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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
7779116 Distinct oligosaccharide content of rheumatoid arthritis-derived immune complexes. 1995 Jun OBJECTIVE: To investigate the association between glycosylation and immune complex formation in various disease groups. METHODS: Immune complexes and IgG were isolated from serum and their carbohydrate content evaluated in a dot-blot assay using specifically binding lectins. RESULTS: Significantly more N-acetylglucosamine was detected in complexes from patients with rheumatoid arthritis (RA) than in those from patients with systemic lupus erythematosus, Crohn's disease, or infectious endocarditis, or from normal controls (P < 0.001). The immune complex concentration in the circulation was strongly associated with N-acetylglucosamine levels (P < 0.001 by chi-square analysis). CONCLUSION: The composition of immune complexes from RA patients is distinct in carbohydrate content from those found in other disease groups.
7806259 Lowered expression of C3b receptor (CR1) on erythrocytes of rheumatoid arthritis patients. 1994 Aug The number of C3b receptors (CR1) on erythrocytes (E) has been quantitated by whole cell enzyme-linked immunosorbent assay (ELISA), using a monoclonal anti-CR1 antibody, in 46 healthy individuals as controls, 58 having rheumatoid arthritis (RA) and 3 hereditary angioedema patients. The mean value of CR1 in RA (381/E) was significantly lower (p < 0.001) when compared to normal controls (646/E). In hereditary angioedema patients CR1 numbers (620/E) were found to be comparable to normal values. No significant difference was found between normal male (708/E) and female (598/E) subjects. Among the patient groups, those on steroid therapy (352/E) showed no change compared to others not receiving such therapy (408/E). The cumulative frequency curve of CR1 in the normal population showed maximum inflection at 32% and 82%. This led us to conclude that there is a trimodal distribution of receptors in the control population. Such a contention is well supported by frequency histogram, when a small group interval (0-50) was chosen. However, if large group intervals (0-100 or 0-150) were considered, a very close approximation to unimodal pattern was obtained. The factors actually contributing to low receptor numbers are yet to be elucidated.
8978962 High dose intravenous immunoglobulin (IVIg) in severe refractory rheumatoid arthritis: no 1996 Nov OBJECTIVE: A number of reports have recently suggested that high doses of intravenous immunoglobulins may exert beneficial effects in rheumatoid arthritis. One proposed mechanism for this effect is suppression of the generation of pro-inflammatory cytokines, particularly tumor necrosis factor alpha (TNF alpha). We have undertaken a prospective open study of IVIg in patients with severe refractory RA who have failed at least four second line drugs, including methotrexate, and who were receiving NSAIDs and prednisone only. METHODS: Four patients, 3 males and 1 female, with an average age of 58.25 years (range 41-69 years) and a mean disease duration of 13 years (range 9-14 years), were given IVIg at a dose of 1 g per day for 2 days once a month for 3 months. All patients had active disease at baseline as indicated by an average tender joint count of 15 and an average swollen joint count of 15.25. Clinical assessments were performed according to the WHO/ILAR recommendations at baseline and at monthly intervals up to 4 months after the initiation of IVIg therapy. Patients were classified as responders or non-responders according to the Paulus criteria. Laboratory assessment included a CBC, ESR, and whole blood cytokine ELISA for TNF alpha, TNF R1, and TNF R2 at baseline, 1 day, 7 days and 3 months after the initiation of therapy. RESULTS: None of the patients met the Paulus criteria for either improvement or worsening. Furthermore, increased TNF alpha production in lipopolysaccharide (LPS) stimulated whole blood assays was consistently noted in 3 out of the 4 patients during the course of therapy which, together with the lack of clinical efficacy, prompted us to curtail further evaluation of this therapy. CONCLUSION: We were unable to discern any beneficial effects of IVIg therapy, and suggestions that it may enhance TNF alpha generation as well as its substantial cost mandate caution in the future use of this agent in RA.
1428342 The diagnostic significance of anti-type II collagen antibody assay in rheumatoid arthriti 1992 An improved enzyme-linked immunosorbent assay (ELISA) for the detection of anticollagen antibodies in human serum has been developed. With the use of this method, antibodies against native human Type II collagen were detected in 22.7% of sera from 480 patients with rheumatoid arthritis (RA). The antibodies were found to be collagen type specific, showing no reaction with human Type I and Type III collagens. The antibodies appeared in high incidence during the early phase of the disease, and RA patients with involvement of a single joint, mono-articular arthritis, were often positive for anti-Type II collagen antibodies. In most of these patients, anti-Type II collagen antibodies preceded the appearance of rheumatoid factors. The antibodies were all negative in sera from patients with gout, osteoarthritis (OA) and non-arthritic diseases. Thus, anti-Type II collagen antibody assay may have diagnostic significance for RA patients, especially those in whom laboratory and clinical findings provide only minimal help in diagnosis.
7524132 [Substance P and rheumatic diseases]. 1994 Jun 15 Substance pertains to a group of linear molecules of 10-30 amino-acid residues produced by nervous fibers and called neuropeptides. It is a mediator of pain transmission, and modulates or stimulates the activity of several cell types, i.e. lymphocytes and mast cells. The concept of neurogenic inflammation is based on the release of substance P and related peptides by an axon eflex mechanism. In rheumatic diseases, substance P may enhance inflammatory joint reactions. In rheumatoid arthritis, high SP levels were demonstrated in synovial fluid by our group and others. Results in fibromyalgia are contradictory. Algoneurodystrophia may be modulated by substance P release. Topical use or capsaicin and development of peripheral inhibitory drugs offer novel treatments based on this concept.
8815859 Accidental injury is a serious risk in children with typical absence epilepsy. 1996 Sep OBJECTIVES: To determine if young adults with a history of typical absence epilepsy (AE) in childhood have a greater risk of accidental injury than controls with juvenile rheumatoid arthritis (JRA). To assess the nature and severity of these injuries. METHODS: All patients with AE or JRA diagnosed between 1977 and 1985, who were 18 years or older at the onset of the study, were identified from review of pediatric electroencephalographic records for the province of Nova Scotia (AE) or review of the medical records database at the only tertiary care pediatric center for the province (JRA). Fifty-nine (86%) of 69 patients with AE and 61 (80%) of 76 patients with JRA participated in an interview in 1994 or 1995, assessing nature, severity, and treatment of prior accidental injuries. Patients with AE were further questioned about injuries sustained during an absence seizure. RESULTS: Sixteen (27%) of 59 patients with AE reported accidental injury during an absence seizure, with risk of injury being 9% per person-year of AE. Most injuries (81%) occurred during anti-epileptic drug therapy. Although the majority of injuries did not require treatment, 2 (13%) of 16 patients required minor treatment and 2 (13%) of 16 were admitted to hospital. The risk of accidental injury resulting from an absence seizure in person-years at risk was highest in juvenile myoclonic epilepsy (45%), moderate in juvenile AE (14%), and lowest in childhood AE (3%). Patients with AE had a greater number of overall accidental injuries than those with JRA (P<.04), but these differences were particularly marked for bicycle (P<.003) and car accidents (P<.05) and for mild head injuries (P=.05). CONCLUSIONS: Accidental injury is common in AE and usually occurs after anti-epileptic drug treatment is started. Injury prevention counseling is indicated both at diagnosis and follow-up. Bicycle accidents pose a special risk and helmet use should be mandatory.
8832977 Retroviral risk factors in patients with autoimmune disease. 1996 Mar OBJECTIVE: Retroviruses can cause immunoregulatory disturbances and may play a role in the pathogenesis of autoimmune disorders. Little is known about the frequency of behavioral risk factors for exogenous retroviral infections in patients with autoimmune diseases. We compare the frequency of recognized risk factors for retroviral infections among patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and controls. METHODS: Patients with SLE and RA from a university rheumatology clinic and control patients were enrolled in this study. The presence of retroviral risk factors (intravenous drug use, prostitution, increased number of sex partners, sexually transmitted diseases, high risk sex partners, blood transfusion) was determined by a self-administered questionnaire. RESULTS: We surveyed 81 patients with SLE and 117 with RA and 100 healthy controls. Patients in all groups reported similar exposure to all risk factors surveyed for retroviral infection except sexually transmitted disease, which was reported more often in patients with SLE (25% of SLE versus 11% of RA and 11% of controls, p = 0.013). CONCLUSION: Self-reported retroviral risk factors were generally not increased in patients with autoimmune disease compared to healthy controls; the role of exogenous retroviruses in the pathogenesis of SLE and RA remains unclear.
9098407 A shared HLA-DRB1 sequence confers RA susceptibility in Greeks. 1993 Oct Previous serological studies of Greek rheumatoid arthritis (RA) patients have failed to demonstrate an association with DR4. Using sequence specific oligonucleotide typing we have identified the DRB1 alleles in panels of Greek RA patients and controls. When patient and control HLA-DRB1 frequencies were compared, significantly higher frequencies of DRB1*0101 (23.3% vs. 7.0%, odds ratio [OR] 4.0, 95% confidence intervals [CI] 1.4-12.0) and DRB1*1001 (20.9% vs. 5.8%, OR 4.3, 95% CI 1.3-13.7) were found in RA patients compared with controls. No association of DRB1*04 with RA was observed (20.9% vs. 14.0% in controls) confirming earlier reports. However DRB1*04 subtyping demonstrated a small but significant increase of DRB1*0405 in patients (14.0% vs. 3.5%, OR 4.5, 95% CI 1.1-18.9). When the frequency of individuals carrying the shared RA susceptibility epitope was compared between patients and controls it was found to be significantly higher in RA patients (60.5% vs. 22.1%, OR 5.4, 95% CI 2.4-12.0). We conclude that the shared epitope is significantly associated with RA in this population, but that it is predominantly accounted for by DRB1*0101 and DRB1*1001. Previous studies of UK RA patients have demonstrated a negative association of DR2 with disease and articular erosions. HLA-DR2 variants, DRB1*1501 and *1502 are not at reduced frequency in Greek RA patients (DRB1*1501, 14.0% in patients vs. 7.0% in controls; DRB1*1502, 7.0% in patients vs. 7.0% in controls). Genes conferring RA resistance may be in linkage disequilibrium with DR2 in UK patients. This does not appear to be the case in Greek RA patients. No association was seen between RA and HLA-DPB1 type.
8951005 Kinematic condylar total knee arthroplasty. 14-year survivorship analysis of 208 consecuti 1996 Nov We performed an independent survivorship analysis on 208 Kinematic Condylar knee replacements with a minimum follow-up of ten years and a mean of 12 years. Seven patients had been lost to follow-up. At ten years the estimated survival was 92% (95% confidence limits 95% and 87%) and when stratified for diagnosis and thickness of polyethylene there was no statistical difference (p > 0.05) in survivorship of knees with osteoarthritis or rheumatoid arthritis. We conclude that the original design of the Kinematic Condylar knee replacement has a good record and that adequate evaluation of new designs of implant should be undertaken before they are widely introduced.
8846538 Pro- and antiinflammatory cytokine balance in rheumatoid arthritis. 1995 Sep High levels of proinflammatory cytokines such as IL-1, TNF-alpha and IL-6 are produced by the rheumatoid synovitis. These cytokines, mainly produced by monocytes/macrophages, are thought to play a major role in chronic inflammation and in the final joint degradation. IL-4, IL-10, and IL-13 have been classified as antiinflammatory cytokines as they inhibit the production of the proinflammatory cytokines by monocytes. Acting on the balance between these two groups of cytokines may lead to new therapeutic approaches to controlling chronic inflammation without interfering at the level of the antigen.
8595635 Assessment of salsalate, a nonacetylated salicylate, in the treatment of patients with art 1995 Sep This study evaluated physicians' use of the occurrence of tinnitus as a tool to establish the optimal dosage of salsalate, a nonacetylated salicylate, in patients with arthritis treated in routine clinical practice. The use of printed educational materials to improve compliance was also studied prospectively. A total of 782 patients were enrolled in this 3-week study by 95 general practitioners in an office setting. Of the 771 assessable patients, 90.0% had osteoarthritis, 9.7% had rheumatoid arthritis, and 0.3% had both types of arthritis. Most patients experienced improvement of symptoms after 3 weeks of treatment. There were no differences in the rates of improvement at the first and third weeks of treatment between patients with osteoarthritis and patients with rheumatoid arthritis. In addition, duration of arthritis had no effect on rates of improvement. Rates of patient satisfaction tended to increase over the study period. Rates of patient satisfaction did not differ significantly at the first and third weeks between patients who did not receive printed educational materials and whose who did not. Treatment was discontinued in 234 patients (30.4%) because of side effects. The most frequent reasons for discontinuation were gastrointestinal symptoms (n = 102; 13.2%) and tinnitus (n = 52; 6.7%). The clinical effectiveness and safety of salsalate were confirmed in patients with arthritis in routine clinical practice settings.
8535647 Clinical efficacy of sulphasalazine--a review. 1995 Nov This review of the use of sulphasalazine (SASP) in the therapy of rheumatoid arthritis refers to the placebo-controlled trials of SASP and the randomized comparative studies with other second-line drugs that have been published over the past decade. The questions relating to appropriate selection of patients for this treatment and the possible relevance of drug interactions are addressed. The favourable effect of SASP on functional, radiological and extra-articular outcome measures is highlighted, as is the reproducibility of published studies. Finally, the results from combination studies and meta-analyses are outlined.
8162456 The epidermal growth factor-like domain of the human cartilage large aggregating proteogly 1994 Jan The large aggregating proteoglycan from human cartilage, aggrecan, has recently been shown to possess an immunologically detectable domain with close homology to epidermal growth factor (EGF), that is variably expressed by alternative mRNA splicing. Using a competitive ELISA we detected this domain in sera from both patients with RA and normal controls. The EGF-like domain could only be detected after digestion of sera with chondroitinase ABC, which demonstrates its proteoglycan origin. The concentration of the aggrecan EGF-like domain was considerably elevated in sera from patients with RA as compared to the control sera (P < 0.001), and the concentration of the domain increased with age in both the patient (r = 0.58, P < 0.05) and the control (r = 0.66, P < 0.01) group. These results demonstrate that the EGF-like domain of aggrecan could be of value as a marker of RA.
8628923 A critical assessment of the relationship between silicone breast implants and connective 1996 Feb Concerns regarding the possible role of breast implants (particularly silicone breast implants) in the development of connective tissue diseases were raised by case reports of connective tissue diseases in women with breast implants. Case reports, however, are not appropriate for causation assessment. Within the past few years, epidemiologic studies have begun to appear. Based on a comprehensive literature search, 15 epidemiologic studies on breast implants and connective tissue diseases, which satisfied certain basic epidemiologic requirements, were included in the critical assessment. These studies utilized either the case-control or the cohort study design. Although each individual study was relatively small, and the statistical power to detect a modest risk increase in specific categories of connective tissue diseases was limited, the results of these studies, however, were strikingly consistent, particularly those reported in case-control studies. To increase statistical power and to take the consistency of results into consideration, meta-analyses were used to summarize results from individual studies quantitatively. Based on data from case-control studies, meta-analyses of rheumatoid arthritis, systemic sclerosis (scleroderma), and systemic lupus erythematosus were performed. These case-control studies represented a combined database of approximately 4000 cases of connective tissue diseases, and the power was sufficient to detect a relatively small increase in risk. Based on the meta-analyses, the relative risks (95% confidence intervals) were 0.85 (0.48-1.51) for rheumatoid arthritis, 0.82 (0. 50-1.35) for systemic sclerosis, and 0.33 (0.06-2.03) for systemic lupus erythematosus, indicating that there was no increased risk of connective tissue diseases associated with breast implants. The findings derived from the meta-analyses of case-control studies were supported by results from cohort or prospective studies. It was concluded that epidemiologic data did not provide any evidence for a causal relationship between silicone breast implants and connective tissue diseases.
7796293 Mechanisms underlying the formation of the T cell receptor repertoire in rheumatoid arthri 1995 Jun The contributions of germline-encoded T cell receptor segments and of HLA-DR polymorphisms in shaping the repertoire of human CD4+ CD45RO- T cells were investigated in healthy unrelated individuals and in patients with rheumatoid arthritis, an HLA-DRB1 04-associated disease. By comparing frequencies of V beta-J beta combinations, healthy individuals segregated into independent clusters, which strongly correlated with the HLA-DRB1 allele expression. The repertoire fingerprint imposed by the HLA-DRB1 alleles involved only a selected group of J beta elements, whereas the distribution of the other J beta segments was HLA independent. The HLA-restricted J beta elements are characterized by a Gly-Pro-Gly sequence within the conserved Phe-Gly-X-Gly motif, which induces rigidity in an otherwise more flexible protein backbone. The T cell receptor repertoire distinguished patients with RA from healthy HLA-DR-matched individuals, suggesting that patients share a selection mechanism that significantly distorts the composition of the T cell receptor repertoire.
7791151 Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rh 1995 Apr OBJECTIVE: To investigate the efficacy of salsalate, a nonacetylated salicylate, in the treatment of patients with rheumatoid arthritis (RA). METHODS: Three hundred and one patients meeting the ACR criteria for RA were drawn from 16 centers. After withdrawal of nonsteroidal antiinflammatory drugs (NSAID) and subsequent flare, patients were randomized to receive either salsalate or diclofenac for 8 weeks, according to a double blind, double dummy protocol. Initial doses of salsalate 3.0 g/day and diclofenac 75 mg/day were titrated for the first 5 weeks. The primary outcome measure was a multivariate analysis at 8 weeks of tender joint count, pain, visual analog scale score, and physician's global assessment. RESULTS: One hundred and ninety patients completed the study. The mean stabilized dose of salsalate was 3.55 g/day, and that of diclofenac 112 mg/day. Discontinuations were due to lack of efficacy (17 salsalate vs 15 diclofenac); adverse events [19 salsalate (mainly tinnitus and hearing loss; p = 0.0001 and p = 0.04, respectively) vs 9 diclofenac]; laboratory abnormalities (3 salsalate vs 1 diclofenac); and other reasons, including protocol violations, intercurrent illness, and personal factors (24 salsalate vs 23 diclofenac). Both treatments produced significant improvement from flare (p < 0.0001). Post hoc power analysis showed that the study had sufficient power (0.60 to 0.90) to detect clinically important differences between the 2 drugs in the primary outcome measures; however, no statistically significant (p = 0.29) or clinically important treatment differences were recorded. Other than a difference in erythrocyte sedimentation rate that favored salsalate, there were no significant differences in secondary outcome measures between the 2 groups. All outcomes showed a tendency for more improvement with salsalate. CONCLUSION: Salsalate is as efficacious as diclofenac. Salsalate may be considered an alternative to other NSAID in the first line treatment of patients with RA.
8578887 [Coping with the illness by patients with chronic polyarthritis. Forms of coping and thera 1995 Sep In rheumatoid arthritis, coping exerts a major influence on the feelings and the compliance of a patient. This signifies its great clinical relevance. This study presents data of 40 patients using a questionnaire for assessing their ways of coping. The main coping strategies proved to be the search for more information and ways to get cognitive control over the threat imposed by the disease. The individual strategies were not influenced by somatic parameters. Unexpectedly, the duration of disease was tightly correlated to a more intensive approach for gaining information. The results have a major influence on the way of treating patients with RA. They open up new therapeutical regimens for the patient/doctor relationship, including patient oriented seminars and various psychological therapies.
1583217 Illness attributions and hopelessness depression: the role of hopelessness expectancy. 1992 May According to hopelessness theory, hopelessness expectancy is the proximal, sufficient cause of hopelessness depression. Consequently, hopelessness expectancy is viewed as mediating the influence of all other factors on hopelessness depression. Using a longitudinal research design, we examined hopelessness expectancy as a mediator of the relation between illness attributions and hopelessness depression in a sample of 57 adults with rheumatoid arthritis. Although hopelessness expectancy was a strong predictor of hopelessness depression, it moderated rather than mediated the relation between attributions and depression. Finding support for a moderating rather than a mediating model is inconsistent with theory but is consistent with the findings of Riskind, Rholes, Brannon, and Burdick (1987).
1540034 Muscle strength, endurance, and aerobic capacity in rheumatoid arthritis: a comparative st 1992 Jan Isometric/isokinetic muscle strength and isokinetic endurance of the lower extremities as well as aerobic capacity were evaluated in 67 patients (43 female, 24 male; mean age 53 years, range 23-65) with classical/definite rheumatoid arthritis (RA) of functional class II. Results obtained were compared with those of a healthy reference group matched for age and sex. Disease characteristics of the group with RA were registered and lifestyle characteristics, such as work load, exercise, diet, smoking, and alcohol habits, were reported by both groups. Generally, results showed that the group with RA had decreased functional capacity. Isometric hip and knee muscle strength of the rheumatoid group was reduced to about 75% of normal function, isokinetic knee muscle strength at the velocities of 60 and 180 degrees/s to about 65% and 75% of normal function respectively, isokinetic endurance of the knee muscle groups to about 45%, and aerobic capacity to about 80% of the results obtained for the healthy reference group. Analyses of variance showed that the rheumatoid group, compared with the healthy group, had significantly reduced function on all isometric and isokinetic tests of the extensors and flexors of the knee. Results for isometric hip muscle strength were similar--all tests but one yielding highly significant differences. To avoid unnecessary functional deficits it seems important to include muscular training in rehabilitation programmes for patients with RA.
1581142 Arthritis and aging. 1992 Apr Thirty-seven million Americans suffer from some form of arthritis and the prevalence of arthritis among the elderly is particularly high. Therefore it is not surprising that there is a large new literature directed toward the epidemiology and health services for the older individual with arthritis. Many studies in osteoarthritis have refined the minutia or confirmed earlier work. Osteoarthritis increases with age and accounts for 46 million patient visits each year, with knee arthritis accounting for the most common complaint initiating such visits. Late stage rheumatoid arthritis has again been strongly associated with shortened life span, and factors predicting early death have been identified. Meanwhile, the "pyramid model" of rheumatoid arthritis treatment has been challenged. Of interest is the identification of obesity as a major risk factor for disability in elderly patients with arthritis and the fact that the incidence of hip fracture in the elderly, already known to be high, may be increasing. A provocative report suggests that mass screening for osteoporosis followed by selective treatment may be more cost effective than empirical treatment of all postmenopausal women.