Wiley
0004-3591
1529-0131
Cơ quản chủ quản: N/A
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Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy Abstract Objective To evaluate predictors of vertebral fractures, including a threshold for bone mineral density (BMD), in patients receiving oral glucocorticoids (GCs). Methods Data were obtained from 2 randomized clinical trials (prevention and treatment trials of risedronate) using similar methods, but different inclusion criteria were applied with regard to prior exposure to GCs. Predictors of vertebral fracture in the placebo group were identified using Cox regression with forward selection. The BMD threshold analysis involved a comparison of the 1‐year fracture risk in postmenopausal women receiving placebo in the GC trials with that in postmenopausal women not taking GCs in 3 other trials. Results The study population comprised 306 patients with baseline and 1‐year followup data on vertebral fractures (111 receiving placebo and 195 receiving risedronate). In the placebo group, the statistically significant predictors of incident fracture were the baseline lumbar spine BMD (for each 1‐point decrease in T score, relative risk [RR] 1.85, 95% confidence interval [95% CI] 1.06–3.21) and the daily GC dose (for each 10‐mg dose increase, RR 1.62, 95% CI 1.11–2.36). In the BMD threshold analysis, compared with nonusers of GCs, patients receiving GCs were younger, had a higher BMD at baseline, and had fewer prevalent fractures; nevertheless, the risk of fracture was higher in the GC users compared with nonusers (adjusted RR 5.67, 95% CI 2.57–12.54). The increased risk of fracture was observed in GC users regardless of whether osteoporosis was present. Conclusion The daily, but not cumulative, GC dose was found to be a strong predictor of vertebral fracture in patients receiving GCs. At similar levels of BMD, postmenopausal women taking GCs, as compared with nonusers of GCs, had considerably higher risks of fracture.
Tập 48 Số 11 - Trang 3224-3229 - 2003
Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids Abstract Objective . To assess the effect of hormone replacement therapy (HRT) on bone mass in rheumatoid arthritis (RA) patients treated with and those not treated with steroids.Methods . Two hundred postmenopausal women with RA (ages 45‐65 years) were randomly allocated to receive transdermal estradiol (hormone replacement therapy; HRT) (50 μg daily) or calcium supplementation (400 mg daily) for 2 years. Forty‐two of the patients (21%) were taking corticosteroids. Bone mineral density of the lumbar spine (BMDLS) and of the proximal femur (BMDF) was measured at study entry and at 12 months and 24 months.Results . In the HRT group overall, mean BMDLS had changed by +2.22% (95% confidence interval [95% CI] +0.72, +3.72) and mean BMDF by −0.41 % (95% CI −1.89, +1.07) after 24 months. In the calcium group, mean BMDLS changed by −1.19% (95% CI −2.29, −0.09) and mean BMDF by −0.56% (95% CI −2.60, +1.48). Differences between treatment groups were significant for the spine only (P < 0.001). In the 21 HRT‐treated patients taking steroids, BMDLS increased by 3.75% (95% CI +0.72, +6.78) and BMDF by 1.62% (95% CI −1.27, +4.51).Conclusion . This study shows that HRT increases spinal BMD and maintains femoral BMD in postmenopausal RA. HRT is also an effective agent in preserving bone mass in patients taking low‐dose corticosteroids.
Tập 37 Số 10 - Trang 1499-1505 - 1994
Cardiac involvement in polymyositis Abstract Cardiac involvement in polymyositis was investigated in 20 autopsied cases. Clinically, 13 of 18 patients had abnormal electrocardiograms, and 9 of the 20 patients had previous evidence of congestive heart failure. Histologically documented myocarditis was detected in 6 patients (4 with congestive heart failure and 2 without), 4 of whom also had small vessel disease of the myocardium. Patients with polymyositis may have a cardiopathy in the absence of overt myocardial inflammatory disease.
Tập 22 Số 10 - Trang 1088-1092 - 1979
Pivotal role of connective tissue growth factor in lung fibrosis: MAPK‐dependent transcriptional activation of type I collagen Abstract Objective Connective tissue growth factor (CTGF; CCN2) is overexpressed in systemic sclerosis (SSc) and has been hypothesized to be a key mediator of the pulmonary fibrosis frequently observed in this disease. CTGF is induced by transforming growth factor β (TGFβ) and is a mediator of some profibrotic effects of TGFβ in vitro. This study was undertaken to investigate the role of CTGF in enhanced expression of type I collagen in bleomycin‐induced lung fibrosis, and to delineate the mechanisms of action underlying the effects of CTGF on Col1a2 (collagen gene type I α2) in this mouse model and in human pulmonary fibroblasts. Methods Transgenic mice that were carrying luciferase and β‐galactosidase reporter genes driven by the Col1a2 enhancer/promoter and the CTGF promoter, respectively, were injected with bleomycin to induce lung fibrosis (or saline as control), and the extracted pulmonary fibroblasts were incubated with CTGF blocking agents. In vitro, transient transfection, promoter/reporter constructs, and electrophoretic mobility shift assays were used to determine the mechanisms of action of CTGF in pulmonary fibroblasts. Results In the mouse lung tissue, CTGF expression and promoter activity peaked 1 week after bleomycin challenge, whereas type I collagen expression and Col1a2 promoter activity peaked 2 weeks postchallenge. Fibroblasts isolated from the mouse lungs 14 days after bleomycin treatment retained a profibrotic expression pattern, characterized by greatly elevated levels of type I collagen and CTGF protein and increased promoter activity. In vitro, inhibition of CTGF by specific small interfering RNA and neutralizing antibodies reduced the collagen protein expression and Col1a2 promoter activity. Moreover, in vivo, anti‐CTGF antibodies applied after bleomycin challenge significantly reduced the Col1a2 promoter activity by ∼25%. The enhanced Col1a2 promoter activity in fibroblasts from bleomycin‐treated lungs was partly dependent on Smad signaling, whereas CTGF acted on the Col1a2 promoter by a mechanism that was independent of the Smad binding site, but was, instead, dependent on the ERK‐1/2 and JNK MAPK pathways. The CTGF effect was mapped to the proximal promoter region surrounding the inverted CCAAT box, possibly involving CREB and c‐Jun. In human lung fibroblasts, the human COL1A2 promoter responded in a similar manner, and the mechanisms of action also involved ERK‐1/2 and JNK signaling. Conclusion Our results clearly define a direct profibrotic effect of CTGF and demonstrate its contribution to lung fibrosis through transcriptional activation of Col1a2. Blocking strategies revealed the signaling mechanisms involved. These findings show CTGF to be a rational target for therapy in fibrotic diseases such as SSc.
Tập 60 Số 7 - Trang 2142-2155 - 2009
Secondary gait changes in patients with medial compartment knee osteoarthritis: Increased load at the ankle, knee, and hip during walking Abstract Objective This study tested the hypothesis that gait changes related to knee osteoarthritis (OA) of varied severity are associated with increased loads at the ankle, knee, and hip. Methods Forty‐two patients with bilateral medial compartment knee OA and 42 control subjects matched for sex, age, height, and mass were studied. Nineteen patients had Kellgren/Lawrence (K/L) radiographic severity grades of 1 or 2, and 23 patients had K/L grades of 3 or 4. Three‐dimensional kinematics and kinetics were measured in the hip, knee, and ankle while the subjects walked at a self‐selected speed. Results Patients with more severe knee OA had greater first peak knee adduction moments than their matched control subjects (P = 0.039) and than patients with less severe knee OA (P < 0.001). All patients with knee OA made initial contact with the ground with the knee in a more extended position than that exhibited by control subjects. An increased axial loading rate was present in all joints of the lower extremity. Patients with more severe knee OA had lower hip adduction moments compared with their matched control subjects. Conclusion The secondary gait changes observed among patients with knee OA reflect a potential strategy to shift the body's weight more rapidly from the contralateral limb to the support limb, which appears to be successful in reducing the load at the knee in only patients with less severe knee OA. The increased loading rate in the lower extremity joints may lead to a faster progression of existing OA and to the onset of OA at joints adjacent to the knee. Interventions for knee OA should therefore be assessed for their effects on the mechanics of all joints of the lower extremity.
Tập 52 Số 9 - Trang 2835-2844 - 2005
Inflammatory back pain in ankylosing spondylitis: A reassessment of the clinical history for application as classification and diagnostic criteria Abstract Objective Back pain associated with ankylosing spondylitis (AS) is referred to as inflammatory back pain (IBP). The value of the clinical history in differentiating IBP from mechanical low back pain (MLBP) has been investigated in only a few studies. In this exploratory study, we sought to evaluate the individual features of IBP and to compose and compare various combinations of features for use as classification and diagnostic criteria. Methods We assessed the clinical history of 213 patients (101 with AS and 112 with MLBP) younger than 50 years who had chronic back pain. Single clinical parameters and combinations of parameters were compared between the AS and MLBP patient groups. Results Morning stiffness of >30 minutes' duration, age at onset of back pain, no improvement in back pain with rest, awakening because of back pain during the second half of the night only, alternating buttock pain, and time period of the onset of back pain were identified as independent contributors to IBP. Importantly, none of the single parameters sufficiently differentiated AS from MLBP. In contrast, several sets of combined parameters proved to be well balanced between sensitivity and specificity. Among these, a new candidate set of criteria for IBP, which consisted of morning stiffness of >30 minutes' duration, improvement in back pain with exercise but not with rest, awakening because of back pain during the second half of the night only, and alternating buttock pain, yielded a sensitivity of 70.3% and a specificity of 81.2% if at least 2 of these 4 parameters were fulfilled (positive likelihood ratio 3.7). If at least 3 of the 4 parameters were fulfilled, the positive likelihood ratio increased to 12.4. Conclusion A new set of criteria for IBP performed better than previous criteria in AS patients with established disease. A prospective study is needed to validate the diagnostic properties of the new candidate criteria set in patients with early disease.
Tập 54 Số 2 - Trang 569-578 - 2006
The 1982 revised criteria for the classification of systemic lupus erythematosus Abstract The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.
Tập 25 Số 11 - Trang 1271-1277 - 1982
Severe valvular regurgitation and antiphospholipid antibodies in systemic lupus erythematosus: A prospective, long-term, followup study
Tập 53 Số 3 - Trang 460-467 - 2005
Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus Abstract Objective Umbilical cord (UC)–derived mesenchymal stem cells (MSCs) have shown marked therapeutic effects in a number of diseases in animal studies, based on their potential for self‐renewal and differentiation. No data are available on the effectiveness of UC MSC transplantation (MSCT) in human autoimmune disease. This study was undertaken to assess the efficacy and safety of allogeneic UC MSCT in patients with severe and treatment‐refractory systemic lupus erythematosus (SLE). Methods We conducted a single‐arm trial that involved 16 SLE patients whose disease was refractory to standard treatment or who had life‐threatening visceral involvement. All of the patients gave consent and underwent UC MSCT. Clinical changes were evaluated before and after transplantation using the SLE Disease Activity Index (SLEDAI), measurement of serum antinuclear antibody (ANA), anti–double‐stranded DNA (anti‐dsDNA) antibody, serum complement C3 and C4, and albumin levels, and assessment of and renal function. Evaluation of potential mechanisms of MSCT effects focused on the percentage of peripheral blood Treg cells and serum levels of cytokines. Results From April 2007 to July 2009, a total of 16 patients with active SLE were enrolled and underwent UC MSCT. The median followup time after MSCT was 8.25 months (range 3–28 months). Significant improvements in the SLEDAI score, levels of serum ANA, anti‐dsDNA antibody, serum albumin, and complement C3, and renal function were observed. Clinical remission was accompanied by an increase in peripheral Treg cells and a re‐established balance between Th1‐ and Th2‐related cytokines. Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment‐related deaths. Conclusion Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines. These data provide a foundation for conducting a randomized controlled trial of this new therapy for severe and treatment‐refractory SLE.
Tập 62 Số 8 - Trang 2467-2475 - 2010
Cellular infiltrates in scleroderma skin Abstract The purpose of this study was to determine the frequency, distribution, and nature of cellular infiltrates in 108 skin biopsies from patients with systemic scleroderma (SS) and localized scleroderma (LS). Cellular infiltrates, perivascular or diffuse, were noted in 49% of SS and 84% of LS patients and consisted of lymphocytes, plasma cells, and macrophages. No correlation was noted between the presence or severity of skin cellular infiltrates and serum serologic abnormalities.
Tập 20 Số 4 - Trang 975-984 - 1977