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ID PMID Title PublicationDate abstract
8702446 Use of a radiolabeled monoclonal antibody against E-selectin for imaging of endothelial ac 1996 Aug OBJECTIVE: To determine the potential of 111In-labeled anti-E-selectin monoclonal antibody (MAb) to image localized endothelial activation in rheumatoid arthritis (RA). METHODS: Fourteen patients with RA were studied after intravenous administration of 111In-labeled F(ab')2 fragments of MAb against the cytokine-inducible endothelial cell activation antigen E-selectin (MAb 1.2B6). To compare uptake of 1.2B6 with that of nonspecific immunoglobulin, 111In-labeled polyclonal human immunoglobulin (HIG) was separately administered to 6 of these patients and the relative uptake of each tracer was determined. RESULTS: Prominent and discrete uptake of the radiolabeled MAb 1.2B6 was clearly visible in inflamed joints of all patients. Compared with 111In-HIG, 111In-1.2B6 provided superior images in terms of sensitivity and image intensity. Furthermore, the distribution of uptake in inflamed joints was different for the 2 tracers, with 1.2B6 showing a more focal localization in synovium. CONCLUSION: This study demonstrates that it is possible to objectively assess E-selectin expression on activated endothelium in vivo in patients with RA, using a radiolabeled MAb. This technique has considerable potential for monitoring disease activity and response to therapy in inflammatory diseases.
8434241 Grip force in patients with rheumatoid arthritis and fibromyalgia and in healthy subjects. 1993 The reliability of the grip force instrument, Grippit was tested on 51 right-handed women of which 18 were healthy, 19 had rheumatoid arthritis (RA) and 14 had fibromyalgia (FM). Normative data was obtained from 169 healthy subjects. Results indicate that the reliability of Grippit was high in healthy and rheumatoid arthritic women and satisfactory in women with fibromyalgia. All patients showed greatly reduced grip force (RA had on average 21% and FM 40% of the control values) when compared to healthy women. Healthy women had on average 54% of men's grip force. The ratio between average force over 10 seconds and peak force was 73% for RA women, 69% for FM women, 83% for healthy women and 85% for healthy men.
1314609 Acute and chronic suppression of leukotriene B4 synthesis ex vivo in neutrophils from pati 1992 Apr OBJECTIVE: To compare the cumulative effects of oral methotrexate (MTX) therapy (after 6-8 weeks) with the acute effects (24 hours after a dose) on arachidonic acid metabolism by the 5-lipoxygenase (5-LO) pathway in neutrophils from patients with active rheumatoid arthritis (RA) who were beginning therapy with MTX. METHODS: Neutrophils and monocytes were isolated from whole blood from 7 patients with RA, immediately before and 24 hours after their first weekly dose of 7.5 mg of MTX, and again after their dose at 6-8 weeks. RESULTS: Total immunoreactive leukotriene B4 (LTB4) formation in neutrophils activated ex vivo with calcium ionophore A23187 was significantly suppressed (by 33%) before the 6-8-week dose, compared with the level before the first dose (mean +/- SEM 8.29 +/- 1.24 ng/10(6) cells at predose 6-8 weeks versus 12.29 +/- 2.13 ng/10(6) cells at predose 1; P = 0.03). Reductions were also observed after the first dose (27%; P = 0.07) and after the 6-8-week dose (43%; P = 0.05) compared with the respective predose levels. MTX treatment produced significant reductions in the total generation of 5-LO pathway products (5-hydroxyeicosatetraenoic acid + 6-trans-LTB4 + LTB4 + omega-oxidation products of LTB4) by calcium ionophore-activated neutrophils, as quantitated by integrated optical density after resolution on reverse-phase high-performance liquid chromatography. Decreases were observed after the first dose (26%; P = 0.025), immediately before the 6-8-week dose (23%; P = 0.05), and after the 6-8-week dose (47%; P = 0.0033) compared with levels before the first dose, and after the 6-8-week dose compared with the level before it (32%; P = 0.04). The generation of LTB4 by calcium ionophore-activated monocytes was not significantly affected by MTX therapy. CONCLUSION: The significant decreases in the formation of omega-oxidation products of LTB4 and in the total generation of neutrophil 5-LO pathway products in the absence of a significant change in the release of 3H-arachidonic acid or the generation of platelet-activating factor suggest that the activity of the 5-LO enzyme in neutrophils is inhibited. We conclude that weekly oral MTX therapy in patients with active RA inhibits neutrophil 5-LO pathway product generation in a pattern consistent with inhibition of the activity of the 5-LO enzyme; an effect is observed after the first dose. The inhibition of 5-LO is cell-selective and cumulative, with a superimposed incremental inhibition observed after the weekly MTX dose.
8451918 Relation between the intra-articular temperature of the temporomandibular joint and the pr 1993 Feb Arthritic temporomandibular joints were examined for the joint fluid content of neuropeptide Y-like immunoreactivity (NPY-LI) and the intra-articular temperature at two separate sessions. Sixteen patients (23 joints) with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and unspecific polyarthritis or monarthritis were investigated in this study. The intra-articular temperature ranged between 35.6 and 37.5 degrees C. The concentration of NPY-LI ranged between 72.1 and 4466.0 pmol/l and was above the normal plasma level in all patients. The intra-articular temperature was negatively correlated with the joint fluid concentration of NPY-LI. Moreover, patients with low intra-articular temperature and high concentration of NPY-LI had a shorter duration of TMJ symptoms than those with high intra-articular temperature and low concentration of NPY-LI.
7916589 Molecular analysis of rheumatoid factors derived from rheumatoid synovium suggests an anti 1993 Mar OBJECTIVE: Understanding the molecular genetic basis for rheumatoid factor (RF) production is necessary to a better understanding of the etiology and pathogenesis of rheumatoid arthritis (RA). We sought to define the genetic basis of RF in RA. METHODS: The heavy and light chain variable region genes encoding 4 human monoclonal RF were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide chain-termination method. RESULTS: The heavy and light chains of the C6 RF and the light chain of the G9 RF were encoded by 3 new RF-related Ig V-region genes. The heavy and light chains of D5 and G4 RFs were identical; most of their mutations caused amino acid substitutions. CONCLUSIONS: The RF-related Ig V-region gene repertoire is large and is still expanding. The data from D5 and G4 strongly suggest that these 2 RFs arise in an antigen-driven response in rheumatoid synovium. The presumed germline V genes for C6 may represent disease-specific RF-related V genes.
8053951 Abnormal hypothalamic-pituitary-adrenal axis function in rheumatoid arthritis. Effects of 1994 Aug OBJECTIVE: To investigate the effects of nonsteroidal antiinflammatory drug (NSAID) therapy and water immersion on hypothalamic-pituitary-adrenal (HPA) axis function in rheumatoid arthritis (RA). METHODS: Plasma levels of adrenocorticotropic hormone (ACTH) and serum and urine levels of cortisol were compared in untreated RA patients, NSAID-treated RA patients, and healthy control subjects. RESULTS: ACTH levels were significantly higher in untreated RA patients (mean +/- SEM integrated area 11,377 +/- 5,246 hours ng/liter) than in NSAID-treated RA patients (2,285 +/- 388 hours ng/liter) or healthy controls (1,845 +/- 35.5 hours ng/liter) (P < 0.001). Serum and urine cortisol levels were not significantly different between groups. Two-hour head-out water immersion had no effect. CONCLUSION: Elevated ACTH levels without hypercortisolemia occur in untreated RA. NSAID therapy alters HPA axis response, but immersion has no effect.
1376121 CD7- T cells in rheumatoid arthritis. 1992 Jun OBJECTIVE: Rheumatoid arthritis (RA) is characterized by decreased expression of CD7 in the peripheral blood and in the synovium. The present study was designed to identify the basis for and functional consequences of this decreased expression. METHODS: Peripheral blood lymphocytes from normal controls and from patients with RA or systemic lupus erythematosus (SLE), and T cell lines derived from rheumatoid synovium, were evaluated using 3-color fluorescence-activated cell sorter analysis. RESULTS: Normal subjects and most SLE patients expressed homogeneous, bright CD7 on CD4+, CD45RA+ cells, whereas RA patients demonstrated a significantly increased proportion of CD7- cells. T cell lines derived from rheumatoid synovium demonstrated a striking deficiency of CD7 on CD4+, CD45RA- cells. CD4+, CD45RA+ cells from RA patients changed phenotype after in vitro activation to CD45RA negativity, with up-regulation of CD7. CD7-, CD4+, CD45RA- cells were assessed for their ability to induce pokeweed mitogen-driven IgM and IgM-rheumatoid factor synthesis, and they were found to be potent helper/inducer cells. An increased population of CD7-, CD4+ cells in peripheral blood was found to predict a low response to recall antigens. CONCLUSION: The low expression of CD7 in RA may explain some of the immune abnormalities which may contribute to the pathogenesis of this disease.
7656469 Sex hormones and rheumatoid arthritis: cause or effect relationships in a complex pathophy 1995 Mar Sex hormones are believed to contribute to the risk of rheumatoid arthritis (RA) because of the disease's female preponderance, especially during the child-bearing years, and because of the dramatic improvements seen during pregnancy. Available controlled data on serum dehydroepiandrosterone sulfate (DHEAS), testosterone (T) and estradiol (E2) in RA patients not treated with glucocorticoids are summarized. Hypotheses of sex hormone contributions to RA are tested by judgemental criteria for the causes or determinants of disease. Available data support hypoandrogenicity in RA patients, especially among premenopausal females and males. Limited prospective studies in women and therapeutic trials of testosterone therapy in men further support a role of sex hormones in RA. Interactions of sex hormones and glucocorticoids are also believed to be important and deserve priority in future research.
9275326 Simultaneous bilateral total knee arthroplasty for rheumatoid arthritis. 1996 Dec OBJECTIVE: To study the result of one staged bilateral total knee arthroplasty (TKA) operation under epidural anesthesia on patients with severe rheumatoid arthritis (RA). METHODS: From April 1987 to December 1992, simultaneous bilateral TKA was performed on 45 patients (90 knees), including 41 patients with RA, 3 with juvenile RA, and 1 with Sjogren syndrome. The mean follow-up period was 63 months. RESULTS: Improved function and pain relief were noted in all patients. There were no wound healing problems. Thrombophlebitis was observed in few cases. Late infection rate was 5.6% (5 knees) and aseptic loosening was revised on 5 knees. CONCLUSIONS: Simultaneous bilateral TKA is not only a procedure of low cost, saving blood, reducing anesthesia risk, drugs' side effect and hospitalization, but also facilitates early rehabilitation. Except for late infection, there is no increase in complications.
7978695 Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A do 1994 Dec 1 OBJECTIVE: To determine the effect of two different weekly doses of folic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo-controlled study. PATIENTS: 79 persons between 19 and 78 years of age who fulfilled the American Rheumatism Association's criteria for rheumatoid arthritis. INTERVENTION: Participants were randomly assigned to visually identical placebo or to 5 mg or 27.5 mg of folic acid each week. MEASUREMENTS: Duration, intensity, and clinical severity of toxic events; efficacy (indices of joint tenderness and swelling and grip strength); plasma and erythrocyte folate levels; and other laboratory variables. RESULTS: Folic acid supplementation at either dose did not affect the efficacy of methotrexate therapy as judged by joint indices and patient and physician assessments of disease. Patients given folic acid supplements had lower toxicity scores than did participants given placebo (P < or = 0.001). Low blood folate levels and increased mean corpuscular volumes were associated with substantial methotrexate toxicity, whereas daily dietary intakes of more than 900 nmol (400 micrograms) of folic acid were associated with little methotrexate toxicity. CONCLUSIONS: Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis who are taking methotrexate from toxicity while preserving the efficacy of methotrexate.
8023521 [IgA rheumatoid factor formation in connection with complement activation and circulating 1994 The IgA-rheumatoid factor (IgA-RF) as well as the complement component C3a in plasma and serum levels of circulating immune complexes (CIC) (C1q binding assay and Raji Cell Replacement assay) were measured with enzyme immunoassays in 81 patients with established rheumatoid arthritis. The serum levels of the complement component C3a were found significantly higher (p < 0.02) in the cases with high IgA-RF (> 6 AU/ml) than in those with low IgA-RF. Distinct significant correlations (r = 0.38; p < 0.001) were observed between production of IgA-RF and activation of the complement fragment C3a, which might be associated with production of antibodies and with complement activation accompanying inflammatory processes. A weaker correlation between CIC and IgA-RF-levels indicates CIC not to be closely related to the production of IgA-RF in the examined R.A.-patients. However, an indirect connection by the way of inflammation and activation of T-cells is possible.
8451069 The role of type IX collagen in osteoarthritis and rheumatoid arthritis. 1993 Feb Articular cartilage consists of a cellular and an extracellular compartment. The extracellular compartment is composed of collagen, proteoglycans, and noncollagenous matrix proteins. Collagen resists tensile forces and serves as an organizing skeleton that helps maintain the structural integrity of cartilage. Fourteen types of collagen have been identified. The cartilage-specific collagens are type II (the principal component), type IX, type X, and type XI. Type IX collagen is hypothesized to be the "glue" that holds together the type II collagen latticework of articular cartilage. Degradation of type IX collagen by proteolytic enzymes has been observed in the primary stages of osteoarthritis and rheumatoid arthritis. This degradation is thought to represent an "ungluing" of the collagen scaffold and has been proposed as the mechanism for the degenerative changes seen in osteoarthritic and rheumatoid cartilage.
7678661 Expression of vascular cell adhesion molecule-1 in normal and inflamed synovium. 1993 Jan BACKGROUND: The intercellular adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) has been implicated in a number of interactions between leukocytes and cells of lymphoid and connective tissue, including endothelial cells. Such interactions within synovial tissue may be important in the pathogenesis of rheumatoid arthritis. EXPERIMENTAL DESIGN: The expression of VCAM-1 on specific cell populations in normal and inflamed synovium was investigated using a range of double-labeling techniques. RESULTS: The strongest VCAM-1 staining was found to be confined to four nonmacrophage populations (as judged in terms of CD68 expression, nonspecific esterase activity, content of prolyl hydroxylase and activity of uridine diphosphoglucose dehydrogenase): (i) type B synoviocytes, (ii) vascular wall cells outside the endothelial layer, (iii) scattered stromal cells with cytoplasmic processes, and (iv) cells resembling follicular dendritic reticulum cells in lymphoid aggregates with germinal centers (in the three samples of rheumatoid arthritic tissue where these were present). Some macrophages of the synovial intima showed weak VCAM-1 staining. Endothelial cell staining was seen but it was consistently weaker than the staining of cells of group ii. CONCLUSIONS: The four cell populations described as showing bright staining for VCAM-1 may all be involved in local interactions with leukocytes of the macrophage or lymphoid series subsequent to initial leukocyte entry into the tissue. Expression of VCAM-1 by these cells may play a role in such interactions.
9273369 Total knee arthroplasty in a group of patients less than 45 years of age. 1995 Oct The long-term follow-up evaluation of total knee arthroplasty (TKA) in patients under age 45 is reviewed. One hundred three knees in 67 patients who had an average follow-up period of 7.2 years were retrospectively reviewed. Fifty-eight percent of the patients had rheumatoid arthritis, and 29% had juvenile rheumatoid arthritis. Thirteen percent of the patients had post-traumatic arthritis, avascular necrosis, hemochromatosis, or lupus. The results demonstrate that the success of TKA in this patient population are comparable to those for TKA in the elderly.
7562769 Interleukin-1 receptor antagonist inhibits proteoglycan breakdown in antigen induced but n 1995 Jul OBJECTIVE: To compare the alterations in proteoglycan metabolism in antigen induced arthritis and polycation induced arthritis and to determine the involvement of interleukin-1 (IL-1) in the cartilage degradation that occurs in these models of rheumatoid arthritis (RA). METHODS: The time course for loss of proteoglycan into the synovial fluid (SF) and inhibition of proteoglycan synthesis, as well as depletion of articular cartilage proteoglycan content, was compared in rabbit antigen arthritis and polycation arthritis. The ability of recombinant IL-1 receptor antagonist IL-1ra to block the acute cartilage loss at 24 h in these models was investigated, compared to its ability to block the cartilage breakdown induced by direct administration of IL-1 in rabbits. RESULTS: Initial loss of cartilage proteoglycan was accompanied by release of high levels of glycosaminoglycan (GAG) into the SF and decrease in proteoglycan synthetic rates in both antigen and polycation induced arthritis SF GAG rapidly returned to control levels, while proteoglycan synthesis and cartilage proteoglycan content remained depressed, suggesting that the inhibition in proteoglycan synthesis prevented recovery to normal levels. GAG loss from the cartilage into the SF in response to IL-1 injection, as well as other effects of IL-1 challenge, was blocked in a dose dependent manner by IL-1ra administered either intraarticularly (ED50 = 160 ng) or intravenously (iv) (ED50 = 0.09mg/kg). In the antigen induced arthritis model, IL-1ra (20 mg/kg, iv -2h) inhibited GAG release by 40%, whereas in polycation induced arthritis no inhibition was observed even with repeated administration of high doses of inhibitor. CONCLUSION: These studies suggest that sustained depression of proteoglycan synthesis may be responsible for the chronic depletion of articular cartilage proteoglycan in the antigen and the polycation model of RA. However, while IL-1 may play a role in the initial breakdown of articular cartilage in antigen induced arthritis, it does not appear to be involved in polycation induced arthritis in the rabbit.
1570480 Pathways of destruction in metacarpal and metatarsal joints of patients with rheumatoid ar 1992 219 metatarsal (MTP) and 69 metacarpal (MCP) capitulae obtained during surgery from patients with definite rheumatoid arthritis (RA) were histologically evaluated. This evaluation, focussing on primary pathways of joint destruction by tumor-like proliferated synovial cell masses revealed 3 pathways of aggression: Pathway A: In 15% aggression onto the articular cartilage only. Pathway B: In 49% direct invasion exclusively into the cortical bone. Pathway C: In 36% a "forceps-like" aggression, a combination of A and B in which the joint is attacked from both sides. In contrast to the hitherto conventional concepts, the findings of this study reveal a clear preference of the synovial aggression for the cortical bone rather than for the articular cartilage. The different concepts of joint destruction in RA are being discussed in the light of our findings. Thus, future pathogenetic considerations with regard to joint destruction in RA should take this fact into consideration.
8840223 Tumor necrosis factor priming of peripheral blood neutrophils from rheumatoid arthritis pa 1996 Jul Recently it was shown that tumor necrosis factor-alpha (TNF) receptors on neutrophils may be down-regulated after stimulation with proinflammatory mediators. Since in rheumatoid arthritis neutrophils are likely to encounter these mediators in the circulation, we tested the hypothesis that rheumatoid arthritis neutrophil TNF receptors are down-regulated. Peripheral blood neutrophils from patients with rheumatoid arthritis and healthy subjects were compared with respect to their TNF binding activity and ability to be primed by TNF. There were no differences between rheumatoid arthritis and control neutrophils in receptor-mediated TNF binding, superoxide release in response to agonist, and TNF priming of this respiratory burst or in the ability to degrade cartilage in vitro and TNF priming for increased cartilage damage. It is evident that rheumatoid arthritis blood neutrophils retain the ability to bind TNF and can be primed by TNF for increased oxygen radical production and augmented cartilage damage. These findings further implicate the role of neutrophils in the pathogenesis of arthritis.
7732485 [Stromelysin-1 (MMP-3) level in the sera from patients with rheumatoid arthritis and other 1995 Feb Stromelysin-1 (MMP-3) is a metalloproteinase that degrades articular cartilage matrix in patients with rheumatoid arthritis (RA). We measured MMP-3 in the sera from patients with RA and other connective tissue diseases using specific sandwich EIA and studied its clinical significance in early onset RA. MMP-3 level in healthy control (n = 170) was significantly higher in male than in female. The level of MMP-3 in RA was significantly and dramatically higher than in healthy control, osteoarthritis, systemic lupus erythematosus, progressive systemic sclerosis, primary sjogren's syndrome, mixed connective tissue disease, gouty arthritis and traumatic arthritis. Serum MMP-3 significantly correlated with serum BUN or serum creatinine levels in SLE patients but not in RA patients. In early onset RA, serum MMP-3 level was significantly elevated. Furthermore, when the relationship between the serum MMP-3 level and X-ray findings of the joints in RA was studied, it was found that MMP-3 level was elevated even in stage I or II and that there was no statistical differences between stage I or II and stage III or IV, suggesting that serum MMP-3 level is elevated in the early stage of initial inflammatory process when only mild cartilage degradation is seen. These results suggest that measurements of serum MMP-3 is an important tool for establishing diagnosis of early onset RA, and that serum MMP-3 level may be a marker of cartilage destruction and of estimating therapeutic efficacy in early onset RA.
7731124 [A case of rheumatoid arthritis with a remarkable left-right difference in pulmonary lesio 1995 Feb A 59-year-old woman had a four-year history of rheumatoid arthritis. Despite treatment with prednisolone for interstitial pneumonia, her chest X-ray films revealed gradual progression of reticular shadows, mainly in the left lung, and during the third hospitalization she died of respiratory failure due to acute exacerbation of pneumonia. At autopsy, there was a remarkable difference in lung weight: left 250 g, right 510 g. Microscopically, the pulmonary lesion was mild fibrosing interstitial pneumonia, with remarkable luminal organization and macrophages in parts. The features of unilateral interstitial pneumonia with bronchiolitis obliterans organizing pneumonia were clearer in the left lung. The cause of the acute exacerbation and of the difference in interstitial pneumonia between sides could not be identified.
8312514 [Radiographic changes of the calcaneus in the framework of chronic polyarthritis]. 1994 Feb Plain films of the calcaneus of 768 patients with confirmed rheumatoid arthritis were examined retrospectively with reference to inflammatory rheumatic changes. 42 patients (5.5%) showed an erosion of the posterior upper calcaneal margin related to an Achilles bursitis. In three patients there were additional plantar erosions. The Achilles bursitis was bilateral in 50% of cases, particularly in patients in stages 2 and 3 according to Steinbrocker. In the majority of bilateral cases (62%) the size or shape of the lesions was asymmetrical. Our observations indicate that involvement of the os calcis is not uncommon in rheumatoid arthritis; routine examination of this bone would appear to be indicated even in patients without symptoms. Since the defect is unilateral in half the patients, unilateral occurrence of an erosive lesion cannot be regarded as a criterion for a bacterial-inflammatory bursitis. Contrary to the symmetrical involvement of joints in the hands in rheumatoid arthritis, defects in the calcaneus are often unilateral or asymmetrical.