Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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16508967 | Treatment of murine collagen-induced arthritis by the stress protein BiP via interleukin-4 | 2006 Mar | OBJECTIVE: Following the demonstration that the stress protein, BiP, prevented induction of collagen-induced arthritis (CIA) in HLA-DRB*0101+/+ (HLA-DR1+/+) mice, we investigated the immunotherapeutic ability of BiP to suppress disease during the active phase of CIA in HLA-DR1+/+ and DBA/1 mice. METHODS: BiP was administered either subcutaneously or intravenously to DBA/1, HLA-DR1+/+, or interleukin-4 (IL-4)-knockout mice at the onset of arthritis. Immune cells were used in adoptive transfer studies or were restimulated in culture with BiP or type II collagen (CII). Proliferation and cytokine release were measured. In addition, serum anti-CII antibodies were measured by enzyme-linked immunosorbent assay. Disease progression was scored using a visual analog scale. RESULTS: BiP was successful in suppressing established CIA in HLA-DR1+/+ and DBA/1 mice. Serum levels of anticollagen IgG antibodies were reduced in BiP-treated mice. T cells from BiP-immunized mice produced Th2 cytokines, in particular, IL-4. Treatment with BiP was also shown to increase the production of CII-specific IL-5, IL-10, and interferon-gamma at the termination of the study. Development of severe CIA was prevented by the intravenous transfer of BiP-specific cells at the time of CIA induction in HLA-DR1+/+ mice or by transferring BiP-specific cells to DBA/1 mice at the onset of disease. BiP failed to ameliorate the development of CIA in IL-4-/-, HLA-DR1+/+ mice. CONCLUSION: These novel results show that BiP can suppress active CIA by the induction of regulatory cells that act predominantly via IL-4. Thus, BiP is a potential immunotherapeutic agent for the treatment of patients with rheumatoid arthritis. | |
16972811 | The health effects of at-home written emotional disclosure in fibromyalgia: a randomized t | 2006 Oct | BACKGROUND: The presence and severity of the chronic pain syndrome fibromyalgia (FM) is associated with unresolved stress and emotional regulation difficulties. Written emotional disclosure is intended to reduce stress and may improve health of people with FM. PURPOSE: This study tests the effects of at-home, written emotional disclosure about stressful experiences on the health of people with FM and uses multiple follow-ups to track the time course of effects of disclosure. METHODS: Adults with FM (intention-to-treat, n=83; completers, n=72) were randomized to write for 4 days at home about either stressful experiences (disclosure group) or neutral time management (control group). Group differences in immediate mood effects and changes in health from baseline to 1-month and 3-month follow-ups were examined. RESULTS: Written disclosure led to an immediate increase in negative mood, which did not attenuate across the 4 writing days. Repeated-measures analyses from baseline to each follow-up point were conducted on both intention-to-treat and completer samples, which showed similar outcomes. At 1 month, disclosure led to few health benefits, but control writing led to less negative affect and more perceived support than did disclosure. At 3-month follow-up, these negative affect and social support effects disappeared, and written disclosure led to a greater reduction in global impact, poor sleep, health care utilization, and (marginally) physical disability than did control writing. Interpretation of these apparent benefits needs to be made cautiously, however, because the disclosure group had somewhat poorer health than controls at baseline and the control group showed some minor worsening over time. CONCLUSIONS: Written emotional disclosure can be conducted at home, and there is tentative evidence that disclosure benefits the health of people with FM. The benefits, however, may be delayed for several months after writing and may be of limited clinical significance. | |
16931026 | Five-year results of the Sigma total knee arthroplasty. | 2006 Oct | The DePuy Sigma total knee arthroplasty (TKA) was introduced in 1997 as a modification of the Press Fit Condylar Knee (PFC) TKA and has been used extensively in the United Kingdom and worldwide. It is the most commonly used TKA in England and Wales, where it accounts for 36% of all primary TKA. The PFC was well established, with reported 10-year survival rates of 93-97%, but this study reports the first 5-year clinical and radiographic follow-up data for the Sigma TKA. Over a 10-month period, 212 Sigma TKAs were performed in 180 patients. Patients were seen at a specialist nurse-led clinic 7 to 10 days before admission and at 6 months, 18 months, 3 years and 5 years after surgery. Data were recorded prospectively at each visit. Radiographs were obtained at the 5-year follow-up appointment. Of 212 knees, 178 (151 patients) were alive at 5 years. Three were lost to follow up. Six knees (3.0%) were revised, five for infection and one underwent change of polyethylene insert at 4.9 years. Five-year survival with an endpoint of revision for any reason was 97.0%; with an endpoint of revision for aseptic failure it was 99.5%. The median American Knee Society knee rating score was 93 out of 100 at 5 years compared with 25 out of 100 at admission. Of 147 radiographs, none showed radiographic loosening of either component. Seventeen (11.6%) showed radiolucent lines. Twenty-eight (19.0%) had alignment outside the range of 7+/-3 degrees valgus. These results suggest that the Sigma TKA gives acceptable clinical results after 5 years. Further follow-up studies are required to see if this performance is maintained in the long term. | |
17091247 | FcgammaRII and multi-system autoimmune disease. | 2006 Dec | The FcR are a crucial link in the immune response between humoral and cellular immunity and cell-based effector systems, mediating a wide variety of physiological and biochemical responses. The FcR for IgG (FcgammaR) and in particular the most widely expressed of these, FcgammaRII, are important in regulating adaptive immunity. Disruption of their function is a key factor in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by chronic, multi-organ inflammation. Studies of the FcgammaRII include structure/function relationships, investigation of the associations between FcR polymorphisms and human disease and animal studies using knockout or transgenic mouse models. These investigations showed that the various forms of FcgammaRII interact with immune complexes to either initiate or inhibit inflammation. In conjunction with environmental antigens and genotype, the FcgammaRII activating and inhibitory receptors determine the nature and magnitude of response to antigens. In this review, the structure and function of the FcgammaRIIs and their role in immune complex-mediated auto-immunity are discussed. | |
15860509 | Comparison of different definitions to classify remission and sustained remission: 1 year | 2005 Nov | OBJECTIVE: To assess methods to calculate achieving and sustaining remission in a double blind randomised trial in patients with RA who received etanercept, methotrexate, or an etanercept/methotrexate combination. METHODS: Remission was defined as DAS <1.6, DAS28 <2.6, and ACR70 response. Sustaining remission was analysed in three ways: (a) analysis of sustained DAS remission, DAS28 remission, or ACR70 response continuously for 6 months; (b) analysis of sustained remission appraised through a continuity rewarded scoring system, which is the weighted sum of all intervals in the study in which patients are in DAS or DAS28 remission; or (c) longitudinal modelling of remission odds using generalised estimating equations. RESULTS: Significantly more patients treated with the etanercept/methotrexate combination reached DAS remission (37%) than those treated with either methotrexate (14%) or etanercept (18%) alone (p<0.01). Results for DAS28 and for the ACR70 response were similar. Agreement between DAS remission and DAS28 remission was good, but agreement between either of these and the ACR70 response was less. Patients in DAS or DAS28 remission had a lower level of disease activity (fewer active joints, lower ESR) than those achieving ACR70 response; the converse was seen using pain VAS. The three methods were comparable for sustainability of remission and showed significant advantage for combination therapy, which increased the number and durability of remission periods. CONCLUSIONS: DAS and DAS28 remission results were similar for assessing achieving and sustaining remission in RA, frequently differing from patients classified as ACR70 responders. The three methods of examining duration of remission produced comparable results. | |
15630719 | Longterm outcome of treatment of Felty's syndrome with intramuscular gold: case reports an | 2005 Jan | OBJECTIVE: To evaluate the incidence, complications, and course of Felty's syndrome (FS) in patients treated with intramuscular (IM) gold. METHODS: Retrospective chart review of all FS cases (1979 to 2003) was conducted in the Mary Pack Arthritis Centre (MPAC) gold clinic. FS was diagnosed if patients had rheumatoid arthritis (RA; American College of Rheumatology criteria) and persistent leukopenia [white blood cell (WBC) count < 4] in the absence of other known causes of leukopenia. Splenomegaly was not part of the inclusion criteria. RESULTS: Thirteen patients with FS were identified in the gold clinic population. The mean age at diagnosis of FS was 58.7 years and the mean duration of RA at time of diagnosis was 6.9 years. The weekly dose of gold ranged from 10 mg to 50 mg depending on tolerability. Gold therapy resulted in normalization of the WBC count in 9 of 13 patients. The mean time to normalization of the WBC was 40 weeks. Only one patient with FS had experienced recurrent infectious complications from FS, and this did not recur after gold treatment was initiated. No patient had vasculitis. CONCLUSION: In our gold clinic population FS is a mild disease and is rarely associated with infectious complications. Gold is an effective treatment of FS. | |
16128193 | [The efficacy of selective Cox-2-inhibitors in comparison with conventional NSAIDs]. | 2005 Aug 4 | The currently approved coxibs celecoxib and etoricoxib, have an equivalent effect in comparison with conventional NSAIDs. This has been established both in comparative studies and by several years of practical application. While celecoxib is approved only for the symptomatic treatment of arthrosis and rheumatoid arthritis, etoricoxib can also be employed in the treatment of acute attacks of gout. | |
17037405 | [Gastropleural fistula due to perforated gastric ulcer]. | 2006 Sep | A 65-year-old woman, who had been taking non-steroidal anti-inflammatory drugs (NSAIDs), prednisolone and methotrexate for rheumatiod arthritis, was admitted to our hospital with a sudden onset of left-back and chest pain and breathlessness. A chest radiograph and computed tomography revealed a left-side pneumothorax and pleural effusion. Chest tube was inserted for drainage and the fluid was formed to contain food residuum. Contrast radiography demonstrated escape of soluble contrast medium into the left pleural space. A thoracotomy and transdiaphragmatic revealed a gastropleural fistula. It was repaired and the gastric origin was resected. Pathologic evaluation revealed evidence of chronic peptic ulceration, but no malignant change. Gastropleural fistula due to peptic ulcer without esophageal herniation, malignancy, or traumatic injury is extremely unusual. The cause of the focal adhesion of the gastric ulcer and diaphragm, fistula formation was not certain but was probably related to the ingestion of NSAIDs in combination with prednisolone and other immunosuppressive agents. Although gastropleural fistula is rare, the prognosis in such patients related to early diagnosis and surgical intervention, emphasizing the importance of including this condition when making a differential diagnosis. | |
17053321 | Effects of insulin-like growth factor I on transforming growth factor beta1 induced chondr | 2006 | The aim of this study was to demonstrate the induction of chondrogenesis by transforming growth factor (TGF)-beta1 from synovium-derived mesenchymal stem cells in a three-dimensional polyglycolic acid (PGA) scaffold, and to evaluate the effects of insulin-like growth factor (IGF)-I on TGF-beta1-induced chondrogenesis. Adult human synovial membranes were obtained from the knees of patients with osteoarthritis or rheumatoid arthritis. Cells were expanded in monolayers, seeded onto a PGA scaffold, and cultured for 4 or 8 weeks in chondrogenic medium containing TGF-beta1 with or without IGF-I. As a control, the cells were cultured in chondrogenic medium without TGF-beta1. The glycosaminoglycan content was quantified using dimethylmethylene blue dye-binding assay, and the DNA content was measured fluorometrically. Histological examination was also performed using safranin-O staining. The expression of mRNA for aggrecan and collagen type II was confirmed by RT-PCR. After 4 weeks of cultivation with TGF-beta1, the cells differentiated to a chondrocytic phenotype, and these chondrogeneses were more potent when cultured for 8 weeks. The combination of IGF-I and TGF-beta1 produced higher amounts of glycosaminoglycan than TGF-beta1 alone at 8 weeks. In conclusions, chondrogenesis from human synovium-derived mesenchymal cells was identified, and IGF-I plays a role in maintaining the extracellular matrix in combination with TGF-beta1. | |
16944142 | ACL reconstruction and the implication of its tibial attachment for stability of the joint | 2007 Aug | The planar topography of the anterior cruciate ligament (ACL) insertion was investigated and correlated to the use of the double-bundle/double tibial tunnel ACL reconstruction technique within the ACL tibial insertion area. The anteroposterior and mediolateral length of the tibial ACL attachment and the distances of the tibial insertion area from the anterior and posterior tibial borders were measured and the stability of the joint was tested using the double-bundle/double tibial tunnel ACL reconstruction technique. The anteroposterior length, 19.54 mm in men and 17.36 mm in women, of the ACL insertion, averaged approximately 40% of the total intercondylar anteroposterior dimension of the plateau. This broad distribution of insertion fibres ensures ligament tension and hence joint stability. The reported anteroposterior broad insertion of ACL fibres to the tibia is not sufficiently reproduced by the use of one or more bundles having a common tibial tunnel for the ACL reconstruction. In our view, this might be better achieved with two different bundles, with separate tunnels, and independent tensioning in different knee angles. This technique might achieve better results in human knee stability as opposed to other reported techniques. | |
17024157 | Acromegaly diagnosed in a young woman presenting with headache and arthritis. | 2006 Oct | BACKGROUND: A 38-year-old woman presented with severe headaches to her primary-care physician. The patient had been diagnosed with rheumatoid arthritis and had begun having headache 4 years previously. An MRI scan revealed an 11-12 mm pituitary tumor. Her physical examination was unremarkable for the classic acral or facial changes characteristic of acromegaly, and she was referred for neuroendocrine consultation for a presumed nonfunctioning adenoma. INVESTIGATIONS: MRI of the pituitary, and laboratory investigations that included measurement of serum insulin-like growth factor 1 (IGF1) and prolactin levels. DIAGNOSIS: In view of the elevated level of IGF1 and presence of a pituitary adenoma, the patient was diagnosed with acromegaly caused by a pituitary adenoma that secretes growth hormone. MANAGEMENT: The patient underwent trans-sphenoidal surgery, which resulted in resolution of joint pain and headache, eradication of the tumor mass, normal IGF1 levels, and appropriate suppression of growth hormone (confirmed by oral glucose tolerance test postoperatively). | |
16301499 | Increased frequency of restless legs syndrome in a French-Canadian population with multipl | 2005 Nov 22 | The authors evaluated the co-occurrence of multiple sclerosis (MS) and restless legs syndrome (RLS) using an RLS questionnaire. They evaluated 200 patients with MS, 100 with rheumatoid arthritis (RA), and 100 controls, all French-Canadians. They found that 37.5% of MS patients, 31% of RA patients, and 16% of controls fulfilled the criteria for RLS. MS can cause RLS, or MS and RLS may have common susceptibility factors. | |
16505706 | Clinical correlation with the PA/plasmin system in septic arthritis of the knee. | 2006 Jun | Substantially more gelatinases appear in effusions of septic arthritis than in effusions of aseptic arthritis. We hypothesized there is greater plasminogen activator/plasmin activity in effusions of septic arthritis than aseptic arthritis. We examined the antigenic values of urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1, cell counts, and levels of matrix metalloproteinase-2 and metalloproteinase-9 in 135 knee effusions from 80 patients with septic arthritis, rheumatoid arthritis, gouty arthritis, and osteoarthritis. Urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1 antigenic values in effusions of septic arthritis were greater than those in effusions of aseptic arthritis. The increases of urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1 antigenic values in effusions were associated with increased levels of prometalloproteinase-9 and the appearance of activated metalloproteinase-2. Antigenic values of urokinase-type plasminogen activator also correlated with the appearance of activated metalloproteinase-9. High plasminogen activator/plasmin activity, prometalloproteinase-9 levels, and the presence of activated metalloproteinase-2 and metalloproteinase-9 in effusions from replaced knees should increase suspicion of infection regardless of neutrophil counts. Joint aspiration reduces bacteria counts, endotoxins, proinflammatory cytokines, and matrix metalloproteinase. It also decreases the plasminogen activator/plasmin activity in effusions that may play a part in extracellular matrix destruction. LEVEL OF EVIDENCE: Diagnostic study, Level III (study of nonconsecutive patients without consistently applied reference "gold" standard). See the Guidelines for Authors for a complete description of levels of evidence. | |
15778239 | Transdifferentiation of polymorphonuclear neutrophils to dendritic-like cells at the site | 2005 Oct | OBJECTIVES: To investigate infiltrated cells in the synovial fluid (SF) of inflamed joints of patients with rheumatoid arthritis (RA), with special reference to polymorphonuclear neutrophils (PMN) and their interaction with T cells. METHODS: Expression on PMN of activation associated receptors CD14, CD64, CD83, and major histocompatibility complex (MHC) class II was examined in the SF of 15 patients with RA, as were the infiltrated T cells. SF cytokines were determined by enzyme linked immunosorbent assay (ELISA). To mimic the in vivo situation, co-culture experiments were carried out using PMN and T cells of healthy donors. RESULTS: The SF contained activated T lymphocytes and abundant PMN. SF PMN expression of CD14 and CD64 was enhanced compared with peripheral blood. Of special interest was the observation that only the SF PMN expressed MHC class II antigens and CD83. Exposure to SF, which contained considerable amounts of cytokines (for example, interferon gamma (IFNgamma), tumour necrosis factor alpha, and interleukin 2), induced a similar receptor pattern on blood derived PMN of healthy donors. Furthermore, PMN acquired MHC class II and CD83 within 24 to 48 hours, when co-cultured with autologous T cells or T cell lines. This effect was also achieved by T cell supernatants, was dependent on protein synthesis, and could be inhibited by antibodies against IFNgamma. CONCLUSIONS: SF PMN from patients with RA undergo major alterations, including transdifferentiation to cells with dendritic-like characteristics, probably induced by T cell derived cytokines. Because MHC class II positive PMN are known to activate T cells, the mutual activation of PMN and T cells might contribute to the perpetuation of the local inflammatory process, and eventually to the destructive process in RA. | |
16896990 | Serious infections under treatment with TNF-alpha antagonists compared to traditional DMAR | 2006 Nov | Biological treatments aiming to neutralize TNF-alpha (tumour necrosis factor alpha) (infliximab, adalimumab and etanercept) are increasingly used to treat rheumatoid arthritis (RA). Although increased frequency has not been observed in randomized clinical trials with TNF-alpha antagonist agents, postmarketing surveillance suggests that infections might be serious consequences of these therapies. Our aim was to compare infections in patients with RA under treatment with disease-modifying antirheumatic drugs (DMARDs) and TNF-alpha antagonists in a university outpatient rheumatology clinic in Turkey. A total of 130 RA patients treated with DMARDs and 48 treated with TNF-alpha antagonists were analysed for the incidence of infections. Patients taking TNF-alpha antagonists were also reviewed for infections before these therapies. The incidence of serious infections was 7/100 patient-years before TNF-alpha antagonists and 8.6/100 patient-years in DMARDs group. The incidence rose to 17/100 patient-years during therapy with TNF-alpha antagonists. In patients with RA on routine follow-up, treatment with TNF-alpha antagonists seems to carry an increased risk of infections compared to traditional DMARDs. | |
16487722 | The effects of leflunomide on clinical parameters and serum levels of IL-6, IL-10, MMP-1 a | 2006 Jan 21 | OBJECTIVE: The purpose of this open pilot study was to assess possible mechanisms of the effects of leflunomide by studying the influence of the drug on the serum levels of MMP-1, MMP-3, IL-10, IL-6 and their possible correlation with clinical disease parameters. PATIENTS AND METHODS: Thirty patients with long standing active rheumatoid arthritis were enrolled in this study. All patients failed at least 5 DMARDs in the past and were on stable treatment for at least 3 months before starting the protocol. The patients received a loading dose of 100 mg for 3 days followed by 20 mg/day thereafter and followed up monthly for 6 months. Disease activity was assessed at baseline, 2 weeks, and every month of therapy thereafter using the following variables: tender joint count, swollen joint count, morning stiffness duration, pain, tiredness, physician's and patient's global assessment, using VAS, ESR and CRP. Clinical effects of the treatment regimen were calculated using the American College of Rheumatology (ACR) criteria for clinical response. Adverse events were recorded. Serum levels of MMP-1, MMP-3, IL-10 and IL-6 were measured before and 3 months after starting the protocol. RESULTS: Except for tiredness, a statistically significant improvement in all clinical and laboratory parameters of disease activity was reached after 3 months. At this time point the ACR-20 response rate was 46.2%. The levels of MMP-1, MMP-3, IL-6 and IL-10 decreased significantly after 3 months. A statistically significant correlation between serum levels of MMP-1, IL-10 and IL-6 and clinical and laboratory parameters was also shown. After 6 months, 16 out of 30 patients withdrew from the study [adverse events (35.4%), lack of efficacy (9.7%), and low compliance (6.4%)]. CONCLUSIONS: Leflunomide was clinically efficacious in this group of long standing resistant RA in an open study "real life" design. These results comply with those reported in previous clinical trials. Serum MMP-1, MMP-3, IL-10 and IL-6 levels decreased significantly. Despite high withdrawal rate, no serious adverse effects were recorded. | |
16583466 | A phase I study assessing the safety, clinical response, and pharmacokinetics of an experi | 2006 May | OBJECTIVE: To assess safety, clinical response, and pharmacokinetics of subcutaneous (SC) and intramuscular (IM) doses of an experimental formulation of infliximab [including experimental SC doses following administration of commercially-formulated intravenous (IV) infliximab] in patients with rheumatoid arthritis (RA) refractory to methotrexate. METHODS: In this randomized, open-label, 3-stage design, 43 subjects were enrolled in 7 dose groups. In Stage I, 15 subjects received single SC doses of 0.5, 1.5, or 3.0 mg/kg. In Stage II, 21 subjects received one of 3 regimens: 100 mg SC every 2 weeks (3 injections); 3 mg/kg commercially-formulated IV infliximab every 2 weeks (2 infusions) followed by 100 mg SC every 2 weeks (3 injections); or 100 mg IM every 2 weeks (3 injections). In Stage III, 7 subjects received 100 mg SC every 4 weeks (3 injections). RESULTS: No treatment-related serious adverse events were observed, and there were no serious injection site reactions. A low-titer infliximab antibody response was detected in 27% of subjects receiving single SC doses, 5% receiving multiple SC doses, and 43% receiving IM doses. SC administration yielded roughly dose-proportional increases in Cmax and AUC. American College of Rheumatology 20% response (ACR20) was achieved 2 weeks after the last injection by 86.7% of subjects receiving single SC doses, 85.7% receiving SC doses every 2 weeks, 85.7% receiving both IV and SC doses, 57.1% receiving multiple IM doses, and 80.0% receiving SC doses every 4 weeks. CONCLUSION: SC and IM treatment with this experimental infliximab formulation was well tolerated and was associated with a favorable ACR response. | |
15564724 | The BAFF/APRIL system: an important player in systemic rheumatic diseases. | 2005 | Many rheumatic diseases have an autoimmune basis, characterized by organ-specific inflammation and tissue destruction. Diseases such as rheumatoid arthritis, systemic lupus erythematosus or Sjögren's syndrome often associate with abnormal B cell function and the production of various autoantibodies. B cell activating factor belonging to the TNF family (BAFF) is a B cell survival factor essential for B cell maturation, but also contributes to autoimmunity when overexpressed in mice. In addition, elevated levels of BAFF have been detected in the serum of patients with various rheumatic diseases, suggesting a role for this factor in these pathologies. BAFF has additional functions that may be important in rheumatic diseases. For instance, excess BAFF leads to the expansion of a subset of B cells named marginal zone (MZ) B cells, a cell type able to activate naïve T cells. In addition, expansion of the MZ B cell population correlates with certain autoimmune diseases, and these cells have been detected in inflamed tissues in mice and humans. Recently, BAFF was shown to also stimulate T cell activation, an aspect that may also contribute to autoimmunity. Finally, BAFF has emerged as a potent survival factor for B cell lymphomas and as such may be involved in promoting B cell cancers. This result possibly offers an explanation for the occasional lymphoma complication observed in a subset of patients with certain rheumatic diseases, particularly Sjögren's syndrome. New elements about BAFF biology indicate that this factor may be involved in a wider range of pathologies than first anticipated, and inhibitors of this factor are likely to provide attractive new treatments for rheumatic diseases and B cell lymphomas. | |
16639484 | [A comparison between the Simplified Disease Activity Index (SDAI) and the Disease Activit | 2006 Jan | OBJECTIVE: To compare the SDAI values to DAS28 scores in RA patients undergoing different DMARD regimens. METHODS: The SDAI is an unweighted numerical sum of five outcome parameters: tender and swollen joint count (based on 28-joint assessment), patient and physician global assessment of disease activity (visual analogue scale: 0-10 cm) and level of C-reactive protein (mg/dl). 80 patients (F/M 68/12; age between 20-68 years, median 52) with active rheumatoid arthritis were prospectively enrolled in the study. The patients were randomly assigned to one of four groups according to the therapeutic regimens: group I: Methotrexate (MTX) 15 mg/weekly + salazopyrin 2 g/daily; group II: MTX 15 mg/weekly + infliximab 3 mg/Kg at time 0, 2, 4 and every 8 weeks; group III: MTX 15 mg/weekly + etanercept 25 mg/twice weekly; group IV: MTX 15 mg/weekly + adalimumab 40 mg/every other week. SDAI and DAS28 were determined at baseline and after 6 months in each patient. Mean changes in SDAI values were compared to those detected in DAS 28 at baseline and after 6 months. RESULTS: SDAI and DAS 28 were found to be significantly correlated at baseline. Moreover, changes in SDAI over time paralleled those in DAS, and were found to be significantly correlated. CONCLUSIONS: SDAI is a valid measure of response to treatment in RA patients undergoing different therapeutic regimens. | |
15958083 | Natural killer cell activity in families of patients with systemic lupus erythematosus: de | 2005 Jul | Natural killer (NK) cell cytotoxic activity and cell frequency, expressed as a percentage of total lymphocytes, have been determined in peripheral blood mononuclear cells from first-degree relatives of patients with systemic lupus erythematosus (SLE), the patients themselves, a group of rheumatoid arthritis (RA) patients and controls. Low levels of killing activity relative to controls were found in some members of all groups with the extent of depression falling into two ranges. Moderate reductions were seen in female (3/31, 10%) and male (4/14, 29%) relatives of SLE patients, female (12/60, 20%) and male (3/4, 75%) SLE patients and female RA patients (6/17, 35%). A more profound depression of killing activity was confined to other female SLE patients (15/60, 25%). There were strong correlations in all groups between killing activity and percentage of NK cells, but analysis of the ratio of these parameters and studies with purified preparations of NK cells suggest that the reduced activity in SLE frequently involves a defect in the killing capacity of the individual cells in addition to the reduced levels of NK cells. Azathioprine (AZA), which was used in treatment of 12 SLE patients, was invariably associated with low values of killing activity. It appears to substantially reduce the percentage of NK and B cells in an action unconnected with the NK cell abnormalities associated with SLE. The finding of low killing activity in relatives and a correlation between their activity and that of their patients support the view that NK cell deficiency is a genetic determinant of SLE. NK cells in SLE may produce insufficient levels of cytokines required for the regulation of IgG production. |