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ID PMID Title PublicationDate abstract
15112089 [Psychosomatics in rheumatology]. 2004 Apr Psychosocial factors influence the course and the outcome of chronic somatic diseases. This is also valid for rheumatic diseases like rheumatoid arthritis, spondyloarthropathies, systemic collagen vascular diseases, and fibromyalgia syndrome. The article summarises the evidence-based findings and it illustrates possibilities of psychosomatic treatment in rheumatic diseases by means of three case reports.
12426295 Lung injury linked to etanercept therapy. 2002 Nov Etanercept is the first anticytokine drug approved to treat rheumatoid arthritis. Side effects are infrequent, the most common being local skin reactions, headaches, and upper respiratory tract symptoms. We report the first case of lung injury that occurred while receiving this agent. Biopsy specimens of lung and skin lesions demonstrated noncaseating granulomas associated with a microscopic particulate. Withdrawal of etanercept achieved clinical stabilization, and the addition of prednisone resulted in rapid improvement.
12108982 Celastraceae sesquiterpenoids: biological activity and synthesis. 2002 Jan Plant extracts of the Celastraceae have been used for centuries throughout South America and China as insect repellents and insecticides in traditional agriculture, and also for the treatment of a plethora of medical ailments from stomach complaints and fever to rheumatoid arthritis and cancer. Many of the medicinally interesting properties associated with these crude preparations have now been attributed to a large family of highly oxygenated sesquiterpenoids based on a tricyclic dihydroagarofuran skeleton. In this article, the structural diversity and range of biological activities associated with this intriguing class of natural products are examined with a view to stimulating interest in their total synthesis. Existing synthetic endeavours towards their synthesis are also evaluated.
11891404 Macrophage migration inhibitory factor. 2002 Jan Macrophage migration inhibitory factor (MIF) has been proposed to be the physiologic counter-regulator of glucocorticoid action within the immune system. In this role, MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control both the "set point" and the magnitude of the inflammatory response. As well as overriding the immunosuppressive effects of glucocorticoids, it is now well established that MIF has a direct proinflammatory role in inflammatory diseases, such as sepsis, rheumatoid arthritis, and glomerulonephritis. The functions of MIF within the immune system are both unique and diverse, and although a unified molecular mechanism of action remains to be elucidated, there have been significant advances in our understanding of how MIF affects cellular processes. This review discusses the pathogenic role of MIF in inflammatory disease and highlights the novel structural, functional, and mechanistic properties of MIF.
15288851 Chronic autoimmune thyroiditis and rheumatic manifestations. 2004 Jul A variety of rheumatic manifestations have been described in association with autoimmune thyroiditis. In the past, most of these manifestations were attributed to the underlying thyroid dysfunction, in particular hypothyroidism. However, a responsibility of the mechanisms involved in the autoimmunity rather than a direct action of thyroid hormones seems supported by the evidences that some rheumatic manifestations may occur even in euthyroid patients, or that they are more frequent in hypothyroid patient with autoimmune thyroiditis than in those without this disease. Rheumatic manifestations could be sometimes attributable to the autoimmune rheumatic diseases frequently associated with autoimmune thyroiditis, such as Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, or scleroderma. Among the most important or frequent rheumatic manifestations there are a mild non-erosive variety of arthritis, polyarthralgia, myalgia, and sicca syndrome without a true Sjögren's syndrome. Although the possible pathogenesis of these manifestations is not completely established, some hypotheses may be proposed, including a role of autoantibodies characteristics of autoimmune thyroiditis, a possible overlap between autoimmune thyroiditis and some autoimmune rheumatic diseases, and a systemic inflammatory reaction associated with thyroiditis.
15246151 Pantalar arthrodesis. 2004 Jul Pantalar arthrodesis is a demanding procedure that serves a useful purpose for stabilization of the ankle, rearfoot, and midfoot. These fusions should be recognized as salvage procedures in the treatment of unstable and debilitating conditions as a result of severe degenerative joint disease, rheumatoid arthritis, neuropathic joint destruction, and paralytic or flail extremity dysfunction. As with all salvage-type procedures, patient and physician expectations must be the same to afford an acceptable and functional postoperative result.
14740998 Gene therapy and control of angiogenesis. 2003 Dec The technology of gene therapy may be one step ahead of the present understanding of angiogenesis. The results of studies to modulate angiogenesis have been encouraging, however, and several of these studies are in the preclinical and clinical phases of testing. It is likely, therefore, that gene therapy for such diseases as diabetes mellitus and age-related macular degeneration will soon become a practical reality. It must be hoped that the lessons learned will be beneficial to others attempting to modulate angiogenesis in systemic disorders such as cancer and rheumatoid arthritis.
14726841 [Neglected spontaneous bilateral rupture of the patellar tendon: a case report]. 2003 Dec A patient taking corticosteroids for rheumatoid arthritis experienced a spontaneous bilateral rupture of the patellar tendon. Initially neglected, the rupture was repaired surgically by tendinoplasty using the semitendinous tendon for the right knee and inversion of the quadriceps tendon for the left. Functional results were similar. On the right knee, the wire cerclage loosened leading to posterior sagittal displacement of the patella, pointing out the difficulties encountered when repairing neglected rupture of the patellar tendon. Due to the small number of cases and difficulties in assessing the techniques proposed, no large-scale series has been reported in the literature.
14515736 [Autologous and allogeneic stem cell transplantation for severe autoimmune diseases]. 2003 Sep Based on data from preclinical studies and anecdotal case reports in patients with co-existent autoimmune diseases, stem cell transplantation, mainly autologous transplantation, has been performed for patients with severs autoimmune diseases since the past decade. Initial results are encouraging despite controversies. In diseases, such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and scleroderma, phase III trails are being designed. Careful selection of patients, mobilization regimens, graft manipulations, and conditioning regimens is the key in order to improve the outcome and avoid the toxicity. Allogeneic transplantation, on the other hand, is still in the initial stage of clinical study, but may be more effective in some diseases that are refractory to immunosuppressive therapies. Ongoing and future trials will prove the value of these approaches.
12582455 The effects of cytokines on the atherosclerotic process. 2002 Oct Atherosclerotic lesions result from a series of highly specific cellular and molecular responses to various endogenous risk factors and potential exogenous antigens. The cellular mechanisms involved in atherogenesis, with the exception of calcification and thrombotic events, are principally no different to those found in chronic inflammatory fibroproliferative diseases such as liver cirrhosis, rheumatoid arthritis, glomerulosclerosis, pulmonary fibrosis or chronic pancreatitis. These responses are mediated by interactions among endothelial cells, monocyte-derived macrophages, smooth muscle cells and specific subtypes of T lymphocytes. Monocyte and lymphocyte activation leads to the release of a wide spectrum of cytokines and chemokines that have key roles in all of the phases of endothelial damage, as well as in the formation and rupture of the atherosclerotic plaques. This review attempts to analyze the role of chemokines and cytokines in the multiple steps of atherosclerotic process.
15989547 Anti-TNF agents for the treatment of spondyloarthropathies. 2002 Oct For the treatment of spondyloarthropathies (SpA), therapeutic options using disease-modifying drugs are rather limited compared to other inflammatory rheumatic diseases such as rheumatoid arthritis (RA). This is especially true for the spinal symptoms of the spondyloarthropathies, of which ankylosing spondylitis (AS) is the prototype. New TNF-alpha blockers have been proven highly effective in improving the spinal symptoms and extra-spinal manifestations of SpA. Convincing data in the form of placebo-controlled trials are already available for AS and psoriatic arthritis (PsA). However, limited data suggests that TNF-alpha blockers might be similarly effective in other spondylolarthropathies. Side effects, mainly infections and allergic reactions, occur similar to those observed in RA treatment. Currently, there is no reason to combine TNF-alpha blockers with other disease-modifying anti-rheumatic drugs (DMARDs) for the treatment of AS and other SpA, as these DMARDs are not effective. Thus, TNF-alpha blockers seem to be a major breakthrough in the treatment of SpA. The patients who are primary candidates for such treatments are yet to be defined, particularly in light of the high costs and unknown long-term side effects involved. Furthermore, future studies need to show whether these biologicals not only suppress inflammation but also prevent long-term bony damage.
15337195 Neuro-ophthalmologic manifestations of systemic disease: rheumatologic/Inflammatory. 2004 Sep Rheumatologic and inflammatory systemic diseases often cause similar neurologic and neuro-ophthalmologic manifestations. A wide variety of conditions can be included in these categories. This article summarizes the most common of these conditions, including sarcoidosis, idiopathic orbital inflammation, inflammatory bowel disease, Wegener's granulomatosis, polyarteritis nodosa, Churg-Strauss syndrome, Behcet's disease, systemic lupus erythematosis, scleroderma, Sjogren's syndrome, and rheumatoid arthritis.
15301985 Musculoskeletal conditions and complementary/alternative medicine. 2004 Aug Complementary/alternative medicine (CAM) is immensely popular for musculoskeletal conditions. It is, therefore, essential to define CAM's value for such indications. This chapter summarises the trial data for or against CAM as a symptomatic treatment for back pain, fibromyalgia, neck pain, osteoarthritis and rheumatoid arthritis. Collectively the evidence demonstrates that some CAM modalities show significant promise, e.g. acupuncture, diets, herbal medicine, homoeopathy, massage, supplements. None of the treatments in question is totally devoid of risks. By and large the data are not compelling, not least due to their paucity and methodological limitations. It is, therefore, concluded that our research efforts must be directed towards defining which form of CAM generates more good than harm for which condition.
15301982 When is physiotherapy appropriate? 2004 Aug The main goal of physiotherapy is to reduce pain and restore (or maintain) optimal physical functioning. A wide range of non-pharmacological treatment modalities can be accessed by physiotherapists, including manual therapies, electrophysical agents, thermotherapy, hydrotherapy and graded exercise. The aim of this chapter is to summarise the evidence to date for the effectiveness of various physiotherapy treatment modalities for patients with chronic musculoskeletal conditions, specifically ankylosing spondylitis, rheumatoid arthritis and osteoarthritis involving the peripheral joints. Some important issues for consideration by the rheumatologist before referral of a patient to physiotherapy are also outlined.
15293106 Depigmentation--a rare side effect to intra-articular glucocorticoid treatment. 2004 Aug Intra-articular glucocorticoid injections are often used in patients with rheumatoid arthritis, either as bridging therapy or in periods with increased disease activity. We present a case of local skin depigmentation that occurred at the site of injection in a dark-skinned patient. Depigmentation is a rare complication of such therapy but may have important implications for dark-skinned patients.
15064428 Tumor necrosis factor as a pharmacological target. 2004 Tumor necrosis factor (TNF) was originally described as a molecule with antitumor properties released by macrophages stimulated with bacterial products. Almost at the same time that TNF was cloned, it was found to be identical to cachectin, a mediator of cachexia. After the finding of this second aspect of TNF action, several studies demonstrated its role as a pro-inflammatory cytokine. These studies led to the use of anti-TNF molecules in rheumatoid arthritis and Crohn's disease. The various strategies used to inhibit TNF are summarized.
24387057 Leflunomide: an immunosuppressive drug with multiple effects on T cell function. 2002 Sep Abstract Leflunomide has recently been introduced as a new treatment for rheumatoid arthritis. Although its immunosuppressive effect has been well demonstrated in experimentally induced autoimmune diseases and in organ transplant rejection in animal models, the exact mechanisms mediating its immunomodulatory effect are not fully understood. As T cells play a central role in the orchestration of immune responses in both physiological and pathological conditions, it has been proposed that the ability of leflunomide to suppress inappropriate and unwanted immunity is related to a functional inhibition of T cells. A precise knowledge of the mechanisms of leflunomide's action on T cells is therefore necessary. As the clinical effect of leflunomide has been well described elsewhere, this review will focus on, and will discuss, current data on the different aspects of leflunomide's effect on T cell function.
14571324 Diversification of the Ig variable region gene repertoire of synovial B lymphocytes by nuc 2003 May Although the changes that occur in Ig V region genes during a B lymphocyte's response to antigen usually result from point mutations, nucleotide insertion and deletion also alter gene sequence. We identified nucleotide insertions and deletions (3 to 12 bp) at a frequency of 1.34%, in Ig V gene cDNA from B lymphocytes residing in the synovial tissues of patients with rheumatoid arthritis. Because the added or lost nucleotides occurred in multiples of 3, they maintained the original reading frame and coded a potentially intact receptor. These V gene modifications were generated somatically, because they were identified in the original cDNA by HCDR3-specific polymerase chain reaction and were not found in other B cells using the same VH genes. Insertions and deletions were detected only in IgG+ and IgA+ transcripts, which exhibited 3 times more point mutations than IgM+ transcripts. In addition, they were usually found in the complementarity determining region, typical targets of somatic mutation. The occurrence of insertion/ deletion in isotype-switched cDNA with higher numbers of V gene mutations that localized to hot spots for V gene mutation suggests that these diversification events were related to the somatic hypermutation process. In support of this, an AGY hot spot motif and a short stretch of DNA similar in sequence to the inserted or deleted segments could be found next to the insertions/deletions, suggesting that these modifications arose from DNA duplication following DNA stand breaks. Thus, nucleotide insertion/deletion can lead to B-cell receptor diversification in B lymphocytes that clonally expand in synovial tissues of patients with rheumatoid arthritis.
12720576 Vitamin D in preventive medicine: are we ignoring the evidence? 2003 May Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.
15361381 Anti-telomere antibodies in systemic lupus erythematosus (SLE): a comparison with five ant 2004 Oct OBJECTIVE: To investigate the prevalence and diagnostic significance of antibodies against telomeric DNA in systemic lupus erythematosus (SLE) and other autoimmune rheumatic diseases, and to make comparisons with five conventional anti-DNA or anti-nuclear antibody (ANA) assays. METHODS: Antibodies to telomeres, which are highly repetitive sequences of DNA (TTAGGG/CCCTAA) at the end of eukaryotic chromosomes, were measured by an enzyme linked immunosorbent assay (ELISA) in 305 patients with SLE and 125 patients with other autoimmune rheumatic diseases (78 rheumatoid arthritis, 32 primary Sjögren's syndrome, eight mixed connective tissue disease, seven miscellaneous rheumatic diseases). Other assays used were two commercial ELISA assays for anti-dsDNA using calf thymus as antigen, Crithidialuciliae immunofluorescence, and radioimmunoassay (RIA) for anti-dsDNA and immunofluorescence using Hep-2 cells for ANA. RESULTS: The prevalence of anti-telomere in SLE was 60%, v 5% in rheumatoid arthritis and 18% in other autoimmune rheumatic diseases. Specificity of anti-telomere for SLE was 91%; positive and negative predictive values were 95% and 46%, respectively. For anti-dsDNA by two ELISA assays using calf thymus as antigen, sensitivities were 69% and 29% and specificities 66% and 96%, respectively. Other anti-dsDNA assays had low sensitivities (RIA 43%, Crithidia immunofluorescence 13%). The association of anti-telomere with a history of nephritis in patients with SLE was stronger (p = 0.005) than by any other assay (p = 0.006-0.999). The correlations between the different assays were good (p<0.001 for all comparisons). CONCLUSIONS: The new ELISA for anti-telomere antibodies using standardised human dsDNA as antigen is a sensitive and highly specific test for SLE.