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ID PMID Title PublicationDate abstract
10415635 Field research on the relationship between stress and disease activity in rheumatoid arthr 1999 Jun 22 We review empirical evidence from two field studies for the role of stressful life events in disease flare-ups among patients with rheumatoid arthritis (RA). RA patients were expected to be more vulnerable psychologically, and physiologically, to stressful events in their everyday lives than other arthritis patients without an autoimmune disease. Findings from two studies are reviewed both for their substantive contribution, but also to provide guidance on measurement issues in future field research of this kind. One study included 41 patients with RA, who were interviewed weekly and called to a clinic for blood work and joint examinations when their levels of interpersonal stress increased significantly. A second study used a similar design but included comparison samples of patients with osteoarthritis (OA) and healthy controls of similar age and the same gender as the RA sample. The findings provided support for the proposition that interpersonal stressors are predictive of increases in disease activity. Not all RA patients, however, showed these relationships, and there was evidence that some participants with OA who were depressed also showed higher disease activity following interpersonal stressors. Significant individual differences in the stress-disease relationship were uncovered that deserve greater attention in future studies. Important improvements in the assessment of stressful events and refinements in panel study design are also presented as guides to research on the role of stress in disease processes.
11094449 Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthrit 2000 There is growing evidence that activated synovial fibroblasts, as part of a complex cellular network, play an important role in the pathogenesis of rheumatoid arthritis. In recent years, significant progress has been made in elucidating the specific features of these fibroblasts. It has been understood that although macrophage and lymphocyte secreted factors contribute to their activation, rheumatoid arthritis synovial fibroblasts (RA-SFs) do not merely respond to stimulation by pro-inflammatory cytokines, but show a complex pattern of molecular changes also maintained in the absence of external stimulation. This pattern of activation is characterized by alterations in the expression of regulatory genes and signaling cascades, as well as changes in pathways leading to apoptosis. These together result in the upregulation of adhesion molecules that mediate the attachment of RA-SFs to the extracellular matrix and in the overexpression of matrix degrading enzymes that mediate the progressive destruction of the joints. In addition, activated RA-SFs exert specific effects on other cell types such as macrophages and lymphocytes. While the initiating step in the activation of RA-SFs remains elusive, several key pathways of RA-SF activation have been identified. However, there is so far no single, specific marker for this phenotype of RA-SF. It appears that activated RA-SFs are characterized by a set of specific properties which together lead to their aggressive behavior.
11392606 Selective matrix metalloproteinase (MMP) inhibition in rheumatoid arthritis--targetting ge 2001 Apr The matrix metalloproteinases (MMP) are a large group of enzymes responsible for matrix degradation. They contribute to joint destruction in rheumatoid arthritis (RA) by directly degrading the cartilage and bone and indirectly promoting angiogenesis (formation of new blood vessels). Inhibition of MMPs is a primary therapeutic target in RA. However, the results of limited clinical trials performed to date are disappointing. Improvements in therapeutic benefit may be achieved by targetting specific MMPs. A subclass of the MMPs, the gelatinases, contribute directly to joint destruction as well as being vital during angiogenesis. Gelatinase A is released as a latent enzyme and must be activated to degrade the matrix. It has a unique mechanism of activation on the cell surface involving membrane-type MMP (MT-MMP). Recently, the serine protease, activated protein C (APC), has been shown to directly activate gelatinase A, without requiring MT-MMP Inhibition of APC represents a selective approach to prevent gelatinase A activation and may prove to be of therapeutic benefit in RA.
9706290 Indications, technique, and results of total shoulder arthroplasty in rheumatoid arthritis 1998 Jul Unconstrained total shoulder arthroplasty is a highly effective and successful operation in the patient with rheumatoid arthritis. Reliable pain relief can be obtained, often with an improvement in range-of-motion and function of the entire extremity. Rheumatoid patients may present with difficult soft-tissue and bony deficiencies, but careful planning and intraoperative procedures help to maximize the outcome and minimize the possible complications.
9467685 Gene therapy for rheumatoid arthritis. Theoretical considerations. 1998 Jan Current understanding of the pathogenesis of rheumatoid arthritis has provided evidence that therapeutic benefit can be achieved by using antagonists targeted to the inflammatory cytokines involved, mainly tumour necrosis factor-alpha and interleukin-1. Gene delivery of antagonists, which can inhibit the production or action of these cytokines and other mediators, has been achieved in experimental animal models. This new method of delivery can produce therapeutic effects at lower concentrations and in a local environment, overcoming the adverse effects that often accompany protein therapy. However, several technological and biological restraints preclude the immediate adaptation of this method to human treatment. Based on the experimental evidence, possible target therapeutic genes, cell types and vector systems that could be used are discussed in this article.
10509842 Early diagnosis and treatment of rheumatoid arthritis for improved outcomes: focus on etan 1999 Sep Early diagnosis and prompt treatment can improve outcomes in rheumatoid arthritis (RA). Significant joint damage occurs early in the course of the disease, when RA is most aggressive. Many rheumatologists now advocate an inverted pyramid approach to therapy, in which treatment with disease-modifying antirheumatic drugs is initiated on diagnosis. The goals of this approach are to preserve patient function and to slow disease progression. Current therapies exhibit varying degrees of efficacy and cumulative toxicity that frequently limit their usefulness, particularly with long-term use. New biologic response modifiers (BRMs) that target specific cells or cytokines involved in the inflammatory response hold great promise for RA therapy because of their improved efficacy and limited toxicity. The first BRM to be approved by the US Food and Drug Administration for use in RA is etanercept, a soluble tumor necrosis factor-receptor fusion protein. Etanercept is highly effective in relieving RA symptoms and has a good safety profile. The availability of well-tolerated therapies may encourage clinicians to diagnose and treat RA more promptly, thereby ensuring patients the best possible outcomes.
10621881 Eye disease in a patient with rheumatoid arthritis. 1999 Nov We report the case of a 40-year-old woman with diffuse uveitis, sensorineural hearing loss and cerebrospinal fluid pleocytosis as features of Vogt-Koyanagi-Harada syndrome who developed symmetric polyarthritis and stiffness of small and large joints, in addition to rheumatoid arthritis. Although their target tissues are distinct, both diseases have a possible autoimmune origin strongly associated with HLA-DRB4.
10648050 An overview of radiographic analysis of joint damage in rheumatoid arthritis and its use i 2000 Jan A brief history of the development of scoring methods to represent the extent of radiographic abnormalities in rheumatoid arthritis shows that grading systems have become more detailed with time. Taken together with the observation that physicians continue to modify scoring methods it is clear that we have not yet arrived at the ideal method. Issues to be considered in evaluating scoring methods include which abnormalities and which joints to score and what scale to use. Data from one early trial indicate that erosion and joint space narrowing scores do not progress in lockstep and progression in one does not predict progression in the other; this leads to the conclusion that including both features in a scoring method is important. Data from the same trial raise the possibility that joint space narrowing scores for the proximal interphalangeal finger joints may not be helpful in detecting treatment differences, illustrating that further investigation of which joints to include in scoring is needed. The possibility that an expanded scoring scale might be more sensitive to recording a change in radiographic damage also was raised. A simple method of determining which patients show progression of damage was proposed based on assessing the distribution of negative progression scores (baseline erosion scores subtracted from followup scores adjusted for time). It was pointed out that radiographic assessment has established that a few drugs slow the progression of joint damage. Radiographic evaluation of disease progression should continue to be utilized as an outcome measure in evaluating new therapies.
9369738 Rheumatoid arthritis and osteoarthritis: a basic comparison. 1997 Sep Osteoarthritis and rheumatoid arthritis are the two major types of arthritis. Osteoarthritis is a degenerative process, whereas rheumatoid arthritis is an inflammatory process. Nurses need to be able to distinguish between the two types to provide patients with appropriate treatments.
11094971 Case management for patients with rheumatoid arthritis. 1999 Jul Mary was in her mid-20s when a long day of shopping made her feet hurt so much that she sought the care of a podiatrist. Radiographs showed no abnormalities in her bones, so it was not until several months later, when her hands became swollen and painful, that she was diagnosed with rheumatoid arthritis (RA) by her primary care physician.
10668521 Early aggressive DMARD therapy: the key to slowing disease progression in rheumatoid arthr 1999 Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation, joint destruction, progressive disability, and premature death. Patients at risk for poor prognoses can be identified by a variety of prognostic indicators. These include sociodemographic factors (e.g., older age, female sex), clinical indicators (e.g., higher joint counts), laboratory variables (e.g., higher erythrocyte sedimentation rate, high rheumatoid factor titer), and radiographic indicators (e.g., the presence of bone erosions). Patients with a poor prognosis, as evidenced by the presence of one or more indicators of poor outcome, should be treated promptly and aggressively with disease-modifying antirheumatic drugs (DMARDs) or combination DMARD therapy to limit or prevent further disease progression. Limiting the severity of RA with early and aggressive treatment is the best way to minimize the dire consequences of untreated or inadequately treated disease.
9782796 Rheumatoid arthritis. Early intervention can change outcomes. 1998 Jul Rheumatoid arthritis (RA) is an autoimmune disease with a predilection for synovial tissues, although it can affect other organs. Although the precise etiology is uncertain, viruses, genetics, immune dysfunction and physical trauma have all been implicated as causes for RA. The most basic definition, therefore, is that RA is inflammatory. The RA patient may have difficulty closing a fist or may have a week grip. The late stages of RA are easy to identify by X-ray, but to really perform a service for a patient, you must be able to identify its early stages. To do this, you must be able to examine joints. If a patient does not have a history of liver disease or heavy alcohol intake, methotrexate is the first treatment choice except in the very mildest of cases, when you can use NSAIDs. Steroids are sometimes an essential treatment, but use them with great caution and pay attention to the minimum effective dose.
11084944 Hormonal and immunologic risk factors for the development of rheumatoid arthritis: an inte 2000 Nov Evidence indicates that women who are susceptible to premenopausal onset of RA and men each have identifiable risk factors or risk markers long before onset of the clinical disease. Accordingly, further definition of such predictive factors promises to identify persons who are susceptible to developing RA during preclinical phases. Like coronary artery disease, once risks for developing RA can be reliably quantitated, research in primary prevention should become a realistic objective. Disease prevention objectives are central to the public health strategy of the National Arthritis Action Plan and the US Public Health Service "Healthy People 2000" plan (2010 plan also proposed). The decade of arthritis and musculoskeletal diseases (2000-2010) offers an incentive to nurture a new paradigm of RA prevention. Further research in neuroendocrine, immunologic, and microvascular risk factors for the development of RA promises to unravel its complex physiopathogenetic mechanisms and permit identification of persons who are at high risk for developing this disease. Successful research in identifying reliable risk factors (or markers) can be expected to lead to prevention strategies. Effective programs in identifying persons susceptible to RA could lead to earlier control measures and significantly reduce the enormous burden of this common disease, which affects all segments of the population.
10662391 Measuring the effects of medication use on health-related quality of life in patients with 1999 Nov As the treatment of rheumatoid arthritis (RA) moves towards earlier and more consistently maintained therapy, often with highly toxic medications, the importance of assessing patients' health-related quality of life (HR-QOL) is of increasing concern to healthcare providers, insurers and policy-makers. As the course of RA can extend 20 years or more, and as patient involvement in their care and evaluation increases, the goal of therapy should be to work towards the HR-QOL desired by the patient. The challenge in HR-QOL measurement is its multidimensional nature, which takes into account not only how a person functions physically, mentally and socially, but also incorporates the individual's perceived well-being in their physical, mental and social aspects of daily life. This review focuses on measuring the HR-QOL outcomes of drug therapy in RA in clinical settings as well as in clinical drug trials. The most commonly used instruments in RAHR-QOL measurement are presented, with particular attention to those that have been used to assess the impacts of drug therapy. Traditionally, RA treatment outcomes assessment has focused on physical functioning and activities of daily living. As a result, there is an abundance of instruments that have been used in RA that measure physical functioning. Social and mental functioning are being assessed more frequently as clinicians and researchers recognise the added value of assessing these dimensions in addition to physical functioning. Patient perceived well-being (especially as it relates to physical, mental and social aspects of their lives), however, is still rarely measured. We conclude that there are few validated instruments which truly assess the impact of drug therapy on HR-QOL in RA; most are intended as measures of functional or health status. In addition, few studies have been conducted in natural clinical practice settings (as opposed to controlled clinical trial settings). Further, our review reveals that the psychological and social dimensions of HR-QOL are often lacking from some of the most popular RA instruments currently in use.
9309230 [Physiopathology of rheumatoid polyarthritis]. 1997 Jul Rheumatoid arthritis is the most common and most severe form of inflammatory arthritis. Its exact aetiology remains unknown but the combination of various risk factors is involved. Two non mutually exclusive concepts have been suggested: one based on the primary contribution of T cells and the other on that of mesenchymal fibroblastic cells. Both initial pathways lead to a common pathway inducing an intra-articular inflammatory reaction which is non-antigen specific. This process results from the combination of an increased production of destruction-inducing cytokines with a reduced expression of regulatory factors with anti-inflammatory properties. These components represent targets for treatment which are now going through extensive clinical investigation.
11469488 Quantitative target values of predictors of mortality in rheumatoid arthritis as possible 2001 Jul Predictors of longterm mortality in rheumatoid arthritis (RA) include patient questionnaire measures, grip strength, walk time, physician and patient assessment of global status, joint examination abnormalities, erythrocyte sedimentation rate (ESR), and morning stiffness. In the rheumatology literature, these measures have been analyzed primarily according to mean values in groups or regression analyses, which are valuable to recognize that mortality in RA is predicted by more severe disease, but do not provide the clinician with specific goals of therapy. Goals for therapeutic intervention are often expressed either as complete remission or as statistically significant differences versus a placebo, as in a 20% or even 50% response of a measure such as the American College of Rheumatology Core Data Set. Remission may be too stringent, while statistically significant efficacy of a drug compared to placebo may not necessarily indicate effectiveness to control longterm damage. An alternative approach might be to identify possible target values for therapeutic efficacy that markers of a poor prognosis be "near normal" rather than necessarily at normal or remission levels, as has been explored in management of hypertension and diabetes. However, it remains uncertain whether the goal of therapy should be a "near normal" or entirely normal values for a clinical marker. Better control of quantitative markers that predict early mortality could provide a valuable approach to improving outcomes in RA.
11410765 Rheumatoid arthritis and the older adult. 2001 May Rheumatoid arthritis (RA) is the second most common rheumatic disease after osteoarthritis, but it is the most destructive to synovial joints. RA can be defined as a chronic, progressive, systemic, inflammatory disease of connective tissue characterized by spontaneous remissions and exacerbations (flare-ups). Unlike osteoarthritis, it involves primary tissue inflammation rather than joint degeneration. Although most individuals develop RA in early to middle adulthood, some experience a late onset RA (LORA) in their older years. The onset may be acute and severe or slow and insidious, making diagnosis difficult and often delayed. Regardless of the age at onset, RA affects many older adults in both community and inpatient settings and presents a challenge for nursing care.
10553979 Neuroendocrine, immunologic, and microvascular systems interactions in rheumatoid arthriti 1999 Oct OBJECTIVE: To review the "core" systems interactions in rheumatoid arthritis (RA): neuroendocrine, immunologic, and microvascular, and to interpret an integrated physiopathogenesis of the disease, beginning at a preclinical phase of risk factors to the later stages of manifest clinical inflammation. METHODS: Publications on stress reactions, serum hormonal levels, biological mediators of inflammation and vascular alterations in RA during its preclinical phase, course of active disease, including pregnancy, and hormonal therapy of active disease were retrieved. In addition, experimental reports on biological models of the disease were considered. Levels of adrenal and gonadal steroids (ie, glucocorticosteroids [GCS], dehydroepiandrosterone [DHEA], its sulfate [DHEAS], estradiol [E2], and testosterone [T]), as well as prolactin (PRL) and other hormones, biological mediators, vascular endothelial system (VES) interactions with hormones, and immunologic mediators of inflammation in RA, were reviewed and interpreted. RESULTS: Women with premenopausal onset of RA not previously treated with GCS had lower basal serum levels of adrenal androgens, that is, DHEA or DHEAS, both before and after onset of clinical disease, compared with controls. Risk factors, including hormonal, immunologic, and hereditary indicators, were found to be uniformly present many years before clinical onset in such younger women, as compared with a frequency of circa 15% in matched controls. Also, a history of heavy cigarette smoking significantly predicted the onset of RA in perimenopausal women, and in men, suggesting that vascular endothelial alterations predispose to the disease. In the same prospective study, 1 or more of 4 risk factors were present an average of 12 years before clinical onset of disease in 83% of male RA cases versus 26% in matched controls (ie, sensitivity of 83% and specificity of 74%). Early RA patients may have lower serum cortisol levels than normal controls, and less than expected for the degree of ongoing inflammation, as well as having upregulated PRL levels. CONCLUSION: Among persons genetically prone to RA, the "core" systems are hypothesized to become "remodeled" during a long preclinical phase as a result of chronic imbalances in their interactive homeostasis. This hypothesis needs to be critically assessed in further studies of such physiological precursors of disease as well as stressors in the development and course of RA. Optimal hormonal management of biological mediators of RA is also a priority challenge for disease control in the future. RELEVANCE: Evidence indicates that men and women who are susceptible to premenopausal onset of RA can each be identified long before their clinical onsets of disease, and that productive research in primary prevention is an achievable objective. Disease prevention objectives are central in the public health strategy of the National Arthritis Action Plan and of the US Public Health Service "Healthy People 2000" (and 2010 proposed). Success in such prevention goals can be expected to significantly reduce the enormous burden of this common disease, which affects all segments of the population.
11263762 Involvement of the hypothalamic--pituitary--adrenal/gonadal axis and the peripheral nervou 2001 Mar From the compendium presented above, the following statements become evident: 1) Inappropriately low secretion of cortisol in relation to inflammation is a typical feature of the inflammatory disease in patients with RA. 2) The secretion of adrenal androgens is significantly reduced, which is a problem in postmenopausal women and elderly men due to a lack of downstream sex hormones. 3) Serum levels of testosterone are markedly reduced in RA. 4) Sympathetic nerve fibers are markedly reduced in the synovial tissue of patients with RA, whereas proinflammatory sensory fibers (substance P) are present. 5) Substance P serves to continuously sense painful stimuli in the periphery, and the nociceptive input from the inflamed joint shows a large amplification in the spinal cord. This leads to continuous pain with stabilization of the afferent sensory input and continuous release of proinflammatory substance P into the lumen of the joint. From these facts it is obvious that alterations of the systemic antiinflammatory feedback systems contribute significantly to the pathogenesis of RA. Disease therapy directed at these alterations must provide a mechanism to replace the adrenal glands (glucocorticoids), the gonadal glands (androgens), and the sympathetic nervous system (adenosine increase by low-dose MTX, sulfasalazine, and salicylates) in order to integrate their immunosuppressive effects at the local site of synovial inflammation. Although local processes of the adaptive immune system are important in pathogenesis in the acute phase of RA, these mechanisms may be less important during the chronic phase of the disease in the absence of a specific trigger. We believe that a defect of systemic antiinflammatory feedback systems is an important factor in the perpetuation of RA. This review reinforces the belief that combined therapeutic approaches on a neuroendocrine immune basis are of crucial importance in a pathogenetically oriented therapy of RA.
10087399 Rheumatoid arthritis--a gene transfer disease. 1999 Sera from patients with rheumatoid arthritis (RA) were from the very start instrumental in detecting and delineating the human immunoglobulin (Ig) allotypes in the Gm system. Knowledge that human Ig production is under Mendelian control and not determined by templates of antigen would not have come to the fore if it were not for RA patients. Worldwide experience shows that RA patients are prone to mount an immune response to human Ig allotypes. Major Gm allotypes are defined at the amino acid and nucleotide levels. Gene technology has been developed for defining these allotypes. Studies of the Gm allotypes and anti-Gms have led to two apparently paradoxical findings: (1) In conflict with Mendelian law, non-nominal or hidden allotypes have been observed and recently documented at the DNA level. (2) In RA, an immune response to other individuals' Mendelian allotypes is prevalent, although RA is generally considered an autoimmune disease. These findings led us to conclude that RA is not initially an autoimmune disease but a gene transfer disease. A brief review of viral high-jacking and transfer of human genes is given along with reasons for considering the herpesvirus family in particular. Genes determining incompatible Ig allotypes are transferred. We have shown that these genes are expressed in RA synovia. Ig-anti-Ig complexes arise and may have arthritogenic potential, as observed in serum sickness.