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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12794051 Hypothalamic-pituitary-adrenocortical and gonadal functions in rheumatoid arthritis. 2003 May Rheumatoid arthritis (RA) as well as most autoimmune disorders results from a combination of several predisposing factors including the relations between epitopes of the trigger agent (i.e., virus, self-antigens) and histocompatibility epitopes (i.e., HLA), the status of the stress response system including the hypothalamic-pituitary-adrenocortical axis (HPA) and the sympathetic nervous system (SNS), as well as the gonadal hormones (hypothalamic-pituitary-gonadal axis, HPG), with estrogens implicated as enhancers of the immune response and androgens and progesterone as natural suppressors. The regular observation of reduced cortisol and adrenal androgen secretion during testing in RA patients not treated with glucocorticoids should clearly be regarded as "relative adrenal insufficiency" in the setting of a sustained inflammatory process, as shown by high interleukin (IL)-6 levels. In polymyalgia rheumatica, several pathogenetic and clinical aspects of the disease might well overlap RA, at least with elderly onset RA (EORA). Therefore, reduced production of adrenal hormones (i.e., cortisol, DHEAS) at baseline in active and untreated patients with polymyalgia rheumatica was detected. The defect was mainly related to altered adrenal responsiveness to ACTH stimulation (i.e., increased 17-OHP), at least in untreated patients with polymyalgia rheumatica. Finally, normal serum estrogen and low androgen levels, but high synovial fluid estrogen and much lower androgen levels, have been found in RA patients, supporting the fundamental role of the peripheral sex hormone metabolism in the manifestations of the disease.
11850995 [Infliximab in aggressive and refractory rheumatoid arthritis. A pilot study]. 2002 Jan Rheumatoid arthritis is a chronic inflammatory disease with a progressive course, that frequently provokes permanent incapacity if not adequately treated. Rheumatoid arthritis may be not responsive to the common second line drugs. This study was aimed to treat 15 patients affected by severe refractory rheumatoid arthritis with infliximab. PATIENTS AND METHODS: Fifteen patients with refractory rheumatoid arthritis were treated with infliximab--monoclonal antibody direct to TNF alpha--in association with methotrexate or azathioprine. Infliximab was administered at the dosage of 3 mg/Kg at the weeks 0, 2 and 6 and then every 8 weeks. RESULTS: About half patients ameliorated in agreement with both ACR 20 criteria and DAS28 evaluation. The clinical improvement was accompanied by a reduction of the steroid daily dosage. No relevant side effects were observed. CONCLUSION: Infliximab is effective in a significant number of patients with severe rheumatoid arthritis, with a good tolerability.
12208376 Effects of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthrit 2002 Aug 15 BACKGROUND: Patients with newly diagnosed rheumatoid arthritis have adverse serum lipid profiles. We sought to determine the effects of treating rheumatoid arthritis with antirheumatic drugs on these abnormal lipid levels. SUBJECTS AND METHODS: We studied 42 patients with newly diagnosed rheumatoid arthritis who had not been treated with corticosteroids or disease-modifying antirheumatic drugs. We measured serum lipid profiles at baseline and 1 year later, and determined whether there were differences in the changes in lipid levels between patients who met the American College of Rheumatology criteria for a 20% improvement in rheumatoid arthritis and those who did not. RESULTS: Of the 42 patients, 27 (64%) met the criteria for a 20% improvement in rheumatoid arthritis during the 12-month study. In these patients, mean high-density lipoprotein (HDL) cholesterol levels increased by 21% (P <0.001), apolipoprotein A-I levels increased by 23% (P <0.001), and the ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol level decreased by 13% (P = 0.10). There were significant between-group differences (responders-nonresponders) in the mean 12-month changes in HDL cholesterol levels (8.0 mg/dL; 95% confidence interval [CI]: 3 to 13 mg/dL; P = 0.002), apolipoprotein A-I levels (21 mg/dL; 95% CI: 8 to 33 mg/dL; P = 0.003), and the LDL cholesterol to HDL cholesterol ratio (-0.6; 95% CI: -0.1 to -1.0; P = 0.03), but not in LDL cholesterol, apolipoprotein B-100, or lipoprotein(a) levels. CONCLUSION: Active rheumatoid arthritis is associated with an adverse lipid profile that improves substantially following effective treatment of rheumatoid arthritis. This improvement may reduce the risk of cardiovascular disease.
15219094 [Minimal changes nephrotic syndrome associated to penicillamine treatment]. 2004 We describe three patients with minimal change nephrotic syndrome associated with penicillamine treatment. Two patients had systemic sclerosis and one had rheumatoid arthritis. Cumulative dose of D-penicillamine was similar in all cases, and nephrotic syndrome appeared after 15-33 months of treatment. The drug was stopped and nephrotic syndrome disappeared in 2-4 months, suggesting a possible causal relationship between penicillamine and minimal change disease.
15449978 Ottawa Panel evidence-based clinical practice guidelines for therapeutic exercises in the 2004 Oct BACKGROUND AND PURPOSE: The purpose of this project was to create guidelines for the use of therapeutic exercises and manual therapy in the management of adult patients (>18 years of age) with a diagnosis of rheumatoid arthritis according to the 1987 American Rheumatism Association criteria. METHODS: Evidence from comparative controlled trials was identified and synthesized using The Cochrane Collaboration methods. An expert panel was formed by inviting professional stakeholder organizations to each nominate a representative. This panel developed a set of criteria for grading the strength of both the evidence and the recommendation. RESULTS: Six positive recommendations of clinical benefit were developed on therapeutic exercises. The efficacy of manual therapy interventions could not be determined for lack of evidence. DISCUSSION AND CONCLUSION: The panel recommends the use of therapeutic exercises for rheumatoid arthritis. Further research is needed to determine the efficacy of manual therapy in the management of this disease.
15576415 Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients w 2005 Jun BACKGROUND: Previous work identified synovial sublining macrophage numbers as a potential biomarker for clinical efficacy in rheumatoid arthritis. OBJECTIVE: To investigate the association between changes in infiltration of synovial macrophages and clinical improvement after antirheumatic treatment. METHODS: 88 patients who participated in various clinical trials were studied. All patients underwent serial arthroscopy before initiation of treatment and after different time intervals. Immunohistochemical and digital image analysis were performed according to standardised procedures to detect changes in CD68+ synovial sublining macrophages in relationship to changes in the 28 joint count Disease Activity Score (DAS28). Statistical analysis was performed using one way analysis of variance, the independent samples t test, linear regression, and the standardised response mean (SRM). RESULTS: For good, moderate, and non-responders, according to the DAS28 response criteria, there was a significant difference in the change in sublining macrophages (mean (SEM) cells/mm(2) -643 (124), -270 (64), and -95 (60), respectively; p<0.0003). There was a significant correlation between the change in the number of macrophages and the change in DAS28 (Pearson correlation 0.874, p<0.01). The change in sublining macrophages explained 76% of the variation in the change in DAS28 (p<0.02). The sensitivity to change of the biomarker was high in patients treated actively (SRM >0.8), whereas the ability to detect changes in placebo treated patients was weak (SRM <0.3). CONCLUSION: The results suggest that changes in synovial sublining macrophages can be used to predict possible efficacy of antirheumatic treatment.
12508764 The "Braids Lady" of Arezzo: a case of rheumatoid arthritis in a 16th century mummy. 2002 Nov OBJECTIVE: To diagnose a probable case of rheumatoid arthritis in a mummified female body from the 16th century and to backdate the first clinical diagnosis, entering the diatribe regarding the ancientness of the disease. METHODS: Image techniques such as normal X-ray, X-ray by mammography, total body CT and high resolution CT were used. Microscopic examination by stereomicroscopy was performed. Samples of tissue were submitted to histology. These data and the review of past literary references, of artistic representations and of paleopathological cases provided an interesting contribution to reconstruct the history of the disease. RESULTS: The body of the "Braids Lady" showed all the "stigmata" of the disease. The left hand revealed large erosions of the metacarpophalangeal joints of both the third and the fourth fingers, volar metacarpophalangeal subluxation of both the third and the fourth fingers and lateral deviation of all the fingers. The carpus showed some minute and marginal erosions of the bones. The bases of the first phalanges were slightly flared. The toes showed partially overlapped fibular deflection. CT evidenced subluxations of the joints. The body showed no involvement of sacroiliac articulation. CONCLUSIONS: The "Braids Lady" was affected by rheumatoid arthritis. A large number of features typical of the disease were recorded. Differential diagnosis supported the findings. The death of the lady was established at the end of 16th century, namely 200 years before the first clinical diagnosis worked out by Landré Beauvais in the early 1800s.
15170914 Expression of tristetraprolin (G0S24) mRNA, a regulator of tumor necrosis factor-alpha pro 2004 Jun OBJECTIVE: To determine the significance of tristetraprolin (TTP) gene expression in synovial tissues of patients with rheumatoid arthritis (RA). METHODS: Gene expression was examined in synovial tissue and peripheral blood lymphocytes of a patient with RA by differential display-polymerase chain reaction (PCR). One of the identified genes, TTP, was selected for further analysis. cDNA was prepared from synovial tissues of 22 patients with RA and 22 with osteoarthritis (OA). Expression of TTP and tumor necrosis factor-a (TNF-a) genes was measured by TaqMan real-time semiquantification PCR. In RA samples, expression of TTP mRNA was compared with TNF-a mRNA, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and steroid and/or disease modifying antirheumatic drug use. RESULTS: Expression of TTP gene was significantly higher in synovial tissues of RA patients than in OA. There was no apparent relationship between expression of TTP and TNF-a genes. TTP gene expression had a tendency to be inversely correlated with serum CRP, measured immediately before surgery. In addition, CRP was higher in patients with a low TTP/TNF-a gene expression ratio (p = 0.0071, Spearman rank correlation). CONCLUSION: A low TTP/TNF-a gene expression ratio could indicate failure of RA patients to produce adequate amounts of TTP in response to increased TNF-a production. Inappropriate TTP production may be one factor that contributes to higher RA disease activity.
15140776 A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid 2004 Jun OBJECTIVES: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. METHODS: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. RESULTS: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. CONCLUSIONS: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment.
15212717 Feline immunodeficiency virus vectors for efficient transduction of primary human synovioc 2004 Jun The potential of gene therapeutics is hindered by the limitations of the delivery systems presently available. Recently, human immunodeficiency virus (HIV) vectors have been developed that allow the efficient and stable transduction of primary nondividing cells in vivo. Because of the safety concerns raised by HIV vectors, we developed a gene delivery system derived from the ungulate lentivirus feline immunodeficiency virus (FIV). We describe in the present study the optimization of the safety and efficiency of this system that proved to be as potent as HIV vectors to transduce nondividing cells, with titers over 10(8) transducing units per ml. We used this tool to transduce TNF-alpha into human primary synoviocytes, and showed a high efficiency of transduction. TNF-alpha-transduced synoviocytes injected into the knee joints of severe combined immunodeficient (SCID) mice induced cell proliferation, as well as cartilage and bone erosion as soon as day 7, creating a standardized, humanized animal model relevant for rheumatoid arthritis. FIV vectors appear to be promising tools for biologic research and gene therapy.
11816257 Celecoxib-induced nonoliguric acute renal failure. 2002 Jan OBJECTIVE: To report a case of nonoliguric acute renal failure secondary to use of celecoxib in a patient with rheumatoid arthritis. CASE SUMMARY: A 43-year-old Hispanic woman started receiving celecoxib 200 mg/d for treatment of rheumatoid arthritis. Fourteen days after initiating therapy, she developed nonoliguric acute renal failure. Celecoxib was discontinued. Renal function improved, but had not returned to normal 30 days after presentation. DISCUSSION: Only 2 cases of reversible oliguric acute renal failure and volume overload have been reported 13 and 14 days after initiating therapy with celecoxib. Renal function in the 2 patients returned to baseline after treatment with diuretics. To our knowledge, the development of nonoliguric acute renal failure secondary to treatment with celecoxib has not previously been reported. CONCLUSIONS: Celecoxib can probably result in reversible, or nonoliguric, acute renal failure. Although renal function improves after discontinuation of celecoxib, it may not return to baseline. Celecoxib should be used cautiously in individuals at risk of developing acute renal failure.
11874835 Bone quality and bone mass as assessed by quantitative ultrasound and dual energy x ray ab 2002 Apr OBJECTIVE: To examine relationships of bone quality as assessed by quantitative ultrasound (QUS) and bone mineral density (BMD, g/cm(2)) with quadriceps strength (QS) in women with rheumatoid arthritis (RA). METHODS: Sixty seven women with RA according to the 1987 American College of Rheumatology (ACR) criteria were examined. Mean (SD) age was 62 (13) years, mean disease duration 15 years. Most were or had been receiving glucocorticoid treatment. Calcaneal bone quality expressed as speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz), and stiffness was measured by QUS. BMD of the femoral neck, spine, and distal forearm was measured by dual energy x ray absorptiometry (DXA). Maximal voluntary isokinetic quadriceps strength (Nm) was assessed by isokinetic dynamometry. Pain was recorded on a visual analogue scale (VAS), disability was scored by the Stanford Health Assessment Questionnaire (HAQ), and the degree of physical impairment was expressed by the Steinbrocker index (SI). RESULTS: In multiple regression analyses, QS predicted SOS, BUA, and stiffness (r(partial) ranging from 0.36 to 0.45, p<0.005) and femoral neck BMD (r(partial)=0.30, p<0.05) independently of age, height, weight, disease duration, HAQ, VAS, SI, and cumulative steroid dose. BMD of the spine and distal forearm was not associated with QS. After adjustment for covariates, women with subnormal BMD of the femoral neck (T score <-1), had a 20% lower QS than those with normal BMD (p<0.0001). CONCLUSIONS: Calcaneal bone quality and femoral neck BMD were associated with QS in women with RA. This finding indicates that physical activity including muscle strengthening exercises may play a part in the prevention of bone loss in these patients.
12236623 Bone and joint destruction in rheumatoid arthritis: what is really happening? 2002 Sep Focal bone erosions occur at the joint margins and in subchondral bone of patients with rheumatoid arthritis (RA). These erosions progress throughout the course of disease and generally correlate with disease severity. Tissue sections from sites of bone erosion in the rheumatoid joint show multinucleated cells with phenotypic characteristics of osteoclasts, the cells responsible for resorbing bone during physiologic remodeling. Factors known to directly or indirectly induce osteoclast differentiation and activation are found in the rheumatoid synovium. These include receptor activator of NF-kappaB ligand (RANKL), which plays a critical role in osteoclast differentiation, as well as a variety of proinflammatory cytokines, including intereukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), which upregulate RANKL. IL-1 also augments osteoclast activation, and TNF-alpha induces differentiation of early osteoclast precursors. In animal models of RA, RANKL is expressed at sites of bone erosion. Moreover, in a serum transfer model of inflammatory arthritis, animals unable to produce osteoclasts did not show evidence of bone resorption despite the presence of intense inflammation. These observations suggest that osteoclasts mediate focal bone erosions in RA and that targeting of osteoclasts and osteoclast mediated bone resorption represents a rational approach to preventing or reducing focal bone loss in RA.
12777636 Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patie 2003 Oct OBJECTIVES: To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. METHODS: Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients. Cultures were stimulated with either bacterial products such as lipo-oligosaccharide (LOS) or Staphylococcus aureus Cowan I (SAC) to activate monocytes or with monoclonal antibodies to CD3 and CD28 to induce polyclonal T-cell activation. We analysed the effect of methotrexate on cytokine production in these systems. RESULTS: We showed that methotrexate inhibits production of cytokines induced by T-cell activation. Among the cytokines inhibited were interleukin 4 (IL-4), IL-13, IFN gamma, tumour necrosis factor-alpha (TNF alpha) and granulocyte-macrophage colony-stimulating factor. Inhibition was seen at concentrations easily achieved in plasma of RA patients taking the drug. IL-8 production was hardly influenced by methotrexate. Furthermore, inhibition was dependent on the stimulus; IL-6, IL-8, IL-1 beta and TNF alpha production induced by LOS or SAC was only slightly decreased by methotrexate. The addition of folinic acid or thymidine and hypoxanthine reversed the inhibitory effects of methotrexate on cytokine production. Concentrations of methotrexate required for inhibition varied between donors. Oral intake of 10 mg methotrexate by RA patients led to marked inhibition of cytokine production in blood drawn after 2 h. CONCLUSIONS: Methotrexate turns out to be an efficient inhibitor of cytokine production induced by T-cell activation in freshly drawn blood. This is due to inhibition of the de novo synthesis of purines and pyrimidines. Cytokines produced by monocytes are hardly affected by methotrexate.
12175089 Levels of antioxidant proteins and soluble intercellular adhesion molecule-1 in serum of p 2002 Summer Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), ceruloplasmin (Cp), and transferrin (Tf) were measured in patients with rheumatoid arthritis (RA) and the correlations of these parameters with disease activity were investigated. Serum sICAM- 1 levels were determined by a sandwich enzyme-linked immunosorbant assay (ELISA) in serums from 42 patients with RA and 30 healthy controls. Erythrocyte sedimentation rate (ESR) was determined by the Westergren method and C-reactive protein (CRP), Cp, and Tf by nephelometric methods. Disease activity was assessed by standard criteria. Serum Tf levels were significantly diminished and serum levels of sICAM-1 and Cp were significantly increased in patients with RA, compared to healthy controls. Serum sICAM-1 levels showed negative correlation with serum Tf levels (r = -0.47, p < 0.01), and positive correlation with serum Cp levels (r = 0.49, p < 0.001). There was weak positive correlation between sICAM-1 levels and the Ritche articular index (RAI) scores (r = 0.32, p <0.05) and serum CRP levels (r = 0.44, p <0.01), but no significant correlations of sICAM-1 levels with ESR, patient's age, or duration of disease. There were no significant correlations between values of serum CRP, RAI score, or ESR with serum CP or Tf levels. This study indicates that serum sICAM-1, together with other parameters, is a useful and novel marker for evaluating the disease status and activity of patients with RA.
12571839 Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor 2003 Feb OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) has been implicated in the pathogenesis of certain inflammatory diseases. Two TNFalpha-neutralizing agents are licensed in the US. Infliximab is licensed for the treatment of Crohn's disease (CD) and, when used with methotrexate, for the treatment of rheumatoid arthritis (RA). Etanercept is licensed for the treatment of RA, including juvenile RA, and, more recently, was licensed for the treatment of psoriatic arthritis. Because of the potential for decreased host resistance to infectious agents due to treatment with anti-TNFalpha agents, we sought to evaluate postlicensure cases of opportunistic infection, including Listeria monocytogenes, in patients treated with these products. METHODS: The FDA Adverse Event Reporting System, a passive monitoring system, was reviewed to identify all reports of adverse events (through December 2001) associated with L monocytogenes infection in patients treated with infliximab or etanercept. RESULTS: Fifteen cases of L monocytogenes infection associated with infliximab or etanercept treatment were identified. In 14 of these cases, patients had received infliximab. The median age of all patients was 69.5 years (range 17-80 years); 53% were female. Six deaths were reported. Among patients for whom an indication for use was reported, there were 9 patients (64%) with RA and 5 patients (36%) with CD (information was not reported for 1 patient). All patients for whom information was reported were receiving concurrent immunosuppressant drugs. CONCLUSION: Postlicensure surveillance suggests that L monocytogenes infection may be a serious complication of treatment with TNFalpha-neutralizing agents, particularly infliximab.
12439850 Gene therapy for rheumatoid arthritis. 2002 Nov Rheumatoid arthritis (RA) is a severe autoimmune systemic disease. Chronic synovial inflammation results in destruction of the joints. No conventional treatment is efficient in RA. Gene therapy of RA targets mainly the players of inflammation or articular destruction: TNF-alpha or IL-1 blocking agents (such as anti-TNF-alpha monoclonal antibodies, soluble TNF-alpha receptor, type II soluble receptor of IL-1, IL-1 receptor antagonist), antiinflammatory cytokines (such as IL-4, IL-10, IL-1), and growth factors. In this polyarticular disease, the vector expressing the therapeutic protein can be administered as a local (intra-articular injection) or a systemic treatment (extra-articular injection). All the main vectors have been used in experimental models, including the more recent lentivirus and adeno-associated virus. Ex vivo gene transfer was performed with synovial cells, fibroblasts, T cells, dendritic cells, and different cells from xenogeneic origin. In vivo gene therapy is simpler, although a less controlled method. Clinical trials in human RA have started with ex vivo retrovirus-expressing IL-1 receptor antagonists and have demonstrated the feasibility of the strategy of gene therapy. The best target remains to be determined and extensive research has to be conducted in preclinical studies.
12509628 Rheumatoid arthritis susceptibility and interleukin 10: a study of two ethnically diverse 2003 Jan INTRODUCTION: IL-10 is an immunoregulatory cytokine which may modulate disease expression in rheumatoid arthritis (RA). The IL-10 gene is highly polymorphic with a number of single nucleotide polymorphisms in the promoter region and two microsatellite loci, IL10.R and IL10.G, 4 kb and 1.1 kb 5' of the transcription initiation site. It has been reported that allele 2 of the IL10.R microsatellite (IL10.R2) is associated with increased IL-10 secretion and IL10.R3 with reduced secretion. Subsequently, over-representation of IL10.R2 and under-representation of IL10.R3 in three independent RA groups has been reported. The aim of the current study is to determine whether there is an association between the IL10.R2 allele and RA in two ethnically distinct populations. METHODS: IL10.R genotypes were determined by semi-automated DNA sequencing technology in 186 UK Caucasians and 138 South Africans of Zulu or Sotho origin, fulfilling the 1987 American College of Rheumatology (ACR) criteria for RA. The Caucasian patients had relatively severe disease and comprised 75 patients with RA vasculitis, 22 with Felty's syndrome and 89 who had undergone a joint replacement (hip or knee) within 15 years of the onset of disease. Allele frequencies were compared with 296 Caucasians and/or 73 South Africans. RESULTS: The frequency of the IL10.R2 allele was significantly greater in the South Africans (RA and controls) than in the Caucasians (0.78 vs 0.66, P=1 x 10(-6)), while the frequency of IL10.R3 was less common (0.16 vs 0.3, P=1 x 10(-8)). No differences were observed in either IL10.R2 or IL10.R3 frequencies between patients and controls in either population. CONCLUSIONS: We were unable to confirm any association between IL10.R alleles and RA in this study. However, significant differences were demonstrated in the frequency of IL10.R2 and IL10.R3 between the two ethnic groups. The relatively high frequency of IL10.R2 in the South African population (0.78) would have reduced the power to detect an association with RA.
12810431 Overexpression of transcripts containing LINE-1 in the synovia of patients with rheumatoid 2003 Jul OBJECTIVE: To identify novel diagnostic markers by comparing gene expression in rheumatoid (RA) and reactive arthritis (ReA) synovium. METHODS: Synovial biopsy specimens were obtained by needle arthroscopy from the knees of 10 patients with either RA or ReA. RNA was isolated from the biopsy specimens and cDNA synthesised for analysis using a customised cDNA macroarray. Confirmatory analysis was performed using in situ hybridisation on a second set of synovial samples. RESULTS: Two unique transcripts (ReXS1 and fibronectin) were consistently more abundant in ReA and three homologous transcripts were more abundant in RA. The latter all mapped within long interspersed nucleotide elements (LINE-1), that form one of the families of repetitive sequences in the human genome. CONCLUSIONS: The abundance of transcripts containing LINE-1 in the RA synovium may be an epiphenomenon or may have pathogenic significance. Further work is required to determine the identity of the full length transcript(s) before its use as a diagnostic marker in RA can be assessed.
12690846 Metacarpophalangeal joint arthroplasty in rheumatoid arthritis. 2003 In patients with rheumatoid arthritis, metacarpophalangeal joint deformities can significantly affect hand function. Flexible hinge implant arthroplasty, designed in the 1960s, remains the most accepted and widely performed technique for treatment of severely involved metacarpophalangeal joints in rheumatoid arthritis. An arc of motion of 40 degrees to 60 degrees can be expected after arthroplasty, with improvement of finger extension and ulnar deviation. Silicone implant arthroplasty, although technically challenging, is the standard surgical procedure for improving hand function in these patients. Complications include recurrent ulnar deviation, extensor lag, implant fracture, infection, and silicone-induced particulate synovitis. Despite these limitations, patient satisfaction is high with enhancement of hand appearance and function and relief of pain.