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ID PMID Title PublicationDate abstract
12661131 Sympathetic skin response and R-R interval variation in cases with rheumatoid arthritis. 2003 Mar To investigate the autonomic nervus system involvement in cases with rheumatoid arthritis (RA) by assesing sympathetic skin response (SSR) and R-R interval variation (RRIV), 14 healthy women and 10 women with RA, all of them without clinic dysautonomies were examined. SSR's were recorded palmar surface of both hands and soles of both feet, after stimulating median and tibial nerves individually. RRIV's were assessed at rest and during six deep breathing in one minute with electrodes placed on dorsal surfaces of both hands. SSR could not be obtained from lower extremities of one case with RA. We could not find any significant difference between two groups in terms of SSR latencies. RRIV values obtained during deep breathing to those recorded at rest (D%/R%) was found to be significantly lower in RA cases than healthy controls. RRIV values increased with deep breathing in healthy subjects, while they decreased in 50% of the RA cases. We conclude that assessment of SSR and RRIV are valuble methods for revelation of subclinical autonomic involvement in cases with RA.
12388047 Antiinflammatory effect of preoperative ketorolac in phacoemulsification. 2002 Oct We report the antiinflammatory effect and efficacy of preoperative treatment with ketorolac in a patient with rheumatoid arthritis having phacoemulsification. This 70-year-old woman was on a maintenance dose of systemic methylprednisolone at the time of uneventful phacoemulsification in the left eye. She developed a sterile hypopyon on the first postoperative day and was treated aggressively with topical and systemic therapy, resulting in a gradual resolution of the inflammatory response. The patient subsequently had phacoemulsification in the right eye. The only significant difference in the preoperative management this time was that the patient received topical ofloxacin and ketorolac 4 days before surgery. The postoperative inflammatory response was much more controlled. The patient was continued on ketorolac and prednisolone acetate, resulting in the usual postoperative inflammatory response.
12027419 Direct transfer of p65 into T lymphocytes from systemic lupus erythematosus patients leads 2002 May The recent identification of a number of molecular defects in T cells from patients with systemic lupus erythematosus (SLE) has raised expectations for gene replacement therapy as an option in the treatment of these diseases. In this report, we have adapted an electroporation-based technique to transfer successfully DNA to peripheral blood T cells from normal individuals and patients with systemic lupus erythematosus and rheumatoid arthritis. Transfection efficiency, judged by the percentage of live cells expressing green fluorescence after transfection with a pGFP (green fluorescence protein), reached 32 +/- 3% in normal, 13 +/- 3% in SLE, and 17 +/- 13% in RA T cells. The transfection efficiency was slightly higher in CD8+ than in CD4+ cells, and the cells maintained acceptable (75%) viability up to the fourth post-transfection day. SLE T cells have been shown to display low levels of the p65 subunit of the NF-kappaB transcription factor and decreased production of IL-2. Since NF-kappaB contributes to the transcriptional regulation of the IL-2 promoter, the effect of the forced replenishment of p65 on IL-2 transcription was tested. The low level of interleukin-2 promoter activity in SLE T cells increased to normal levels following transfection with cDNA encoding the NF-kappaB p65 subunit. Taken together, these results demonstrate the feasibility of transfection of T cells from SLE patients by electroporation and the reversal of decreased interleukin-2 promoter activity in SLE T cells, and are an early step toward gene therapy as a method of treatment for these individuals.
12119414 Regional analysis of p53 mutations in rheumatoid arthritis synovium. 2002 Jul 23 The p53 tumor suppressor protein plays a central role in cell cycle regulation, DNA repair, and apoptosis. Recent studies indicate that DNA damage and somatic mutations in the p53 gene can occur because of genotoxic stress in many tissues, including the skin, colon, and synovium. Although somatic mutations in the p53 gene have been demonstrated in rheumatoid arthritis (RA) synovial tissue and synoviocytes, no information is available on the location or extent of p53 mutations. Using microdissected RA synovial tissue sections, we observed abundant p53 transition mutations, which are characteristic DNA damage caused by oxidative stress. p53 mutations, as well as p53 mRNA expression, were located mainly in the synovial intimal lining rather than the sublining (P < 0.01). Clusters of p53 mutant subclones were observed in some microdissected regions, suggesting oligoclonal expansion. Because IL-6 gene expression is regulated by wild-type p53, IL-6 mRNA expression in microdissected tissues was quantified by using real-time PCR. The regions with high rates of p53 mutations contained significantly greater amounts of IL-6 mRNA compared with the low mutation samples (P < 0.02). The microdissection findings suggest that p53 mutations are induced in RA synovial tissues by inflammatory oxidative stress. This process, as in sun-exposed skin and inflamed colonic epithelium, provides some of the mutant clones with a selective growth advantage. A relatively low percentage of cells containing p53 mutations can potentially affect neighboring cells and enhance inflammation through the elaboration of proinflammatory cytokines.
12223111 Molecular profile of synovial fibroblasts in rheumatoid arthritis depends on the stage of 2002 The aim of this study was to explore the molecular profile of proliferating rheumatoid arthritis synovial fibroblasts (RA-SF). Total RNA was extracted from two cultures of RA-SF (low-density [LD] proliferating cells and high-density [HD] nonproliferating cells) and suppression subtractive hybridization was performed to compare differential gene expression of these two cultures. Subtracted cDNA was subcloned, and nucleotide sequences were analyzed to identify each clone. Differential expression of distinct clones was confirmed by semiquantitative RT-PCR. The expression of certain genes in synovial tissues was examined by in situ hybridization. In both LD and HD cells, 44 clones were upregulated. Of the 88 total clones, 46 were identical to sequences that have previously been characterized. Twenty-nine clones were identical to cDNAs that have been identified, but with unknown functions so far, and 13 clones did not show any significant homology to sequences in GenBank (NCBI). Differential expression of distinct clones was confirmed by RT-PCR. In situ hybridization showed that certain genes, such as S100A4, NFAT5, unr and Fbx3, were also expressed predominantly in synovial tissues from patients with RA but not from normal individuals. The expression of distinct genes in proliferating RA-SF could also be found in RA synovium, suggesting that these molecules are involved in synovial activation in RA. Most importantly, the data indicate that the expression of certain genes in RA-SF depends on the stage of proliferation; therefore, the stage needs to be considered in any analysis of differential gene expression in SF.
12525380 Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predic 2003 Feb OBJECTIVE: To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA). METHODS: 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde. RESULTS: Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years. CONCLUSION: Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.
15378265 Bronchiolitis obliterans with organizing pneumonia in rheumatoid arthritis--a fatal case a 2005 Jun Bronchiolitis obliterans with organizing pneumonia (BOOP) is characterized by excessive proliferation of granulation tissue within small airways (proliferative bronchiolitis) and alveolar ducts associated with chronic inflammation in the surrounding alveoli. It is generally idiopathic but may occur during the resolution of viral or mycoplasmic pneumonia. It is also associated with a variety of systemic illnesses and clinical settings. Complete resolution occurs in 65-85% of patients treated with corticosteroid therapy, and recurrence is not uncommon. Although rapidly fatal BOOP is rare, respiratory failure leading to death may occur in up to 5% of patients. We describe a fatal case of BOOP suspicious for pneumonia in a patient with rheumatoid arthritis.
14969078 Role of infliximab in the treatment of early rheumatoid arthritis. 2003 Sep Data has been generated that infliximab may be more effective when initiated earlier in the course of disease. A subset analysis of the Attract trial has demonstrated better efficacy of infliximab in reducing joint damage in an early rheumatoid arthritis (RA) population. Recently a randomized double-blind controlled trial revealed that infliximab in combination with methotrexate (MTX) in an early RA population improved signs and symptoms as well as inhibition in radiographic progression compared with patients receiving infliximab or MTX alone. The possibility of withdrawing infliximab after induction of remission with a combination of infliximab and MTX has been shown in a small pilot trial. Taken together, the results support the early use of infliximab in the treatment of patients with moderate to severe disease.
12508396 The Influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical characte 2003 Jan OBJECTIVE: To investigate the associations of the HLA-DRB1 rheumatoid arthritis shared epitope (SE) with clinical characteristics and radiological outcome in patients with psoriatic arthritis (PsA). METHODS: One hundred fifty-eight patients with well documented PsA and 250 controls were typed for HLA-DRB1 alleles including the SE by polymerase chain reaction. Clinical data collected on the patient group included disease subset, swollen and tender joint counts, the psoriasis area severity index (PASI), and the presence of radiological erosions. Clinical and radiological associations with HLA-DRB1 and SE alleles were determined. RESULTS: There was an increased frequency of HLA-DR7 (41 vs 25%; puncorr = 0.001, OR 2.02, pcorr = 0.01) and a decreased frequency of HLA-DR2 (19 vs 28%; puncorr = 0.03, OR 0.59, pcorr = 0.3) in the patient population compared with controls. There was no significant difference in the frequency of HLA-DR1 and HLA-DR4 between patient and control populations. There was no significant difference in the prevalence of SE alleles between the patient and control populations (48 vs 54%). There was no increase in the prevalence of the SE in the polyarthritis subgroup, but there was a marginal decrease in those who remained in the oligoarthritis subgroup. There were no differences with respect to sex, age of onset of disease, family history, Health Assessment Questionnaire score, joint score, skin score, or nail score between those patients who were SE positive and those who were SE negative. However, significantly more patients who were SE positive developed radiological erosions (60 vs 43%; p = 0.03, OR 2.11). CONCLUSION: Overall, the prevalence of the SE in patients with PsA did not differ from our control population. However, it was overrepresented in those who developed radiological erosions. It is possible that the SE does have a role in the clinical severity of PsA.
15039493 Patient-reported outcomes better discriminate active treatment from placebo in randomized 2004 May BACKGROUND: Recent randomized controlled trials (RCTs) in rheumatoid arthritis (RA) have used patient- and physician-reported outcomes, ESR and/or CRP as components of ACR response criteria to assess efficacy. OBJECTIVES: Mean changes from baseline in patient- and physician-reported outcome measures, ESR and CRP were compared in two RCTs in patients with active RA. Comparisons between active and placebo treatment used mean percentage improvements and standard effect sizes (SESs). RESULTS: In both protocols, patient-reported assessments of disease activity, pain and physical function reflected little or no improvement with placebo, best discriminating between active and placebo therapy, as did ESR and CRP. CONCLUSION: Improvements in signs and symptoms of active RA in placebo RCTs appear to be best reflected by patient-reported measures of physical function, as long as reported changes in global assessments of disease activity and/or pain reflect similar benefit. Patient-reported outcome measures should be considered objective; treatment-associated changes are congruent with measures of inflammation, and appear less susceptible to the placebo response.
12828448 Metacarpophalangeal joint arthroplasty in rheumatoid arthritis. 2003 May Although metacarpophalangeal joint arthroplasty is occasionally performed for joints affected by osteoarthritis, it is most often done in patients with rheumatoid arthritis. The metacarpophalangeal joint is critical for proper finger function but is the most common site of involvement in the rheumatoid hand. A thorough understanding of the anatomy, pathophysiology, and mechanics of the metacarpophalangeal joint is a prerequisite for the evaluation and treatment of patients requiring metacarpophalangeal arthroplasty. Silicone rubber implants are the most frequently used device for treatment of revised metacarpophalangeal arthroplasty. Follow-up studies show that this surgery improves function and deformity and achieves nearly uniform patient satisfaction.
12152246 [Cytokines and their antagonists in the treatment of rheumatoid arthritis]. 2002 Rheumatoid arthritis (RA) is a chronic inflammatory disease involving synovium and periarticular tissues, often with several systemic manifestations. Proinflammatory cytokines play an important role in promoting inflammatory responses and articular tissue destruction. Presence of anti-inflammatory cytokines in rheumatoid synovium seems to be too low to effectively neutralize their action. In this review we describe the possibilities of the alternative treatment strategies modifying the balance of cytokine network, in the RA patients, towards anti-inflammatory state. Several trials, in which the action of proinflammatory cytokines was inhibited with their specific inhibitors or with anti-inflammatory cytokines, have shown significant clinical benefits.
15338488 Indirect and total costs of early rheumatoid arthritis: a randomized comparison of combine 2004 Sep OBJECTIVE: To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported. METHODS: Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques. RESULTS: In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost). CONCLUSION: COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.
15290731 Etanercept (Enbrel) in patients with rheumatoid arthritis with recent onset versus establi 2004 Aug OBJECTIVE: To compare etanercept-induced improvement in disability of patients with recent onset of rheumatoid arthritis (RA) to that of patients with established RA. METHODS: Health Assessment Questionnaire (HAQ) scores were collected over 3 years in 2 groups of patients with RA who were treated with etanercept. The first group consisted of 207 patients with recent onset RA (mean duration of 1 year) who had not previously received methotrexate, and the second group consisted of 464 patients with established RA (mean duration of 12 years) who had failed one or more disease-modifying antirheumatic drugs. RESULTS: Baseline demographics and disease characteristics were similar in the 2 groups, except for HAQ scores and C-reactive protein levels, which were higher in the established RA group. Patients in both groups showed rapid and sustained clinical responses with etanercept therapy, but patients with recent onset RA showed significantly greater improvement in HAQ scores compared with patients with established RA. The difference in magnitude of HAQ score improvement between groups was observed as early as week 2 after initiation of etanercept and persisted throughout the 3-year time frame. At year 3, significantly more patients with recent onset RA had a HAQ score of zero (26%) versus those with established RA (14%, p = 0.0095). CONCLUSION: Although etanercept therapy significantly improved disability scores in both groups, patients with recent onset of RA showed greater benefit in HAQ scores than patients with established RA. These results support prompt treatment of RA at an early stage of disease to minimize patient disability.
12910565 Impact of socioeconomic status on the course of rheumatoid arthritis and on related use of 2003 Aug 15 OBJECTIVE: To quantify the impact of socioeconomic status (SES) among patients with rheumatoid arthritis on 1) health outcomes and related health care utilization in relation to disease duration and 2) changes in health outcomes and related health care utilization over a 2-year period. METHODS: A questionnaire survey was conducted among 878 patients with rheumatoid arthritis (RA), varying in disease duration from 0 to more than 15 years. To determine the impact of SES on the health outcomes and health care use, patients were compared within and between 3 disease duration groups. Additionally, longitudinal changes in health outcomes and health care use were assessed with a followup questionnaire sent out 2 years later. RESULTS: Patients with low SES have worse disease activity, physical health, mental health, and quality of life than patients with high SES. These differences, however, decreased over time. Regarding health care use, we found that patients with low SES made considerably less use of allied health care than patients with high SES. CONCLUSION: Efforts should be undertaken in health care to alleviate the health disadvantages of RA patients in lower socioeconomic groups. In particular, the access to allied health care could be improved.
12590220 Occipitocervical fusion for rheumatoid arthritis using the inside-outside stabilization te 2003 Feb 15 STUDY DESIGN: A retrospective study investigating the clinical outcome of the inside-outside cranial bolt technique for occipitocervical stabilization used to manage rheumatoid arthritis was conducted. OBJECTIVE: To evaluate the safety and efficacy of the inside-outside technique for occipitocervical stabilization used to manage rheumatoid patients. SUMMARY OF BACKGROUND DATA: Achieving occipital cervical fusion for patients with rheumatoid arthritis is a complex and challenging problem. Complications related to placement of occipital screws have been reported. METHODS: Occipitocervical stabilization was used for atlantoaxial subluxation or basilar invagination in 21 patients with rheumatoid arthritis. The patients were assessed for pre- and postoperative neurologic status (Ranawat classification), neck pain, fusion and alignment, hardware complications, and continued posterior cranial settling. All the patients underwent stabilization using inside-outside occipital screws. The technique involves bilateral fixation of cervical plates to the occiput using inside-outside screws, and to the cervical spine using pars screws at C2 or lateral mass screws at subaxial levels. Bone grafting was accomplished with autologous rib or iliac crest graft. RESULTS: During the study, 14 women and 7 men with rheumatoid arthritis underwent occipitocervical stabilization and fusion. The average age of the patients was 65 years, and the mean follow-up period was 25.5 months. There were no surgical complications. Neck pain was reduced from an average Ranawat pain score of 2.40 to 0.4 (P < 0.0001). The Ranawat neurologic grade improved in 62% of the patients with preoperative neurologic deficit. Further cranial settling was not observed in any patient. There were no complications from implants and no incidence of instrumentation failure. CONCLUSIONS: The "inside-outside" technique is safe and effective for stabilizing the occipitocervical junction in rheumatoid patients. It is associated with significant reduction of neck pain, improved neurologic status, and maintenance of alignment and stability.
15466894 Relationship between growth hormone-IGF-I-IGFBP-3 axis and serum leptin levels with bone m 2005 Jan OBJECTIVES: Hormonal factors playing a role in bone mass and body composition have been rarely assessed in rheumatoid arthritis (RA). In this study, we aimed to evaluate the growth hormone (GH)-insulin-like growth factor-I (IGF-I)-insulin-like growth factor binding protein-3 (IGFPB-3) axis and serum leptin levels in patients with RA and to determine whether these hormonal/growth factors may influence bone mass and body composition in RA. METHODS: Serum GH, IGF-I, IGFPB-3 and leptin were evaluated in 38 corticosteroid-treated RA patients, 14 non-RA patients under corticosteroids (corticosteroid controls, CC) and 32 healthy controls (HC). Bone density was evaluated using dual X-ray absorptiometry (DEXA), and expressed as bone mineral density (BMD), and quantitative ultrasound (QUS). Body composition was assessed by DEXA. RESULTS: The three groups differed regarding femoral neck, total body BMD, lean mass and QUS parameters with lower values in the RA group (all P < or = 0.05). Growth hormone was higher in RA patients (P=0.0001) while IGF-I and IGFBP-3 did not differ between the three groups. In RA patients there was a tendency to high serum leptin levels and leptin strongly correlated with fat mass (r=0.83, P<0.0001), but not with bone mass measurements or inflammatory parameters. There were no differences for lean mass, GH and leptin between CC and HC. CONCLUSION: Our results suggest that these GH and leptin modifications could have an influence on both bone mass and body composition in RA.
15212592 Single nucleotide polymorphism profiling across the methotrexate pathway in normal subject 2004 Jul Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug in rheumatoid arthritis (RA). Polymorphisms occur in several genes encoding key enzymes in the folic acid pathway, which is influenced by MTX, but have not been evaluated in patients with RA. The effect of race on allele frequency has also not been evaluated. In this study, the allele frequencies of polymorphisms in six key enzymes in the MTX-folate pathway in patients with RA and healthy controls, including several common racial groups were studied. European- and African-American patients with RA and European and African healthy controls were genotyped for 22 genetic loci in six genes in the MTX cellular pathway. Differences in genotype distributions between the different racial groups were evaluated using chi(2) tests. Allele frequencies were significantly different (p < 0.001) for eight single nucleotide polymorphisms between the European and African controls. The allele frequencies of two polymorphisms showed significant differences (p < 0.001) between the African- and European-American patients with RA. Thus, racial differences exist between the allele frequencies of several polymorphisms in enzymes in the MTX-folate pathway in patients with RA and healthy controls. Whether such differences contribute to a differential response to MTX in patients with RA deserves to be investigated.
15172039 Consideration of the risk and treatment of tuberculosis in patients who have rheumatoid ar 2004 May Evidence supports the association of tuberculosis (TB) with tumor necrosis factor inhibitor therapy in patients who have rheumatoid arthritis. There seem to be differential risks of TB with the currently available inhibitors. Screening for latent TB infection with purified protein derivative is indicated for patients who are being considered for treatment; it seems to be effective in reducing the occurrence of TB in treated patients.
12596276 Maintaining wrist function in severe rheumatoid arthritis: a case study of revision Swanso 2002 Dec We present a case of revision Swanson wrist arthroplasty staged via a wrist fusion in a patient with rheumatoid arthritis. Due to extensive bone loss in the rheumatoid patient, it may not be possible initially to revise a wrist arthroplasty; however after fusion with a bone graft to regain bone stock we have demonstrated that this is possible. It may even be possible to convert such a fusion to a total wrist arthroplasty.