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ID PMID Title PublicationDate abstract
9864833 [Immunopharmacologic profile and therapeutic prospects of anti-TNF-alpha therapy]. 1998 Oct Clinical trials with monoclonal antibodies directed against TNF alpha (anti-TNF mAbs) and soluble TNF receptor fusion proteins (sTNFR-IgGs) have demonstrated that systemic and synovial trapping of TNF alpha results in long lasting anti-inflammatory and anti-nociceptive effects in patients with rheumatoid arthritis. Clinical indices of inflammatory synovitis and laboratory parameters (CRP and ESR) respond to single and repeated administrations of anit-TNF alpha therapies in a dose-dependent fashion. Studies on the immuno-pharmacological profile in patients suggest evidence that TNF alpha trapping down-regulates the effector mechanisms involved in the immuno-inflammatory response in rheumatoid arthritis. Inhibition of PLA 2- and COX-2-derived pathways of mediators of inflammation (prostanoids and leukotrienes) decreases signs and symptoms of inflammatory synovitis such as joint swelling, tenderness and pain. Down-regulating of the cytokine-inducible adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in endothelial cells and synoviocytes results in a marked inhibition of transendothelial migration of inflammatory and immune cells. A decrease of cytokine-regulated metalloproteinase expression results in normalization of circulating MMP-1 and MMP-3 levels. The effect of TNF alpha neutralization on mechanisms of rheumatoid joint destruction has the long-term potential for preventing or decreasing the rate of erosive changes of cartilage and bone.
11508597 Effort testing in patients with fibromyalgia and disability incentives. 2001 Aug OBJECTIVE: To examine whether symptom exaggeration is a factor in complaints of cognitive dysfunction using 2 new validated instruments in patients with fibromyalgia (FM). METHODS: Ninety-six patients with FM and 16 patients with rheumatoid arthritis (RA) were administered 2 effort or symptom validity tests designed to detect exaggerated memory complaints as part of a battery of psychological tests and self-report questionnaires. RESULTS: A large percentage of patients with FM who were on or seeking disability benefits failed the effort tests. Only 2 patients with FM who were working and/or not claiming disability benefits and no patient with RA scored below the cutoffs for exaggeration of memory difficulties. CONCLUSION: This study illustrates the importance of assessing for exaggeration of cognitive symptoms and biased responding in patients with FM presenting for disability related evaluations.
9133924 Post-partum flare in MRL-lpr/lpr mice is associated with a parallel increase of N-acetylgl 1997 Feb Our objective was to investigate IgG glycosylation and disease activity post partum in the MRL-lpr/lpr mouse. Disease activity was monitored using bimalleolar ankle swelling. Levels of galactose and N-acetylglucosamine (GlcNAc) on IgG isolated from serum were measured using biotinylated lectins. Our results show that disease severity increased post partum. This post-partum flare correlated significantly with an increase in IgG GlcNAc expression. The disease severity increased post partum in the MRL-lpr/lpr mouse model similar to the changes seen in rheumatoid arthritis (RA).
9098938 HLA-DRB1 in eight Finnish monozygotic twin pairs concordant for rheumatoid arthritis. 1997 Mar This study presents the results of HLA-DRB1 typing of the eight monozygotic twin pairs with both members affected by rheumatoid arthritis (RA), sampled in the nationwide Finnish twin cohort. The shared epitope, associated with RA in case-control studies, was present in all eight twin pairs, being significantly more frequent than among RA patients in a recent Dutch case-control study. Furthermore, 4 out of 8 twin pairs were homozygous for the shared epitope, while in 73 Dutch healthy controls encoding the shared epitope only 13 (18%) were homozygous: this suggests a gene dose effect in RA susceptibility. Combining these results with data from other sources may help to clarify the contribution of HLA alleles in the genetic predisposition to RA.
9217554 Emerging treatments for rheumatoid arthritis. 1997 Jan 27 Rheumatoid arthritis was considered for centuries to be a nuisance condition, limiting in its effects on an individual's range of motion and the source of considerable distress, but not a life-threatening disease. Recently, however, it has become apparent that patients with severe rheumatoid arthritis may have a decreased life span. Current pharmacologic therapies for patients with rheumatoid arthritis, which include nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, methotrexate, and corticosteroids, have been moderately successful in alleviating the discomforts associated with swollen, painful joints. Many practitioners have sought to improve use of these agents and slow joint destruction by challenging traditional treatment paradigms, altering the sequence in which drugs are given. Nevertheless, most standard medical approaches to treatment have had little or no impact on the course of rheumatoid disease. Innovative strategies, particularly those based on new concepts in the immunobiology of rheumatoid arthritis, are being developed to target cellular inflammatory mechanisms and actually prevent disease progression. Some agents, such as inhibitors of 5-lipoxygenase-omega-3 fatty acid and zileuton-may be most useful in treatment of milder disease manifestations such as moderate synovitis. Other agents, such as oral type II collagen, minocycline, subcutaneous interleukin-1ra, and anti-CD4 monoclonal antibodies, have produced such inconsistent results that substantial additional research will be required before any conclusions may be drawn about their value. Among the most promising agents, and the most extensively studied, are tumor necrosis factor-alpha monoclonal antibodies, immunosuppressive drugs such as cyclosporine and mycophenolate mofetil, and the novel compound tenidap, which has both cytokine-modulating and anti-inflammatory properties.
9224237 Long-term followup of rheumatoid forefoot surgery. 1997 Jul Rheumatoid forefoot deformities were treated originally at the Rheumatism Foundation Hospital by metatarsal head resection (II-V) and resection of the base of the proximal phalanx of the great toe. Recurrent great toe deformity with pain in numerous cases led to a comparative series of arthrodesis of the first metatarsophalangeal joint with resection of lesser metatarsal heads. At an average followup period of 3 years, the clinical evaluation and patient assessments were slightly in favor of arthrodesis. However, the patients' evaluation at 14 years was slightly in favor of resection. Measured in the plane of the first metatarsophalangeal joint, the recommended fusion position is 15 degrees valgus and 30 degrees dorsiflexion (females) and 25 degrees dorsiflexion (males). The position of the fusion is critical for a successful surgical outcome. Although both surgical methods give good pain relief and patient satisfaction, there is a risk of reoperation in the long term.
10450678 Influence of radiation synovectomy on articular cartilage, synovial thickness and enhancem 1999 Aug Radiation synovectomy is a safe and effective treatment for chronic synovitis that is refractory to the repetitive, intra-articular application of glucocorticosteroids in patients with rheumatoid or seronegative arthritis. Short-term and long-term effects of radiation synovectomy on articular cartilage, synovial enhancement and thickness were assessed in a prospective, clinical trial by MRI. METHODS: Thirteen patients (mean age 39+/-13 y) were treated with a median activity of 8.4 GBq 165Dy ferric hydroxide, a radionuclide with favorable physical properties and a well-documented clinical safety and efficacy profile. MRI was performed on a 1.5-T MR unit using a circular polarized knee coil. RESULTS: After a mean observation period of 13 mo, a marked reduction in synovial enhancement was observed in 10 patients. The mean reduction in baseline synovial thickness (mean 7.6+/-3.0 mm) was 24% (P = 0.03) at 1 wk and 42% (P = 0.01) about 1 y after treatment, respectively. Clinically, 9 of 13 patients (69%) exhibited persistent response to radiation synovectomy. The local clinical score, as defined by the reduction in pain, pannus, joint effusion and by the increase in the range of motion, improved significantly (P = 0.01), from a median of 7 (range 4-10) to a median of 2 (range 0-9). One year after treatment, changes in the local clinical score were related to the decrease in synovial enhancement in MRI (r = 0.7, P = 0.008, n = 12). There were no persistent adverse effects, nor was there evidence for any severe radiation-induced damage to the articular cartilage. On later follow-up images, the structure of the articular cartilage remained unaltered in all but 3 patients, who had new, superficial erosions most likely attributed to an active disease with persistence of inflammation. CONCLUSION: This study suggests that radiation synovectomy with 165Dy-ferric hydroxide is effective in terms of reducing chronic synovitis without causing detectable harm to the articular cartilage, as shown by MRI.
9088526 Early rheumatoid arthritis. Future treatment. 1997 Feb As the pathophysiology of rheumatoid arthritis (RA) becomes more clearly defined there is the expectation that biotechnological advances may allow additional forms of therapeutic intervention that are specific for the disease process. The purpose of this review is to describe the use of biological agents in the treatment of RA. Encouraging results in animal models using vaccines based on the pathogenic T-cell or the autoantigen have prompted the design of selective immune-based therapies. Preliminary studies following this strategy have not yet shown clinical efficacy. The results of early studies with monoclonal antibodies against leukocyte surface antigen were promising but were not sustained in controlled studies. Exciting data have been collected from placebo-controlled studies of monoclonal antibodies against TNF alpha. The development of biological agents in RA may not be as quick as expected but the steady progress makes it likely that our weapons to combat unwanted autoimmune responses will become more accurate and effective.
9438581 Lacrimal immunoglobulins in rheumatoid arthritis patients with or without Sjögren's syndr 1998 The aim of the present study was to analyse immunoglobulin G, A, and M levels in tears of patients with rheumatoid arthritis with or without keratoconjunctivitis sicca (KS) which define Sjögren's syndrome (SS). Tears were collected from the lower cul-de-sac by capillarity (100-300 microl). Tear IgG, IgA and IgM levels were determined by radial immunodiffusion. Samples diluted 1:10 were used for IgA and IgG and non-diluted ones for IgM. Fifty-three patients with rheumatoid arthritis and 30 healthy control subjects were studied. In all individuals IgA predominated in tears, IgG levels were low but with a very wide range and IgM was present in very low concentrations. The IgG concentration in tears showed statistically significant differences between the control group and that of rheumatoid arthritis and KS. IgG in tears correlated positively with the rose bengal test (r=0.2848, p<0.05) and negatively with the Schirmer test (r=0.3042, p<0.05). Tear IgG measurement might provide a marker for eye involvement in patients with rheumatoid arthritis and KS which define SS.
10913061 Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. 2000 Aug BACKGROUND: Recent epidemiological studies have suggested that smoking is a risk factor for rheumatoid factor (RF) positive rheumatoid arthritis (RA). Being overweight, high serum cholesterol, and dietary factors have in some studies been found to be associated with the risk of RA. No attention, however, has been paid to coffee consumption as a risk determinant, though it is a shared covariate of the alleged risk factors. OBJECTIVES: This study aimed at examining coffee consumption for its associations with RF positivity and with the risk of RA. METHODS: Coffee consumption was studied, firstly, for its association with RF (sensitised sheep cell agglutination titre >/=128) in a cross sectional survey of 6809 subjects with no clinical arthritis, and secondly, for its prediction of RA in a cohort of 18 981 men and women who had neither arthritis nor a history of it at the baseline examination in 1973-76. Up to late 1989, 126 subjects of the cohort study had developed RA, of whom, 89 were positive for RF by the time of diagnosis. RESULTS: In the cross sectional survey the number of cups of coffee drunk daily was directly proportional to the prevalence of RF positivity. Adjusted for age and sex this association was significant (p value for linear trend, 0.008), but after further adjustment for smoking the linear trend declined below significance (p=0.06). In the cohort study there was an association between coffee consumption and the risk of RF positive RA that was not due to age, sex, level of education, smoking, alcohol intake, body mass index, or serum cholesterol. After adjustment for these potential confounders the users of four or more cups a day still had a relative risk of 2.20 (95% confidence interval 1.13 to 4.27) for developing RF positive RA compared with those drinking less. Coffee consumption did not predict the development of RF negative RA. CONCLUSION: Coffee consumption may be a risk factor for RA, possibly through mechanisms contributing to the production of RF. This hypothesis remains to be tested in further studies.
10571014 Glycosylation and rheumatic disease. 1999 Oct 8 Rheumatoid arthritis (RA) and other rheumatic diseases are associated with a significant defect in the galactosyltransferase enzyme that results in a profound change in the galactosylation of immunoglobulin G. This change has been demonstrated to be integrally associated with pathogenic mechanisms associated with inflammation in RA. It is not thought that these changes are unique to RA, but it is thought that there may be subtle changes in the disruption of glycosylation homeostasis causing a unique sugar change to be associated with a number of other rheumatic diseases. This is referred to as 'sugar printing the rheumatic diseases' and may be a concept useful both diagnostically and therapeutically.
11502070 TNF and TNFR biology in health and disease. 2001 Jun Many insights have been gained into cytokine-regulated control of inflammatory processes and host defence in recent years. Evidence has also gradually accumulated that cytokine cascades play a central role in events regulating cell death and differentiation. Further developments include an understanding that the biological effects of the tumor necrosis factor-alpha (TNF-alpha or TNFSF) cytokine may be regulated by soluble TNF receptor binding and that modulation of receptor levels may permit physiological inhibition of TNF action. There has been a gradual realisation of the value of TNF/TNFR ratios as predictors of disease outcome, and the discovery of functional regulatory polymorphisms of the TNF gene and mutations of TNFRSF1A (TNFR1 receptor) have led to conceptual breakthroughs in our understanding of the genetic control of inflammation. However the exact mechanisms by which TNFRSF1A mutations give rise to disease susceptibility are not yet well understood. Over the past 10 years these concepts have been used as the basis for successful anti-TNF therapy of autoimmune diseases like rheumatoid arthritis (RA) and Crohn's disease.
11708414 Effect of recombinant human erythropoietin and intravenous iron on anemia and disease acti 2001 Nov OBJECTIVE: To investigate whether treatment of anemia of chronic disease (ACD) in patients with rheumatoid arthritis (RA) with recombinant human erythropoietin (rHu-Epo) in combination with intravenous (i.v.) iron influences health related quality of life (HRQoL) and clinical outcome including disease activity. METHODS: Thirty patients with ACD and RA were treated with 150 IU/kg rHu-Epo twice weekly for 12 weeks. As well, in case of functional iron deficiency 200 mg of iron-sucrose per week was given intravenously. Vitality and fatigue as dimensions of HRQoL were evaluated by the vitality subscale of the Short Form-36 (SF-36-VT) and the Multidimensional Assessment of Fatigue (MAF). Muscle strength was measured by the Muscle Strength Index. RESULTS: All 28 patients completing the study responded to treatment; 23/28 patients developed functional iron deficiency and received i.v. iron (mean absolute dose 710 +/- 560 mg). Average hemoglobin concentration increased from 10.7 +/- 1.1 to 13.2 +/- 1.0 g/dl after a mean treatment period of 8.7 +/- 2.3 weeks. Muscle strength increased from 43.5 +/- 11.2 to 49.1 +/- 12.9 and SF-36-VT from 28.2% +/- 14.3% to 47.1% +/- 20.8%. while fatigue decreased (MAF from 34.7 +/- 9.3 to 25.0 +/- 11.3). Among the disease activity variables the number of swollen/tender joints, erythrocyte sedimentation rate, Disease Activity Score, and RA Disease Activity Index improved significantly during treatment. CONCLUSION: Treatment of ACD in RA patients with rHu-Epo and i.v. iron is safe and effective in correction of anemia, increases muscle strength. improves vitality, and lowers fatigue. In addition we observed a reduction of disease activity.
10399795 Structural mechanisms of bone loss in iliac biopsies: comparison between rheumatoid arthri 1999 To assess the mechanisms that cause generalized osteoporosis in rheumatoid arthritis (RA), 40 postmenopausal women with RA (46-74 years) and 40 age-matched controls with osteopenia underwent iliac bone biopsies. A structural analysis of histomorphometry and two-dimensional strut analysis were performed. As compared to those with primary osteoporosis, there were a few unique characteristics in those with RA. Trabecular thickness and wall thickness declined with age, and this decline was especially accelerated by glucocorticoids. Decreased connectivity of the trabecular (Nd.Nd) was more prominent than the disappearance of the nodes. The connectivity of cortical bone to the nodes (Ct.Nd) and cortical thickness significantly decreased with age. With glucocorticoid therapy, the disappearance of the nodes was accelerated. In the case of vertebral compression fractures, the parameters of Nd.Nd and Ct.Nd significantly decreased. Although a bone biopsy is needed to analyze strut, this method is useful to evaluate the quality or intensity of the bone.
9440143 Effect of steroid treatment on the migration behaviour of neutrophils in patients with ear 1997 The influence of methylprednisolone on the migratory characteristics of neutrophil granulocytes was investigated in 10 patients with early rheumatoid arthritis (RA) and compared to 12 controls. The migration of neutrophils was measured with a whole-blood membrane filter assay with and without stimulation by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP). Total migration index (TMI), distribution characteristics (DC) and the product of TMI and DC (neutrophil migratory activity; NMA) served to characterize the migratory behaviour of neutrophils. The data demonstrated an increased polymorphonuclear leucocyte (PMN) migration in patients with early RA, indicating a bystander role of PMNs in inflammatory joint injury. Treatment with methylprednisolone reduced significantly the penetration depth (DC) of neutrophils, but did not influence the number of migrating cells (TMI). The unstimulated NMA was significantly reduced due to the marked DC reduction, whereas steroids did not influence the stimulated NMA of neutrophils. A significant reduction in PMN penetration depth was demonstrated only after a steroid therapy of at least 10 days, suggesting that a longer period of steroid therapy is necessary to provide effective inflammatory control.
10527958 Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthrit 1999 Oct 15 We investigated 43 patients with seropositive rheumatoid arthritis (RA) under a therapy with methotrexate (MTX) or azathioprine (AZA). All patients fulfilled the American Rheumatism Association criteria. It has been a retrospective study over 2.6 years (MTX: 26 patients, average age 54 +/- 14.6 years, female/male 19:7, AZA: 17 patients, average age 59.4 +/- 12.5 years, female/male 12:5). The mean duration of disease was 8 years (+/- 5.3) in the MTX-group and 7 years (+/- 7.3) in the AZA-group. The mean dose of MTX was 13. 3mg/week and of azathioprine 142.6mg/ daily. The drugs were administered orally. - Radiographs of hands, wrists and feet obtained at enrollment and at review were scored by a rheumatologist according to a modified Larsen score. Radiographic damages were counted in 25 joints of each hand and in 25 joints of each foot. The change in radiological score was calculated by subtracting the joint damage scores at follow up with first damage score at inclusion. The rate of radiological progression (YP) was calculated by dividing the change in radiological score by the number of years during the period of study. - Only 3 patients with MTX showed no radiologic progression. All other patients of both groups showed progressive radiological changes. - The study demonstrated no significant difference in the rate of radiologic progression between the different treatment-groups. However, there was a trend that MTX treated patients (YP 5 +/- 4.4) had a slower radiographic progression compared with those treated with AZA (YP 8.5 +/- 7.7). MTX may be more effective in patients at an earlier stage of rheumatoid arthritis. - When we started a therapy with AZA or MTX in a later period of disease we revealed a better influence of radiologic progression under AZA and a trend towards an increase of the radiologic progression under MTX. - Probably there is a decreasing effect of MTX in later periods of the disease. - The corticoid dose reduction was higher under AZA (AZA: Reduction about 58.6%, MTX: 25%) over the study duration. - Our investigation demonstrated a trend towards reduced radiological progression in MTX treated patients compared to AZA, however statistic analysis showed no significant difference in the rate of radiologic progression. At an earlier stage of the disease there is a better influence of MTX in radiologic progression, at the later stage we showed a slowing of radiological deterioration in AZA treated group.
9376989 Seroreactivity to Borrelia burgdorferi antigens in early rheumatoid arthritis: a case-cont 1997 Sep This study investigates the seroreactivity to Borrelia burgdorferi antigens of patients suffering from rheumatoid arthritis (RA) for < 5 yr. Subjects were matched with controls for age, sex and area of residence in order to minimize the risk of differential exposure to B. burgdorferi. A total of 57 pairs were tested by immunofluorescence assay (IFA) and Western blotting. Only two RA patients showed positive IFA results, and another was positive by Western blot analysis. No significant difference in Lyme seropositivity was detected between cases and controls using either serological test. Furthermore, no significant difference in antibody response was observed to specific or non-specific proteins (e.g. Osp C, 93 kDa protein, flagellin, heat shock proteins). These results do not support the previous suggestions that B. burgdorferi may be involved in the aetiology of RA, or that RA favours the production of antibodies that cross-react with B. burgdorferi proteins.
10778801 HLA-DR expression of synovium and correlation with clinical features of patients with rheu 2000 Mar To investigate whether the expression of human leukocyte antigen-DR (HLA-DR) in synovial tissues obtained at synovectomy contributes to the clinical features of patients with rheumatoid arthritis (RA), immunohistochemical analysis was performed to determine the intensity and pattern of HLA-DR expression in synovial tissue from 96 patients with RA. The clinical features before and 1 year after the synovectomy were investigated. At the time of the surgery, duration of morning stiffness was associated with the degree of HLA-DR expression in synovial lining layer, and this synovial lining expression of HLA-DR was more frequently observed in elbow and wrist joints than in knee joint. In patients who underwent knee synovectomy, erythrocyte sedimentation rate and C-reactive protein level one year after the surgery were significantly higher in the patients with intense expression of HLA-DR in the synovial lining. Our findings showed that the expression of HLA-DR in the synovial lining contributes to several clinical features, and the expression in large joint such as knee may related with disease course of patients with RA.
9227349 The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-ind 1997 May Collagen-induced arthritis was produced in rats by intradermal immunization with type II collagen and the expression and production of monocyte chemoattractant protein-1 (MCP-1) were examined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Northern blot analysis. Two to three weeks after the immunization, the hindfeet showed swelling and redness, followed by the development of severe arthritis, particularly in the ankle joints. During this period, prominent infiltration of neutrophils and macrophages was observed. Sandwich ELISA and Northern blot analysis revealed that MCP-1 concentrations in the joint lavages and MCP-1 mRNA levels in the joint tissues both peaked at 2 weeks after the immunization. By immunohistochemistry, various types of cells, particularly neutrophils, macrophages, synovial cells, and vascular endothelial cells, stained positively for MCP-1. Finally, injection of a neutralizing monoclonal antibody against rat MCP-1 significantly decreased the number of exudate macrophages in the lesions and reduced the ankle swelling by about 30 per cent compared with controls. These results suggest that MCP-1 plays a critical role in this model in the recruitment of monocytes and in the development of arthritis.
9608323 T cells and related cytokines. 1998 May T cells play a critical role in rheumatoid arthritis. They are probably continuously involved in pathogenesis, from the initiation to the chronic stage. As recent studies have demonstrated, the part they play in rheumatoid arthritis is closely linked to the roles of macrophages and mesenchymal cells, because they all interact through autocrine, paracrine, and cell-contact pathways. This paper reviews recent work and research regarding the specific role of T cells in the pathogenesis of rheumatoid arthritis.