI 0.743-0.972, P = 0.018) were negatively associated. These data suggest that a decline to low levels of disease activity in lupus patients seems to be multifactorial; this study also underscores the importance of social support for lupus patients.
Lupus 2006
PMID:Systemic lupus erythematosus in a multiethnic U.S. cohort (LUMINA) XXVII: factors predictive of a decline to low levels of disease activity. 1648 40

Defective invariant natural killer T-cells (iNKT cells) have been implicated in the etiology of type 1 diabetes in nonobese diabetic (NOD) mice. In a genome scan of a cross between NOD and C57BL/6 mice, the most significant locus controlling the number of iNKT cells, referred to as Nkt1, was recently mapped to distal chromosome 1. Here, using congenic mice for this chromosomal segment, we definitively demonstrate the existence of Nkt1 and show that introgression of the C57BL/6 allele onto the NOD background improves both the number of iNKT cells and their rapid production of cytokines elicited by alpha-galactosylceramide treatment, explaining at least half of the difference between the NOD and C57BL/6 strains. Using new subcongenic lines, we circumscribed the Nkt1 locus to a 8.7-cM segment, between the NR1i3 and D1Mit458 markers, that notably includes the SLAM (signaling lymphocytic activation molecule) gene cluster, recently involved in murine lupus susceptibility. However, despite a significant correction of the iNKT cell defect, the Nkt1 locus did not alter the course of spontaneous diabetes in congenic mice. Our findings indicate a complex relationship between iNKT cells and autoimmune susceptibility. Congenic lines nonetheless provide powerful models to dissect the biology of iNKT cells.
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PMID:Genetic and functional analysis of the Nkt1 locus using congenic NOD mice: improved Valpha14-NKT cell performance but failure to protect against type 1 diabetes. 1656 43


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