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ID PMID Title PublicationDate abstract
9026271 Differential changes of corticotropin releasing hormone (CRH) concentrations in plasma and 1996 Apr Corticotropin releasing hormone (CRH) and ACTH concentrations in plasma and CRH and IL-6 concentrations in synovial fluid in patients with rheumatoid arthritis (RA) were examined to clarify the relationship between cytokines and the hypothalamic-pituitary-adrenal axis (HPA axis). Concentrations of serum amyloid A protein (SAA), one of the acute phase proteins, were also measured as an indicator of inflammation. CRH and IL-6 concentrations in synovial fluid were higher in RA patients than in control patients (osteoarthritis, OA). Plasma ACTH and CRH levels were significantly lower in RA patients than in OA patients. This suggests that CRH secretion in synovial fluid is regulated differently from plasma CRH secretion, as CRH levels in synovial fluid and plasma showed opposite changes in RA patients. SAA levels were positively correlated with the levels of CRH or IL-6 in synovial fluid, whereas there was no correlation between CRH and IL-6 levels. The results suggest that CRH and IL-6 play important independent roles in producing SAA in synovial fluid.
1373912 Are lymphocytes a target for substance P modulation in arthritis? 1992 Feb The contribution of the neuropeptide substance P to the pathogenesis of rheumatoid arthritis (RA) has recently been suggested. The presence of immunoreactive substance P in the serum and joint fluid of RA patients was significantly increased compared with age-matched control patients. To investigate the ability of substance P to alter lymphocyte activity during the disease, lymphocytes were isolated from the synovial fluid and blood of RA patients and their ability to respond to substance P as measured by [3H]thymidine uptake was characterized. Upon exposure of RA synovial fluid and peripheral blood lymphocytes to various concentrations of substance P in vitro, no increase in proliferation was witnessed. To the contrary, control peripheral blood lymphocyte proliferation was significantly enhanced by various concentrations of substance P. However, synoviocytes from the joints of RA patients were responsive to substance P stimulation. These data suggest that substance P receptors may be desensitized on systemic and local lymphocytes in RA, or the proinflammatory activities of substance P may be mediated via the synovial membrane during chronic inflammation.
8997924 Reducing work disability associated with rheumatoid arthritis: identification of additiona 1996 Oct OBJECTIVE: To study additional risk factors for rheumatoid arthritis (RA)-related work disability and to identify the groups of individuals at high risk and the potentially modifiable factors which place them at risk. METHODS: A cross-sectional mail survey was conducted among 469 adults with RA. Work disability was defined as unemployment due to RA. A broad range of explanatory factors was examined, including sociodemographic, health, work, support given by others, and commuting difficulty. Employed and work-disabled subjects were compared by t-test and chi-square. Attributable fractions were calculated to assess the predictive value of factors. A recursive partitioning procedure identified individuals at varying risks for work disability, and their characteristics were defined. RESULTS: The risk factors joint pain and functional status, commuting difficulty, physical demands of the job, and disease duration were important predictors of work disability in both the attributable fraction and recursive partitioning analytic models. Having a professional or administrative job was protective, provided the salary earned was not low. Younger individuals with RA of shorter duration were placed at high risk by potentially modifiable factors. While older persons with RA of long duration were at high risk, modifiable factors could not be identified. CONCLUSION: Commuting difficulty, a previously overlooked factor, is an important predictor of RA work disability. Younger individuals with RA of relatively short duration can be placed at high risk by potentially modifiable factors including commuting difficulty, physically demanding jobs, greater joint pain and poor functional status, and nonprofessional/non-administrative jobs.
7835013 Vegetarian diet for patients with rheumatoid arthritis--status: two years after introducti 1994 Sep We have previously reported that a significant improvement can be obtained in rheumatoid arthritis patients by fasting followed by an individually adjusted vegetarian diet for one year. The patients who changed their diet could be divided into diet responders and diet nonresponders. After the clinical trial the patients were free to change diet or medication and after approximately one year they were asked to attend a new clinical examination. We compared the change from baseline (i.e. at the time of study entry) to the time of the follow-up examination for diet responders, diet nonresponders and controls who ate an omnivorous diet. The following variables favoured diet responders: pain score, duration of morning stiffness, Stanford Health Assessment Questionnaire index, number of tender joints, Ritchie's articular index, number of swollen joints, ESR and platelet count [corrected]. The difference between the three groups were significant for all the clinical variables, except for grip strength. There was no significant difference between the groups with regard to laboratory or anthropometric variables. At the time of the follow-up examination all diet responders but only half of the diet nonresponders still followed a diet. Our findings indicate that a group of patients with rheumatoid arthritis benefit from dietary manipulations and that the improvement can be sustained through a two-year period.
1316742 Production of angiotensin converting enzyme by rheumatoid synovial membrane. 1992 Apr Vascular proliferation and mononuclear cell infiltration are prominent changes observed in synovium from actively inflamed joints of patients with rheumatoid arthritis. Angiotensin converting enzyme (ACE) is a halide activated peptidase produced mainly by endothelial cells and by activated monocytes. It has been proposed that levels of ACE activity in synovial fluid might reflect changes in membrane vascularity, the degree of monocyte infiltration, or the thickness of the lining layer. In this study, ACE activity in serum and synovial fluid samples from 18 patients with inflammatory arthritis was measured and compared with levels in 12 control subjects with non-inflammatory arthritis. Although serum levels were similar in the two groups, ACE activity in synovial fluid was significantly increased in the group with inflammatory arthritis compared with controls (mean (SE) 37 (5) v 19 (3)). Staining of synovial membranes from patients with rheumatoid arthritis with a monoclonal antibody to ACE localised ACE to the endothelium and to mononuclear cells of macrophage origin. ACE activity was then measured in supernatants of synovial membrane from patients with rheumatoid arthritis after one and seven days of culture. A significant increase in ACE activity was observed after seven days of culture (mean (SE) day 1, 17 (5) v day 7, 25 (3)). Levels of ACE activity, however, did not correlate with the lining layer thickness, with the number of macrophages per square millimetre, nor with the number of blood vessels per square millimetre of synovial tissue. No correlation was observed either between levels of ACE in the supernatant of synovial membrane and levels of interleukin 1 or interleukin 6. In conclusion, ACE is produced by the synovial membrane of patients with rheumatoid arthritis and is localised to monocytes and endothelial cells. Levels of activity do not directly reflect membrane vascularity, monocyte or macrophage number, or the thickness of the lining layer.
8440075 Suppressive effect of interleukin-4 (IL-4) on IL-6 production by adherent rheumatoid synov 1993 Jan Interleukin-6 (IL-6) has recently been characterized as a mediator of multiple inflammatory responses. Excessive production of this cytokine has been demonstrated in the joints of patients with rheumatoid arthritis (RA). On the other hand, anti-inflammatory effects of IL-4 have recently been demonstrated. We therefore investigated the suppressive effect of IL-4 on IL-6 production by synovial cells in patients with RA. Freshly prepared adherent rheumatoid synovial cells expressed IL-6 mRNA and spontaneously produced a large amount of IL-6 in culture. This spontaneous production of IL-6 was significantly suppressed by IL-4. The suppressive effect of IL-4 on IL-6 production was demonstrated in all patients with RA tested in this study. On the other hand, IL-6 mRNA levels already expressed in adherent synovial cells were not reduced by IL-4 in 24 hr of culture. The suppressive effect of IL-4 on IL-6 production suggests that IL-4 is an important physiological regulator of IL-6 production in synovial cells.
8639177 Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice. A 1996 May OBJECTIVE: To examine the role of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), and IL-1 beta in collagen-induced arthritis (CIA), immediately after onset and during the phase of established arthritis. METHODS: Male DBA/1 mice with collagen-induced arthritis were treated with antibodies against murine TNF alpha and IL-1 alpha/beta at different time points of the disease. IL-1 receptor antagonist (IL-1Ra) was administered using Alzet osmotic minipumps. The effect of anticytokine treatment was monitored by visual scoring. Histology and cytokine reverse transcription polymerase chain reaction (RT-PCR) analyses were performed at the end of the treatment period. RESULTS: Anti-TNF alpha treatment showed efficacy shortly after onset of the disease, but had little effect on fully established CIA. Histologic analysis after early treatment revealed that anti-TNF alpha significantly reduced joint pathology, as determined by infiltration of inflammatory cells and cartilage damage. Anti-IL-1 alpha/beta treatment ameliorated both early and full-blown CIA. This clear suppression of established arthritis was confirmed by administration of high doses of IL-1Ra. Dose-response experiments showed that a continuous supply of 1 mg/day was needed for optimal suppression. Histologic analysis showed markedly reduced cartilage destruction both in the knee and the ankle joints. Autoradiography demonstrated full recovery of chondrocyte synthetic function of articular cartilage. In addition, we found that the IL-1 beta isoform plays a dominant role in established CIA. Profound suppression of CIA was observed with anti-IL-1 beta, although elimination of both IL-1 alpha and IL-1 beta still gave better protection. Analysis of messenger RNA with RT-PCR revealed that IL-1 beta was highly upregulated in synovium and cartilage at late stages of CIA, whereas anti-IL-1 beta treatment markedly reduced IL-1 beta message in the synovium. CONCLUSION: The present study identified different TNF alpha/IL-1 dependencies in various stages of CIA and revealed that blocking of TNF alpha does not necessarily eliminate IL-1. Continuous, high doses of IL-1Ra are needed to block CIA.
8639182 Enrichment of differentiated CD45RBdim,CD27- memory T cells in the peripheral blood, synov 1996 May OBJECTIVE: To delineate in greater detail the phenotype of T cells that reside in the synovial tissue (ST) and synovial fluid (SF) of patients with rheumatoid arthritis (RA), in order to determine their precise differentiation status, and to determine whether the accumulation of these specific T cell subsets in these synovial compartments could be related to their capacity for transendothelial migration. METHODS: Lymphocytes from normal subjects or from the peripheral blood (PB), ST, and/or SF of RA patients were phenotypically analyzed by flow cytometry. Normal PB CD4+ T cells were also characterized using an in vitro assay of transendothelial migration. RESULTS: ST and SF were found to be enriched with memory (CD45RA-,CD45RO+,CD11abright,CD44bright and activated (CD69+) T cells. Moreover, ST and SF cells from RA patients were enriched in differentiated CD4+,CD45RBdim,CD27- T cells, a subset of mature memory T cells that develops after prolonged antigenic stimulation. In addition, PB of some RA patients contained an increased number of CD4+,CD45RBdim,CD27- T cells. The CD4+,CD11abright,CD44bright memory T cells, which included the CD45RBdim,CD27- more mature memory cells, exhibited an enhanced capacity for transendothelial migration that is likely to contribute to their enrichment in the rheumatoid synovium. CONCLUSION: RA patients manifest an increased number of mature memory T cells in the SF and ST, and some also have an increased number of these cells in PB that is likely to reflect chronic antigenic stimulation. The enrichment of these cells in the SF and ST reflects, in part, an enhanced capacity to migrate from the vascular space into inflamed tissue.
8792511 Dapsone in rheumatoid arthritis. 1996 Jun Dapsone, a synthetic sulfone with chemical similarities to sulfapyridine, has been used for a number of years to treat leprosy and dermatitis herpetiformis. Recently, a number of prospective, randomized, double-blind trials have shown their success in the management of rheumatoid arthritis, with dapsone being superior to placebo and comparable to chloroquine and hydroxychloroquine. Its mode of anti-inflammatory actions in rheumatoid arthritis is not clearly understood, but modulation of neutrophil activity or inhibition of neutrophil inflammatory product formation or release appear to play a role. The major limiting side effect is hemolytic anemia, which may be mitigated through careful patient selection, conservative drug dosing, close monitoring, and possibly, concurrent administration of antioxidants or cytochrome P450 inhibitors. Methemoglobinemia is another common finding among patients receiving dapsone therapy, but rarely does it result in prominent symptoms other than transient pallor. Less common adverse events to dapsone include the idiosyncratic reactions of leukopenia and agranulocytosis, cutaneous eruptions, peripheral neuropathy, psychosis, toxic hepatitis, cholestatic jaundice, nephrotic syndrome, renal papillary necrosis, severe hypoalbuminemia without proteinuria, an infectious mononucleosis-like syndrome, and minor neurological and gastrointestinal complaints. In this report, two patients with advanced rheumatoid arthritis, who were safely and effectively treated with dapsone after failure with other second-line agents, are described and the literature is reviewed. We suggest that dapsone is an effective second-line agent in the treatment of rheumatoid arthritis.
10130384 An approach to preventing methotrexate prescribing errors in rheumatoid arthritis. 1993 Nov Methotrexate is an effective treatment for rheumatoid arthritis and is fairly well tolerated by patients when used appropriately. However, errors do occur due to a lack of awareness of the normal dosage range and potentially serious dose related side effects of methotrexate among physicians, pharmacists, and nurses. The approach taken by one hospital to prevent methotrexate prescribing errors includes daily monitoring of methotrexate by a pharmacist, building caution flags in the order loading program of the pharmacy computer system, and educating healthcare professionals to heighten awareness when prescribing, dispensing, and administering methotrexate for rheumatoid arthritis. At the hospital, since the institution of these policies and education of pharmacists, nurses, and physicians, there have been no incidents of methotrexate prescribing errors.
7893278 Studies on the efficacy of unconventional therapies. Problems and designs. 1995 Jan Many unconventional therapies (e.g. dietary, phytotherapy, acupuncture, homeopathy) are well known and often applied, but their efficacy has hardly been proven. New trial designs and study components must be found to meet the specific demands of the particular unconventional therapy on one hand and keep the high methodological standard of controlled clinical trials on the other hand. Biometricians and unconventional therapists are challenged to develop such designs. Typical problems in designing studies of unconventional therapies include that placebo is not possible, therapies cannot be masked, outcome variables are not reliable, therapy is highly individualized, and studies on the efficacy of soft therapies require many patients and long treatment periods. Studies with unconventional therapies should be performed by practitioners (because they use these therapies), but this leads to further problems. Some solutions are given in examples: A study is described investigating the herbal remedy Kava-Kava for patients in the state of anxiety, tension and restlessness; a study on classical homeopathy for chronical headaches is specified; some designs for dietary studies in patients with rheumatoid arthritis are compared. A design called "cross-allocation of patients to two treatments with randomization option" and the "N-of-1 design", also called "single case design" are described and discussed. The "change-to-open-label design" could be useful to investigate soft and natural therapies which require studies with many patients and long-term treatment.
8474056 Hypothesis: cartilage catabolic cofactors in human arthritis. 1993 Feb Cartilage degradation in rheumatoid arthritis (RA) and osteoarthritis (OA) is commonly thought to be mediated by interleukin 1 (IL-1) and tumor necrosis factor (TNF). However, recent new evidence suggests that IL-1 and TNF on their own do not mediate all the cartilage changes seen in RA and OA. We propose that cartilage degradation is mediated by a complex network of cytokines, including IL-1, TNF and at least one cofactor present in synovial fluid.
1440313 [The clinical aspects of the diagnosis of rheumatoid arthritis]. 1992 Altogether 212 patients aged 16 to 73 years with rheumatoid arthritis (RA) lasting 3 months to 32 years were examined. Of these, 78 patients had grade I, 111 grade II, and 23 grade III disease activity. 34 patients had stage I, 76--stage II, 56--stage III, and 24--stage IV disease. In 22 patients, roentgenography failed to reveal pathology of the joints. The reference group comprised 65 patients suffering from gouty arthritis, 46 having osteoarthrosis deformans with phenomena of secondary synovitis, 30 with Bekhterev's disease, 10 with systemic lupus erythematosus, 6 with Reiter's disease, 5 with psoriatic arthropathy, and 50 with non-rheumatic diseases. When trying the diagnostic criteria for ARA (revised in 1987), criteria 1-4 and 7 were found to be most sensitive (from 88.2 to 93.8%), criteria 5 and 6 appeared most specific (100 and 98.6%, respectively). The specificity of the remaining criteria ranged from 85.4 to 96.3%. The use of the revised criteria for ARA in clinical practice was dictated by the necessity of improving RA diagnosis.
7882210 Biaxial total wrist arthroplasty in rheumatoid arthritis. 1995 Feb OBJECTIVE: To judge the outcome of total wrist arthroplasty. DESIGN: A retrospective study of 13 patients. SETTING: A university hospital. PATIENTS: Seventeen patients with stage III or IV rheumatoid arthritis of the wrist. Only 13 patients were studied because 3 died and 1 was lost to follow-up. INTERVENTION: Biaxial total wrist arthroplasty (15 procedures). MAIN OUTCOME MEASURES: Clinical assessment and the Hospital for Special Surgery scoring system and radiologic review. RESULTS: Good or excellent results were achieved in all patients after an average follow-up of 54 months. CONCLUSION: Biaxial total wrist arthroplasty is a reasonable treatment in rheumatoid patients when preservation of wrist motion is critical.
8004814 Anti-endothelial cell antibodies in sera of patients with autoimmune diseases: comparison 1994 Jun In some patients suffering from rheumatoid arthritis (RA), vasculitis is a clear clinical manifestation, mentioned as rheumatoid vasculitis (RV). Autoantibodies directed against endothelial cells (AEA) have been implicated in the pathogenesis of this disorder, and it has been suggested in a number of studies that testing for AEA should be included in diagnosing RV. To test this hypothesis, we have evaluated the presence of AEA in sera of patients suffering from various autoimmune diseases, employing an ELISA with fixed cultured endothelial cells (EC). In all the groups of patients ELISA-positive sera were present. A significant difference in percentage of positivity was found between the RA and RV group (P < 0.05). In addition, our results indicated that not only antibodies directed against antigens on the EC membrane were detected, but also antibodies directed against intracellular components like DNA, histones and cytoskeletal components. Therefore, we also tested all these patient sera on unfixed intact EC using indirect immunofluorescence followed by FACS analysis. Whereas in the total patient population 34 out of 65 patients were AEA-positive as determined in the ELISA, only seven patients were weakly positive when examined by flow cytometry. We conclude that: (i) an ELISA on fixed EC does not specifically detect AEA. A positive test result is, however, to some extent correlated with the occurrence of vasculitis, and may therefore be helpful in diagnosing this disease; (ii) FACS analysis is a more suitable method than ELISA to measure the presence of membrane-specific AEA in patient sera; (iii) specific IgG-AEA are less common in patients suffering from autoimmune disorders than was assumed previously.
8212923 Transient increase of aminotransferases in RA patients treated with methotrexate. 1993 Jul Sixty-two patients with rheumatoid arthritis (RA) were treated with methotrexate (MTX) for 3 months. Methotrexate was given orally in a single dose of 7.5-15.0 mg/week. At the onset of the treatment increased activity of aminotransferases has been observed. Eighteen patients (29%) displayed higher enzyme activity in the first 3 weeks. Despite the continuous drug administration the activity of aminotransferase became normal at week 12 in all but one patient. In this patient MTX had to be withdrawn.
8732486 Echo-Doppler left ventricular filling abnormalities in patients with rheumatoid arthritis 1996 Apr Our investigation aimed at verifying diastolic abnormalities in rheumatoid patients, without clinically evident cardiovascular disease and other confounding complaints, by using pulsed Doppler examination of transmitral blood flow. We selected 40 patients fulfilling revised American Rheumatism Association (ARA) criteria for the diagnosis of rheumatoid arthritis having no symptoms of cardiac disease or clinical findings of other extracardiac diseases. We also studied 40 rheumatoid-matched healthy volunteers as a control group. An echocardiographic examination was carried out on each subject. Left ventricular structural and functional measurements were obtained. Interventricular, septal thickness and left ventricular mass index were significantly higher in rheumatoid patients than in the control group. We also found in rheumatoid patients higher mean values of peak A velocity and A/E ratio. When multiple linear regression analysis was performed on the data of rheumatoid patients we found an independent relationship only between A/E ratio and left ventricular mass. In conclusion, our results confirm diastolic abnormalities in rheumatoid patients and point out that these abnormalities also affect echo-Doppler parameters of left ventricular filling. Moreover, further analysis of our data may suggest the possibility that structural left ventricle changes could be responsible for left ventricular filling impairment.
8252159 Predictive value of synovial fluid analysis in rheumatoid arthritis. A 7.5-year follow-up 1993 May OBJECTIVES: To evaluate the prognostic value of some synovial fluid variables in patients with rheumatoid arthritis. METHODS: Twenty-nine patients with erosive rheumatoid arthritis and hydropsy in a knee joint were followed for 7.5 years in a prospective study. At the start of the study the knee joints were aspirated and 15 synovial fluid variables were analyzed. The patients were divided into two groups according to whether or not there had been progress of radiologically detected destruction in the knee joints during the follow-up. RESULTS: Of the synovial fluid variables at the start, only C3 (p = 0.030) and acid phosphatase (p = 0.047) differed significantly between the groups, the former being lower and the latter higher in patients with deterioration of knee joints. CONCLUSIONS: These preliminary results may indicate that low synovial fluid C3 and high acid phosphatase predict poor prognosis in a joint affected by rheumatoid arthritis.
1582068 Benign breast disease in systemic sclerosis (SSc). A case-control study. 1992 May We hypothesized that Systemic Sclerosis (SSc) may affect the breast in the form of Benign Breast Disease (BBD). For the purpose of this study BBD was defined as breast symptoms either detected by the patient resulting in physician consultation, or detected by a physician during the course of a routine consultation, or detected by a physician during the course of a routine physical exam. Forty-one of 47 women with SSc were matched to case controls from two disease groups (RA and OA). Case matching was done for age (+/- 5 years), disease duration (+/- 3 years) and gender. A structured telephone interview was administered to all subjects and controls to determine the frequency of BBD and associated risk factors. The SSc group had a higher prevalence of BBD compared to the RA group (12/41 versus 4/41, p less than 0.04). However, a similar proportion of the SSc patients and OA case controls had BBD (7/28 versus 9/28). These differences could not be attributed to any of the evaluated risk factors. The RA group had a higher frequency and longer duration of NSAID use, suggesting that the increased use of NSAIDs in the RA patients may account for the lower prevalence of BBD, although genetic, hormonal or undetermined factors may be operative. Without an age-matched, "healthy" general population control group it is impossible to determine if the observed difference in prevalence of BBD represents a less than normal prevalence in RA or a greater than normal prevalence in SSc and OA.
8650590 Clinical expression of rheumatoid arthritis in Chilean patients. 1995 Dec In populations such as Northern Europeans in which the HLA-DR4 subtypes DW14 and Dw4 show strong association with rheumatoid arthritis (RA), these alleles and the double allelic dose of the shared epitope are considered severity markers. The clinical expression of RA varies in different populations, which may be determined by variation in the prevalence of these markers. In the present study we analyzed the expression of RA in 112 consecutive Chilean patients and its relation to the prevalence of genetic factors, prompted by our previous observation that DR4 is weakly associated to RA in this population. Mean age was 50 +/- 14 years; 90% were seropositive and 87% were female, with a disease duration of 10 +/- 8 years. Extra-articular manifestations were found in 38% of patients, rheumatoid nodules in 27%, vasculitis in 8%, and Sjogren's syndrome in 29%. Functional capacity (ACR, 1991) I or II: 82%.15% of patients stopped working. Hand radiographs scored according to Steinbrocker in 89 patients: I, 21%; II, 15%; III, 43%; IV, 21%. In this series, patients with less formal education seemed to have more benign arthritis. In 97 controls and in 65 (56%) RA patients the presence of DRB1 alleles corresponding to DR1 and DR4 serotypes, to DR4-Dw subtypes, and homozygocity, were determined by polymerase chain reaction followed by specific oligonucleotide hybridization. The shared epitope was present in 53% of RA patients and in 30% of controls (P = .0048, odds ratio [OR] = 2.64). A double allelic dose of the epitope was present in 15% of RA patients compared with 4% of controls (P = .026, OR = 4.23). In a subgroup of 31 erosive RA patients we did not find a significant association of disease severity with the shared epitope in a single or double allelic dose. None of the DR4 subtypes that associate with RA in other populations was found significantly more prevalent in our patients. The severity of RA in our study compared with published series was intermediate between British patients with severe RA and Greek patients with milder disease. This may be due to the high prevalence of Dwl3*0403 in our population.