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ID PMID Title PublicationDate abstract
1471430 [Possibilities and limits of daily coping with illness by patients with chronic polyarthri 1992 A central problem of persons with chronic polyarthritis is the necessary adaptation to deteriorating health in everyday activities. Difficulties and burdens of this adaptation are parts of the study undertaken in the Unna Model, which was part of the research on "Local Services for CP-Patients". In the first part two female patients are described with regards to these everyday problems of "normalization", i.e., including health conditions resp. daily activities. An important element is the microsocial context: mutual expectations and support in the family and at the work place. In the second part some quantitative results of interviews with 93 cP-patients are presented. They show the importance that is given by these interviewed persons to these daily adaptations, self help, and support.
8324935 Therapy of rheumatoid arthritis with mycophenolate mofetil. 1993 Mar Mycophenolate mofetil, a pro-drug for mycophenolic acid, is an investigational immunosuppressive compound that is being developed for the treatment of rheumatoid arthritis (RA). The drug and its primary metabolite, mycophenolic acid, inhibit the de novo pathway of purine biosynthesis and have greater anti-proliferative effects on lymphocytes than on other rapidly dividing cells. Significant clinical improvement has been seen in many mycophenolate mofetil-treated RA patients who have been refractory to treatment with a variety of disease-modifying anti-rheumatic drugs (DMARDs). Treatment with mycophenolate mofetil reduces rheumatoid factor titres, immunoglobulin (IgG, IgM, and IgA) levels, and the total number of T cells (CD2) in RA patient peripheral blood; in addition, lymphocyte mitogen responses are inhibited and delayed hypersensitivity skin test reactivity is decreased. A dose of 2 g daily is more effective than lower doses, including several pulsing regimens. The most frequent adverse events reported by patients on mycophenolate mofetil are gastrointestinal, mainly nausea, vomiting, abdominal pain, and diarrhea. RA studies have demonstrated no clinically significant nephrotoxicity, hepatotoxicity, or bone marrow toxicity attributable to mycophenolate mofetil.
8531840 The estrogen connection: the etiological relationship between diabetes, cancer, rheumatoid 1995 Aug For some considerable time, there has been a growing awareness that defective essential fatty acid metabolism plays a causal role in the pathogenesis of both schizophrenia and non-insulin-dependent diabetes mellitus (NIDDM) but the influence of defective essential fatty acid metabolism in the pathogenesis of rheumatoid arthritis and cancer is less well appreciated. An EFA deficiency, or defective EFA metabolism, negatively influences prostaglandin synthesis and glucose regulation and transport. Moreover, defective EFA metabolism negatively influences estrogen availability which contributes to the observed gender bias some of these illnesses manifest. While fluctuations of estrogen are known to contribute to the pathogenesis of these conditions, so also do fluctuations of IGF-II and there is some suggestion that IGF-II and insulin may well be inversely regulated. In addition, insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, and schizophrenia are thought to be autoimmune disorders, while cancer is associated with immune system failure. Consequently, this paper aims to examine the pathophysiological similarities and differences between mental illness, diabetes, rheumatoid arthritis and cancer in respect of which the causal relationship that obtains between essential fatty acids, estrogen, IGF-II, glucose regulation and autoimmunity will be addressed.
7783072 The relationship between self-reported pain and sociodemographic variables, anxiety, and d 1995 Mar OBJECTIVE: Self-reported pain is one of the core endpoint measures in RA. The objective of this cross sectional study of 238 patients with rheumatoid arthritis (RA) was to examine the relationship between self-reported pain intensity, sociodemographic variables, anxiety, and depressive symptoms. METHODS: A weighted sum score of pain intensity was constructed by combining a visual analog pain scale with items from the Arthritis Impact Measurement Scales (AIMS) and the Nottingham Health Profile. Symptoms of anxiety and depression were measured by subscales of RESULTS: Multiple regression analyses showed no significant effects of age, sex, income, or level of education on self-reported pain intensity, whereas there was a significant association between the pain index and anxiety and depressive symptoms. The correlation between the pain index and anxiety, and the pain index and depression, was 0.46 for both. Controlling for sociodemographic variables, the Ritchie index, erythrocyte sedimentation rate, and C-reactive protein, the standardized regression coefficients were 0.33 and 0.31 of the pain index on the AIMS anxiety and depression subscale, respectively. Furthermore, the results indicate that the effect of inflammation on mental distress is mediated by pain. CONCLUSION: Self-reported pain in RA is not significantly influenced by sex, age, level of education, or income. Even when controlling for disease activity, there was a considerable correlation between self-reported pain and mental distress. Furthermore, our study lends support to the hypothesis that mental distress is mainly secondary to pain rather than vice versa.
8489537 Marital status and the progression of functional disability in patients with rheumatoid ar 1993 May OBJECTIVE: To determine if marital status is associated with differences in rates of progression of functional disability in patients with rheumatoid arthritis (RA). METHODS: A community cohort of 282 persons with RA was followed prospectively for up to 9.5 years. The progression of functional disability over time was determined using the Health Assessment Questionnaire Disability Index, which was completed by study participants every 6 months. RESULTS: At study entry, the Disability Index was 1.1 +/- 0.8 (mean +/- 1 SD) (possible range 0-3) among the 188 married participants and 1.3 +/- 0.9 among the 94 unmarried participants. Over time, the rate of progression of functional disability was generally higher among unmarried participants. However, the extent of this difference varied somewhat over the disease course, with rates of progression higher among unmarried than among married participants during years 5-7 and years 17-29 of RA. Overall estimated rates of progression, adjusted for the effects of other sociodemographic factors, were 0.03 Disability Index units per year in unmarried participants and 0.01 Disability Index units per year in married participants (P < 0.0001). CONCLUSION: Marriage, possibly reflecting the influence of social support, is associated with a lower rate of progression of functional disability in persons with RA.
7582720 Antineutrophil cytoplasmic antibodies in inflammatory arthritis--potential for misdiagnosi 1995 Sep Antineutrophil cytoplasmic antibodies (ANCA) are well described in Wegener's granulomatosis and some forms of vasculitis. They have also been described in patients with arthritis, but the specificity of these ANCA and their relationship to the presence of vasculitis, antinuclear antibodies (ANA) and granulocyte-specific ANA (GS-ANA), and to disease activity are uncertain. We studied 101 patients with forms of inflammatory arthritis and detected four cytoplasmic ANCA, eight perinuclear ANCA and 16 atypical ANCA. There was no association between the presence of ANCA and ANA or rheumatoid factor. No anti-PR3 antibodies were found and no strong anti-myeloperoxidase antibodies were detected. Four GS-ANA were detected and were distinct from ANCA. There was no association between rheumatoid arthritis disease activity or disability and ANCA status. ANCA did not predict vasculitis over a 3 yr follow-up. These ANCA appear to be epiphenomena. Their importance lies in their potential to mislead physicians towards a misdiagnosis of vasculitis.
7532319 Tenidap: a novel cytokine-modulating antirheumatic drug for the treatment of rheumatoid ar 1994 Tenidap is a novel, once-daily, cytokine modulating antirheumatic drug indicated for the treatment of rheumatoid arthritis (RA). In vitro, tenidap significantly inhibits the production of the pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumour necrosis factor in human cell lines, and inhibits cytokine-mediated processes such as cartilage degradation, bone resorption, metalloprotease synthesis, endothelial cell adhesion and monocyte differentiation. Tenidap also inhibits cyclo-oxygenase. In RA patients, tenidap 120 mg/day is clinically equivalent to the combination of disease-modifying antirheumatic agents plus non-steroidal anti-inflammatory drugs (NSAIDs) and significantly more effective than NSAIDs. Tenidap also produces rapid, profound and sustained reductions in the serum levels of the acute phase proteins, C-reactive protein and serum amyloid A, an effect suggestive of disease modifying properties. In addition, tenidap reduces circulating levels of IL-6 in RA patients. Tenidap is well tolerated.
7718957 Amyloidosis secondary to rheumatoid arthritis associated with plexiform change in bilatera 1994 Dec A 70-year-old woman with rheumatoid arthritis (RA) and secondary amyloidosis presented repeated consciousness loss. The pathological findings at autopsy revealed multi-organic deposits of amyloid A-protein and so-called 'plexiform change' of blood vessels in bilateral temporal lobes. The arterial plexiform change, which is found in the lung specimen of primary pulmonary hypertension, might be a new pathological cerebrovascular change associated with RA.
9065054 [Pathology and progression of intra-articular inflammation in rheumatoid arthritis]. 1996 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of the connective tissue preferentially involving joints. It is considered an autoimmune disease. Autoantibodies against immunoglobulins, so called rheumatoid factors, are detected in 80% of the patients. The etiology of the disease is unknown. An interesting association to different HLA types is observed. An overview about pathology and pathogenesis of the arthritis is given. After an initial vasculitis the synovial membrane is colonised by T and B cells. Among the more frequent T cells more CD4+ cells than CD8+ cells are found. Additionally activated cytotoxic T cells and NK cells are present. Migration of the lymphocytes is realised by adhesion molecules. By homing of lymphocytes the synovial membrane is structurally transformed an appears morphologically like a secondary immunoorgan. Enhanced pathogenic humoral and cellular immune responses are going on influenced by activated CD4+ cells associated with macrophages via MHC class II molecules. Rheumatoid factors and antibodies against type II collagen are produced, cytotoxic immune complexes are formed. Cellular interactions induce the expression of proinflammatory cytokines and growth factors, the so called pannus is formed. Aggressiveness of the pannus depends on the HLA pattern. T cell rich synovial tissue is positive for HLA-DR4 in 70% of the cases. Only 15% of B cell rich membranes show this HLA type. The T cell rich type shows a high aggressiveness. Pannus destroys articular cartilage and subchondral bone. Cells at the invasion site of the pannus are classified differently. The majority of the investigators characterizes them as macrophages others as activated fibroblasts. The latter opinion is supported by experiments done in SCID mice. RA is characterized by three pathogenic mechanisms: 1. chronic inflammation of the synovial membrane, 2. enhanced pathogenic T and B cell dependent immunoreactions including autoimmune phenomenons, 3. hyperplasia of synovial tissue. Which mechanisms is on the beginning and induces the others consecutively is an open question. Macrophages and CD4+ cells associated via MHC class II molecules play a central role in the pathogenesis of RA.
8358973 Electrophoretic separation of alkaline phosphatase isoenzymes in synovial fluid and serum 1993 Jun The alkaline phosphatase enzyme in both serum and synovial fluid from 28 cases of rheumatoid arthritis and from the serum of 30 controls was measured. The enzyme was further studied by separating its isoenzymes to clarify their origin in both synovial fluid and serum of 10 patients with elevated level of the enzyme in their sera. The level of the enzyme in serum was elevated in 37% of patients confirming previous reports on that point. The most abundant isoenzyme in the synovial fluid (66.9%) was found to be bone in origin while in serum the most abundant isoenzyme was found to be hepatic (60.5%). This may be responsible for increased bone turn-over in rheumatoid joints whether in formation or resorption.
1609236 [Therapeutic maintenance dose with methotrexate in rheumatoid polyarthritis. Prospective s 1992 Mar One hundred and ninety one patients with rheumatoid arthritis were included in an open prospective trial with the aim of evaluating the acceptability, efficacy and therapeutic maintenance levels of methotrexate. The mean treatment duration was 19 +/- 13.2 (3-58) months and the mean weekly dose of methotrexate 10.2 +/- 0.2 mg. Analysis of the 191 patients by intention to treat showed a statistically significant improvement in all clinical parameters as well as a significant fall in sedimentation rate with a corticosteroid-sparing effect. The therapeutic maintenance level of methotrexate was 73% at one year, 65% at 2 years and 46% at 5 years. Adverse reactions occurred in 71 patients (37.1%) including 30 who stopped methotrexate permanently as a result. With cautious and strict patient selection, methotrexate could be used in RA as basic treatment of first choice.
8403540 Selective infiltration of B cells committed to the production of monoreactive rheumatoid f 1993 Oct B cells were directly cloned using EBV transformation fron the synovial tissue of patients with rheumatoid arthritis (RA), the objective being to investigate the B cell repertoire at the site of inflammation. The frequency of clones producing antibodies with rheumatoid factor (RF) activity was approximately 10% in those from the RA synovial tissue. Similar percentages of B cell clones from the peripheral blood of both RA patients and healthy controls also produced RF. However, almost all of these clones from the peripheral blood produced RF reactive not only with rabbit IgG or human IgG Fc but also with several other antigens (polyreactive). Only one of 654 clones (0.15%) from the RA peripheral blood produced RF specific to rabbit IgG or human IgG Fc (monoreactive). On the other hand, the frequency of clones producing monoreactive RF was approximately 30 times higher in RA synovial tissue. Furthermore, these B cells were activated in vivo to produce antibodies, since monoreactive RF was spontaneously produced from synovial tissue cells without the addition of B cell stimulators. No clones producing monoreactive RF were obtained from the synovial tissue of patients with osteoarthritis. These results suggest selective infiltration and/or proliferation of B cells committed to the production of monoreactive RF in RA synovial tissue.
1581147 Surgery of rheumatoid arthritis in peripheral joints. 1992 Apr The wide range of publications that are the basis of the following discussion highlight the difficulties of scientific assessment of surgical treatment in rheumatoid arthritis. Some factors that bedevil objective assessment include the variable clinical course of the disease, parallel pharmacologic and surgical treatments, the virtual impossibility of identifying appropriate control subjects and imprecision in endpoint measurement. Nevertheless, study design in rheumatoid arthritis surgery is becoming more sophisticated through the efforts of numerous individuals and groups such as the European Rheumatoid Arthritis Surgical Society.
7748020 Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheuma 1995 Mar OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.
8448609 The relationship of haemoglobin to serum erythropoietin concentrations in the anaemia of r 1993 Mar Previous studies of the erythropoietin response to anaemia in RA have yielded conflicting findings. Some have found the response to be impaired and others have found a normal response. We have compared erythropoietin (EPO) levels measured by radioimmunoassay, in 54 anaemic rheumatoid patients and 55 patients with iron deficiency anaemia but no inflammatory disease. The erythropoietin response in the rheumatoid patients was impaired compared with the control group (P < 0.025) but only seven rheumatoid patients showed a response which fell below the 95% confidence intervals predicted for the control group. Rheumatoid patients who fell within the highest quartile for serum ferritin concentrations (i.e. those most likely to have anaemia of chronic disease) had significantly lower EPO levels compared with the control group (P < 0.01). EPO levels in rheumatoid patients within the lowest quartile for ferritin (i.e. those with iron deficiency anaemia) were not significantly different from the control group (P = 0.670). The difference in EPO response between the RA patients in the upper and lower quartile for ferritin approached but did not achieve significance (P = 0.056). In a second study 15 anaemic RA patients were given a 5-day course of oral prednisolone 1.5 mgkg-1. Hemoglobin did not rise significantly until day 4 but EPO levels fell by day 1 (P < 0.005) and remained lower than pretreatment values throughout the study. Thus, in RA patients, anaemia of chronic disease is associated with inappropriately low EPO concentrations but this does not appear to be the major cause of the anaemia and Hb response to prednisolone does not depend upon an increase in EPO concentration.
8012330 [Evaluation of a quality of life scale (AIMS2) in rheumatology]. 1993 Oct OBJECTIVES: To evaluate the feasibility, relevance, and sensitivity of the French version of the revised Arthritis Impact Measurement Scale (AIMS2) in patients with rheumatoid arthritis or osteoarthritis of the hip. METHODS: translation of the English-language AIMS2 into French using the back-to-back technique; evaluation of feasibility on the basis of a) time needed to complete the AIMS2; b) percentage of questionnaires with at least one missing answer or one answer indicating that the question was misunderstood; evaluation of relevance on the basis of correlations between AIMS2 scores and conventional parameters for evaluating the activity of rheumatoid arthritis (85 patients); evaluation of sensitivity on the basis of total hip replacement-induced improvements in AIMS2 scores versus other conventional scores used to evaluate activity of osteoarthritis of the hip (48 patients). RESULTS: feasibility, mean time needed to complete the AIMS2 was 23 minutes in rheumatoid arthritis patients and 26 minutes in osteoarthritis patients. Forty per cent of patients failed to answer at least one question and 21% misunderstood at least one question; relevance: conventional parameters used in rheumatoid arthritis accounted for 51% of AIMS2 score variance, suggesting that the AIMS2 provided information not supplied by conventional parameters. SENSITIVITY: after total hip replacement for osteoarthritis, there were statistically significant decreases in all AIMS2 scores (with the exception of function and work). CONCLUSION: These data suggest that the AIMS2 score is not an easy evaluation tool but is both relevant and sensitive. These findings require confirmation by longitudinal studies.
7768056 Targeting TNF alpha for the therapy of rheumatoid arthritis. 1994 Nov Our pre-clinical studies have demonstrated a pathogenic role for TNF alpha in RA. Firstly, TNF alpha and its receptors are upregulated and co-expressed in the synovium and cartilage-pannus junction of RA joints. Secondly, mononuclear cells from RA joints maintained in culture produce many cytokines with pro-inflammatory activity, including TNF alpha. Neutralizing TNF alpha antibodies in vitro reduces the production of these pro-inflammatory cytokines, including IL-1, IL-8, and GM-CSF. Thirdly, when injected into arthritic DBA/l mice with collagen-induced arthritis, monoclonal anti-TNF antibodies decrease inflammatory damage of joints. Clinical trials employing cA2, a monoclonal chimeric anti-TNF alpha antibody, in open-label and randomized placebo-controlled studies have demonstrated a dose-dependent efficacy with impressive improvement in disease activity and acute phase responses lasting several weeks. We conclude that TNF alpha is a critical mediator of inflammation in RA and is an important therapeutic target in this disease.
7880187 Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass 1995 Mar OBJECTIVE: Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population. METHODS: Patients with active RA diagnosed at age > or = 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years. RESULTS: During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group. CONCLUSION: Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period.
8967184 [Radiologic healing phenomena in chronic polyarthritis treated with methotrexate or sodium 1996 Jul PROBLEM: Do radiographs of hands and forefeet obtained from patients with rheumatoid arthritis present with healing phenomena? What is their importance relative to progressive changes? METHODS: Dorsopalmar/-plantar radiographs of hands and forefeet of 43 patients with early rheumatoid arthritis (median disease duration 1.7 years, anatomical Steinbrocker's age < or = 2, patients selected from a prospective study, treatment with methotrexate vs gold-sodiumthiomalate) were obtained at months 0, 6, 12, 24 and 36. Radiographs were evaluated without knowing the mode of treatment at 34 sites according to their time sequence for the following variables: a modified Larsen index, numbers of erosive and of radiologically active joints, and the numbers of joints being improved vs. deteriorated in relation to the preceding x-ray. RESULTS: The radiologic progression could be measured by both a score derived from the modified Larsen index as well as by the numbers of erosive joints with the result of an increasingly crescent, but flattening curve. The number of erosive joints was more sensitive to progression than the score derived from Larsen index. The number of joints deteriorating, compared with the preceding x-ray, decreased from month 6 to month 36 from 16.1% to 7.1% resp. At the same time, 90% of patients increasingly developed radiologic improvement in 2.9% zu 9.3% of joints, including diminution in size and recortication of erosions and particular cysts with a "filling in" by trabecular bone and recovery of a bony outline. There were no relevant differences between therapy groups. CONCLUSIONS: Progression in early rheumatoid arthritis is best measured by the number of joints with erosions. Reparative signs show up with increasing frequency during the course of the disease. After 3 years of treatment the numbers of joints exhibiting improvement predominate those with deterioration. The data support the concept of early aggressive therapy of rheumatoid arthritis and suggest the inclusion of reparative phenomena into the criteria for improvement of this disease.
1346960 Novel genetic markers of rheumatoid arthritis in Chilean patients, by DR serotyping and re 1992 Mar OBJECTIVE: The analysis of genetic markers of rheumatoid arthritis (RA) in a population in which the DR4 serotype is not strongly associated with the disease. METHODS: Chilean RA patients (56 seropositive and 22 seronegative) and 141 controls were studied by serotyping. Southern blot analysis of Bam HI restriction fragment length polymorphism (RFLP) was done in genomic DNA from 46 patients with seropositive RA, 17 patients with seronegative RA, and 45 controls, using a complementary DNA probe specific for DRB1 genes. RESULTS: The prevalence of the HLA-DR9 haplotype was strikingly higher in seropositive RA patients (21%) than in controls (3%) (Pcorr less than 0.0008, by Fisher's exact test; relative risk [RR] = 9.34). The prevalence of DR4 and DR1 haplotypes, although slightly increased, did not achieve a significant preponderance. The simultaneous presence of two Bam HI fragments (3.6 kb and 4.5 kb) was found with higher prevalence in seropositive patients (83%; RR = 9; Pcorr less than 0.00002) than in controls (36%), and seemed higher in seronegative RA patients as well (71%; RR = 4). Furthermore, its prevalence remained increased in comparisons of DR4 positive controls (36%) with DR4 positive seropositive patients (100%; RR = 67; Pcorr less than 0.0002) and DR4 positive seronegative patients (100%; RR = 36; Pcorr less than 0.006), even after excluding the DR9 positive individuals. A tendency toward higher association with DR1 seropositive RA patients (67%; RR = 12), a group with no DR4 or DR9 positive individuals, than in DR1 positive controls (14%), was also observed. CONCLUSION: The HLA-DR9 haplotype was definitively consolidated as a very strong genetic marker exclusively for seropositive RA in Chilean patients, as suggested by our previous observations. RFLP analysis showed that the simultaneous presence of 3.6-kb and 4.5-kb Bam HI fragments constituted a better RA marker than did any of the heretofore studied haplotypes. These fragments together would be linked to RA independently of the DR1, DR4, and DR9 haplotypes. The overall evidence indicates that Chilean seropositive RA patients display a genetic background that is different from that underlying RA susceptibility in other populations and suggests the existence of common, as well as distinct, genetic elements predisposing to seronegative and seropositive RA.
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