Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
1554495 Fine structure of neutrophils from turpentine-induced pleuritis in mice, simulating rheuma 1992 Feb Pleural effusions were made by intrapleural turpentine installation in mice. The fine structure of inflammatory cells from the effusions was normal except for lipid inclusions. The same type of inclusion was previously found in neutrophils from pleural effusions in patients with tuberculous infection, rheumatoid disease, or carcinomatosis. The lipid inclusions observed in neutrophils from an irritative turpentine-induced pleurisy should be considered as "fatty change", and are structurally similar to the rheumatoid arthritis cells seen in patients with different diseases.
8019489 Tumor necrosis factor alpha, a cytokine coregulating sugar uptake by cultured human synovi 1994 Mar Confluent cultures of osteoarthritic and rheumatoid human synovial cells were treated with human recombinant tumor necrosis factor alpha (TNF-alpha). The cytokine increased uptake of 2-deoxy-D-[1-3H]-glucose (2-DOG) in a time- and concentration-dependent manner. In synovial cells obtained from osteoarthritic patients (OA cells), the stimulation of 2-DOG uptake occurred 3 hours following addition of TNF-alpha (1 ng/ml) and was maximal by 24 hours. Rheumatoid synovial cells (RA cells) appeared less sensitive to the cytokine: 2-DOG uptake stimulation was only significant after 6 hours of incubation. In both OA and RA cells, the effect was protein synthesis-dependent, and was not secondary to prostaglandin E2 synthesis or cell growth. Interleukin-1 beta was more efficient than TNF-alpha for 2-DOG uptake stimulation. The two cytokines seemed to act in an additive manner.
8399428 Medical student use of history and physical information in diagnostic reasoning. 1993 Jun Clinical data gathering is central to clinical competence. Although research has demonstrated the value to experienced clinicians of information obtained from the history, little is known of how medical students use this information. In the present study, two case simulations (in rheumatoid arthritis and systemic lupus erythematosis) were developed to assess medical student information gathering and utilization. The results indicate that most of the students were already considering the correct diagnosis as a possibility after the presenting complaint and patient description. However, the medical history exerted the strongest influence on transforming the correct diagnosis from just another diagnostic possibility into the favored diagnostic candidate. Students who failed to list the correct diagnosis in the differential diagnosis after obtaining the history were significantly less likely to reach the correct diagnosis at the end of the case. These results confirm the critical importance of the history in medical problem solving.
7754550 [Changes of biochemical blood parameters under conditions of treatment with vaulen and pol 1994 May Alteration of the biochemical blood indices has been studied in patients with rheumatoid arthritis and lupus erythematosus that were treated with vaulen (V) and polysorb (P) enterosorbents. It was determined that alanine aminotransferase activity grew and albumin, urea, uric acid levels enhanced after the V treatment. Glucose level and alanine-, asparagine aminotransferases activities decreased after the P treatment. It is necessary to take into consideration these results when choosing an enterosorbent for treatment of patients with the immunocomplex rheumatic diseases accompanied by the liver parenchyma lesion and hyperuricemia.
8748335 A meta-analysis of breast implants and connective tissue disease. 1995 Dec Case reports have raised questions about an increased risk of connective tissue diseases (CTDs) among women with breast implants. From the reviews of more than 2,600 manuscripts, abstracts, and dissertations, this meta-analysis included 13 epidemiology studies that provided a relative risk (RR) estimate for the possible association between breast implants and CTDs. The meta-analysis summary RR was 0.76 for CTD in general (95% confidence interval [CI]: 0.55, 1.04; homogeneity p-value = 0.073) and was 0.98 for scleroderma (95% CI: 0.57, 1.64; homogeneity p = 0.006). Irrespective of which studies were aggregated in this meta-analysis, there was no significant increased risk for scleroderma, rheumatoid arthritis, or CTD in general. Conclusions from this study are consistent with the most recent review by the British Medical Devices Agency that found no scientific evidence to date of an increased risk of CTD associated with silicone gel breast implants.
7598790 HLA disease associations: models for the study of complex human genetic disorders. 1995 The genes of the human leukocyte antigen (HLA) region, the major histocompatibility complex (MHC) of humans, control a variety of functions involved in immune response and influence susceptibility to over 40 diseases. Theoretical studies in the development of models to determine the modes of inheritance of the HLA-associated diseases have led to a better understanding of the inheritance patterns in insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, hemochromatosis, celiac disease, and others. It is now clear that many of the HLA-associated diseases involve heterogeneity in their HLA components, as well as non-HLA genetic factors. This review is presented using HLA-associated diseases, and in particular IDDM, as the example of interest, but the observations and techniques presented have direct relevance to the study of all human diseases with a complex genetic component. Three methods for localizing disease-predisposing genes are presented: (1) association studies, including population, family, and relative predispositional effects, (2) affected sib pair and other affected-relative methods, and (3) lod score analysis. A variety of complementary methods for studying the mode(s) of inheritance of the alleles at the disease-predisposing locus and for identifying the alleles and amino acids directly involved in the disease process also are presented.
8457284 Induction of an anti-vaccine response by T cell vaccination in non-human primates and huma 1993 Feb Experimental and spontaneous autoimmune disease in animals can effectively be prevented and treated by application of pathogenic autoreactive T cells in an attenuated form. This approach has become known as T cell vaccination. T cell vaccination exploits specifically the ability of the immune system to regulate its autoreactive T cells by mechanisms of network control. The success of T cell vaccination in a variety of rodent animal models has raised hopes for its use as an effective and specific therapy in human autoimmune disease. The aim of this study was to induce an anti-T cell response by T cell vaccination in humans and primates as a pre-clinical study into the feasibility and toxicity of T cell vaccination. Using bulk cultures of T cells from the peripheral blood or an inflamed joint, it was possible to induce a T cell response specific for the injected vaccine and its activation state both in rhesus monkeys and in two patients with active rheumatoid arthritis. In one of the patients there was already a spontaneous T cell response against a mitogen driven T cell line from the peripheral blood, but not against a control T cell line specific for tetanus toxoid, suggesting that regulatory T cell networks are operative in patients with autoimmune disease. Significant clinical effects or side-effects were not observed. The results suggest that T cell vaccination in humans is feasible and non-toxic. It is likely to influence an already ongoing regulatory process. Conditions for making T cell vaccination an effective therapy need still to be worked out by further studies both in primates and in less complex human immune processes.
7499850 Naturally processed peptides from rheumatoid arthritis associated and non-associated HLA-D 1995 Dec 15 Naturally processed peptides from immunoaffinity-purified HLA-DRB1*0401, -DRB1*0404 (rheumatoid arthritis (RA)-associated), and -DRB1*0402 (non-RA-associated) molecules were analyzed by capillary liquid chromatography and mass spectrometry. The molecular weights observed for more than 60 eluted peptides from each HLA-DR protein ranged from 788 to 3535 atomic mass units, corresponding to peptides 7 to 32 amino acids in length. Sequencing of more than 60 of the abundant peptides revealed nested sets of peptides that were derived from only 12 different proteins. The majority of these proteins were membrane-associated (HLA class I, class II, and Ig molecules). Synthetic peptides, corresponding to endogenous peptide sequences, bound with high affinity (5 to 80 nM) to the HLA-DR molecules from which they were eluted. In addition, most were promiscuous binding peptides in that they also bound to other HLA-DR molecules. Truncations of eluted peptide sequences and alanine scanning mutational analysis of a Mycobacterium leprae peptide were used to identify the peptide residues involved in binding to DRB1*0404 and DRB1*0402 molecules. Furthermore, an invariant chain peptide was eluted from the DRB1*0402 molecules but not from the RA-associated molecules. The lack of invariant chain peptides from DRB1*0401 and DRB1*0404 molecules may contribute to the loading of autoantigen peptides into these molecules and to their association with disease.
7986216 Interleukin-4 inhibits bone resorption through an effect on osteoclasts and proinflammator 1994 Dec OBJECTIVE: To assess local bone resorption in the context of rheumatoid synovitis and its modulation by interleukin-4 (IL-4). METHODS: We developed an ex vivo model of bone resorption using juxtaarticular samples of bone obtained during joint surgery. We studied the histomorphometric parameters of bone resorption and the regulation of the production of IL-6, leukemia inhibitory factor (LIF), and the collagen cross-link pyridinoline, which is released during bone resorption in vivo. RESULTS: This was a sensitive and dynamic model of bone resorption. The bone samples produced high levels of pyridinoline and as much cytokine as synovium pieces obtained from the same joint. IL-4 induced a 70% reduction of IL-6 and LIF production by bone pieces and reduced pyridinoline levels. Histomorphometric studies performed on bone samples indicated a 35% increase in the mean total bone area after 7 days of treatment with IL-4. More importantly, with IL-4, osteoclasts were not detectable in the bone sections. CONCLUSION: The inhibitory effect of IL-4 on bone resorption extends our knowledge of its antiinflammatory properties and suggests that the inflammatory cytokine imbalance in rheumatoid synovium also contributes to defects in bone resorption in RA.
8313667 Imaging of small airways diseases. 1993 Dec The idiopathic (BOOP) and secondary forms of proliferative bronchiolitis have similar radiographic appearances. Both are characterized radiographically by patchy airspace disease, which often is peripheral. The radiographic presentation of BOOP may have prognostic significance. In primary or secondary constrictive bronchiolitis, the chest radiograph often is nonspecific, but the CT appearance of patchy, lobular areas of hyperlucency, with or without bronchiectasis, may be diagnostic. Respiratory bronchiolitis usually can be distinguished from IPF on the chest radiograph, and the diagnosis may be suggested on HRCT by the presence of hazy increase in lung density or fine centrilobular nodules.
8164205 Health status assessment in rheumatoid arthritis. II. Evaluation of a modified Shorter Sic 1993 Sep OBJECTIVE: To develop a shortened form of the Sickness Impact Profile (SIP) for routine practice. METHODS: We used data from a study of health status in 99 women with rheumatoid arthritis (RA). A stepwise analysis model used physical discomfort (global rating), self-assessed pain (Body Symptom Scale), mental well-being (Mood Adjective Check List) and joint function (Keitel Index) to define important aspects of health. RESULTS: Short forms of the SIP for discrimination (53 items), evaluation (25 items) and prediction (28 items) compared well in validity to the original 136-item SIP. The discriminative short form showed excellent reliability (internal consistency), matching the level of the generic SIP. The evaluative and predictive short forms had acceptable but lower internal consistency than the original Profile. CONCLUSION: We suggest a 64-item core health status questionnaire (SIP-RA) to be included and further tested in the arsenal of routine measurements in outpatients with RA. The questionnaire should include physical (Body care and movement, Mobility), psychosocial (Emotional behavior, Social interaction, Alertness behavior, Communication) and free-standing (Sleep and rest, Home management, Recreation and past-times, Eating) SIP categories, and it will improve the description of patients with RA.
9102148 [Surgical treatment of the rheumatoid hand]. 1996 Oct In rheumatoid arthritis, involvement of the hand is serious, frequent and occurs early. It reaches synovial sheets, articular or tendinous, and causes painful and invalidating deformities. Our experience, based on 537 operations of the hand, indicates that reconstructive surgery can be practised at all levels. For the wrist, inferior radio ulnar arthrodesis strengthens the articulation and eradicates pain when performed in the early stage. Segmentar resection of ulnar diaphysis ensures the conservation of "prono- supination". In the case of destruction or luxation of the wrist, a choice has to be made between prosthesis and arthrodesis. We tend to prefer the latter which confers a strong, painless and definitive articulation. Ulnar deviation of metacarpo-phalangeal articulations of long fingers can be corrected by ligamentar or tendinous plasties. But the results are not always durable and they cannot be used when the articulations are destroyed. In that case prostheses have to be implanted. Swanson's silastic implants enable to straighten the fingers and to suppress pain but ensure a limited mobility. Likewise, interphalangeal deviations generally call for implants or arthrodeses. Trapezo-metacarpal or phalangeo-metacarpal deformities of the thumb are stabilised by arthrodeses, ensuring a strong and painless prehension. In conclusion, reconstructive surgery allows many possibilities but its results are often incomplete. It is therefore advisable to perform synovectomy as early as possible before the occurrence of deformities. Surgical synovectomy competes with isotopic, chemical or corticoid synoviosthesis. But at tendinous level, synovectomy alone should be used, since it gives excellent results. Even though rehabilitation after synovectomies is not always easy, we hope that it will prevent the occurrence of articular or tendinous destruction for many years.
1504062 Melatonin levels are decreased in rheumatoid arthritis. 1992 Jan The hormone, melatonin, is a product of the pineal gland. This methoxy-indole, also known as N-acetyl-5-methoxy-tryptamine, is structurally related to indomethacin, a derivative of methylated indole. The fact that indomethacin has been used successfully in patients suffering from certain chronic inflammatory conditions (such as rheumatoid- and osteoarthritis) gives rise to the question as to whether melatonin also possesses anti-inflammatory virtues. This hypothesis has been tested by determining melatonin concentration levels by means of a radioimmunoassay in patients with rheumatoid arthritis. The daytime melatonin levels of untreated patients were significantly lower (mean concentration = 5.76 pg/ml) than the normal value (mean concentration = 15-33 pg/ml). The second part of this study showed that the administration of indomethacin (100 mg/day) to normal healthy subjects led to a 14.7 pg/ml decrease in plasma melatonin levels. This may indicate that melatonin and indomethacin act synergistically.
8452762 Epidemiology of the rheumatic diseases. 1993 Mar Emerging osteoarthritis studies suggest that certain occupations are associated with a high risk for development of hip and knee osteoarthritis, at least in men. The main activities identified are regular lifting for the hip and knee bending for the knee. Obesity is a well-known risk factor for the knee, and it has been suggested that this risk can be halved by losing weight. Studies of the natural history of knee osteoarthritis suggest that many individuals do not develop osteoarthritis, although precise prognostic indicators are lacking at present. No new etiologic information on rheumatoid arthritis has appeared recently, although hormonal and reproductive factors in women continue to be studied with variable results. Agreement is slowly being reached on how to define vertebral fractures for epidemiologic study, which should produce more consistent results. In a study from Rochester, Minnesota, US incidence rates were produced for clinically diagnosed vertebral fracture (117/100,000) that are similar to hip rates, although they occur at an earlier age. Continued study of risk factors continues to show them to be of little use in screening. In systemic lupus erythematosus, hair dyes have not been confirmed as a risk factor, although there may be a link with domestic pets. There are conflicting data on the roles of obesity and occupational factors in carpal-tunnel syndrome.
7685682 Diclofenac/misoprostol. A review of the major clinical trials evaluating its clinical effi 1993 The results of 4 pivotal multicentre double-blind trials demonstrating the clinical efficacy of diclofenac/misoprostol in the treatment of rheumatoid and osteoarthritis are reviewed. In each study, diclofenac 50mg and diclofenac/misoprostol 50mg/200 micrograms 2 or 3 times daily were of similar therapeutic efficacy. Upper gastrointestinal endoscopy performed at baseline (day 0) and at study completion, in one study in patients with rheumatoid arthritis and one study in patients with osteoarthritis, indicated that fewer patients receiving diclofenac/misoprostol than those receiving diclofenac alone had significant erosions or ulcers at study completion. Thus, the antiarthritic efficacy of diclofenac/misoprostol was similar to that of diclofenac in the treatment of the signs and symptoms of rheumatoid and osteoarthritis, and, in addition, was associated with significantly fewer gastroduodenal mucosal erosions and ulcers than diclofenac.
1356679 Immunological follow-up of 17 patients with rheumatoid arthritis treated in vivo with an a 1992 Jul Seventeen patients with steroid-refractory rheumatoid arthritis were treated with a monoclonal antibody: anti-T CD4/B-F5 (IgG1) for 10 days. The daily dose was 20 mg. No severe side effects were observed and clinical improvement was seen in 15 patients, accompanied by a steep decline in C reactive protein levels. This improvement persisted as long as 12 months in 3 patients. A decline in lymphocyte counts was observed 2 hours after infusion. CD3+, CD4+, CD8+ and B cells were affected. Monocyte levels also decreased, whereas NK cell levels remained unchanged. After 24 hours a subsequent recovery of lymphocyte cell numbers made it possible to return to pre-treatment levels. Residual CD4+ cells coated with CD4 antibody were sporadically found even if residual antibody could be detected in the serum. These results indicate insufficient mAb concentrations. No patients developed detectable anti-mouse Ig antibodies during the treatment period, but 5 patients developed antibodies 15 to 30 days after the end of the treatment. Proliferative responses (mainly the response to ConA) were reduced at the end of the treatment. One month later the proliferative response returned to pre-treatment levels. mAb treatment did not induce long lasting cell activation, as indicated by the low levels of CD25+ or DR+ cells. Soluble IL2 receptor levels were significantly higher before treatment, but did not change after treatment. Soluble CD8 and soluble CD4 molecules were also more numerous before treatment and this increase was correlated with clinical parameters. Of interest was the correlation between the variations in soluble CD8 and the Ritchie index during treatment. The increased levels of serum TNF alpha and IL6 were not modified by treatment. A randomized study now appears necessary to prove the efficacy of the treatment. Such a study would also provide biological data and thus help to define factors predictive of a response in this heterogeneous disease.
1319486 Potential role of Epstein-Barr virus in Sjögren's syndrome and rheumatoid arthritis. 1992 Jan In the pathogenesis of Sjögren's syndrome (SS), a role for Epstein-Barr virus (EBV) has been suggested because; (a) EBV is present in salivary gland epithelial cells of healthy individuals, and exaggerated immune responses against EBV could play a role in the destruction of salivary glands in SS; (b) SS salivary gland biopsies contain increased levels of EBV DNA compared to normal salivary glands, indicating viral reactivation and inability of lymphoid infiltrates to control EBV replication in patients with SS; and (c) salivary gland epithelial cells in patients with SS express high levels of HLA-DR antigens and may present EBV associated antigens to immune T cells in patients with SS. Therefore, SS may represent a situation where genetically predisposed individuals (i.e., HLA-DR3-DQA4-DQB2) have a persistent but ineffectual T cell immune response against EBV at its site of latency. In the case of rheumatoid arthritis (RA), evidence for a potential role of EBV includes the following: (a) EBV encoded proteins share antigenic and sequence similarity to proteins found in the synovial tissues. These crossreactive proteins include EBV protein gp110 (BALF-4) and the beta chain of HLA-DR4. Also, the human and mycobacterial 65 kDa heat shock proteins have a sequence similar to that of EBV encoded proteins; (b) patients with RA have increased frequency and levels of antibodies against specific epitopes on EBV encoded EBNA-1 (BKRF-1) and EBNA-3 (BERF-1) antigens; and (c) lymphocytes from patients with RA have decreased ability to limit outgrowth of autologous EBV infected lymphocytes, probably due to defects in release of interferon gamma.(ABSTRACT TRUNCATED AT 250 WORDS)
7967091 [Osteoporosis in collagen diseases]. 1994 Sep The pathogenesis of osteoporosis in patients with rheumatic diseases, especially rheumatoid arthritis (RA), is poorly understood. The duration of the disease, the severity of the inflammatory process, gender, age, steroid therapy and menopause have been suggested as risk factors for osteoporosis in patients with RA. Although these factors may contribute to the development of osteoporosis, the influence of one specific factor is difficult to evaluate. It is said that the treatment with steroids has a deleterious effect on bone turnover, but this effect has been controversial. The dose margin of prednisone that will lead to osteoporosis is not known but has been estimated to be 10 mg per day. Fractures and stress fractures in patients with RA are probably much more common. Further study concerning osteoporosis in rheumatic diseases is necessary.
1626283 A debate: should patients with rheumatoid arthritis on methotrexate undergo liver biopsies 1992 Jun The question of whether it is appropriate to perform liver biopsies in rheumatoid arthritis patients receiving long-term weekly methotrexate therapy is debated. This debate includes a detailed discussion of the literature to support the debaters' respective views. Points made in favor of biopsy include (1) the significant prevalence of hepatic abnormalities in psoriatic patients; (2) the need to continue administration of the drug to sustain a clinical response; (3) the high incidence of elevations in aspartate amino-transferase, which correlate significantly with hepatic histological outcome; and (4) the fact that the rheumatology community has had relatively short experience with the widespread use of the drug. Arguments against biopsy include (1) the poorly defined specific role of methotrexate in the development of hepatic histological abnormalities; (2) the nonquantitative histological grading system, which makes precise assessment of progression in hepatic disease difficult; (3) the poorly defined role of other factors in the progression of hepatic changes in patients taking methotrexate; and (4) the cost and potential morbidity of the procedure itself. The role of the hepatic Ito cell in the development of fibrosis is also discussed. The protagonists agree on the need to continue studies of liver biopsy tissue from rheumatoid arthritis patients receiving methotrexate to better define this key issue.
8519408 Design of a non-constrained, non-cemented, modular, metacarpophalangeal prosthesis. 1995 A non-constrained, non-cemented, modular prosthesis for replacement of the metacarpophalangeal joints of the fingers has been developed. The prosthesis is of a surface design which is modular in construction and is implanted into the bones with a press fit. The prosthesis is designed to be implanted into patients with traumatic injuries, post-traumatic osteoarthritis and into patients with rheumatoid arthritis at an early stage in the disease where the muscles and ligaments that surround the joint are still functional and can provide joint stability.