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ID PMID Title PublicationDate abstract
7897264 C3b receptor (CR1) genomic polymorphism in rheumatoid arthritis. Low receptor levels on er 1994 The number of complement receptor 1 (CR1, CD35) molecules on erythrocytes is genetically determined by two codominant alleles. The numerical expression of CR1 on erythrocytes correlates with a HindIII-RFLP or CR1 gene using CR1-1, a complementary DNA probe. We have found low CR1 on erythrocytes in patients with rheumatoid arthritis (RA) in an Indian population. Low levels in RA patients may be acquired or genetically determined. Fifty-two patients with RA, 48 nonrelated healthy subjects and 19 consanguineous relatives of patients were genotyped. CR1 numbers on erythrocytes were quantitated by the enzyme-linked immunosorbent assay using monoclonal anti-CR1 antibody. Normal subjects and patients were followed up for a period of 6 months to evaluate the stability of their CR1 expression. The gene frequency for allele H and L (7.4- and 6.9-kb HindIII restriction fragment, respectively), which correlated with high and low expression of CR1 on erythrocytes was 0.77 and 0.23 in the normal controls. Gene frequency in RA patients was 0.78 and 0.22 for H and L allele, which did not differ significantly from either controls or relatives (0.80 and 0.20 for H and L allele, respectively). However, RA patients expressed fewer CR1 on erythrocytes within each genotype than their relatives and controls. CR1 on erythrocytes were found to be stable in consecutive samples in controls. In RA patients, the number varied between low and high during the course of the disease. The variation in number was significantly correlated (p < 0.05, r = -0.85 to -0.98) with disease activity as monitored by erythrocyte sedimentation rate. Our results suggest that low levels of CR1 on erythrocytes in patients with RA are not inherited, rather they are acquired during the course of the disease.
8324934 Antibiotics as disease modifiers in arthritis. 1993 Mar The tetracyclines, especially minocycline, are supposed to have antiarthritic properties. Their efficacy has been tested in open clinical studies on RA patients. Recently a double-blind placebo-controlled trial was performed which revealed the antirheumatic properties of minocycline. The mode of action of the tetracyclines in arthritis is unknown, but could be linked to the immunosuppressive activity seen in vitro. The antiproliferative effect of minocycline in cloned synovial T-cells is demonstrated; moreover IFN-gamma production in cloned synovial T-cells is inhibited by minocycline.
7644624 Quantification of inflammation in the wrist with gadolinium-enhanced MR imaging and PET wi 1995 Sep PURPOSE: To quantify the activity of joint inflammation with magnetic resonance (MR) imaging and positron emission tomography (PET). MATERIALS AND METHODS: Gadolinium-enhanced MR imaging and 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) PET of the wrist were performed prospectively in 12 patients receiving antiinflammatory therapy. Patients were studied three times: off medications for 2 weeks, after 2 weeks of treatment with prednisone or nonsteroid antiinflammatory drugs, and after 12 weeks of treatment with methotrexate. Volume of enhancing pannus (VEP) was determined from fat-suppressed MR images (12 patients). FDG uptake was calculated from PET images (11 patients). RESULTS: VEP and FDG uptake were closely correlated (r > .86, P < .0001), as were changes in VEP and standardized uptake volume (r > .91, P < .0002). VEP and FDG uptake were strongly associated with clinical findings in wrists (P < .002) but not with treatment outcomes (P > .05). CONCLUSION: Contrast material-enhanced MR imaging and PET allow quantification of volumetric and metabolic changes in joint inflammation and comparison of efficacies of antiinflammatory drugs.
8646367 Increased matrix metalloproteinases as possible cause of osseoarticular tissue destruction 1996 Apr Immunolocalization of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in periarticular tissues of beta 2-microglobulin amyloidosis patients was investigated. MMP-1 (interstitial collagenase) the most strongly expressed of the MMPs, was localized in the synovial lining cells, mesenchymal cells in granulation tissue and nodular amyloid deposits, and chondrocytes within areas of cartilage erosion. Expression of MMP-1 was correlated with the degree of macrophage infiltration and synovial cell hyperplasia, but it was not correlated with the degree of amyloid deposition or haemodialysis period. Expression of MMP-1 appeared more intense than that of TIMP-1 and TIMP-2 in highly inflammatory cases. MMP-2 was mildly expressed in the interstitial fibroblasts and MMP-3 was faintly stained in the extracellular matrix of the synovial membrane. MMP-9 (gelatinase B) was found to be strongly positive in the osteoclasts which increased in the progressing osteolytic lesion from the destructive arthropathy. These results suggest involvement of MMPs in inflammation with an imbalance between expression of MMPs and TIMPs being closely related to pathogenesis of the destructive arthropathy.
8821776 Serum from NSAID-treated patients attenuates the capacity of rat leukocytes to synthesize 1996 Jan The synthesis of leukotriene B4 by A23187-stimulated rat peritoneal leukocytes was studied in the presence of 0.1% normal human serum, serum from patients treated with NSAIDs for either an inflammatory (rheumatoid arthritis, RA) or a non-inflammatory condition (lumbar disc protrusion, LDP), and serum from RA patients drawn one week after withdrawal from NSAID treatment. The capacity for LTB4 synthesis was significantly lower in the presence of serum from NSAID treated patients: thirty per cent less than observed in presence of normal serum in the RA group, and fifty per cent in the LDP group. When NSAIDs were withdrawn from RA patients, the LTB4 production in presence of serum increased, but was not completely normalized after one week. These results indicate that NSAID treatment may down-regulate the capacity for leukotriene synthesis by an indirect effect.
1459183 Modulation of lymphocyte subsets due to psychological stress in patients with rheumatoid a 1992 Oct The influence of a 1-hour neuropsychological stress test on the distribution of lymphocyte subpopulations and on plasma catecholamine levels was investigated in 18 patients with rheumatoid arthritis (RA) and 14 sex- and age-matched controls. Despite significant increases in lymphocyte counts in both groups, lymphocyte subsets did not change accordingly. A wide scattering of catecholamine levels in plasma before and after stress was observed. Plasma levels of lymphokines such as interleukin (IL)-1 beta and IL-6 could not be detected in RA patients. Enzyme immunoassay of markers of lymphocyte activation such as HLA-DR and cell-bound IL-2 receptor showed only a significant elevation of HLA-DR marked cells in RA patients at baseline. Significantly higher amounts of the soluble IL-2 receptor were detected in patients with RA before the stress test, but stress testing did not alter this parameter. In conclusion, lymphocyte activation in RA and a defect in the expression of IL-2 receptor on the cell surface of lymphocytes were confirmed in the present study.
7492236 Survival analysis of disease modifying antirheumatic drugs in Spanish rheumatoid arthritis 1995 Nov OBJECTIVES: To evaluate the duration of treatment and the reasons for discontinuing therapy with disease modifying antirheumatic drugs in Spanish rheumatoid arthritis patients. METHODS: An observational study was made of 629 patients with rheumatoid arthritis treated with disease modifying antirheumatic drugs between 1979 and 1991. The outcomes (treatment termination because of toxicity and lack of response) of 991 treatment starts with intramuscular gold salts, D-penicillamine, azathioprine, and methotrexate were subjected to survival analysis. Cumulative probability of continuation of each drug (drug survival) was calculated by the Kaplan-Meier method and comparison between the survival curve of each was made by log rank testing. RESULTS: Median drug survival (95% confidence interval) was 51 (25-76.9) months for methotrexate, 39.9 (19.9-48.2) months for azathioprine, 34.9 (29.4-41.4) months for gold salts, and 16.4 (13.9-21) months for D-penicillamine. The highest cumulative probability of drug survival at five years was for methotrexate (45%); that at 10 years was for gold salts (15%). Up to 60% of the patients discontinued D-penicillamine in the first two years. Lack of response was the major limiting factor for all drugs except D-penicillamine, for which it was toxicity. D-Penicillamine was associated with a greater rate of discontinuations because of toxicity in women and patients older than 65. Previous disease modifying antirheumatic drug administration did not influence current drug survival. CONCLUSION: Overall, gold salts remain useful for the treatment of rheumatoid arthritis over long periods of time in the population studied. Because of the high rate of continuation of treatment (survival) and the optimal efficacy and toxicity profiles observed with methotrexate after five years of treatment, it should be the drug of first choice for second line treatment of these RA patients.
8966686 [Orthopedic examination techniques of the knee joint--basis for diagnosis and indications] 1996 Oct The work up of indication is the aim of each thorough examination. Using the example of the knee joint, we subdivide into five group of diagnosis: anterior knee pain (femoropatellar syndrome), intraarticular derangement, osteoarthritis, infectious and rheumatoid arthritis, forms of bursitis and tendinitis. Clinical signs, diagnosis and natural history are listed, which present the basis of indication.
7648943 [Serum anti-subtypical Klebsiella pneumoniae antibodies in ankylosing spondylitis]. 1995 Mar This study was performed in order to probe the possible pathogenesis of Klebsiella pneumoniae (KP) in ankylosing spondylitis (AS). 34 anti-KP antibody positive serum samples, including 26 patients with AS, 5 patients with rheumatoid arthritis (RA) and 2 healthy individuals, were selected to detect anti-subtypical KP antibodies by using an immunoblotting technique. The results showed that the number of antigenic bands to KP on nitrocellulose membrane was higher in AS patients than in RA patients and healthy individuals. Patients with AS had common antibodies response to KP components weight 64,600 (80.7%), 48,200 (61.5%) and 36,000 (65.4%), patients with RA and healthy individuals had anti-36,000 (75%) and anti-30,000 (50%) antibodies. Human anti-HLA-B27 serum and rabbit antisera against KP-derived synthetic peptide containing the hexapeptide sequence shared by HLA-B27 were able to cross react with 64,600 and 48,200 KP components. Our findings suggest that KP might play a role in the pathogenesis of AS by molecular mimicry between it and HLA-B27.
8508278 Excessive and dysregulated secretion of prolactin in rheumatoid arthritis: immunopathogene 1993 Jun Prolactin (PL) is essential for the normal function of the immune system. It is required for the induction of a number of autoimmune conditions in experimental animals. The role of prolactin in the immunopathogenesis of autoimmune human disease has not been established. RA is characterized by a variety of immune and inflammatory processes which determine disease activity. It has a pronounced diurnal periodicity with a peak at 03.15 hours. Since PL has a diurnal rhythm of secretion in man with a peak at about 02.00 hours, it may contribute to the nocturnal worsening of RA. We show that patients with RA secrete an excess of prolactin as evidenced by an upregulated diurnal periodicity and an abnormal increase in plasma prolactin concentration following surgery. By contrast, patients with chronic osteomyelitis, who had chronic inflammation of similar severity to patients with RA, had a normal prolactin diurnal rhythm and response to surgery. Hence, the abnormal changes in prolactin physiology seen in RA appear to be a feature of the disease per se rather than related to chronic inflammation. The elevated levels of prolactin may contribute to disease activity by augmenting immune processes and may be an additional genetic factor, independent of HLA-DR4, in the immunopathogenesis of RA. Furthermore, the effective inhibition of prolactin secretion and/or action may have potential as therapy for RA.
16841447 [Morphological analysis of synovial exsudate in rheumatoid arthritis. II. Transmission ele 1996 Dec Synovial exsudate cells from patients with rheumatoid arthritis were investigated by transmission electron microscopy. Most of them represented polymorphous leukocytes. They contained vacuoles full of material reminding of immune complexes (in addition to typical granules) and plentiful alpha and beta glycogen granules. Some lymphoid cells nuclei were alike to those of Sézary disease with frequent ring-shaped nucleoli and enlarged mitochondria. Variegated non-lymphoid mononuclear cells had lateralized nuclei with marginated chromatin, mitochondria with sparse crists, short membranes of reticulum, conspicuous cisterns in trans-Golgi area and lysosomes with myeline bodies as a sign of big capacity of phagocytosis. Importance of using transmission electron microscopy in analysis of synovial exudate was discussed.
7940345 [Diclonate P in rheumatoid arthritis]. 1994 Diclonate P (sodium diclofenac, Pliva, Zagreb) was used in the treatment of 74 patients with rheumatoid arthritis as the basic antirheumatic drug. Analgesic and antiinflammatory activity and good tolerance of three dosage forms (tablets, suppositories, ampoules) of diclonate P were established on a statistically significant basis. In some parameters the drug compares very favourably with its chemical analogs.
1588752 [Hematologic abnormalities associated with rheumatoid arthritis]. 1992 Mar Anemia is frequently found in patients with rheumatoid arthritis (RA) and is the most common extra-articular manifestation RA. The majority of patients with RA have a mild normocytic hypochromic anemia which correlates with the erythrocyte sedimentation rate and with activity of the disease. White blood cell counts are usually in the normal range or only slightly elevated. The differential white blood cell count is usually within normal limits. Eosinophilia and thrombocytosis are often associated with RA. Hematologic abnormalities of RA is correlated to the activity of the disease, and therefore the most important aspect of treatment lies in the general control of the chronic inflammation.
7747121 Joint-derived T cells in rheumatoid arthritis proliferate to antigens present in autologou 1995 The histopathological features of rheumatoid joint-inflammation suggest that an antigen-driven activation of T cells plays a central role in the onset and/or perpetuation of the inflammatory process. However, the disease-associated antigens responsible for the activation of T cells in the joint are unknown. In this project we study the response of IL-2 expanded T-cell lines from the synovial fluid (SF) of rheumatoid arthritis (RA) patients against autologous SF in a proliferation assay. Sixteen out of 32 RA patients were found to have CD4+ T cells that proliferate in response to autologous SF. The presence of T cells able to respond to SF antigens in inflamed joints suggests that these T cells play an active role in the pathogenesis of RA. T cell clones reactive to autologous SF were isolated from SF-derived T-cell lines of two RA patients. All clones were of the CD4+, CD8-, alpha/beta+ phenotype. SF-reactivity of T-cell clones from the DR4/DR12-positive RA patient was restricted via the Dw4 subtype of DR4. SF reactivity of T cells of the DR12/DR15 patient was DP-restricted. Some of the T-cell clones responded specifically to autologous and not to allogeneic SF, whereas others revealed responsiveness against a limited number of allogeneic SF samples. The (restricted) specificity of T cells towards autologous SF antigens is indicative for heterogeneity of the epitopes recognized and argues against ubiquitous nonpolymorphic joint constituents as the relevant antigens recognized by the SF-autoreactive T cells.
8209561 Cervical spine arthrodesis in rheumatoid arthritis: a long-term follow-up. 1993 May Forty-one patients with rheumatoid arthritis involving the cervical spine had a posterior cervical arthrodesis. They were followed for a minimum period of seven years. The diagnoses prior to surgery included cranial settling, atlantoaxial subluxation, subaxial subluxation, and any combination of these three. All patients had posterior arthrodesis, with or without methylmethacrylate, and iliac crest autogenous bone graft. In addition, one patient had an anterior vertebrectomy, and two had transoral resection of the odontoid. Follow-up consisted of a subjective questionnaire, standard radiographs, and physical examination, including a neurologic exam. This information was compared to preoperative data available in the patient's medical record, postoperative data, and the information obtained in a similar study undertaken in 1987. At the time of follow-up, thirteen patients were known to be dead. One patient could not be located. Of the remaining twenty-six patients, eighteen underwent the full examination, including physical exam and radiographs. The remaining nine patients were contacted and interviewed, but were unavailable for exam and radiographs. All patients considered the operation a success. Only one patient at follow-up had a non-union. This was stable over time. No patient had a deterioration in neurologic function. There was no significant degeneration or instability seen at levels adjacent to the fused segments as compared to the rest of the cervical spine. Posterior cervical spine arthrodesis for rheumatoid involvement of the neck is a safe, efficacious procedure with no significant deterioration of effects over time.
1556274 Neuroticism and the pain-mood relation in rheumatoid arthritis: insights from a prospectiv 1992 Feb For 75 consecutive days, 54 Ss with rheumatoid arthritis supplied daily reports of their mood and joint pain. After aggregating daily reports, the relation between chronic mood and chronic pain remained statistically significant when controlling for neuroticism, depression, disease activity, disability, and characteristic responses to increasing pain. Findings of a path analysis suggest that (a) individuals higher in neuroticism experience more chronic distress regardless of their responses to pain, their pain intensity, and depressive symptomatology, and (b) the relation between neuroticism and chronic pain is mediated by the propensity of high-neuroticism individuals to catastrophize their pain. Within-subject analyses that controlled for autocorrelation and linear trends in the time series revealed that 40% of the Ss experienced significantly worse moods on more painful days. Although individuals higher in neuroticism reported more intense pain and more negative mood, their daily mood was less strongly linked to their daily pain.
1588736 [Diagnosis of rheumatoid arthritis--using biochemical technique]. 1992 Mar Rheumatoid arthritis is a systemic disease. Onset of the disease occurs most often between the ages of 20 and 60 years with a peak at 30 and 50 years. The diagnosis of rheumatoid arthritis (RA) is usually based on the revised criteria for the classification of RA. The presence of 4 or more of 7 criteria defines "rheumatoid arthritis". There is today much interest in development of a biochemical "marker" of RA, to detect the early phase of RA. Some approach employs measurement of serum and joint fluid levels of articular cartilage macromolecules, antibodies, and so on. In the section, we would like to describe some materials available now. It is difficult to point out a single material superior to rheumatoid factor to make a diagnosis of RA at the present time.
1329776 Light microscopic characterization of the fibroblast-like synovial intimal cell (synoviocy 1992 Oct OBJECTIVE: To reassess synovial intimal cell populations by light microscopy. METHODS: Non-inflamed, rheumatoid and osteoarthritic synovia were analyzed as tissue sections and cytospin preparations by a series of combined immunohistochemical and cytochemical staining techniques. RESULTS: Two populations of intimal cells were identified. The first carried macrophage markers. The second showed high uridine diphosphoglucose dehydrogenase (UDPGD) activity, minimal cytoplasmic CD68, absent non-specific esterase (NSE) activity, and absent leukocyte and endothelial antigens. The majority of these cells showed a high content of prolyl hydroxylase. CONCLUSION: Combined cytochemical staining for NSE and UDPGD activity allows effective separation of intimal cell populations. We suggest that the cells of high UDPGD activity are the fibroblast-like or type B synovial intimal cells defined by electron microscopy. High UDPGD activity probably reflects a preferential ability to synthesize glycosaminoglycans, including hyaluronan.
1506510 Psychological factors in rheumatoid arthritis. 1992 Aug This article provides a review and discussion of recent developments in psychological research related to rheumatoid arthritis (RA). A description of the medical aspects of the disease is followed by an overview of the literature relating psychological variables to pain and disability in RA; a summary evaluating affective reactions, disease-related beliefs, and coping strategies in RA patients; and a discussion of psychological interventions with this patient population. Methodological weaknesses in the literature are noted and directions for future collaborative research between rheumatologists and psychologists are suggested.
7989613 CDR3 sequence motifs shared by oligoclonal rheumatoid arthritis synovial T cells. Evidence 1994 Dec T lymphocytes reactive with as yet undefined joint-localized foreign or autoantigens may be important in the pathogenesis of RA. Molecular studies demonstrating skewed T cell antigen receptor (TCR) variable gene usage and selective expansion of particular T cell clones within the synovial compartment support this view. Based on our recent study documenting selective expansion of V beta 17+ T cells in RA, we have pursued the identification of T cells relevant to the disease process, in an informative patient, by combining molecular analysis of freshly explanted RA synovial tissue V beta 17 TCR transcripts with in vitro expansion of V beta 17+ synovial tissue T cell clones. Peripheral blood V beta 17 cDNA transcripts proved heterogeneous. In contrast, two closely related sequences, not found in the peripheral blood, dominated synovial tissue V beta 17 transcripts, suggesting selective localization and oligoclonal expansion at the site of pathology. CD4+, V beta 17+ synovial tissue-derived T cell clones, isolated and grown in vitro, were found to express TCR beta chain transcripts homologous to the dominant V beta 17 synovial tissue sequences. One clone shares with a dominant synovial tissue sequence a conserved cluster of 4/5 amino acids (IGQ-N) in the highly diverse antigen binding CDR3 region, suggesting that the T cells from which these transcripts derive may recognize the same antigen. These findings have permitted a complete characterization of the alpha/beta TCR expressed by putatively pathogenic T cell clones in RA. Functional analysis suggests that the conserved CDR3 sequence may confer specificity for, or restriction by, the MHC class II antigen, DR4.