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ID PMID Title PublicationDate abstract
7944636 Role of Fc gamma receptors in the activation of neutrophils by soluble and insoluble immun 1994 Aug OBJECTIVES: Synovial fluid from patients with rheumatoid arthritis contains both soluble and insoluble immunoglobulin aggregates which activate reactive oxidant production in human neutrophils. The objectives were to determine the roles played by Fc gamma receptors in activation of neutrophils by these complexes. METHODS: Pronase treatment was used to remove Fc gamma RIII from the neutrophil surface and blocking monoclonal antibodies were used to prevent the binding of complexes to Fc gamma RII and Fc gamma RIII. RESULTS: When Fc gamma RIII was removed from the cell surface by pronase treatment, activation by the soluble aggregates did not occur [mean (SD) inhibition 89 (16)%, n = 6] whereas activation via the insoluble aggregates was less affected [34 (16)%, n = 6]. Blocking the binding to Fc gamma RIII with antibodies decreased activation in response to the soluble aggregates [mean (SD) inhibition 71 (22)%, n = 8] but again had a lower effect on activation by the insoluble aggregates [40 (17)%, n = 9]. When binding to Fc gamma RII was blocked, activation via the soluble aggregates was substantially inhibited [mean (SD) 93 (13)%, n = 8] whereas that via the insoluble aggregates was inhibited to a much lesser extent [28 (38)%, n = 9]. When Fc gamma RII and III were simultaneously blocked, activation by the insoluble aggregates was only inhibited by 45% [(19), n = 5]. CONCLUSION: These data thus indicate that activation of human neutrophils by soluble immunoglobulin aggregates from rheumatoid synovial fluid occurs via cooperative occupancy of both Fc gamma RII and III: perturbation of binding to either of these receptor classes will abrogate activation.
8019788 Constitutive mRNA and protein production of macrophage colony-stimulating factor but not o 1994 Jul This study analyses the mRNA and protein production and their regulation of macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8 and IL-6 by synovial fibroblasts obtained from patients with RA and OA. M-CSF was found to be produced constitutively as opposed to other cytokines. Stimulation of the cells with IL-1 beta caused a marked increase of GM-CSF, IL-8, IL-6 and as well as of M-CSF mRNA levels. In parallel, a time-dependent increase of M-CSF, GM-CSF, IL-8 and IL-6 protein production was observed. Among the cytokine mRNAs examined only that of M-CSF exhibited a pronounced stability in unstimulated synovial fibroblasts, whereas the other cytokines displayed short mRNA half-lives of 1-2 h. Induction by IL-1 beta markedly prolonged IL-8, IL-6 and GM-CSF mRNA half-lives to > 8 h which indicates increased mRNA stability. These findings suggest that among the cytokines that are produced in the inflamed synovium M-CSF may be particularly important for sustaining long-term influx, activation and survival of mononuclear phagocytes. GM-CSF, IL-8 and IL-6, by contrast, may be more involved in more acute cellular responses.
7944254 Early results of total condylar knee arthroplasty. 1994 May A total of 109 consecutive total condylar knee replacements in 73 patients were assessed at one to eight years postoperatively. The average age at surgery was 66.9 years and the range was from 52 to 84 years. The primary disease was rheumatoid arthritis in 12 and degenerative osteoarthritis in 97 knees. Out of the 109 prostheses; 101 were Miller-Galante kinematic condylar type I or II prostheses, seven were Insall-Burstern type I or II and one was a Whiteside prosthesis. The fixation technique was hybrid (only the tibial prosthesis cemented) in 63, both components uncemented in two and both components cemented in 44 knees. One hundred and five (96.3%) knees showed significant improvement in the Hospital for Special Surgery score postoperatively. The average preoperative score was 48.1 and the postoperative score was 85.4. Sixty-four patients (100 knees) were satisfied or very satisfied with the result of surgery. One hundred and four (95.4%) knees had achieved either an improvement in the range of motion and/or deformity. Complications included loosening in four (3.7%) knees, infection in three (2.8%), dislocation of the patella in four (3.7%), periprosthetic fracture in one (0.9%) and severe lateral collateral ligamentous laxity in one (0.9%).
8174315 Superoxide production from cytokine-treated adherent rheumatoid neutrophils. 1994 Feb We have compared superoxide (O2-) production from cytokine-treated rheumatoid arthritis (RA) vs. control neutrophils (PMN). Exposure of adherent peripheral blood PMN to cytokines known to be present in RA joints (IL-1 beta, TNF-alpha, GM-CSF) resulted in enhanced O2- production from both RA and controls. With few exceptions, we did not find significant differences in enhanced O2- production, between RA and controls. By enhancing O2- production from PMN adherent to articular cartilage, cytokines may influence the potential for joint damage in RA.
8047835 The binding of synovial tissue-derived human monoclonal immunoglobulin M rheumatoid factor 1994 Aug There are several sites on IgG Fc that have been reported to be the epitopes for binding rheumatoid factors (RF). It is now established that there are alterations in the oligosaccharides on IgG from patients with rheumatoid arthritis and it has been suggested that these changes may enhance immune complex and cryoglobulin formation. We have used a series of IgG preparations differing in their content of oligosaccharide chains lacking galactose from 18 to 86% to determine whether changes in sugar content affect the binding of rheumatoid factor. Five of 16 monoclonal rheumatoid factors prepared from synovial tissue, from patients with juvenile or adult rheumatoid arthritis, bound better to IgG which was deficient in galactose. Six of the 16 rheumatoid factors from the same patients bound independently of the galactose content. Four of the 16 rheumatoid factors could not be absolutely grouped in this manner but seemed to demonstrate a preference for agalactosyl IgG. One rheumatoid factor bound better to fully galactosylated IgG. There was an association between enhanced binding to galactose-deficient IgG and monoreactivity and a very strong association between the functional affinity of the rheumatoid factors and the dependent binding.
8085040 [Value of continuous passive motion in the early rehabilitation of total knee arthroplasty 1993 The purpose of our study was to evaluate the interest of passive motion rehabilitation with an automatic device. Our protocol has been made of 120 TKA performed in the same surgical department between february 1987 to June 1990. We draw lots, a group "RC" with usual rehabilitation program and a second group "AM" with the same program added with passive motion two hours per day. The passive motion device was Toronto Mobilimb. Passive range of motion (ROM) of flexion and extension, pain level, deep venous thrombosis existence, volume of blood postop drainage, mobilisation under anaesthesia, device tolerance were studied. The results showed a flexion ROM average of 86.7 degrees in the RC group at discharge and 90 degrees in the AM group. This difference is statistically significant and evokes the efficacy of passive motion. At the term of one year postop, the flexion averages reaches 108 degrees in both groups. The extension lag falls from 8.2 degrees and 9.2 degrees average in AM and RC group at discharge to 3 degrees and 3.7 degrees in the same groups at one year. The mean of blood postop drainage by suction was very different in the RC group than AM group (1149ml-968ml). In conclusion, we can say that passive motion device is useful to reach enough flexion in the first days after surgical day and may give some comfort. In our experience the classical rehabilitation program with physiotherapist must be continued.
8350337 Fatigue in ankylosing spondylitis--why is it ignored? 1993 Jun OBJECTIVE: Fatigue in ankylosing spondylitis (AS) is largely ignored by physicians and classical texts. By contrast, patients frequently allude to it as a major complaint. METHODS: To address the situation, 3 studies were performed: (1) Symptoms were defined in a cross sectional evaluation of 1950 consecutive patients with AS. (2) From each of the 3 groups who specified a particular main symptom (pain, stiffness or fatigue), a random cohort of 20 was selected and all 60 were prospectively followed over a 14-day period. (3) An additional 100 patients [50 randomly selected with AS and 50 with rheumatoid arthritis (RA)] took part in a comparative prospective study. RESULTS: In the first study for those with a definitive major symptom, 34% (n = 670) described pain while stiffness and fatigue were reported by 25% (n = 492) and 6% (n = 124), respectively. Thirty-two percent (n = 616) could not distinguish between the 3. Strikingly, when prospectively studied over a 2-week period, over 50% of the patients revealed that fatigue was the main symptom. Moreover, in the cohort which expressed pain as their major problem initially, fatigue had the highest prevalence (mean fatigue value versus mean stiffness, p = 0.009; fatigue versus pain, p < 0.001). In the direct comparison between patients with RA and those with AS, the RA cohort had statistically more fatigue and pain than the AS cohort (p = 0.002, p = 0.007, respectively) with a similar amount of stiffness expressed by both groups (n = 0.149). In both subsets, pain had the least impact on the patients (mean 2.60 and 1.87, respectively). CONCLUSION: Our data reveal that fatigue should be considered a major problem for patients with AS, worthy of further exploration in terms of both etiology and therapy.
1519577 Multiple strictures of the small intestine after long-term nonsteroidal anti-inflammatory 1992 Sep A 60-yr-old female patient with rheumatoid arthritis presented with nonsteroidal anti-inflammatory drug (NSAID)-induced ileal ulcers which caused intestinal bleeding and multiple strictures. Results of investigations, including radiological, pathological, and bacteriological examinations, were not consistent with Crohn's disease or intestinal tuberculosis. Rather, the lesion was characteristic of "diaphragm disease" caused by NSAIDs. Discontinuance of NSAIDs in combination with administration of ornoprostil (prostaglandin E1-derivative), sucralfate, and sulfasalazine put an end to the intestinal bleeding. This is a rate case of a patient with multiple strictures of the small intestine caused by NSAIDs.
10119159 Seeing the forest despite the trees. The benefit of exploratory data analysis to program e 1992 Jun In the present article, it is argued that there is a benefit to applying techniques of exploratory data analysis (EDA) to program evaluation. To exemplify this, an evaluation of a rehabilitation program for people with rheumatoid arthritis is presented. The perceived health status of patients receiving intensive rehabilitation services from a major rehabilitation institute was compared with that of patients receiving customary office-based care over an 18-month period. The data were analyzed in a conventional way (analysis of variance) and then by way of EDA techniques (graphic display of medians and boxplots). The conventional analysis suggested that all patients improved over time and that intensive rehabilitation services provided no particular benefit or harm. The exploratory analysis showed that the distribution of the outcome variable was patently nonnormal, thus casting doubt on the validity of the conventional analysis. The EDA further showed that the rehabilitation group lagged behind the comparison group for a year, with a precipitious improvement at the 18-month period. This suggests that a selection factor was operating (i.e., those in the rehabilitation group could have been sicker) or that the patients in the rehabilitation group were made more aware of their condition by the intensive health services they received. The EDA provided an important insight.
7582718 A study of the role of parvovirus B19 in rheumatoid arthritis. 1995 Sep Serum and synovial tissue from 26 patients with rheumatoid arthritis (RA) (according to the diagnostic criteria of the American Rheumatism Association) and 26 patients with osteoarthritis (OA) were examined. Among the RA group, the female to male ratio was 4.2:1, and the age range was 44-82 yr with a mean of 64.0 yr; joints from which synovium was sampled were hip (n = 12), knee (n = 9), ankle (n = 3) and shoulder (n = 2). The duration of rheumatoid disease ranged from 6 to 24 yr with a mean of 13.9 yr. Among the OA group, the female to male ratio was 2.25:1, and the age range was 51-88 yr with a mean of 68.2 yr; joints from which synovium was sampled were hip (n = 18) and knee (n = 8). Twenty-one patients from the RA group and 20 patients from the OA group had evidence of previous parvovirus B19 infection (serum anti-B19 IgG), and all patients from both groups were serum anti-B19 IgM negative. Synovial sections from all 52 patients were stained with mouse monoclonal antibodies, 3H8 (to B19 capsid proteins) and alpha-P (to blood group P antigen). All tissue sections examined were found to be negative for both B19 capsid proteins and blood group P antigen. Using a nested polymerase chain reaction (PCR) assay, all patients were negative for serum B19 DNA. However, B19 DNA was demonstrated in the synovium of 10 of 26 RA patients and 9 of 26 OA patients; uncorrected chi 2 value = 0.08; degrees of freedom = 1; P = 0.77. All 19 patients testing positive for synovial B19 DNA had evidence of prior exposure to B19 infection (serum anti-B19 IgG). In conclusion, although there is published evidence of chronic rheumatoid-like arthropathy following acute parvovirus B19 infection, our findings do not support the involvement of B19 in the aetiopathogenesis of RA.
8921695 [Expression of decay-accelerating factor on CD8-positive lymphocytes as an index of aging 1996 Aug Decay-accelerating factor (DAF) is a membrane glycoprotein that prevents complement activation on blood cells. Among CD8+ T cells, DAF-negative cells can be distinguished from DAF-positive cells. We computed the proportion of DAF-negative CD8+ T cells in the peripheral blood of 59 normal healthy subjects, 27 to 93 years old, and analyzed the differences between subjects of different ages. The proportion of CD8+ T cells that were DAF-negative correlated significantly and positively with age. We also studied these lymphocytes in patients with cerebrovascular dementia, Alzheimer's dementia, cancer, rheumatoid arthritis and systemic lupus erythematosus. The proportion of CD8+ T cells that were DAF-negative did not correlate significantly with age in patients with cerebrovascular dementia, Alzheimer's dementia or cancer, but it correlated significantly and positively with age in patients with rheumatoid arthritis and in those with systemic lupus erythematosus. Therefore, healthy subjects and patients with various diseases can be classified according to age and to the proportion of CD8+ T cells that are DAF-negative. This proportion can then be used as an index of aging and of host defense function.
1471519 Perioperative factors associated with septic arthritis after arthroplasty. Prospective mul 1992 Dec Perioperative factors associated with late septic arthritis after knee and hip arthroplasties were prospectively investigated. All patients received a short course of perioperative cefuroxime. After a follow-up of 1 year, septic arthritis was diagnosed in 9/362 patients (2.5 percent) after knee arthroplasty and in 17/2651 patients (0.64 percent) after hip arthroplasty. For the knee, factors associated with septic arthritis after arthroplasty were rheumatoid arthritis, wound infection, an unhealed wound, and a painful, limited knee function at discharge from the hospital. For the hip, corresponding risk factors were diabetes, failed fracture osteosynthesis, a breakdown of sterility during operation, wound infection, postoperative urinary tract infection, and an unhealed wound at discharge from the hospital or a difficult rehabilitation course. Reoperation after knee and hip arthroplasty was also clearly associated with a higher incidence of septic arthritis.
8636310 Androgen and estrogen receptors are present in primary cultures of human synovial macropha 1996 Feb Macrophages, as antigen-processing and -presenting cells to T lymphocytes, play a key role in the immune system and are suspected to be target cells of the sex hormone-related dimorphism in the immune response peculiar to rheumatoid arthritis (RA) pathology. In the present study, the use of specific monoclonal antibodies revealed immunostaining for androgen and estrogen receptors in primary cultures of macrophages obtained from synovial tissues of patients affected by RA and controls without RA disease. Soluble and nuclear type I (high affinity, low capacity) and type II (lower affinity, greater capacity) sites of androgen or estrogen binding were detected in primary cultures of RA macrophages using radioligand binding assay. Higher levels of type I and type II estrogen receptor compared to those of androgen receptor were found, particularly in the soluble fraction; however, contrary to what was observed in whole synovial tissues, higher steroid receptor concentrations were found in the soluble than in the nuclear fraction of RA synovial macrophages. Binding affinities and receptor contents of cultured synovial macrophages were comparable to those previously reported in other well established sex hormone-responsive cells and tissues. Further, specific messenger ribonucleic acids for sex hormone receptors, encoding for a sequence of the DNA-binding domain of the receptor proteins were revealed by RT-PCR.
8923354 Suppression of in vitro IgM rheumatoid factor production by diphtheria toxin interleukin 2 1996 Nov OBJECTIVE: To investigate the effect of diphtheria toxin interleukin 2 recombinant fusion protein (DAB 486IL-2) on in vitro synthesis of immunoglobulin and rheumatoid factor (RF) in patients with severe refractory rheumatoid arthritis (RA) enrolled in a phase II, double blind, placebo controlled study. METHODS: Anticoagulated venous blood samples were obtained before (Day 1) and after (Day 28) intravenous infusion of either DAB 486IL-2 at 0.075 mg/kg/day (12 patients) or saline placebo (10 patients) on Days 1-5. Peripheral blood leukocytes (PBL) were prepared by density gradient centrifugation, cultured in the presence and absence of pokeweed mitogen (PWM) for one week, and culture supernatants assayed for immunoglobulins and IgM RF by ELISA. RESULTS: Compared to placebo treated patients, PWM induced IgM RF synthesis by PBL decreased after treatment with DAB 486IL-2 (p = 0.043). However, there was no apparent correlation with clinical improvement. PWM induced IgM, IgA, and IgG synthesis also tended to decrease, although the changes did not attain statistical significance. In contrast, PWM induced IgM RF, IgM, IgA, and IgG synthesis by PBL from patients treated with placebo tended to increase during the observation period. Spontaneous immunoglobulin and IgM RF production by PBL from either the DAB 486IL-2 or placebo patients remained stable. CONCLUSION: These observations raise the possibility that DAB 486IL-2 may diminish B cell function either directly or indirectly through effects on T cell function, but the change may not correspond to clinical response.
8493195 Drug treatment of arthritis. Update on conventional and less conventional methods. 1993 May 15 Nonsteroidal anti-inflammatory drugs comprise an important class of medications that reduce the signs and symptoms of osteoarthritis and rheumatoid arthritis. They bring relief to millions of people but do not eliminate underlying disease. Disease-modifying antirheumatic drugs also bring relief, but these drugs are often ineffective and not well tolerated. Failure to provide long-term benefits combined with the high toxicity of most of the disease-modifying agents has prompted a search for more effective treatments. New methods using modern technologies have generated much enthusiasm and hold promise for the future. In the meantime, administration of nonsteroidal anti-inflammatory drugs and judicious use of disease-modifying agents remain the cornerstone of therapy for arthritis.
8712882 Retinal toxicity in long term hydroxychloroquine treatment. 1996 Mar OBJECTIVE: To report clinical experience from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who were receiving recommended doses of hydroxychloroquine for more than six years, and were monitored for evidence of hydroxychloroquine related retinopathy every six months. METHODS: A prospective (and continuing) evaluation was made of the potential retinal toxicity of hydroxychloroquine in a cohort of 360 Greek patients followed for RA and SLE, 58 of whom have received long term treatment ( > six years). Fundoscopy, colour vision tests, dark adaptation tests, visual field testing, automated perimetry, and electroretinogram were performed every six months. RESULTS: Among 58 patients receiving hydroxychloroquine for more than six years, two relatively young women (3.5%), one treated for RA and the other treated for SLE, developed characteristic hydroxychloroquine related toxic retinal lesions after cumulative doses of 700 g (6.5 years) and 730 g (8 years) of hydroxychloroquine, respectively. Bilateral visual acuity was 6/6 and 6/7.5, respectively; both patients had normal colour perception. Despite an early diagnosis and cessation of treatment, permanent visual field paracentral scotomata in both patients, and persisting lesions in fluorescein angiography in the patient with SLE, were observed at 4.5 and 3 years of follow up, respectively. No other specific cases of hydroxychloroquine related retinopathy have to date been identified in the remaining 302 patients. CONCLUSION: Cases of irreversible, hydroxychloroquine related retinopathy in patients who did not receive overdoses have not been reported previously. The present observations in two relatively young patients should raise our concern regarding the long term usage of an increasingly popular medication in rheumatology practice.
8991975 Induction of TNF-alpha and proinflammatory secretory phospholipase A2 by intravenous admin 1995 Oct OBJECTIVE: To test the effect of infusions of CAMPATH-1H on levels of proinflammatory secretory phospholipase A2 (sPLA2) and tumor necrosis factor alpha (TNF-alpha) in patients with rheumatoid arthritis (RA). METHODS: Two patients with RA were infused with CAMPATH-1H; extracellular nonpancreatic sPLA2 activity was tested using radiolabelled E. coli membrane phospholipid, and circulating TNF-alpha levels were tested by ultrasensitive immunoassay. RESULTS: Circulating TNF-alpha began to rise within the first 2 h after infusion, reaching > 1000-fold values compared to preinfusion levels. Circulating sPLA2 activity began to rise a few hours after the start of infusion and reached extremely high values in 12 h, concomitant with fever and hypotension. The activity of sPLA2 decreased to pretreatment values in 3-18 days after infusion. CONCLUSION: The mechanism leading to the increase of TNF-alpha and hyperphospholipasemia A2 has not been elucidated. It is possible that CAMPATH-1H activates cells that synthesize and release TNF-alpha and sPLA2, and/or that it induces interleukin 2 release, which in turn activates TNF-alpha, with subsequent release of sPLA2.
8578222 NSAID-associated upper gastrointestinal damage in patients with rheumatoid arthritis. 1995 AIM OF THE STUDY: The main aim of the present study was to identify the patient with rheumatoid arthritis (RA) taking non-steroidal anti-inflammatory drugs (NSAIDs) at risk for peptic ulcer disease (PUD) and its life-threatening complications. PATIENTS AND METHODS: During a retrospective study in which more than 1000 patients were interviewed, current gastrointestinal (GI) complaints were of no use in detecting current PUD. RESULTS: A history of PUD was an important predictor of current PUD, while the predictive value of serologic parameters, such as serum values of pepsinogen and antibodies to Helicobacter pylori, was disappointingly low. A prospective study in which 81 consecutive RA patients underwent a gastroscopy revealed 16% PUD; again a history of PUD was the most important predictive parameter. Since no study had been undertaken into the effects of a NSAID on intragastric pH we performed such a study, the main conclusion being that indomethacin does not influence the intragastric pH of RA patients. A placebo-controlled study of ranitidine 300 mg b.i.d. for the prevention of recurrent PUD in RA patients on NSAIDs is underway.
8416681 New approaches to the therapy of autoimmune diseases: rheumatoid arthritis as a paradigm. 1993 Jan Several therapeutic agents currently are used to treat rheumatoid arthritis (RA). However, there is no compelling evidence that any of these agents substantially alters the long-term destructive course of RA. Advances in biotechnology have led to a better understanding of mechanisms that underlie autoimmune diseases such as RA. Although the etiology of RA remains unknown, there now is considerable insight regarding the immune and inflammatory pathways that ultimately lead to cartilage and bone destruction. Therapies with monoclonal antibodies directed against cell surface constituents, fusion toxins against cell activation markers, and cytokine inhibitors all have been shown to be safe and possibly efficacious in early open trials in RA. They now are being more rigorously tested in double-blind, placebo-controlled trials. Early experience with these biologic agents in humans, as well as data obtained from the use of these agents in animal models of autoimmune disease, are reviewed. In addition, experimental studies with "blocking peptides" and immunization with autoreactive T cell receptor peptides will be reviewed, and implications for therapy in RA will be discussed.
1424263 Systemic lupus erythematosus presenting with 'rheumatoid nodules'. 1992 Jan A patient with systemic lupus erythematosus who presented with subcutaneous nodules over the flexor aspect of the fingers in association with arthritis and Raynaud's phenomenon is described. Histopathological examination of the nodules showed appearances consistent with rheumatoid nodules. Further investigations revealed leucopenia and circulating anti-nuclear antibody but negative rheumatoid factor. Immunofluorescence studies of normal non-light exposed skin showed the presence of IgM deposits at the dermo-epidermal junction consistent with systemic lupus erythematosus. The nodules almost disappeared following treatment with hydroxychloroquine. Rheumatoid-like nodules have been reported in systemic lupus erythematosus, although rarely. However, the distribution of the nodules and the patient's clinical course differ from the few cases previously reported in the literature.