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ID PMID Title PublicationDate abstract
8608361 Folate supplementation and methotrexate. 1995 Dec This review concentrates on the influence of folate supplementation on the toxicity and efficacy of methotrexate (MTX) in rheumatoid arthritis patients. The design, type of folate supplementation and timing of supplementation vary considerably between the six published controlled studies. Folate supplementation seems to have no effect on the efficacy of MTX but may influence toxicity in a favourable way. Further studies are needed to assess the type of supplementation (folic acid, folinic acid), the predisposing factors for toxicity and cost effectiveness.
1411092 Analysis of glycosaminoglycans in human serum after oral administration of chondroitin sul 1992 Chondroitin sulfate was administered orally to six healthy volunteers, six patients with rheumatoid arthritis and six patients with osteoarthritis. Blood was collected at intervals before and after treatment and the glycosaminoglycan concentration was analyzed in serum using a sensitive assay based on the metachromatic reaction with 1,9-dimethylmethylene blue. The glycosaminoglycan concentration in serum before and after ingestion of chondroitin sulfate was statistically unchanged in all of the subjects studied. We suggest that chondroprotection by orally administered chondroitin sulfate is a biologically and pharmacologically unfounded theory. Any possible benefit to osteoarthritic patients after ingestion of chondroitin sulfate should be sought at the gastrointestinal rather than at the plasmatic or articular cartilage level.
8148854 [LP 200mg flurbiprofen versus LP 200mg ketoprofen in rheumatoid arthritis in rheumatologic 1993 Jul A multicentre, randomised, double-blind, double-dummy, parallel-group study in outpatients with rheumatoid arthritis compared the efficacy and safety of flurbiprofen 200 mg and ketoprofen 200 mg, both in sustained-release form. One hundred and sixteen patients aged 18 to 75 years were randomised to receive either one capsule of flurbiprofen sustained-release 200 mg (n = 60) or one tablet of ketoprofen sustained-release 200 mg (n = 56). Both drugs were taken once daily in the evening for 28 days. Patients were assessed at entry and after two and four weeks. Overall efficacy as evaluated on a four-point scale by the investigator and patient, and overall spontaneous pain as evaluated by the patient showed significant improvements in both treatment groups with a trend favouring greater benefit with flurbiprofen. Adverse events were recorded in 14 patients receiving flurbiprofen and 22 patients receiving ketoprofen. Neither the incidence nor the type of adverse events were significantly different in the two groups. Withdrawal rates for adverse events were very similar with both drugs. In conclusion, flurbiprofen sustained-release 200 mg is as effective as ketoprofen sustained-release 200 mg in the treatment of symptoms of rheumatoid arthritis, and exhibits a comparable safety profile.
8978954 Antibody epitopes probed by immunoselected phage-display library peptides in members of a 1996 Nov OBJECTIVE: The random peptide combinatorial phage library approach overcomes the problem of lack of structural information about the aetiological agent or the antigen responsible for a given disease. Here, we used such a strategy to gain insight into the aetiology of rheumatoid arthritis (RA). METHODS: We analyzed the reactivity of serum antibodies from a family with various rheumatic manifestations against RA-immunoselected nanopeptides displayed on phage particles. RESULTS AND CONCLUSION: We found that within the same family, there was a difference in antibody reactivity against the peptides tested. The IgG isotype of the peptide reactive antibodies indicated that the observed reactivities were not related to the presence of polyreactive IgM antibodies. Furthermore, it is unlikely that the observed reactivity was due to rheumatoid factors (RF), since two patients who were positive for the immunoselected Pep3 peptide (LSSREPQAR) were RF negative. We also found that the serum of one patient with polyarthralgias also reacted with the same peptide bound by the RA serum, which may suggest the implication of a common aetiological agent in the apparition of this antibody reactivity. Finally, we noted that one patient with Sjögren's syndrome had antibodies to the RA peptide, which may indicate a potential relationship between these two autoimmune diseases.
8011377 Film-screen vs. digital radiography in rheumatoid arthritis of the hand. An ROC analysis. 1994 Jul In a prospective investigation the diagnostic accuracy of film-screen and digital radiography in rheumatoid arthritis of hands was compared. Seventy hands of 36 patients with established rheumatoid arthritis were included in the study. Each of 11 joints in every hand was evaluated regarding the following radiologic parameters: soft tissue swelling, joint space narrowing, erosions and periarticular osteopenia. The digital images were obtained with storage phosphor image plates and evaluated in 2 forms; as digital hard-copy on film and on a monitor of an interactive workstation. The digital images had a resolution of either 3.33 or 5.0 lp/mm. ROC curves were constructed and comparing the area under the curves no significant difference was found between the 3 different imaging forms in either resolution group for soft tissue swelling, joint space narrowing and erosions. The film-screen image evaluation of periarticular osteopenia was significantly better than the digital hard-copy one in the 3.33 lp/mm resolution group, but no significant difference was found in the 5.0 lp/mm group. These results support the view that currently available digital systems are capable of adequate diagnostic performance.
8919199 Determination of metalloproteinases, plasminogen-activators and their inhibitors in the sy 1996 Jan 15 The concentrations of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), lactoferrin and urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA) and the inhibitors, tissue inhibitor of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor (PAI-2), and alpha2-macroglobulin in the synovial fluids of patients with rheumatoid arthritis was determined before and during chemical synoviorthesis with a sodium salt of the fatty acids from cod-liver oil (Varicocid). Synovial fluids were obtained before treatment from 37 patients with rheumatoid arthritis and, in most cases, at 8 and 24 h after injection of the agent. Well-established ELISAs were used to determine the amounts of all proteins. All patients with rheumatoid arthritis revealed very high levels of metalloproteinases (about 1-15 mu g/ml) in their synovial fluids. During the inflammation inducing treatment the granulocyte enzymes increased. In contrast to this, the level of MMP-1 decreased. All granulocyte-derived enzymes were strongly correlated with each other, whereas their dependence on the granulocyte count was only weak. uPA and PAI-2 showed good correlations with the granulocytes-derived enzymes, but were also only weakly correlating with the cell counts. t-PA was not detected by the ELISA used. The proteases, MMP-8, MMP-9 and uPA were increased 8 h after the treatment, whereas the specific inhibitors TIMP-1, PAI-1 and PAI-2 showed significant changes only 24 h after the injection. Matrix metalloproteinases are important factors in the pathogenesis of rheumatoid arthritis. The inflammatory activity in the joint could be better correlated to the granulocyte enzymes than to the granulocyte counts. The levels of uPA and PAI-2 are also parallel to the granulocyte enzyme levels and might underly the same regulatory mechanism.
7482405 Cellular localization of enzymatically active thrombin in intact human tissues by hirudin 1995 May Cellular sites of coagulation activation within complex, intact tissues have been studied by immunohistochemical techniques. Hirudin, a specific and high affinity inhibitor of the active site of thrombin, together with antibody to hirudin were applied to sections of AMeX-fixed specimens of normal lung, kidney, placenta, freshly incised skin and unperturbed skin obtained at fresh autopsy; to rheumatoid synovial tissue; and to malignant tissue from a variety of tumor types. Staining for thrombin was observed selectively on pulmonary alveolar, rheumatoid synovial, and placental macrophages that express an intact extrinsic coagulation pathway. Staining was also observed restricted to the endothelium of capillaries in freshly incised skin but not in either unperturbed skin or in aged incisions. Staining of tumor cell bodies was observed in small cell carcinoma of the lung, renal cell carcinoma, and malignant melanoma tissues that we found previously to show tumor cell-associated procoagulant activity. This staining occurred commonly on cells within the tumor mass that were distant from stromal fibrinogen/fibrin. By contrast, tumor-associated macrophage but not tumor cell staining was seen in adenocarcinoma and squamous cell carcinoma of the lung, and little or no staining was seen colon cancer tissue. Negative controls in which either the hirudin probe or its antibody were omitted failed to show staining. These results are in accord with previous findings and suggest that such techniques may be useful for studying the cellular sites of thrombin generation in intact tissues. We postulate that administration of potent and specific thrombin antagonists, such as hirudin, to patients with relevant tumor types might be followed by homing of hirudin to tumor cells in vivo so that effects of local thrombin generation on malignant progression can be determined.
8168300 Open reduction internal fixation of supracondylar fractures above total knee arthroplastie 1994 May Seven patients who had low supracondylar fractures above total knee arthroplasties were treated using the intramedullary supracondylar rod. Six of the seven patients were steroid-dependent, long-standing severe polyarticular rheumatoid arthritics with marked osteopenia. The intramedullary supracondylar rod provided stable fixation that allowed early range of motion of the knee. Union occurred in good position in all patients; return to prefracture function was achieved in three months. The surgical procedure was reliable and was associated with minimal morbidity.
1604412 [Detection of intracranial lesions of rheumatoid vasculitis with magnetic resonance imagin 1992 Feb Vasculitis in malignant courses of rheumatoid arthritis is found in many systems, but rarely in the central nervous system. It has been reported that magnetic resonance imaging (MRI) is capable of depicting minute infarctions and/or lesions of demyelination more clearly than does X-ray computed tomography (CT). In the present study, we compared MRI and/or CT of the brain in 3 cases with rheumatoid vasculitis to gauge their relative usefulness for detecting cerebrovascular damages in such patients. In one case with focal neurological symptoms (case 1), MRI depicted lesions responsible for the symptoms more clearly than did CT. In the other two cases (cases 2 and 3), which had no neurological nor psychiatric symptoms, MRI detected multiple microinfarcts in each brain; CT revealed no such lesions. These results indicate that MRI may be more useful than CT to detect brain lesions in patients with rheumatoid vasculitis, and that patients with rheumatoid vasculitis who show no CNS symptoms may in fact still have cerebrovascular lesions. Further studies with MRI in more patients with rheumatoid vasculitis should establish the incidence of cerebrovascular involvement such patients; it is probably much higher than has been previously reported.
8556805 Methotrexate in rheumatoid arthritis: when NSAIDs fail. 1995 Nov Methotrexate has become the agent of choice for rheumatoid arthritis that does not respond to nonsteroidal anti-inflammatory drugs. In appropriately selected patients and with diligent monitoring, methotrexate in low weekly doses is effective and has a much better safety profile than was originally perceived.
7867262 Technical report: ultrasound guidance for injection of soft tissue lesions around the heel 1995 Feb We describe the use of ultrasound guidance for local steroid injection of the retrocalcaneal bursa and the tibialis posterior tendon sheath in patients with chronic inflammatory arthropathy. Ultrasound guidance may be the injection technique of choice but is particularly indicated for patients with lesions unresponsive to injections guided by palpation.
7800598 Hydroxyapatite in total hip arthroplasty: five-year clinical experience. 1994 Sep Excellent clinical and radiographic results are seen with HA-coated femoral components at 5-year follow up. These stems are well fixed proximally, and the transmission of stress is noted to occur at the transition from the coated to uncoated stem. Longer follow up is needed to determine if the currently stable HA-coated implants will become threatened by wear debris and subsequent osteolysis, as has been the case in many long-term studies of other hip implants.
8853228 Cytokine mRNA repertoire of articular chondrocytes from arthritic patients, infants, and n 1996 Articular chondrocytes from nine arthritic patients, five infants, and Balb/c neonatal mice were analyzed for the presence of various cytokine mRNAs by a reverse transcriptase polymerase chain reaction (RT-PCR). Four cytokine mRNAs, interleukin (IL)-6, IL-8, IL-11, and macrophage colony stimulating factor (M-CSF), were detected in all human chondrocytes, regardless of source. IL-10, IL-12p35, and tumor necrosis factor alpha (TNF-alpha) transcripts were found in at least 12 of the 14 human samples. IL-13, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), and TNF-beta mRNAs were found more predominantly in infant samples and in samples from patients with rheumatoid arthritis (RA) compared with samples from patients with osteoarthritis (OA). Another group of cytokine mRNAs, IL-1 (alpha, beta), IL-4, IL-5, and IL-7, were only weakly expressed in some human samples. The cytokine transcripts that were not found were IL-2, IL3, and interferon gamma (IFN-gamma). Because of the large array of cytokine transcripts detected, human chondrocyte preparations were further purified by reacting them with a monoclonal antibody specific to chondrocyte differentiation antigen and subjecting them to fluorescent-activated cell sorting. A similar array of cytokines was found between the sorted and unsorted chondrocytes, although TNF-alpha, G-CSF and GM-CSF transcripts appeared to be upregulated during the sorting process. Human chondrocytes that dedifferentiated into fibroblasts (a 40-day and a 77-day culture) no longer expressed mRNAs for IL-1, G-CSF, GM-CSF, and TNF-alpha, but all other cytokine mRNAs remained detectable. Although certain phenotypic characteristics were lost, including reactivity to chondrocyte-specific monoclonal antibodies and morphological features, chondrocytes in long-term culture still expressed cytokine mRNAs. As expected, more consistent results were obtained when seven preparations of chondrocytes from neonatal Balb/c mice were examined using available cytokine primers. They contained IL-1, IL-5, IL-6, IL-7, IL-12, GM-CSF, M-CSF, transforming growth factor beta (TGF-beta), TNF-alpha, and TNF-beta mRNAs but lacked IL-2, IL-3, IL-4, IL-10, and IFN-gamma mRNAs. Future experiments to define conditions by which these cytokine protein products are expressed are needed to help assess their roles in chondrocyte biology and in disease states.
8149442 Exercise for arthritis. 1994 Feb The data available indicate that ROM, strengthening and aerobic conditioning exercises are safe for patients with OA, RA or AS, despite earlier concerns that exercise might exacerbate joint symptoms or accelerate disease. Less clear are the therapeutic benefits of exercise. In patients with OA, stretching, strengthening, and aerobic conditioning programmes can improve the deficits observed in these patients. The improvements observed generally have been small, and the evidence that these individual improvements result in improved overall function is minimal. None the less, it is likely that exercise will reduce pain, improve endurance for physical activities and improve cardiovascular fitness. Study of the long-term effects of exercise in the geriatric population, for sustaining independent living and functioning, is critically important for future health care and social expenditures. In RA, strengthening and aerobic conditioning exercise programmes can increase muscle strength and cardiovascular fitness and probably improve physical function as well. Improvements demonstrated in patients with RA seem more convincing than those in patients with OA and AS; this probably represents their poorer physical status prior to exercising. For patients with AS, intensive physiotherapy brings statistically significant short-term improvements in spinal and hip ROM which are only modestly clinically significant. It is possible that spinal mobility exercises decelerate loss of mobility over the long term, but controlled studies are needed to confirm this. Improvement in respiratory function with exercise appears to be related to cardiopulmonary fitness and perhaps to improvements in diaphragmatic respiration rather than to changes in thoracic cage mobility. Given the overall safety and likely benefits of the described forms of exercise, exercise should be included in the overall treatment of patients with OA, RA or AS. Careful patient evaluation and education about exercise should be a part of the exercise programme.
1465644 Superolateral erosions of the humeral head in chronic inflammatory arthropathies. 1992 Erosive lesions on the superolateral aspect of the humeral head were studied in 127 patients with chronic inflammatory arthropathies including rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis (AS), and psoriatic arthropathy (PA), as well as in a control group of 53 patients with non-inflammatory shoulder joint disease. Superolateral erosions were found in 39 out of 127 patients (31%), comprising 11/56 RA cases (20%), 22/50 JRA cases (44%), 4/9 cases of AS (44%), and 2/12 cases of PA (17%), but were absent in non-inflammatory disorders. Two morphologically distinct types of erosions were observed, an extensive one, present in all of the inflammatory conditions studied, and a circumscribed one occurring predominantly in JRA patients.
8350831 Calculation of beta dosimetry in radiation synovectomy using Monte Carlo simulation (EGS4) 1993 May Using the EGS4 Monte Carlo code, absorbed dose rate factors were estimated for four radionuclides of interest in radiation synovectomy, an intra-articular radiation therapy to treat rheumatoid arthritis. The treatment consists of the injection of a beta-emitting radionuclide into the joint capsule in order to eliminate diseased synovium through irradiation. The radionuclides investigated are 32P, 90Y, 165Dy, and 198Au. Calculations reveal the absorbed dose factor (cGy cm2/MBq s) as a function of distance (mm) in an EGS4 model of the rheumatic joint. The model incorporates bone, articular cartilage, joint capsule, and tissue (synovium) components found in all synovial joints, with dimensions in the model corresponding to dimensions typically found in larger joints, e.g., the knee, shoulder, or hip. Results are compared with previous, analytical approaches to beta dosimetry in radiation synovectomy. In addition, radiation backscatter due to the presence of bone is investigated and determined to have a negligible enhancement effect on absorbed dose to synovium.
8448611 Elevated resting heart rate in rheumatoid arthritis: possible role of physical decondition 1993 Mar Thirty-four patients with RA, 76 diabetic subjects (DM) and 67 healthy controls (CR) were studied in order to study cardiovascular autonomic function in RA. Valsalva manoeuvre, deep breathing test and active orthostatic test were used. Resting heart rate (resting HR) was markedly elevated in the RA and DM groups. Therefore, the groups were compared using analysis of variance with age and resting HR as covariates. The analyses showed no differences in cardiovascular responses between the RA group and CR group but cardiovascular responses were significantly diminished in the DM group compared with both the CR group and RA group. Our data indicate that the parasympathetic efferent pathway mediating cardiovascular reflexes via the nervus vagus is intact in RA. Thus elevated resting HR in RA does not seem to be due to peripheral parasympathetic damage. Physical deconditioning may explain the elevation of resting HR in patients with RA.
8743124 Antibodies reactive with HIV-1 antigens in systemic lupus erythematosus. 1996 Apr Antibodies reactive with retroviral gag proteins have been detected in patients with systemic lupus erythematosus (SLE). We investigated the immune responses against human immunodeficiency virus (HIV) 1 antigens in the sera of 44 Turkish patients with SLE. Serum samples were tested by using two different commercial enzyme immunoassay (EIA) kits and by Western blotting. EIA studies revealed positive results in 12 patients (27%) for HIV-1 antigens by one of the kits that coated with purified viral antigens. Immunoblot analysis showed antibodies mainly to retroviral gag proteins in 23 patients (52%). The most frequent reactivity was against the p18 gag protein (n = 9). Although antibodies reactive particularly with p24 antigen were described in the previous reports, antibodies to p24 were found in only two patients. These findings might reflect a serologic diversity in different ethnic groups and also suggest the involvement of different triggers in the etiopathogenesis of SLE.
1578151 Clonally related IgM rheumatoid factors undergo affinity maturation in the rheumatoid syno 1992 May 15 Using hybridoma technology we established a panel of human monoclonal rheumatoid factors (RF) from the synovial tissues of two patients with rheumatoid arthritis (RA), and one patient with polyarticular juvenile RA. Nucleotide sequence analysis of the V regions of these RF indicates that two independently derived antibodies from one of the RA patients are clonally related. One of these antibodies appears to be close to germ-line configuration, whereas the other has accumulated a total of 36 substitutions in both H and L chains. Measurements of the affinity for human IgG of the two RF show that the extensively mutated RF has 100-fold higher affinity for IgG than the RF close to germline. These findings indicate that IgM RF in RA can undergo affinity maturation and suggest that certain RF may be the product of an Ag-driven immune response.
1373620 Synovial fluid analysis of two groups of proteoglycan epitopes distinguishes early and lat 1992 Apr OBJECTIVE: To investigate whether fragmentation of proteoglycans in arthritis results in domains that have different levels of release from cartilage at different stages of the disease. METHODS: Two regions of the proteoglycan, the hyaluronan-binding region and the glycosaminoglycan-rich region of the core protein, were measured, by immunoassay, in knee joint synovial fluids of patients with rheumatoid arthritis or reactive arthritis. RESULTS: Synovial fluid concentrations of the glycosaminoglycan-rich region were highest in rheumatoid arthritis patients who had little cartilage damage as determined by radiography, whereas release of the hyaluronan-binding region predominated in patients with advanced cartilage destruction. In reactive arthritis, release of the glycosaminoglycan-rich region predominated. CONCLUSION: These findings indicate that the hyaluronan-binding region is initially retained in the tissue during the development of cartilage destruction. The combined analysis of these markers offers a new avenue for assessment of the degree of cartilage damage in arthritis.