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ID PMID Title PublicationDate abstract
10446871 The relationship between synovitis and bone changes in early untreated rheumatoid arthriti 1999 Aug OBJECTIVE: The interrelationship between synovitis and bone damage in rheumatoid arthritis (RA) is a subject of controversy. Using magnetic resonance imaging (MRI), this study followed the bone changes in early RA and determined their relationship to synovitis. METHODS: Thirty-one patients with early RA who had swelling of the metacarpophalangeal (MCP) joints and 31 healthy control subjects with no clinical evidence of arthritis underwent MRI of the second through fifth MCP joints of the dominant hand by use of a 1.5T scanner. Coronal T1-weighted and T2-fat suppressed (FS) sequences were performed to evaluate bone edema, and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) pulse sequences were obtained to evaluate synovitis. Bony abnormalities were described as bone edema (low signal on T1-weighted sequences and intermediate/high signal on T2 FS sequences adjacent to the bone cortex) or as bone cysts (circular juxtacortical abnormalities with low signal on T1-weighted images and with very high signal on T2 FS sequences). Contrast and noncontrast MRI films were scored in a blinded manner, and Fisher's exact probability test was used to determine differences between groups. RESULTS: Twenty-one of the 31 RA patients (68%) had bone edema, which was seen in 43 of 124 joints (35% of joints) and 3 of the 31 control subjects had bone edema seen in 3 of 124 joints (2% of joints) (P < 0.0001). Thirty RA patients (97%) had Gd-DTPA-confirmed MCP joint synovitis, and bone edema was seen in 40 of the 75 joints with Gd-DTPA-proven synovitis (53%), but in only 3 of 49 without (6%) (P < 0.0001). CONCLUSION: MCP joint bone edema is present in the majority of patients with RA at presentation, but is seen only occasionally in normal control subjects. The fact that bone edema occurred rarely in the absence of synovitis in patients with RA suggests that bony changes in RA are secondary to synovitis.
11249572 TNF inhibitors in the treatment of arthritis. 2000 Oct Rheumatoid arthritis (RA) is a chronic destructive arthritis leading to joint destruction as a consequence of chronic inflammatory processes. Established therapy with slow-acting disease-modifying anti-rheumatic drugs (DMARDs), as with low-dose methotrexate (MTX), leads to a significant improvement of disease symptoms, but are unable to stop joint destruction. Novel therapeutic agents like monoclonal antibodies (mAb), cytokine receptor-human immunoglobulin constructs or recombinant human proteins have been tested in RA and in other chronic arthritides like ankylosing spondylitis or psoriatic arthritis with convincing success. In particular, clinical trials testing anti-TNF alpha agents either alone or in combination with MTX have proven the feasibility and efficacy of these novel approaches.
9700765 The corticotrophin-releasing factor-binding protein: an act of several parts. 1998 Previously the function of hormone binding proteins has been viewed entirely as one of either sequestering ligand activity or of delivering ligand to target tissues. However, some binding proteins have the ability when complexed with ligand to interact directly with target tissues and can undergo considerable post-translational and post-secretional modifications that serve to modify their action. We propose that for the corticotrophin-releasing factor-binding protein (CRF-BP), this adds a further level at which hormonal action may be regulated. This contrasts with previous concepts of a passive role and shows them as important regulators of hormonal action in their own right.
10700434 Development of additional autoimmune diseases in a population of patients with systemic lu 2000 Mar OBJECTIVE: In view of the recognised clustering of autoimmune diseases (AID), the chronology of development of other autoimmune diseases in systemic lupus erythematosus (SLE) patients was considered. METHODS: A retrospective review of a well documented population of 215 patients with SLE was undertaken. The duration of follow up ranged from 2 to 18 years. RESULTS: Of these 215 patients, 65 (30%) had at least one other AID-including 51 (24%) having one other AID, 12 (6%) having two and two (1%) having three other AID in addition to their SLE. Twelve different autoimmune diseases were identified. The majority of patients developed a further AID after SLE had been diagnosed (62%) reflecting the relatively early age of onset of SLE. There was no significant difference in the age of onset of rheumatoid arthritis, Sjögren's syndrome and hypothyroidism that had developed before SLE compared with those who developed these diseases after SLE. However, those who developed autoimmune thrombocytopenia (AITP) before SLE were significantly younger than those who developed AITP after SLE (16.7 v. 38.7 years respectively, p<0.05). CONCLUSIONS: Physicians caring for SLE patients should remain alert to the possible development of a second AID during follow up. Further well matched case-control studies are required to define the exact relation between SLE and other AID.
9219314 The gastroenterologist's caseload: contribution of the rheumatologist. 1997 Jun Rheumatological conditions often give rise to gastrointestinal (GI) symptoms and vice versa, but the greatest point of contact between rheumatologists and gastroenterologists arises through gastrointestinal toxicity resulting from the use of nonsteroidal antiinflammatory drugs (NSAIDs). Standard NSAIDs are toxic to the entire GI tract. The point prevalence of ulcers in patients on long-term NSAID treatment is about 20% and the annual incidence of complications in these patients is 1% to 4%; 1,200 patients in the United Kingdom die each year as a result. Withdrawing NSAID treatment, or reducing the dose, is not always possible, and approximately 25% of patients require continued long-term antiinflammatory treatment. Misoprostol and acid-suppressing drugs such as ranitidine and omeprazole are helpful as prophylactic treatment in high risk patients, and in healing established ulcers, especially in patients carrying Helicobacter pylori, but there is a pressing need for new, safer antiinflammatory drugs toease the burden of NSAID gastropathy. Selective inhibition of the COX-2 isoform of cyclooxygenase has been proposed as a new and safer therapeutic option. Clinical studies with meloxican, a selective COX-2 inhibitor, support this view. Meloxicam has been extensively studied in arthritis patients and combines antiinflammatory efficacy with a lower incidence of GI toxicity than currently available NSAIDs.
9099177 Amyloid beta protein and Alzheimer disease. 1997 Apr 1 Amyloid beta protein is predominant in senile plaques, the neuropathologic hallmarks of Alzheimer disease. Researchers in Winnipeg have shown that this protein can overstimulate certain hydrolytic enzymes to break down the phospholipid building blocks of the brain-cell wall. They speculate that the abnormal destruction of phospholipids gradually drains the energy resources a neuron uses to rebuild its membrane. As neurons "burn out," the brain loses its ability to function normally. In view of evidence that NSAID therapy may interfere with the hydrolysis of phospholipids, the researchers will focus on finding an NSAID-related compound effective against Alzheimer disease.
9768897 Total knee arthroplasty with the PFC system. Results at a minimum of ten years and survivo 1998 Sep A consecutive series of 235 total knee arthroplasties using the PFC system was followed prospectively for at least ten years in 186 patients. The operation was for osteoarthritis in 150 knees, for rheumatoid arthritis in 83, and for Paget's disease and femoral osteonecrosis in one knee each. At the latest review 56 patients had died, five were too ill to assess and three could not be traced. The PFC knee replacement utilised was a non-conforming posterior-cruciate-retaining prosthesis with a polyethylene insert which is flat in the sagittal plane. The patella was resurfaced using a metal-backed component in 170 cases, but later in the series we used an all-polyethylene component in 22 knees; 43 patellae were not resurfaced. The survival without need for reoperation for any reason was 90% at ten years. Nineteen revisions were component-related due to failure of nine metal-backed patellae, nine polyethylene inserts, and one unresurfaced patella; two reoperations were for synovectomy (one for recurrent haemarthrosis and one for recurrent rheumatoid synovitis) and three were for metastatic joint infection. There were no revisions for aseptic loosening of femoral or tibial components, or the all-polyethylene patellar replacement. The PFC system provides good and predictable results in tricompartmental arthritis of the knee. Loosening appeared to be negligible, but there were wear-related problems in 8%. The change from a metal-backed patella and an increase in the contact area of the tibial insert should provide further improvement by minimising wear.
10442072 Ultrasound in inflammatory disease. 1999 Jul US may be used effectively to diagnose and treat a wide range of musculoskeletal inflammatory conditions. It is likely that its usage will increase with regards to such conditions especially in the management of rheumatology clinic patients.
10342625 Comparison of free and peptide-bound pyridinoline cross-links excretion in rheumatoid arth 1999 Feb OBJECTIVE: To investigate urinary fractions of free and peptide forms of pyridinoline cross-links in arthritis. PATIENTS AND METHODS: The free and total forms of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured by high-performance liquid chromatography (HPLC) in 30 pre-menopausal and 22 post-menopausal normal women, 38 women with rheumatoid arthritis (RA) and 62 women with osteoarthritis (OA). Peptide forms were calculated as total minus free. Free Dpyr and peptide form were also measured by deoxypyridinoline and carboxy-terminal telopeptide of type I collagen (CTx) immunoassays. RESULTS: In normal women, all fractions of Pyr and Dpyr and immunoassays were elevated in post-menopause compared to pre-menopause. In post-menopausal normal women, the free form increased more than the peptide form. In RA, an increase in the fractions of Pyr was greater than Dpyr. Peptide and total cross-links correlated with the disease activity of RA and they were elevated in RA patients with high disease activity. Free Dpyr and CTx were significantly lower in OA than in normal women. Peptide and total Pyr and Dpyr, and immunoassayed Dpyr were significantly higher in the radiographic later stage of OA than in the early stage of OA. CONCLUSIONS: The menopause, RA and OA may have different effects on the urinary excretion of free and peptide-bound pyridinoline cross-links.
9842435 Occipito-cervical fusion with the cervical Cotrel-Dubousset rod system. 1998 Diseases and conditions which cause instability of the craniocervical junction and the adjacent upper cervical spine are relatively common and potentially life-threatening. Direct internal occipitocervical fusion (OCF) is a modern means of surgical treatment in such cases, and has some advantages over simple immobilization of the affected segments. The present study was designed to evaluate surgical handling, results, and complications with a recently developed instrumentation for OCF, the Cotrel-Dubousset rod-and-hook system (CD). Fourteen consecutive patients with occipito-cervical instability due to fractures, degenerative or neoplastic disease or malformations underwent OCF with the CD system. Autologous or allogeneic bone and bone substitutes such as hydroxyapatite were used to augment the CD fusion. Patients were followed clinically and neuroradiologically for 1 to 4 years (mean 20 months). Assessments were routinely performed at 1 week, 1 month, 3 months, 1/2 year, and every year after surgery. There was no immediate surgery-related morbidity or mortality, and no major late complications due to hardware failure. A stable bony fusion according to radiological criteria was achieved in all cases. No implant breaks or loosening and dislocation of the hooks or the screws were encountered. In no case did neurological deterioration occur after surgery. Short-term evaluation at 1 week after surgery showed no difference with respect to neurological symptoms as compared with the pre-operative findings, except for a patient reporting improvement of paraesthesia on the first postoperative day. The long-term effects were, however, beneficial to most patients, as the fusion alleviated neck pain in 13 cases and improved neurological deficits in 3 of the 4 cases with pre-operative motor weakness or paraesthesia. In conclusion, internal OCF with the CD system, an implant which is easy to handle and safe for the patient, is a technique with a high rate of successful bony fusion. Since no halo placement is needed after surgery, patients have considerable gain of quality of life as compared to other standard surgical techniques.
9166000 Characterisation of fibroblast-like cells in pannus lesions of patients with rheumatoid ar 1997 Apr OBJECTIVE: To better understand the characteristics of synoviocytes located in the rheumatoid arthritis (RA) pannus. METHODS: One cell line, termed PSC, was cloned from RA pannus lesions. Phenotypic analysis was done by contrast microscopy, indirect immunostaining, and safranin O staining. Transcription of several protooncogenes and matrix degrading enzymes was evaluated. The expression of mRNA for collagen II was detected by in situ hybridisation. The ability of anchorage independent growth was assessed by soft agarose culture. RESULTS: PSCs showed a high transcription of protooncogenes c-fos, c-myc and c-jun. They also expressed mRNA for matrix degrading enzymes, such as collagenase, cathepsin B, and cathepsin L. Anchorage independent growth assay demonstrated that PSCs formed colonies in soft agar culture. Phenotypic analysis showed that this fibroblast-like PSC was stained intensely with anti-vimentin and anti-fibroblast antibody. In situ reverse transcriptase assay showed that the cell line expressed type II collagen mRNA. CONCLUSION: Alternative fibroblast-like cells were identified in the pannus lesion of RA sharing properties of fibroblasts and chondrocytes. These findings suggest that this fibroblast-like cell derived from pannus lesions may contribute to the destruction of the cartilage in RA.
10515651 A Fas promoter polymorphism at position -670 in the enhancer region does not confer suscep 1999 Sep OBJECTIVE: We examined whether there are associations between a polymorphism in the Fas promoter, recently found to be associated with rheumatoid arthritis (RA), and Felty's syndrome or large granular lymphocyte (LGL) leukaemia. METHODS: Thirty-five patients with Felty's were studied, along with 18 patients with LGL syndrome and arthritis, 17 patients with LGL syndrome but no arthritis, and 128 controls. The polymorphism was typed by polymerase chain reaction followed by digestion with the restriction enzyme MvaI. RESULTS: No significant difference was found in genotype or allele frequencies between the groups. CONCLUSION: This promoter polymorphism is not a significant risk factor responsible for the LGL expansions seen in Felty's and LGL syndromes. Abnormal, constitutive expression of Fas ligand may be more relevant to the aetiology of these diseases.
10860865 Differential gene expression in synovium of rheumatoid arthritis and osteoarthritis. 2000 Mar Rheumatoid arthritis (RA) and osteoarthritis (OA) are the major types of arthritis. Although both diseases are characterized by joint destruction, their etiologies are different. To get insights into pathophysiological pathways, we used the suppression subtractive hybridization (SSH) method to identify differentially expressed genes in RA. DNA sequencing identified 12 gene products including cytoskeletal gamma-actin and extracellular matrix components such as fibronectin, collagen III alpha(1), and superficial zone protein. Interferon gamma-inducible genes such as a novel thiol reductase, two genes of unknown function (HSIFNIN4, RING3), and annexin II were also found. Two genes encoded proteins involved in proliferation such as elongation factor 1 alpha and the granulin precursor. Furthermore, the protease cathepsin B and synovial phospholipase A2 group IIA were detected by SSH. To confirm the differential expression of the genes, we performed RT-PCR analyses of RA and OA synovial tissues. Compared to OA patients, 9 of the 12 genes were overexpressed in RA, suggesting that SSH is a powerful tool for the detection of differential gene expression in synovial tissues. Further characterization of the gene products may help to identify pathophysiological mechanisms in arthritic diseases.
10902766 Lack of CD80 expression by fibroblast-like synoviocytes leading to anergy in T lymphocytes 2000 Jul OBJECTIVE: To investigate whether contact with HLA-DR+, but CD80-, fibroblast-like synoviocytes (FLS) in the presence of antigen leads to the induction of anergy in, rather than stimulation of, T cells. METHODS: Cell surface expression of activation and costimulatory markers on FLS were studied by flow cytometry. Functional changes were investigated by T cell proliferation to tuberculin purified protein derivative or allogeneic responses to FLS, in the presence or absence of DAP3.B7 cells, a human CD80-transfected mouse fibroblast cell line. Induction of anergy was investigated by a 2-stage culture system. T cells were cocultured with allogeneic FLS in the primary culture, rested, and restimulated in the secondary culture by FLS in the presence or absence of DAP3.B7 cells or interleukin-2 (IL-2). RESULTS: Direct contact between T cells and FLS caused up-regulation of CD69 on T cells and HLA-DR on FLS in both the allogeneic and autologous cultures. The addition of DAP3.B7 cells to FLS-T cell cocultures restored the depressed allogeneic responses of T cells. The allogeneic response by T cells to FLS in the presence of DAP3.B7 cells could be completely inhibited by blocking CD80 with CTLA-4 Ig. Indirect evidence that T cells cocultured with FLS were anergic was the up-regulation of CD25, negligible T cell proliferation, and the restoration of proliferation by the addition of exogenous IL-2. Direct evidence of anergy was obtained when T cells from the primary cultures with FLS remained unresponsive to secondary culture with FLS even in the presence of DAP3.B7 cells. In contrast, primary culture of T cells with FLS plus DAP3.B7 cells initiated a good allogeneic response in all subsequent cultures. CONCLUSION: It is possible that T cells within the synovium may be anergized by contact with HLA-DR+ CD80- FLS.
10883433 Experimental photodynamic laser therapy for rheumatoid arthritis with a second generation 2000 Photodynamic laser therapy has been shown to be a new method for the treatment of synovitis in various animal models. Its principle is the accumulation of a photosensitizing drug in the inflamed synovium which is destroyed by photoactivation of the drug. In the present animal study we demonstrate the effect of a second-generation photosensitizer and suggest a concept for light dosimetry within the joint. We used 38 inbred rabbits for the IgG-induced arthritis model; 2 mg/kg of the benzoporphyrin derivative monoacid ring-A (BPD-MA) Verteporfin were administered 3 h before irradiation, which was performed using a 690-nm diode laser coupled to quartz glass fiber with a cylinder diffusor tip at a total light energy of either 180 or 470 J. During irradiation specific fluorescence of BPD-MA was monitored using a spectroscopy unit. The effect of the photodynamic laser therapy was documented grossly and histologically after 1 week. Within the 470 J-group a complete necrosis of the inflamed synovium was observed. The bradytrophic structures of the joint, however, remained unchanged. Throughout the 180 J-group the extent of necrosis was minor. During irradiation the tissue fluorescence of BPD-MA showed a dose-dependent decrease. Using BPD-MA as a photosensitizer a highly selective and minimal invasive synoviorthesis can be performed. At a dose of 2 mg/kg the histological effect depends on the light dose. For optimum efficacy a total energy of 470 J seems favorable. Online fluorescence detection can be used to monitor the effect of light administration. For dosimetry therefore an online tissue fluorescence detection may represent a technical solution.
11692104 Could TH1 and TH2 diseases coexist? Evaluation of asthma incidence in children with coelia 2001 Nov BACKGROUND: Asthma is generally regarded as a disease with strong T(H)2-type cytokine expression, whereas in autoimmune disorders, such as coeliac disease (CD), insulin-dependent diabetes mellitus (IDDM), and rheumatoid arthritis (RA), T(H)1-type expression is seen. According to the cross-regulatory properties of T(H)1 and T(H)2 cells, one would assume that these diseases exist in different patient populations. OBJECTIVE: We sought to test the hypothesis that asthma could exist in children with T(H)1-type diseases, such as CD, IDDM, and RA. METHODS: Comparison was made of the cumulative incidence of asthma in children with CD, IDDM, or RA by linking Finnish Medical Birth Register data on the whole 1987 birth cohort (n = 60,254 births) with the data of several national health registers to obtain information on the incidences of these diseases during the first 7 years of life. RESULTS: The cumulative incidence of asthma in children with CD (24.6%) or RA (10.0%) was significantly higher than in children without CD (3.4%) or RA (3.4%; P < .001 and P = .016, respectively). Asthma tended to be more common in children with IDDM than in children without IDDM. CONCLUSION: These data indicate that the T(H)1 and T(H)2 diseases can coexist, indicating a common environmental denominator behind the disease processes.
10941819 Lipoprotein(a) and lipids in relation to inflammation in rheumatoid arthritis. 2000 The aim of this study is to evaluate whether lipoprotein(a) (Lp(a)) acts as the acute phase reactant and whether changes of lipids are related to inflammation in rheumatoid arthritis (RA). Lp(a) and lipids were measured after an overnight fast, before and after 14 days use of antiinflammatory agents and correlated with laboratory findings in 21 untreated RA patients and 19 healthy controls. Nine (42.3%) of 21 RA patients and 6 (31.6%) of 19 controls had high Lp(a) levels (> 30 mg/dl) and the Lp(a) level was higher in RA patients compared with controls (27.1 +/- 5.3 vs 19.0 +/- 4.2 mg/dl) without significant difference (p > 0.05). There was no significant correlation between ESR and Lp(a) and lipids in RA patients except for HDL cholesterol (r = -0.563, p = 0.008). After antiinflammatory agent use for 14 days, change in ESR (ESRsample1-ESRsample2) was significantly and negatively correlated to changes in total and HDL cholesterols in RA patients. In conclusion, although Lp(a) tended to be higher in RA, we could not find a distinct acute phase pattern of Lp(a). But changes in total and HDL cholesterols were negatively correlated with inflammation in RA. Our data support the phenomenon that dyslipoproteinemia observed in RA is associated with inflammation.
10587545 Autocrine induction of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD- 1999 Dec OBJECTIVE: The purpose of this study was to examine how gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) is involved in the molecular mechanism of cartilage degradation in rheumatoid arthritis (RA) with special reference to the GLS-induced gene expression and protein synthesis of matrix metalloproteinase (MMP)-1 (collagenase-1) and MMP-3 (stromelysin-1). METHODS: Fibroblast-like synoviocytes (FLSs) obtained from RA patients were cultured and stimulated by GLS. Changes in the expression levels of GLS, MMP-1 and MMP-3 were assessed by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) for GLS, and by RT-PCR and enzyme-linked immunosorbent assay for MMPs and tissue inhibitor of metalloproteinase 1. RESULTS: GLS demonstrated a self-induction of mRNA in cultured RA FLSs. GLS evoked a dose-dependent induction of MMP-1 and MMP-3 mRNAs, and subsequently their extracellular secretion. CONCLUSION: These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs.
10342041 Characteristics of the protease activity in synovial fluid from patients with rheumatoid a 1999 Mar OBJECTIVE: To clarify which proteases are specifically activated in the lesions of rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The activity levels of the serine proteases of the coagulation and fibrinolytic systems, and of elastase and collagenase as controls, in synovial fluid from 27 RA patients and 28 OA patients were measured using fluorogenic synthetic substrates which had methylcoumarylamide (MCA) at their COOH-termini. The thrombin-antithrombin III complex (TAT) content was also measured by ELISA. RESULTS: Among the proteases, thrombin-like activity was the highest in both RA and OA. The profiles of protease activity were similar in RA and OA, but their activities were in general significantly higher in RA than in OA (p < 0.01). The levels of both thrombin-like activity and TAT were about 7.5-fold higher in RA than in OA, while the levels of CRP and fibrinogen were only about 2-fold higher. Biochemical characterization of the thrombin-like activity in the synovial fluid of RA patients showed that this activity was due to thrombin. Thrombin-like activity positively correlated with the TAT concentration in RA (r = 0.750, p < 0.0001), but not in OA. CONCLUSION: Activation of the coagulation system was more marked in RA than in OA, strongly suggesting that in RA there is an imbalance between thrombin and its inhibitors, and that thrombin is more closely linked to the pathogenesis of RA than to that of OA. Our results also show that analysis of the synovial fluid may be useful to estimate the activation of the coagulation system in RA, but not that of the fibrinolytic system.
10825114 Early results of isoelastic hemiarthroplasty in chronic shoulder arthritis. 2000 May Fourteen isoelastic shoulder hemiarthroplasties were studied in patients with shoulder pain due to chronic rheumatoid arthritis and osteoarthritis unresponsive to conservative means. The average follow-up was 27 months (range: 12-46 months) and the average patient age was 66.4 years (range: 54-79 years). A Constant shoulder score was used to assess results. Pain relief was obtained in 85.7% of patients. Function scores averaged 8 preoperatively and 13 postoperatively. Subjectively, 12 patients improved. Average gain was 33 degrees of abduction, 35 degrees of flexion, and 21 degrees of external rotation. Internal rotation improved by two levels on the spine. Total shoulder scores improved from an average of 42 points preoperatively to 78 points postoperatively. There was 1 complication of immediate postoperative dislocation. Early results with isoelastic (polyacetyl resin) shoulder hemiarthroplasty are encouraging. The prosthesis is inexpensive and easy to use, requires minimal bone resection, involves cementless fixation, and has established results in tumor surgery. Its long-term value for chronic arthritis will be reported as part of an ongoing prospective study.