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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12723306 | [Extensor tendon rupture after dorsal surgery of the rheumatoid wrist: analysis of nine re | 2003 Feb | We led a retrospective study to determine the causes of the tendon ruptures post-operating in the surgery of the wrist rheumatoid dorsal and to estimate the clinical result. At follow-up, we measured the extension lag and the rolling-up of fingers by the distance palm-pulps. Nine patients were so revised in the average of 40 months, average age was of 50.7 years. The tendon ruptures arose in 3 months in 67% of the cases. Seven times, a procedure on the distal radio-ulnar joint had been necessary (5 Sauvé-Kapandji and 2 Darrach). Thirty tendons had been concerned in this study, that is 3.3 tendons on average (1-5). Two main causes were found: attrition on the stub ulnaire and great intra-tendinous synovitis (per operating observation). At the revision, the lag extension means was 23 degrees (0-40). Rolling-up of the long fingers was complete 4 times on 7. The best results were observed after tendinous grafting or index proprius transfer with a lateral suture. Tendinous adhesions had arisen 6 times and persisted still at 3 patients. Our study underlines the interest to stabilize the stub ulnaire to prevent the post-operating ruptures and proposes a transfer or a graft in front of tendons very weakened by the synovitis. | |
12924245 | [Characterization of anti-DNA antibody on IgG3-kappa type M-protein in a patient with rheu | 2003 Jul | A 66 year-old male patient with rheumatoid arthritis, was admitted due to bronchial pneumonia. Anti-nuclear antibody and anti-DNA antibody were both detected in the patient's serum and many LE-like cells were found in the pleural effusion. In addition, M-proteins(IgG-kappa type, IgM-kappa type) were detected in both serum and pleural effusion by immunofixation electrophoresis. Purified IgG fraction by gel filtration(Superdex 200HR) showed high titer of anti-nuclear antibody(x160) and anti-DNA(39.2 AU/ml) antibody. Furthermore, anti-DNA antibody was detected in the fraction III(fraction of M-protein) by ion-exchange chromatography. In conclusion, these results indicate that M-protein(IgG3-kappa type) contains anti-DNA antibody and it is suggests that M-protein induces the production of LE like cell in this case. | |
14534529 | Human wee1 kinase is directly transactivated by and increased in association with c-Fos/AP | 2003 Oct 9 | Wee1 kinase downregulates the M-phase promoting factor, a complex of cdc2 and cyclin B kinase, that controls mitotic cell division. We isolated human wee1 kinase gene promoter and found that it contained one AP-1-binding motif in its promoter region (5'-CGAGTCA-3'; -823/-817), through which wee1 kinase gene was directly transactivated by c-Fos/AP-1. In rheumatoid synovial cells, wee1 kinase was increased in conjunction with the increase of c-Fos/AP-1 and the substrate of wee1, cdc2, was phosphorylated. The amount of wee1 and c-Fos and the phosphorylation of cdc2 were decreased after treatment of the cells with an inhibitor of AP-1, curcumin. A significant proportion of cultured synovial cells of the patients with rheumatoid arthritis, but not those of osteoarthritis, shifted to a tetraploid (4C) state upon long-term culture. Thus, human wee1 kinase gene is directly transactivated by and increased in association with c-Fos/AP-1, and rheumatoid synovial cells overexpressing these genes go into aberrant mitosis. | |
12931800 | Positioning of total knee arthroplasty with and without navigation support. A prospective, | 2003 Aug | We conducted this prospective randomised and externally evaluated study to investigate whether the use of a navigation system during total knee arthroplasty leads to significantly better results than the hand-guided technique. A total of 240 patients was included in the study. All patients received a condylar knee prosthesis. Two surgeons performed all the operations using the Stryker knee navigation system. Exclusion criteria included the necessity for the primary use of constrained implants. The results revealed a highly significant difference between the two groups in favour of navigation with regard to the mechanical axis, the frontal and sagittal femoral axis and the frontal tibial axis (p < 0.0001). The use of a navigation system was therefore shown to improve the alignment of the implant. | |
11851642 | Contraindicated NSAIDs are frequently prescribed to elderly patients with peptic ulcer dis | 2002 Feb | AIMS: To establish the frequency with which NSAIDs were prescribed to elderly patients after admission to hospital for serious gastrointestinal complications and to study which factors are determinants of the prescription of these contraindicated drugs. METHODS: A retrospective cohort study of patients from The Rotterdam Elderly Study, a prospective population-based cohort study of people older than 55 years of age was carried out. Elderly patients with a hospital admission for serious gastrointestinal complications were followed until prescription of an NSAID, death, removal to another area or end of the study period, whichever came first. The following baseline determinants for receiving a contraindicated prescription were studied: gender, age, presence of rheumatoid arthritis or osteoarthritis, presence of cardiovascular risk factors, number of GP visits, number of visits to a medical specialist, cognitive function and the prescriber being a GP or a medical specialist. RESULTS: Prescriptions of an NSAID after discharge from hospital, were identified in 73 patients (73%). Fifty-one percent were prescribed aspirin of whom the large majority used it as an antithrombotic agent, and 49% were prescribed a nonaspirin NSAID after discharge from hospital. Twenty percent of the patients used more than one NSAID on one or more occasions after discharge. For patients who were prescribed NSAIDs before admission as well as after discharge, the proportion of contraindicated prescriptions with concomitant use of antiulcer drugs rose significantly from 0.19 before discharge to 0.60 after discharge for aspirin and from 0.11 to 0.61 for nonaspirin NSAIDs. In the multivariate analysis the only remaining factor with prognostic influence on prescription of NSAIDs was a history of NSAID use before cohort enrollment. A history of rheumatoid arthritis or osteoarthritis was not associated with NSAID prescription after discharge. CONCLUSIONS: Contraindicated NSAIDs are prescribed to a great extent in elderly patients, despite their greater vulnerability for life-threatening gastrointestinal blood loss. It is remarkable that a history of rheumatoid arthritis or osteoarthritis is no significant determinant for receiving a contraindicated prescription, which suggests that these drugs are mainly prescribed for uncomplicated arthralgia. | |
15457445 | CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phe | 2004 Sep | OBJECTIVE: In mice, CD4(+)CD25(+) regulatory T cells play a pivotal role in preventing autoimmunity. Regulatory T cells are also present and functional in healthy humans. We investigated the presence, phenotype, and function of CD4(+)CD25(+) regulatory T cells in peripheral blood (PB) and synovial fluid (SF) from patients with rheumatoid arthritis (RA). METHODS: The presence and phenotype of CD4(+)CD25(+) regulatory T cells were determined by flow cytometry. Anergy and suppressive activity were assessed by culturing CD4(+)CD25(-) and CD4(+)CD25(+) T cells with anti-CD3 monoclonal antibodies and antigen-presenting cells, followed by proliferation and cytokine detection. RESULTS: The percentage of CD4(+)CD25(+) T cells in RA SF was significantly increased compared with that in RA PB, and both of these percentages were higher than that in PB from controls. The cells in RA PB were similar in phenotype and function to CD4(+)CD25(+) regulatory T cells from controls. In SF, however, approximately 40-50% of CD4(+)CD25(+) T cells expressed an activated phenotype, i.e., CD69+, class II MHC(+), OX-40(+), with high levels of CTLA-4 and glucocorticoid-induced tumor necrosis factor receptor. These synovial CD4(+)CD25(+) T cells displayed an increased suppressive capacity compared with blood CD4(+)CD25(+) T cells. However, this enhanced suppressive activity was counterbalanced, because activated responder T cells from SF were less susceptible to CD4(+)CD25(+) T cell-mediated suppression than were responder cells from PB. CONCLUSION: We demonstrate that CD4(+)CD25(+) regulatory T cells are present and functional in patients with RA, with higher numbers of regulatory T cells with increased suppressive activity found in SF compared with PB. These findings suggest a negative feedback system that is active at the site of inflammation. The balance between activated responder and regulatory T cells appears to influence the extent of immunoregulation in RA. | |
12176803 | Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical expe | 2002 Sep | OBJECTIVE: To explore the feasibility of prospectively monitoring treatment efficacy and tolerability of infliximab, etanercept, and leflunomide over a two year period in patients with established rheumatoid arthritis (RA) in clinical practice using a structured protocol. METHODS: All patients with RA at seven centres in southern Sweden, for whom at least two disease modifying antirheumatic drugs, including methotrexate, had failed or not been tolerated, who started treatment with either infliximab, etanercept, or leflunomide were included. They were evaluated at predefined times using a standardised protocol including items required for evaluating response to the American College of Rheumatology (ACR) or EULAR criteria. All adverse events were recorded using World Health Organisation terminology. Concomitant treatment and survival while receiving a drug were recorded. RESULTS: During the study 166 patients were treated with etanercept, 135 with infliximab, and 103 with leflunomide. Treatment response as determined by the ACR and EULAR response criteria was similar for the tumour necrosis factor (TNF) blockers. The TNF blockers performed significantly better than leflunomide both as determined by the response criteria and by survival on drug analysis. Thus 79% and 75% continued to receive etanercept or infliximab compared with 22% of patients who started leflunomide after 20 months. The spectrum of side effects did not differ from those previously reported in the clinical trials. The initial two year experience of a protocol for postmarketing surveillance of etanercept, infliximab, and leflunomide shows that a structured protocol with central data handling can be used in clinical practice for documenting the performance of newly introduced drugs. CONCLUSIONS: Efficacy data for the TNF blockers comply with results in clinical trials, whereas leflunomide appeared to perform worse than in clinical trials. Prolonged monitoring is required to identify possible rare side effects. | |
14872484 | Novel tumor necrosis factor alpha-regulated genes in rheumatoid arthritis. | 2004 Feb | OBJECTIVE: To determine novel genes regulated by tumor necrosis factor alpha (TNFalpha) signaling in primary rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Oligonucleotide microarrays were used to measure gene expression levels in 6 independent replicate samples of RASFs. RASFs were transfected for 18 hours with AdIkappaB-dominant negative (AdIkappaB-DN) (n = 3) or with control AdTet expressing the reverse tetracycline trans-activator (n = 3). The cells were stimulated for 3 hours with TNFalpha, and total RNA was prepared. Several novel parametric and nonparametric methods were used to rank genes in terms of the magnitude and significance of intergroup differences. Microarray expression differences were confirmed by real-time quantitative reverse transcription-polymerase chain reaction. Small interfering RNA (siRNA) was used to specifically down-modulate microarray-identified genes to demonstrate their role in the promotion of apoptosis, proliferation, or matrix metalloproteinase (MMP) expression. RESULTS: Blocking of NF-kappaB by AdIkappaB-DN was associated with a down-modulation of antiapoptosis genes, including BIRC-3, and several novel genes, including GG2-1, a TNFalpha-inducible FLIP-like gene. Other families of genes that were significantly down-regulated by AdIkappaB-DN included cytokines/chemokines (interleukin-1beta [IL-1beta], IL-8, IL-15, and RANTES), adhesion molecule (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), and unique genes that have not previously been reported to be regulated by TNFalpha in RA. Inhibition of the GG2-1 gene using the siRNA technique resulted in significantly enhanced apoptosis, decreased proliferation, and decreased production of MMP-1 in TNFalpha-stimulated RASFs. CONCLUSION: These studies provide a comprehensive analysis of genes that are differentially regulated by TNFalpha signaling and NF-kappaB nuclear translocation in RASFs and demonstrate methods for confirming the expression and functional significance of such genes. | |
12046510 | [Problems in the selection of surgical approach for the treatment of non-traumatic deformi | 2002 Mar | Developmental abnormalities or inflammatory disorders provoke deformations and instability of the craniocervical junction. The most dangerous results of these lesions are: sudden brainstem compression or cervical myelopathy. The authors propose the guidelines for surgical management of non-traumatic deformities caused by: a) rheumatoid arthritis of the spine, b) congenital anatomic changes of the occipit and odontoid. Main goals of surgical treatment are decompression and stabilization. The choice of surgical approach and method depends on pathology. It is very important to estimate individual anatomic changes and mobility--possibility of reduction. The authors discuss surgical methods actually used for fusion and decompression of the occipitocervical junction. | |
15290728 | Increased CD40 expression on articular chondrocytes from patients with rheumatoid arthriti | 2004 Aug | OBJECTIVE: To examine expression of CD40 on articular chondrocytes derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate roles of CD40 on articular chondrocytes in production of inflammatory mediators associated with degradation of articular cartilage. METHODS: Articular cartilage samples were obtained from patients with RA and OA at total knee arthroplasty. Expression of CD40 on chondrocytes was examined using immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR), and flow cytometry. Tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), matrix metalloproteinase (MMP)-3, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in culture supernatants of chondrocytes were measured by ELISA. RESULTS: Immunohistochemical staining revealed that CD40 was expressed on RA chondrocytes in vivo, but not in OA chondrocytes. RT-PCR and flow cytometry showed that cultured articular chondrocytes from RA patients, but not from OA patients, constitutively expressed CD40, and that interferon-gamma (IFN-gamma) enhanced the expression of CD40 on chondrocytes from both RA and OA patients. Membrane fraction of mouse myeloma Ag8 cells that was transfected with human CD154 (Ag8-hCD154) induced production of TNF-alpha, IL-6, and MMP-3 in RA chondrocytes, and pretreatment of RA chondrocytes with IFN-gamma enhanced the response. OA chondrocytes did not respond to stimulation with the membrane fraction of Ag8-hCD154 cells alone, but the cells did produce TNF-alpha, IL-6, and MMP-3 after pretreatment with IFN-gamma. CONCLUSION: CD40-CD154 interaction augments the expression of inflammatory cytokines and MMP in chondrocytes and contributes to an intrinsic process of cartilage degradation in RA. | |
15353352 | IFN-beta in rheumatoid arthritis. | 2004 Sep 1 | IFN-beta is a cytokine with pleiotropic effects and is expressed in rheumatoid synovial tissue. Based on in vitro work and experiments in animal models of rheumatoid arthritis (RA), the effects are mainly anti-inflammatory. Of special interest is the ability of IFN-beta to reduce the secretion of TNF-alpha, IL-1 beta, and IL-6, which are all key players in the pathogenesis of RA. At the same time IFN-beta could enhance the production of anti-inflammatory mediators like IL-1 receptor antagonist (IL-1Ra) and IL-10. Treatment of mice and monkeys with collagen-induced arthritis with daily IFN-beta injections resulted in clinical improvement, decreased synovial inflammation, and protection against joint destruction. Similar data were obtained after IFN-beta gene therapy. However, treatment of RA patients with IFN-beta has been unsuccessful so far, presumably due to pharmacokinetic issues. Novel approaches leading to constitutive IFN-beta production at the site of inflammation may be required to induce clinical efficacy in patients. | |
20217660 | Outcomes for patients with RA: a rheumatology nurse practitioner clinic compared to standa | 2003 Mar | OBJECTIVES: The study aimed to extend our previous work by comparing the outcome of patients with rheumatoid arthritis (RA) attending a rheumatology nurse practitioner (RNP) clinic with those of patients attending the more traditional junior hospital doctor's clinic (JHD). METHOD: A randomised controlled trial of 80 people with RA were allocated to either an RNP or JHD clinic and seen six times in 12 months. The primary outcome measure was the DAS28. Secondary measures included stiffness, fatigue, physical function, psychological status, knowledge and satisfaction. RESULTS: Number of patients: RNP 39 (8 males); JHD 41 (9 males). Age of patients: RNP 36-76 years (median 57); JHD 35-74 years (median 57). Median disease duration: RNP 12 years (range 2-40); JHD 17 years (range 1.5-41). Years of full time education: RNP 8-17 years (median 10); JHD 9-20 years (median 10). Week 48 DAS scores compared to baseline: RNP 19 unchanged, 6 worse and 11 better; JHD 22 unchanged, 7 worse, 6 better. Length of morning stiffness increased significantly at week 24 (p = 0.05) in the JHD cohort but improved to become non-significant at week 48 (p = 0.09). By week 48 fatigue had improved in the RNP cohort (p = 0.038) and deteriorated in JHD patients (p = 0.008). The AIMS showed decreases in pain in the RNP cohort (p = 0.044) and worsening physical function in JHD patients (p = 0.038). Patient satisfaction in the RNP cohort increased significantly (overall satisfaction p = 0.000). The JHD cohort showed a decrease in satisfaction with access and continuity (p = 0.027). CONCLUSIONS: The findings from this research confirm that care from the RNP is both effective and safe. Furthermore, a specialist RNP can bring additional benefits in the form of greater symptom control and enhanced patient self-care. | |
14605699 | [Sonography of the hand and wrist]. | 2003 Oct | In the recent years US has gained wide diffusion as a useful imaging tool in the evaluation of musculoskeletal disorders. Recognized advantages of US over the other imaging modalities are low costs, non-invasiveness, possibility to perform a dynamic examination and readiness. Unfortunately, US has a long learning curve and allows good results only when performed by well-trained and experienced examiners. Specifically, utilization of the recent small transducers allows to perform dynamic examination of the hand during flexion-extension movements of the fingers, while their high frequency (till 15 MHz) have increased the possibility to evaluate small anatomic structures of the hand and wrist as well as to detect subtle pathologic changes. The purpose of this article is to present first the normal basic anatomy and US appearance. Then the main pathological conditions including joint and tendon disorders, foreign bodies and other traumatic lesions, entrapment neuropathies and expansible lesions will be presented. | |
15570644 | Prolactin and growth hormone responses to hypoglycemia in patients with rheumatoid arthrit | 2004 Dec | OBJECTIVE: Prolactin (PRL) and growth hormone (GH) are pituitary hormones with immunomodulating properties. Their upregulated secretion may play a role in the pathogenesis of chronic inflammatory diseases. We evaluated PRL and GH responses to secretion stimulus in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Insulin hypoglycemia (0.1 IU/kg) was induced in 15 women with RA, 18 men with AS, and healthy controls matched for age, sex and body mass index. Plasma concentrations of glucose, PRL, GH, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-a) were analyzed. RESULTS: RA patients had significantly lower area under the curve (AUC) of PRL (p = 0.049) compared to RA controls. During hypoglycemia double or higher increase of plasma PRL occurred in 5 RA (33%) patients and in 8 RA controls (57%). Using the General Linear Model procedure, no significant differences in PRL or GH responses were observed in patients with RA and AS. TNF-a was higher in patients with RA compared to RA controls (p < 0.05). There was no significant difference in TNF-a concentrations between AS patients and AS controls. IL-6 was higher in RA patients compared to controls (p < 0.05) and in AS patients compared to controls (p < 0.01). Significant positive correlation was found between TNF-a levels and AUC of PRL in AS patients (r = 0.46, p = 0.047), but not in the 2 control groups or in RA patients. CONCLUSION: Our results indicate no upregulated PRL or GH responses to stimulation in premenopausal women with RA or men with AS. | |
14726963 | Pathophysiological functions of CD30+ CD4+ T cells in rheumatoid arthritis. | 2003 Dec | High levels of soluble CD30 (sCD30) were detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA), indicating the involvement of CD30+ T cells in the pathogenesis. We investigated the induction of CD30 and its functions in CD4+T cells from patients with established RA (disease duration >_2 years). CD4+ T cells from both the peripheral blood (PB) and synovial tissue (ST) of RA patients expressed surface CD30 when stimulated with anti-CD3 antibody (Ab) and anti-CD28 Ab, but their CD30 induction was slower and weaker compared with PB CD4+ T cells of healthy controls (HC). Immunohistochemical analysis showed that only a small proportion of lymphocytes expressed CD30 in the ST (-1%). RA PB CD4+ T cells, after recovery from 6-day stimulation with anti-CD3 Ab and anti-CD28 Ab, showed in intracellular cytokine staining that CD30+ T cells could produce more interleukin-4 (IL-4) but less interferon-gamma. In the culture of RA PB CD4+ T Cells with anti-CD3 Ab and anti-CD28 Ab, blocking anti-CD30 Ab similarly inhibited the cell proliferation and activation of nuclear factor-kappaB on day 4 in RA and HC, but inhibited the apoptotic cell death on day 6 only in RA. These results indicate that despite high-level expression of sCD30, the anti-inflammatory activity of IL-4-producing CD30+ CD4+ T cells may be limited in the ST due to a poor induction of surface CD30 and a susceptibility to CD30-mediated cell death. | |
14625816 | Estrogen and other female reproductive risk factors are not strongly associated with the d | 2003 Oct | OBJECTIVE: Endogenous and exogenous reproductive hormones have been associated with rheumatoid arthritis (RA) in women, but data are inconsistent and no studies have assessed RA risk factors exclusively in elderly women. METHODS: The authors examined the association between reproductive factors, exogenous hormone exposure, and RA in a prospective cohort study of 31,336 Iowa women who were aged 55 to 69 years at cohort baseline in 1986. RESULTS: During 11 years of follow-up, 158 incident cases of RA were identified and validated. Age at last pregnancy (P trend =.01) and age at menopause (P trend =.03) were inversely associated with RA, whereas a history of polycystic ovary syndrome (relative risk [RR], 2.58; 95% confidence interval [CI], 1.06 to 6.30), endometriosis (RR, 1.72; 95% CI, 0.93 to 3.18), and former use of hormone replacement therapy (RR, 1.47; 95% CI, 1.04 to 2.06) were positively associated with RA. In multivariate analysis models, a history of polycystic ovary syndrome remained the most consistent predictor of RA, whereas the RRs for other factors attenuated. CONCLUSION: Few reproductive factors showed a strong or statistically significant association with RA in elderly women. The association of polycystic ovary syndrome may be indicative of perturbations of endocrine-immune activity that may influence the development of RA. This prospective cohort study adds to the understanding of the potential contribution of hormonal factors to the cause of RA in older women. | |
12351899 | Crystallization of HLA-DR4 fused to an immunodominant collagen II peptide implicated in rh | 2002 Oct | Major histocompatibility complex (MHC) class II molecules are key players in antigen-specific CD4(+) T cell stimulation, despite their lack of discrimination between "self" and foreign antigens. The susceptibility of many individuals to autoimmune diseases is directly attributed to this lack of specificity, as well as to the expression of subclasses of MHC class II molecules. Increased susceptibility to the autoimmune disease rheumatoid arthritis (RA) has been attributed to the expression of the MHC class II alleles HLA-DR1 and HLA-DR4. To define the structural requirements of the HLA-DR4 protein in the autoimmune response of RA, we have crystallized HLA-DR4 with the immunodominant peptide from human collagen II, covalently linked to the N-terminus of the beta-chain [HLA-DR4/hCII(257-273)]. Crystallization time, crystal size, and reproducibility were greatly improved by macroseeding into microdialysis buttons. | |
11932879 | Step-down approach using either cyclosporin A or methotrexate as maintenance therapy in ea | 2002 Feb | OBJECTIVE: To evaluate the feasibility and outcome of the step-down approach using either cyclosporin A (CSA) or methotrexate (MTX) as maintenance therapy following 6 months treatment with these 2 agents in combination in early, nonerosive rheumatoid arthritis (RA). METHODS: Fifty-seven patients younger than 65 years with early, nonerosive RA were first treated with CSA and MTX in combination for 6 months. They were then randomly stepped down to single-agent maintenance treatment for another 18 months. Safety, clinical efficacy, survival on treatment, and radiographic progression were evaluated. RESULTS: When being treated with combination therapy, 7 of the 57 patients (12.3%) withdrew because of adverse events. Of the remaining 50 patients, 42 (84.0%) were American College of Rheumatology (ACR) 20% responders, 30 (60.0%) were ACR 50% responders, and 23 (46.0%) were ACR 70% responders. At month 6, 22 patients were randomized to CSA and 27 to MTX. During this trial period, the treatment was discontinued by 16 patients taking CSA (mainly because of loss of efficacy) and by 4 taking MTX. At month 24, the probability (+/- SEM) of survival on treatment was 0.273 +/- 0.09 for CSA and 0.852 +/- 0.07 for MTX. Of the 6 CSA patients who completed the trial, 4 (66.7%) were ACR 20% responders, and 3 (50%) were both ACR 50% and ACR 70% responders. Of the 23 completers in the MTX arm, 21 (91.3%) were ACR 20% responders, 18 (78.3%) were ACR 50%, and 10 (43.5%) were ACR 70% responders. The treatment was not responsible for severe adverse events. Radiography showed a slow progression in the damage score and number of eroded joints in both treatment groups. CONCLUSION: Stepping down to single agent maintenance therapy following 6 months of combination treatment with CSA and MTX in early RA was only successful with MTX. Because this treatment did not prevent some radiographic progression, other approaches (e.g., step-up approach) may be more appropriate in early RA. | |
12887301 | Clinical potential of mannose-binding lectin-replacement therapy. | 2003 Aug | Mannose-binding lectin (MBL; also known as mannan-binding lectin) is an important component of innate immunity. MBL levels are mainly genetically determined. Low serum MBL levels and their cognate haplotypes have been associated with a wide range of infections. However, most subjects with MBL deficiency remain healthy. MBL deficiency is also associated with non-infectious diseases including systemic lupus erythematosus, rheumatoid arthritis, cystic fibrosis and common variable immunodeficiency. MBL deficiency may affect susceptibility to (e.g. meningococcal disease), or alter the natural history of (e.g. rheumatoid arthritis, cystic fibrosis), a disease. MBL (plasma-derived or recombinant) therapy has yet to be shown to be safe and effective. Potentially it may be useful in MBL-deficient patients to reduce susceptibility to, or enhance recovery from, bacterial infection or to alter the natural history of a disease (disease-modifying drug). In practise the place of MBL therapy may be as a disease-modifying drug to reduce the severity of rheumatoid arthritis and to preserve lung and liver function in cystic fibrosis. MBL therapy may also ameliorate various immunodeficiency syndromes. A potential hazard of MBL therapy is enhanced complement-mediated host damage. The place of MBL therapy will await results of randomized controlled clinical trials. | |
11891691 | Patient with rheumatoid arthritis and MCA/MR syndrome due to unbalanced der(18) transmissi | 2002 Mar 15 | A girl with psychomotor retardation and a pattern of minor anomalies was found to have a slightly enlarged short arm of chromosome 18 by conventional GTG-banded chromosome examination. The 18p+chromosome has also been found in the father. FISH studies using chromosome 18-and chromosome 20-specific painting probes confirmed a reciprocal whole arm translocation between chromosomes 18 and 20 in the father, resulting in monosomy of the short arm of chromosome 18 and trisomy of the short arm chromosome 20 in the patient. FISH analysis using a chromosome 18 alpha-satellite-specific probe showed a reduced signal intensity. The patient presented with a flat, oval face, upslanting palpebral fissures, periorbital fullness, and mental retardation; she also had chronic diarrhea with milk protein intolerance and juvenile rheumatoid arthritis at age 5 years. Juvenile rheumatoid arthritis, like several other immunologic disorders, has occasionally been reported in patients with deletion of 18p, and thus most likely loss of a gene or genes on 18p is responsible for various immunologic disorders occurring in these patients. |