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ID PMID Title PublicationDate abstract
9035014 Low dose etodolac in rheumatoid arthritis: a review of early studies. 1997 Feb Short and longterm safety and efficacy of etodolac in a wide range of dosages in patients with rheumatoid arthritis (RA) are summarized. Data from 8 studies, one longterm (1 year) and 7 short term (< 10 weeks) were analyzed. All studies were double blind and randomized; 6 had a placebo control group and 7 had an active comparator (aspirin, piroxicam, or sulindac) group. In the 1 year study, doses of etodolac were titrated up from 50 mg bid until clinical efficacy was achieved and maintained; the highest dose for > 80% of patients was 150 mg bid. In 6 of the 7 short term studies, dosages were fixed and ranged from 50 to 300 mg bid. Continuation rates and 4 efficacy measures (patients' and physicians' global assessments and numbers of painful and swollen joints) were assessed. The 1 year study enrolled 475 patients. Overall continuation rates for etodolac and aspirin were comparable, but more patients taking aspirin discontinued the study because of adverse events. Most patients given etodolac who discontinued treatment for lack of efficacy did so during the titration phase. Four of 236 patients received aspirin and none received etodolac developed ulcers. For patients continuing to take the study medication, improvement in efficacy variables in the etodolac group was comparable to that in the aspirin group. In the 7 short term studies, dose related improvement in patients' and physicians' global assessments and number of swollen joints was noted in the etodolac group compared with the placebo group; this improvement was statistically significant at dosages of > or = 200 mg bid. Pooled analysis showed the efficacy of etodolac at dosages of 300 mg bid to be similar to that of comparator drugs. These short and longterm studies show that etodolac in a wide range of dosages, starting at 200 mg bid, has clinical efficacy in the treatment of RA. It is significantly better tolerated than aspirin, and at doses of 300 mg bid, it is as effective as sulindac, aspirin, and piroxicam.
10410264 Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate wit 1999 May OBJECTIVES: To measure MTX polyglutamates in circulating erythrocytes (E-MTX), mononuclear cells (MNC-MTX) and polymorphs (PMN-MTX) in rheumatoid arthritis (RA) patients and to see whether these correlated with clinical efficacy and side effects. METHODS: Sixty-five patients (40F, 25M; mean age 57 yrs.) with RA (ARA revised criteria) who had been on weekly pulse MTX (2.5-37.5 mg) for at least 2 months were entered into this study. The patients were classified as responders (R), partial responders (PR) or non-responders (NR) when blood was sampled for the MTX determination. Side effects since the initiation of MTX were also recorded. MTX-polyglutamates were measured (blinded to clinical details) using an enzymatic assay. RESULTS: E-MTX in responders and partial responders were significantly higher (p < 0.001) than in non-responders. Similarly, PMN-MTX were also higher, but the difference was only significant for the R group (p = 0.0019). The differences in concentrations could not be explained on the basis of the dose, which tended to be higher in NR than in R (p = 0.085). The concommitant prednisolone dose was significantly lower in R than in NR (p = 0.001), as were the ESR and CRP (p = 0.007, and p = 0.05 respectively), but the MCV was higher (p = 0.047). E-MTX tended to be higher in patients with side effects, but this difference did not reach statistical significance (p = 0.15). CONCLUSION: The results suggest that circulating intracellular levels of MTX polyglutamates in RBC and PMN correlate with clinical efficacy but not with toxicity in patients with RA.
9305751 Expression of arachidonate platelet-type 12-lipoxygenase in human rheumatoid arthritis typ 1997 Sep 1 In the present study, we have demonstrated platelet-type 12-lipoxygenase (12-LOX) expression in human rheumatoid arthritis (RA) type B synoviocytes by reverse-transcription polymerase chain reaction (RT-PCR). The presence of 12-LOX mRNA in these cells was revealed by classical RT-PCR analysis using platelet-type 12-LOX cDNA primers and the PCR fragment (246 bp) was purified, amplified and sequenced. By sequence analysis, this fragment was determined to be 100% identical to that from platelet-type 12-LOX cDNA. Immunofluorescence data demonstrate that interleukin-1beta (IL-1beta) increases cellular 12-LOX protein. Other results associate specific inflammatory cytokines with the activity of 12-LOX in human RA type B synoviocytes. IL-1beta increased 12S-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) production (4-fold) and we also observed an increase in 12-HETE production (2.5-fold) after incubation of human RA type B synoviocytes with TNF alpha. In contrast to the action of IL-1beta on 12-HETE synthesis, IL-4 and IL-6 did not enhance 12-HETE production. This is the first demonstration of platelet-type 12-LOX cDNA derived from the mRNA of cultured human RA type B synoviocytes.
9797554 A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with spe 1998 Aug OBJECTIVES: (1) To analyse the in situ expression of adhesion molecules in rheumatoid nodules. (2) To compare the endothelial expression of adhesion molecules in synovial tissue and subcutaneous nodules obtained from the same patients. (3) To compare the expression of adhesion molecules and activation markers on T cell lines from nodules and synovium. METHODS: (1) Immunohistochemical analysis by APAAP technique of E selectin, CD44, ICAM-1, PECAM-1, and VCAM-1 was performed on 10 rheumatoid nodules from seven patients with rheumatoid arthritis (RA); nodules and synovium were simultaneously analysed from three patients. (2) T cell lines were generated from RA nodules (n = 7) and synovium (n = 7) by interleukin 2 expansion, and subsequently characterised by flow cytometry for surface expression of alpha E beta 7, alpha 4 beta 7, CD44, L selectin, LFA-1a, PECAM-1, and CD30. RESULTS: (1) In rheumatoid nodules, the palisading layer strongly stains for ICAM-1 and PECAM-1, but less pronounced for CD44. VCAM-1 staining was usually negative. ICAM-1 is upregulated in the vessels surrounding the central zone of fibrinoid necrosis. The immunohistological picture in different nodules derived from the same patient was similar. (2) The endothelial expression of adhesion molecules is comparable in RA nodules and synovium on an individual level, except for E selectin, which is overexpressed in nodule endothelium. (3) T cell lines from nodules and synovium display similar adhesion molecule profiles. However, the expression of CD30, a T cell activation marker linked with Th2 subsets, is higher in nodules compared with synovium. CONCLUSION: These data support a recirculation hypothesis of T cells between articular and extra-articular manifestations in RA, although the activation state of the T cells in each of these localisations may differ.
9820598 D6S273 microsatellite polymorphism and susceptibility to rheumatoid arthritis. 1998 Oct Rheumatoid arthritis (RA) is a chronic articular inflammatory disease associated with HLA-DR genes that share a five amino acid sequence motif, QKRAA or QRRAA, from position 70 to 74 in the third hypervariable region of the DRB1 molecule. Since these associations between DRB1 genes and susceptibility to RA are incomplete, we examined the role of a CA repeat polymorphic microsatellite marker, D6S273, located between HSP70 and Bat2 genes in the class III region of MHC, in susceptibility to RA. Ninety-seven adult patients with seropositive RA and 100 normal healthy subjects were studied. Two D6S273 alleles (132 and 138) showed significant differences in their prevalence in RA patients as compared to normal controls; allele 132 was significantly higher in total patients and in DRB1 QKRAA/QRRAA epitope-positive patients, and allele 138 was significantly higher in QKRAA/QRRAA-negative patients. Analysis of data suggested that the association of D6S273 132 allele with RA was secondary to that of DRB1 genes. On the other hand, D6S273 138 allele showed primary association with RA susceptibility in QKRAA/QRRAA epitope-negative patients. The D6S273 138 allele thus provides an additional risk in RA susceptibility. The results in the present study therefore suggest that two regions in MHC, DRB1 and D6S273, contribute to susceptibility to RA.
11809000 Atherosclerosis and connective tissue diseases. 2001 Dec Large increases in mortality related to premature atherosclerosis with coronary artery disease and stroke have been reported in patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APLS), or rheumatoid arthritis (RA). Studies found relative risks of 5 for myocardial infarction, 6 to 10 for stroke in SLE patients, and 3.6 for cardiovascular deaths in RA patients. The main risk factors for atherosclerosis included not only the classic factors identified in epidemiological studies such as the Framingham study (advanced age, high cholesterol levels, hypertension, diabetes mellitus, and obesity), but also prolonged glucocorticoid therapy, long duration of SLE, postmenopausal status, and heart failure. SLE per se is an independent risk factor. The current pathogenic hypothesis for atherosclerosis involves an inflammatory response (erythrocyte sedimentation rate, C-reactive protein, and fibrin), autoantibodies, immune complexes (containing antibodies to phospholipids, to oxidized LDLs, and to endothelial cells), cytokine-producing activated T cells, and bacterial or viral infections responsible for an immune response against heat shock proteins (endogenous HSP60 and its equivalent, bacterial HSP65). Early risk factor intervention and effective control of inflammation should be incorporated into the management of connective tissue disease with the goal of protecting patients against atherosclerosis.
11718817 Hydrodynamics of cryogelation. 2001 Dec 10 Cryogel, prevalent in the plasma of rheumatoid arthritis patients, is a plasma fibronectin (pFN)-extra domain A containing FN [EDA(+)FN]-fibrinogen (Fbg) aggregate formed by the addition of heparin (Hep) at low temperature. Although EDA(+)FN is not usually present in normal plasma, its prevalence in rheumatic patients induces cryogelation. In this study, we determined the hydrodynamic radius (R(h)) ratio (R(h)/R(h30)) of the cryogel component by dynamic light scattering in vitro. R(h)/R(h30) was normalized to R(h) at 30 degrees C (R(h30)) at several temperatures. The R(h)/R(h30) of Fbg was found to increase only by self-aggregation, whereas the R(h)/R(h30) of FNs does not increase in response to temperature changes. The R(h)/R(h30) of the Fbg/FN aggregate is increased by the addition of Hep, and the R(h)/R(h30) (12.5) of the Hep-induced EDA(+)FN/Fbg aggregate is greater than that (2.5) of the pFN/Fbg aggregate. These results suggest that cryogelation requires Fbg self-aggregation and the interaction between EDA(+)FN and Hep.
11327238 Expression of interleukin 10 mRNA and protein by synovial fibroblastoid cells. 2001 Apr OBJECTIVE: To determine if fibroblast-like synoviocytes (FLS) express interleukin 10 (IL-10) mRNA and protein and functional IL-10 receptors. METHODS: The pattern of IL-10 production was analyzed in inflammatory synovial tissues by immunohistochemistry. Expression of IL-10 mRNA and protein was determined by Northern blot analysis and ELISA in resting FLS and following stimulation with IL-1beta and tumor necrosis factor-alpha (TNF-alpha). IL-10 receptor expression was measured on cultured FLS by immunohistochemistry and FACS analysis after treatment with biotinylated IL-10. Responsiveness of FLS to IL-10 was determined by multigene assay and inhibition of prostaglandin E2 induced morphologic changes. Bioactivity was confirmed by downregulation of interferon-gamma stimulated HLA-DR expression by FACS and inhibition of TNF-alpha production by U937 cells. RESULTS: Using immunohistochemistry, we detected IL-10 in the lining layer of inflamed synovial tissue and FLS. ELISA on unstimulated third passage FLS culture supernatants revealed IL-10 production that varied over time and among cell lines. FLS produced IL-10 mRNA constitutively. IL-10 production was upregulated by IL-1beta and TNF-alpha. IL-10 bound to receptors on FLS and induced functional changes. Endogenously released FLS IL-10 was biologically active. CONCLUSION: Mesenchymal lining cells in the inflamed joint produce IL-10. In addition, cultured FLS constitutively produce IL-10 mRNA and protein that is bioactive and can be upregulated by IL-1beta and TNF-alpha. FLS express functional IL-10 receptors. These results suggest that IL-10 released by mesenchymal cells in inflammatory arthritis can modulate synovial inflammation and joint destruction by paracrine and/or autocrine mechanisms.
11284594 The effects of severe femoral bone loss on the flexion extension joint space in revision t 2001 Feb Five revision total knee arthroplasties (TKAs) involving severe femoral bone loss were performed in 1994. Each had sufficiently severe femoral bone loss in which collateral ligament origins and posterior capsular attachments were violated. A paradoxical phenomenon was observed in each case. Unlike primary TKAs, in which larger distal femoral bone resection leads to laxity of the knee joint in extension, these cases with severe distal femoral bone loss, after initial component selection, developed the opposite situation, a flexion contracture. It was hypothesized that femoral bone loss involving collateral ligament origins would permit distraction of the tibia below the femur with the knee held in flexion, but when the knee was brought to full extension, intact posterior structures would maintain a normal tibial position. To investigate this hypothesis, six fresh-frozen cadaveric lower limbs were tested in full extension and 45 degrees and 90 degrees of flexion after release of the femoral attachments of the collateral ligaments and the posterior capsule from the femur. Joint space changes were measured via a motion tracking device. Results showed that with loss of collateral attachments, 17.2+/-8.9 mm of joint space is created in 90 degrees of flexion, whereas the joint space in full extension is conserved (1.5+/-1.7 mm). With additional loss of the posterior capsule, the joint space at 90 degrees of flexion increased to 26.2+/-6.1 mm, with minimal changes in the extension gap (3.4+/-0.8 mm). Distal femoral bone loss was associated with an increase in the flexion gap compared to the extension gap.
9858442 Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship wit 1998 Dec OBJECTIVE: Pentosidine is an advanced glycation endproduct formed by glycosylation and oxidation. Our aim was to develop a means to measure pentosidine in synovial fluid (SF), and to compare its concentration in SF in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to investigate the relationship between its concentration in SF and the disease activity of RA. METHODS: SF was collected from knee joints in 31 patients with RA and 40 with OA, who had hydrarthrosis. One patient with RA and 7 with OA who had the complication of diabetes mellitus or chronic renal failure made up the DM/CRF group, and the remaining patients made up the RA group (n = 30) and the OA group (n = 33). Pentosidine was measured by the direct HPLC method with column switching after hydrolysis of SF. RESULTS: Pentosidine was detected in all SF and was greater in RA (83.9 +/- 46.0 nmol/l, mean +/- SD) than in OA (40.1 +/- 19.6 nmol/l). Three DM/CRF patients undergoing hemodialysis had markedly high pentosidine levels (482.5 +/- 280.8 nmol/l). There was a significant correlation between pentosidine and C-reactive protein (CRP), erythrocyte sedimentation rate, and Lansbury Index (p < 0.01). Patients with RA were divided into high and low activity groups according to the CRP and Lansbury Index. Pentosidine was significantly higher in the high activity group (CRP > or = 2.0 mg/dl and Lansbury Index > or = 50%) than in the low activity group (CRP < 2.0 and/or Lansbury Index < 50) (100.9 +/- 42.8 vs 58.5 +/- 39.6 nmol/; p = 0.0013). CONCLUSION: Pentosidine in synovial fluid was higher in RA than in OA. Pentosidine levels in SF were related to the disease activity in RA.
11502617 A pilot study of a long acting somatostatin analogue for the treatment of refractory rheum 2001 Sep OBJECTIVE: To evaluate the efficacy and safety of a long acting somatostatin analogue in a subset of patients with refractory rheumatoid arthritis (RA). METHODS: Ten patients with active, refractory RA, who had failed to respond to at least four disease modifying antirheumatic drugs (DMARDs), were treated with monthly intramuscular injections of 20 mg of a long acting preparation of octreotide (Sandostatin-LAR) for three months. They were evaluated every two weeks in an open label pilot study. The primary measure of clinical response was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR 20). RESULTS: Eight patients completed the 14 week trial, while two patients received only one or two doses of the somatostatin analogue, but were eligible for evaluation. On an intention to treat basis 6/10 patients responded: four patients met the ACR 20 criteria at weeks 6-10, while two patients continued to improve with time, and met the ACR 50 and 70 criteria respectively, at week 14. On evaluation of the 10 patients as a group, a significant improvement (p<0.05) was noted in the mean visual analogue scales of pain, doctor's and patient's global assessment of disease activity, and in the mean number of swollen joints. Adverse effects were minor: transient bloating and loose stools, an urticarial rash (n=1), and a transient increase of liver enzymes (n=1). CONCLUSION: Treatment with a long acting somatostatin analogue led to significant clinical improvement in a subset of patients with active, refractory RA. The treatment was relatively safe and well tolerated. Further large, placebo controlled studies are required to evaluate this drug as a potential DMARD for patients with RA.
10502534 Neuroendocrine host factors and inflammatory disease susceptibility. 1999 Oct The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures.
10875323 Septic arthiritis due to Prevotella bivia in a patient with rheumatoid arthritis. 2000 Prevotella bivia is a gram-negative anaerobic bacteria traditionally classified in the genus Bacteroides, and usually reported in obstetric and gynecologic infections. To date, there has been only one description of infectious arthritis secondary to this germ. We report the first case of septic arthritis due to Prevotella bivia in a patient with severe, long-lasting rheumatoid arthritis (RA) treated with low doses of corticosteroids. RA is a well-known predisposing factor to septic arthritis, whose causes are multifactorial (general immunosuppression induced by the disease and its therapy, presence of prosthetic joints, etc.). However, infectious arthritis due to anaerobic bacteria is rarely observed. In general, clinical presentation varies widely: insidious onset, apyrexia, and lack of inflammatory signs or systemic disturbance are frequent features. Joint infection is generally secondary to hematogenous spread, the Bacteroides fragilis group being the most commonly isolated pathogens. Early diagnosis and prompt treatment, with drainage and debridement of the affected joint and specific antimicrobial treatment with Metronidazole are essential for a successful outcome.
9355001 The Stanmore total hip arthroplasty. A 15- to 20-year follow-up study. 1997 Oct An ongoing study was made of 804 primary Stanmore total hip prostheses implanted in 839 patients between 1973 and 1991. The earliest surviving implants were brought back for radiologic and clinical review in 1995 at an average of 17 years after surgery. The remainder of the patients still living were sent a questionnaire to assess their current status. Survivorship was 95% at 10 years, 85% at 15 years, and 73% at 20 years. The average Merle d'Aubigné-Postel score was excellent up until 14 years. Patient satisfaction remained high until 22 years. Overall, 10% of the prostheses had failed. The results of this study suggest that the Stanmore prosthesis is capable of producing satisfactory long-term results that compare favorably with those of other cemented prostheses.
11056661 The effects of 1 alpha,25-dihydroxyvitamin D(3) on matrix metalloproteinase and prostaglan 1999 INTRODUCTION: 1alpha,25-dihydroxyvitamin D(3)[1alpha,25(OH)(2)D(3)], the biologically active metabolite of vitamin D3, acts through an intracellular vitamin D receptor (VDR) and has several immunostimulatory effects. Animal studies have shown that production of some matrix metalloproteinases (MMPs) may be upregulated in rat chondrocytes by administration of 1alpha,25(OH)(2)D(3); and cell cultures have suggested that 1alpha,25(OH)(2)D(3) may affect chondrocytic function. Discoordinate regulation by vitamin D of MMP-1 and MMP-9 in human mononuclear phagocytes has also been reported. These data suggest that vitamin D may regulate MMP expression in tissues where VDRs are expressed. Production of 1alpha,25(OH)(2)D(3) within synovial fluids of arthritic joints has been shown and VDRs have been found in rheumatoid synovial tissues and at sites of cartilage erosion. The physiological function of 1alpha,25(OH)(2)D(3) at these sites remains obscure. MMPs play a major role in cartilage breakdown in the rheumatoid joint and are produced locally by several cell types under strict control by regulatory factors. As 1alpha,25(OH)(2)D(3) modulates the production of specific MMPs and is produced within the rheumatoid joint, the present study investigates its effects on MMP and prostaglandin E(2) (PGE(2)) production in two cell types known to express chondrolytic enzymes. AIMS: To investigate VDR expression in rheumatoid tissues and to examine the effects of 1alpha,25-dihydroxyvitamin D(3) on cultured rheumatoid synovial fibroblasts (RSFs) and human articular chondrocytes (HACs) with respect to MMP and PGE(2) production. METHODS: Rheumatoid synovial tissues were obtained from arthroplasty procedures on patients with late-stage rheumatoid arthritis; normal articular cartilage was obtained from lower limb amputations. Samples were embedded in paraffin, and examined for presence of VDRs by immunolocalisation using a biotinylated antibody and alkaline-phosphatase-conjugated avidin-biotin complex system. Cultured synovial fibroblasts and chrondrocytes were treated with either 1alpha,25(OH)(2)D(3) or interleukin (IL)-1beta, or both. Conditioned medium was assayed for MMP and PGE(2) by enzyme-linked immunosorbent assay (ELISA), and the results were normalised relative to control values. RESULTS: The rheumatoid synovial tissue specimens (n=18) immunostained for VDRs showed positive staining but at variable distributions and in no observable pattern. VDR-positive cells were also observed in association with some cartilage-pannus junctions (the rheumatoid lesion). MMP production by RSFs in monolayer culture was not affected by treatment with 1alpha,25(OH)(2)D(3) alone, but when added simultaneously with IL-1beta the stimulation by IL-1beta was reduced from expected levels by up to 50%. In contrast, 1alpha,25(OH)(2)D(3) had a slight stimulatory effect on basal production of MMPs 1 and 3 by monolayer cultures of HACs, but stimulation of MMP-1 by IL-1beta was not affected by the simultaneous addition of 1alpha,25(OH)(2)D(3) whilst MMP-3 production was enhanced (Table 1). The production of PGE(2) by RSFs was unaffected by 1alpha,25(OH)(2)D(3) addition, but when added concomitantly with IL-1beta the expected IL-1beta-stimulated increase was reduced to almost basal levels. In contrast, IL-1beta stimulation of PGE(2) in HACs was not affected by the simultaneous addition of 1alpha,25(OH)(2)D(3)(Table 2). Pretreatment of RSFs with 1alpha,25(OH)(2)D(3) for 1h made no significant difference to IL-1beta-induced stimulation of PGE(2), but incubated for 16h suppressed the expected increase in PGE(2) to control values. This effect was also noted when 1alpha,25(OH)(2)D(3) was removed after the 16h and the IL-1beta added alone. Thus it appears that 1alpha,25(OH)(2)D(3) does not interfere with the IL-1beta receptor, but reduces the capacity of RSFs to elaborate PGE(2) after IL-1beta induction. Cells within the rheumatoid lesion which expressed VDR were fibroblasts, macrophages, lymphocytes and endothelial cells. These cells are thought to be involved in the degradative processes associated with rheumatoid arthritis (RA), thus providing evidence of a functional role of 1apha,25(OH)(2)D(3) in RA. MMPs may play important roles in the chondrolytic processes of the rheumatoid lesion and are known to be produced by both fibroblasts and chondrocytes. The 1alpha,25(OH)(2)D(3) had little effect of basal MMP production by RSFs, although more pronounced differences were noted when IL-1beta-stimulated cells were treated with 1alpha,25(OH)(2)D(3), with the RSF and HAC showing quite disparate responses. These opposite effects may be relevant to the processes of joint destruction, especially cartilage loss, as the ability of 1alpha,25(OH)(2)D(3) to potentiate MMP-1 and MMP-3 expression by 'activated' chondrocytes might facilitate intrinsic cartilage chondrolysis in vivo. By contrast, the MMP-suppressive effects observed for 1alpha,25(OH)2D3 treatment of 'activated' synovial fibroblasts might reduce extrinsic chondrolysis and also matrix degradation within the synovial tissue. Prostaglandins have a role in the immune response and inflammatory processes associated with RA. The 1alpha,25(OH)2D3 had little effect on basal PGE2 production by RSF, but the enhanced PGE2 production observed following IL-1beta stimulation of these cells was markedly suppressed by the concomitant addition of 1alpha,25(OH)2D3. As with MMP production, there are disparate effects of 1alpha,25(OH)2D3 on IL-1beta stimulated PGE2 production by the two cell types; 1alpha,25(OH)2D3 added concomitantly with IL-1beta had no effect on PGE2 production by HACs. In summary, the presence of VDRs in the rheumatoid lesion demonstrates that 1alpha,25(OH)2D3 may have a functional role in the joint disease process. 1 alpha,25(OH)2D3 does not appear to directly affect MMP or PGE2 production but does modulate cytokine-induced production.
9536820 Analysis of LMP and TAP polymorphisms by polymerase chain reaction-restriction fragment le 1998 Jan OBJECTIVE: The aim of this study was to investigate the relation between the polymorphism of large molecular weight proteasome (LMP) (LMP2-LMP7) and transporter associated with antigen processing (TAP) (TAP1-TAP2) genes and rheumatoid arthritis (RA). METHODS: Sixty RA patients and 102 ethnically matched unrelated healthy subjects were typed for LMP, TAP, and disease associated HLA-DRB1 alleles by using a new strategy based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with amplification created restriction sites. RESULTS: The polymorphism of LMP (LMP2-LMP7) and TAP (TAP1-TAP2) genes was examined in shared epitope positive and negative RA patients and controls. No significant differences in the LMP or TAP allele frequencies were observed between the total patient and control groups or the patients and controls groups or the patients and controls positive or negative for the shared epitope. CONCLUSION: The data suggest that the polymorphisms of LMP and TAP genes do not have an important influence in the pathogenesis of RA, although larger studies will be needed to provide more conclusive evidence on the role of these genes in RA. A new, highly reliable strategy for typing LMP alleles is also described.
10863325 [Synovial fluids from patients with rheumatoid arthritis induce the differentiation of hum 2000 Apr Bone marrow abnormalities have been found to play a role in the pathogenesis of rheumatoid arthritis (RA). Recent studies have also confirmed the presence of undifferentiated hematopoietic progenitor cells as well as the expression of stem cell factor in the synovial membranes in RA. The present study investigates whether RA synovial fluids contain factors that can induce differentiation of CD 14 positive/HLA-DR positive cells from undifferentiated hematopoietic cells. Synovial fluid specimens from 18 patients with RA and from 10 control patients, including patients with osteoarthritis and Behcet's disease, were studied. Human promyelocytic leukemia cell line HL 60 (5 x 10(4)/well) were cultured in the presence or absence of the synovial fluids for 5 days, after which the expression of CD 14 and HLA-DR was examined by flow cytometry. The induction of differentiation of CD 14 positive/HLA-DR positive cells or HLA-DR positive cells from HL 60 cells was significantly enhanced more in the presence of synovial fluids from RA patients than in the presence of those of control patients. However, the sera from the RA patients could not induce the differentiation of CD 14 positive/HLA-DR positive cells or HLA-DR positive cells from HL 60 cells. Most cytokines found in RA synovial fluid could not induce the differentiation of HL 60 cells. Of note, treatment of synovial fluids with hyaluronidase significantly decreased or abrogated their capacity to induce the differentiation of HLA-DR positive cells from HL 60. There was no significant difference in the concentration of hyaluronic acid in the synovial fluid between the RA patients and the control patients. These results indicate that there are factors that can induce differentiation of HLA-DR positive cells from undifferentiated hematopoietic cells in the synovial fluid of RA. The data also suggest that such differentiation factors might be related with qualitative abnormality of hyaluronic acid.
10914844 Genetic association between rheumatoid arthritis and estrogen receptor microsatellite poly 2000 Jul OBJECTIVE: To investigate estrogen receptor (ER) microsatellite allele frequencies in patients with rheumatoid arthritis (RA), and possible associations of ER microsatellites with osteoporosis and disease progression. METHODS: We typed 144 Japanese females with RA and 200 healthy postmenopausal Japanese controls for ER microsatellites by polymerase chain reaction methods using fluorescent labeled primer and semiautomatic genotyping. Bone mineral density (BMD) of patients was measured in the spine by dual energy x-ray absorptiometry, and recent radiographs of the hands and wrists were scored according to the method described by Sharp, et al. RESULTS: The ER genotype was classified according to number of dinucleotide (thymine-adenine, TA) repeats between 10 and 27. The frequency of allele 14 (14 repeats of TA) was significantly increased in patients versus controls. No association of ER microsatellites with osteoporosis or radiographic progression in the RA patients was noted. CONCLUSION: These results suggest that a genetic variation at the ER locus may be associated with other pathogenetic factors in patients with rheumatoid arthritis, but not with BMD and disease aggressiveness.
10615020 Aortic valve rheumatoid nodules producing clinical aortic regurgitation and a review of th 1999 Nov The majority of cardiac involvement in rheumatoid arthritis (RA) is an incidental finding at postmortem, as less than 3% of patients with RA have clinical cardiac signs or symptoms. Most cardiac involvement in RA involves the pericardium and has been known since Charcot first described an RA patient with pericarditis in 1881. Cardiac involvement takes two different forms: non-specific inflammatory changes and specific granuloma formation. Specific rheumatoid nodules in the heart are an infrequent complication of RA. This is the first case report of a surgically excised heart valve with rheumatoid nodules. A 74-year-old RA patient with a high seropositive rheumatoid factor presented with severe aortic regurgitation and underwent a valve replacement. The native aortic valve showed significant stenosis with multiple, classic rheumatoid nodules.
10473064 Elevated plantar pressure and ulceration in diabetic patients after panmetatarsal head res 1999 Aug Panmetatarsal head resection (variously called forefoot arthroplasty, forefoot resection arthroplasty, the Hoffman procedure, and the Fowler procedure) was developed for the relief of pain and deformity in rheumatoid arthritis. Although there are successful retrospective series reported in the literature, such an approach is not supported by carefully designed controlled trials. This procedure has also been advocated by some for the relief of plantar pressure in diabetic patients who are at risk for plantar ulceration. The efficacy of the procedure in this context is not supported by existing pressure measurements on rheumatoid arthritis patients in the literature, which has tended to show that although pain relief is obtained, the procedure results in elevation of forefoot pressure. Case reports are described of two patients (three feet) with sensory neuropathy who presented to our clinic 1 to 2 years after panmetatarsal head resections had been performed. Peak plantar pressures in these feet during first step gait were above the 99th percentile and outside the measuring range of the device used (EMED SF platform; NOVEL Electronics Inc., St. Paul, MN). Both patients had also experienced plantar ulcers subsequent to the surgery. Combining the information on patients with rheumatoid arthritis (RA) with that from our two case studies, we conclude that panmetatarsal head resection does not necessarily eliminate focal regions of elevated plantar pressure.