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ID PMID Title PublicationDate abstract
10904452 Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the 2000 Jul 24 BACKGROUND: Depression and anxiety are common in medical patients and are associated with diminished health status and increased health care utilization. This article presents a quantitative review and synthesis of studies correlating medical patients' treatment noncompliance with their anxiety and depression. METHODS: Research on patient adherence catalogued on MEDLINE and PsychLit from January 1, 1968, through March 31, 1998, was examined, and studies were included in this review if they measured patient compliance and depression or anxiety (with n>10); involved a medical regimen recommended by a nonpsychiatrist physician to a patient not being treated for anxiety, depression, or a psychiatric illness; and measured the relationship between patient compliance and patient anxiety and/or depression (or provided data to calculate it). RESULTS: Twelve articles about depression and 13 about anxiety met the inclusion criteria. The associations between anxiety and noncompliance were variable, and their averages were small and nonsignificant. The relationship between depression and noncompliance, however, was substantial and significant, with an odds ratio of 3.03 (95% confidence interval, 1.96-4.89). CONCLUSIONS: Compared with nondepressed patients, the odds are 3 times greater that depressed patients will be noncompliant with medical treatment recommendations. Recommendations for future research include attention to causal inferences and exploration of mechanisms to explain the effects. Evidence of strong covariation of depression and medical noncompliance suggests the importance of recognizing depression as a risk factor for poor outcomes among patients who might not be adhering to medical advice.
10201961 IL-16 as an anti-inflammatory cytokine in rheumatoid synovitis. 1999 Apr 1 T lymphocytes are a major component of the inflammatory infiltrate in rheumatoid synovitis, but their exact role in the disease process is not understood. Functional activities of synovial T cells were examined by adoptive transfer experiments in human synovium-SCID mouse chimeras. Adoptive transfer of tissue-derived autologous CD8+ T cells induced a marked reduction in the activity of lesional T cells and macrophages. Injection of CD8+, but not CD4+, T cells decreased the production of tissue IFN-gamma, IL-1beta, and TNF-alpha by >90%. The down-regulatory effect of adoptively transferred CD8+ T cells was not associated with depletion of synovial CD3+ T cells or synovial CD68+ macrophages, and it could be blocked by Abs against IL-16, a CD8+ T cell-derived cytokine. In the synovial tissue, CD8+ T cells were the major source of IL-16, a natural ligand of the CD4 molecule that can anergize CD4-expressing cells. The anti-inflammatory activity of IL-16 in rheumatoid synovitis was confirmed by treating synovium-SCID mouse chimeras with IL-16. Therapy for 14 days with recombinant human IL-16 significantly inhibited the production of IFN-gamma, IL-1beta, and TNF-alpha in the synovium. We propose that tissue-infiltrating CD8+ T cells in rheumatoid synovitis have anti-inflammatory activity that is at least partially mediated by the release of IL-16. Spontaneous production of IL-16 in synovial lesions impairs the functional activity of CD4+ T cells but is insufficient to completely abrogate their stimulation. Supplemental therapy with IL-16 may be a novel and effective treatment for rheumatoid arthritis.
10813281 Direct and indirect costs associated with the onset of seropositive rheumatoid arthritis. 2000 May OBJECTIVE: To examine the direct and indirect costs of rheumatoid arthritis (RA) during the first year of disease. METHODS: As part of a longitudinal observational study, 150 patients with seropositive RA of 5.9 +/- 2.9 mo duration were recruited through the Western Consortium of Practicing Rheumatologists. Subjects completed questionnaires about health care services and resources utilized and about the number of days of usual activity lost as a result of RA during the 6 month period prior to enrolment. RESULTS: Study participants had active RA as evidenced by mean tender and swollen joint counts of 24.9 +/- 13.5 and 20.6 +/- 11.6, respectively, and moderate functional impairment reflected by a mean Health Assessment Questionnaire (HAQ) score of 1.24 +/- 0.7. The average total direct cost of RA was $200/month. Health care visits, medications, and radiographs accounted for 78% of the total direct cost, while expenditures for hospitalizations accounted for only 3.5% of the total. The average number of days of usual activity lost per month because of RA was 3.8 +/- 7.7, translating into an average indirect cost of $281/month. Of the 95 subjects who were gainfully employed prior to disease onset, 12 were disabled and 5 were on sick leave as a result of RA, corresponding to a work disability rate of 18%. Work disabled subjects reported significantly lower total household incomes and higher HAQ disability and global disease activity scores than subjects who continued working. CONCLUSION: In this group of patients with seropositive RA substantial costs, both direct and indirect, were incurred during the first year of disease.
9627948 Inhibition of interleukin-8 synthesis by intraarticular methotrexate therapy in patients w 1998 Apr 5 Patients with definite RA and knee effusions under constant doses of DMARD therapy were treated with up to 6 intraarticular injections of 10 mg methotrexate (MTX) every 3 to 7 days. A matched randomized control group who received a single i.a. injection of 40 mg triamcinolone hexacetonide (TC) was monitored according to the same protocol. The intraarticular granulocyte counts and IL-8 levels decreased in all MTX treated patients on day 10-13 and stayed low in those patients who could be re-evaluated after 13 weeks. Compared to the IL-8 levels, the other tested cytokine levels showed only minor changes on day 10-13. There was no need for re-injection in the TC group during the 13 week study phase. We conclude that intraarticular MTX therapy results in a strong decrease of SF-granulocyte counts. This effect may be due to the impairment of IL-8 mediated chemotaxis by decreased IL-8 synthesis in synovial fluid mononuclear cells. Clinically, repeated intraarticular MTX therapy results in a worse 13 week outcome than i.a. steroid treatment measured in an intention-to-treat analysis.
11709606 Bone turnover, joint damage and bone mineral density in early rheumatoid arthritis treated 2001 Nov OBJECTIVES: Exploration of bone metabolism changes at different levels of disease activity, both with and without oral corticosteroid therapy, and prediction of changes in joint damage and bone density from the observed changes in markers of bone turnover. METHODS: Data analysis from a randomized clinical trial with 155 rheumatoid arthritis (RA) patients; median age 50 yr, early and active disease (diagnosis < 2 yr); one group treated with a combination of sulphasalazine (SSZ; 2000 mg/day), methotrexate (MTX; 7.5 mg/week) and prednisolone (initially 60 mg/day, tapered in six weekly steps to 7.5 mg/day), the other group with SSZ alone. Prednisolone and MTX were tapered and stopped after weeks 28 and 40, respectively, while SSZ was continued. Urine and serum samples were collected at baseline and weeks 16, 28, 40 and 56. Measurements of urinary pyridinoline (PYD) and deoxypyridinoline (DPD) and serum alkaline phosphatase (tAP) and osteocalcin (OC) were performed, as well as standard clinimetry and bone densitometry. RESULTS: Over time and in both treatment groups, bone formation and bone resorption markers showed a pattern similar to erythrocyte sedimentation rate (ESR): a significant decrease compared with baseline and a larger decrease with combined treatment at weeks 16 and 28. PYD excretion, tAP, OC, and joint damage scores were significantly lower in the combined treatment group. Changes in bone density (of spine and hips) did not significantly differ between treatment groups. Mainly cumulative ESR explained progression of joint damage. CONCLUSIONS: Prednisolone and disease-modifying anti-rheumatic drug therapy in patients with early and active RA are both independently associated with decreased levels of urinary excretion of bone collagen resorption markers PYD and DPD. Markers of bone formation and resorption closely followed changes in ESR in both treatment groups. Reduced bone resorption together with reduced bone formation-initially at a somewhat faster pace-resulted in less bone turnover and explain the observed (non-significant and partially reversible) extra bone loss in the lumbar spine associated with prednisolone (combined treatment).
11149655 Synovial inflammation and hyperplasia induced by gliostatin/platelet-derived endothelial c 2000 Dec Neovascularization, proliferation of synovial cells, and mononuclear cell influx and activation are characteristic events observed in synovial joints in the pathohistology of rheumatoid arthritis (RA). The objective of this study was to examine synovial inflammation in rabbit knees induced by intra-articular administration of human gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF), which shares a high degree of chemical homology with thymidine phosphorylase (dThdPase) and is known to have angiogenic activity. Purified recombinant human gliostatin (rHuGLS) and its mutant protein, which was prepared by site-directed mutagenesis and which lacks dThdPase activity, were administered at various doses to rabbit knee joints. The effects of rHuGLS and the mutant were examined histologically. Intra-articular injection of rHuGLS resulted in the development of diffuse synovitis resembling RA. The mutant protein also brought about the same effect. These findings suggest that human GLS can cause RA-like synovitis in rabbit knee joints via a mechanism other than its dThdPase activity.
10867393 [Parameters of normality in multifrequency tympanometry]. 2000 Apr Multifrequency tympanometry studies consist of tympanography using probe tone frequencies ranging from 200 to 2000 Hz, improving the study of acoustic transmission through the tympano-ossicular system because then two components of admittance, conductance and susceptance, can be separated. The resonance frequency is the frequency at which mass and spring elements of the middle ear cancel each other out, leaving only the friction component. This measurement has been found to be more sensitive to the presence of pathologies that affect the tympano-ossicular system, such as otosclerosis and rheumatoid arthritis. It is necessary to know normal pattents of tympanometric parameters to improve the study of these diseases. Multifrequency tympanometry performed on 136 patients, 91 women and 45 men, age range 11-78 years. The mean resonant frequency of the middle ear was 1132.33 Hz, mean static admittance 0.76 dapa, and mean tympanometric amplitude 94.31 mmhos ac. Age showed no systematic effect of age on any of these measures in this population, and no significant association was found between static admittance or tympanometric amplitude and resonance frequency.
10192501 The relationship between defects in lymphocyte production of transforming growth factor-be 1999 Transforming growth factor beta (TGF-beta) comprises of a family of proteins with pleiotropic signaling properties and potent immunoregulatory effects. In SLE we recently reported that lymphocyte production of the total and active forms of TGF-beta1 was decreased. Here we asked whether these defects correlate with disease activity and/or severity. TGF-beta1 production by blood lymphocytes from 17 prospectively studied SLE patients was compared with 10 rheumatoid arthritis (RA) patients and 23 matched healthy controls. The RA levels of active TGF-beta1 were lower than controls, but were not deceased to the extent found in SLE. Levels of constitutive and anti-CD2 stimulated active TGF-beta1 detected in picomolar amounts were markedly reduced in six untreated patients hospitalized with recent onset, very active and severe SLE and similarly reduced in 11 patients with treated, less active disease. By contrast, decreased production of total TGF-beta1 inversely correlated with disease activity. These studies suggest, therefore, that although impaired lymphocyte secretion of the latent precursor of TGF-beta1 may result as a consequence of disease activity, a decreased capacity to convert the precursor molecule to its active form may pre-date disease onset. Insufficient exposure of T cells to picomolar concentrations of TGF-beta1 at the time they are activated can result in impaired down-regulation of Ig synthesis. Therefore, decreased lymphocyte production of active TGF-beta1 in SLE could be an immunologic defect which contributes to the B cell hyperactivity characteristic of this disease.
11879539 Cytokine-stimulated T cells induce macrophage IL-10 production dependent on phosphatidylin 2002 IL-10 is an anti-inflammatory cytokine produced in the joint in rheumatoid arthritis by macrophages and infiltrating blood lymphocytes. Regulation of its expression is poorly understood, but previous findings have suggested that physical interactions with T cells may play a role. This report investigates signalling mechanisms involved in the production of macrophage IL-10 upon interaction with fixed, cytokine-stimulated T cells (Tck). Elutriated monocytes were differentiated to macrophages by macrophage-colony-stimulating factor (M-CSF) and co-cultured with fixed T cells chronically stimulated in a cytokine cocktail of IL-2/IL-6/tumour necrosis factor (TNF)-alpha in the presence or absence of wortmannin and LY294002, inhibitors of phosphatidylinositol 3-kinase (PI3K), or of rapamycin, an inhibitor of p70 S6-kinase (p70S6K). Spontaneous IL-10 production by rheumatoid arthritis synovial-membrane mononuclear cells (RA-SMCs) and co-cultures of rheumatoid arthritis T cells (RA-Ts) and macrophages was also assessed. RA-T and Tck induction of macrophage IL-10 production was suppressed by cell separation and inhibition of PI3K and p70S6K. PI3K involvement was also shown by phosphorylation of the downstream effector protein kinase B. Spontaneous IL-10 production by RA-SMCs was also inhibited by LY294002 and depletion of the nonadherent (T-cell-enriched) fraction of the cell population. IL-10 production in RA-SMCs and M-CSF-primed macrophages, activated by interaction with Tck, is PI3K- and p70S6K-dependent.
11112193 The effect of epidemiologic and intraoperative factors on survival of the standard Souter- 2000 Dec Previously published work has revealed an 87% survivorship after 12 years for the standard Souter-Strathclyde total elbow arthroplasty in patients with rheumatoid arthritis. Of the 13% that were revised, 75% were due to loosening of the humeral component. The aim of this research was to identify the specific epidemiologic and intraoperative factors that predisposed to this humeral loosening. Specifically, factors such as age, sex, radiologic staging of the disease, position of the implant in bone, and size of the implant inserted were evaluated. After analysis of 186 cases, we concluded that the position of the humeral component within the humerus is crucial for long-term survivorship. Specifically in the lateral plane, the stem should be aligned in the plane of the humerus and the implant inserted to the correct depth. The articular surface of the implant should lie at the level of the normal trochlea. At the anteroposterior plane, the implant should sit centrally and not be lateralized. We conclude that good surgical technique is crucial to the long-term effectiveness of this implant.
11285378 Expression of interleukin-18 and its monokine-directed function in rheumatoid arthritis. 2001 Mar OBJECTIVES: To investigate the expression of and monokine induction by interleukin 18 (IL-18; also called interferon-gamma inducing factor, IGIF), in peripheral blood mononuclear cells (PBMC) and cultured synoviocytes from rheumatoid arthritis (RA) patients. METHODS: We carried out IL-18 Western blotting and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) of cytokines in PBMC [IL-18, IL-1beta and tumour necrosis factor alpha (TNF-alpha)] and long-term cultured fibroblast-like synoviocytes (FLS) [IL-18, IL-1beta, TNF-alpha, IL-6, interferon gamma (INF-gamma) and [granulocyte-macrophage colony stimulating factor (GM-CSF)] from RA patients and controls. FLS were isolated from RA synovial membranes (FLS(SM)) and RA synovial fluids (FLS(SF)), osteoarthritis (OA) FLS(SM) and FLS(SF) from spondyloarthropathy patients. FLS were characterized by fluorescence-activated cell sorting of the FLS. PBMC and FLS from RA patients and control subjects were stimulated with recombinant human IL-18 and IL-1beta (rHuIL-18/rHuIL-1beta), and TNF-alpha, IL-1beta and MMP-1 were measured by ELISA in supernatants. RESULTS: Constitutive expression of IL-18 mRNA was significantly reduced whereas that of TNF-alpha was enhanced in RA PBMC. Persistent low expression of IL-18, TNF-alpha, GM-CSF and IL-1beta was observed in RA and OA FLS(SM) as well as spondyloarthropathy FLS(SF). In contrast, high constitutive expression of IL-18 in FLS (CD90/Thy-1- and CD54-positive, CD14- and CD86-negative), accompanied by persistent high levels of TNF-alpha, GM-CSF and IL-1beta expression, was restricted to synovial fluid-derived FLS obtained from RA patients. IFN-gamma was not detectable in any culture, but IL-6 mRNA was equally expressed in all FLS cultures. rHuIL-18 was effective in stimulating TNF-alpha and IL-1beta secretion in PBMC from healthy controls, but failed to stimulate TNF-alpha and IL-1beta secretion from PBMC in 11 of 12 RA patients, and all FLS cultures. rHu-IL-1beta, but not rHu-IL-18, induced interstitial collagenase (MMP-1) in FLS. CONCLUSIONS: Persistent high production of proinflammatory cytokines in RA-FLS(SF) may be relevant for chronic progression in RA synovitis. Levels of TNF-alpha and IL-1beta expression are increased in RA-FLS(SF), but are independent of IL-18. The pathological function of enhanced IL-18 expression in RA-FLS(SF) remains to be further elucidated.
10839031 Self-efficacy in chronic illness: the juxtaposition of general and regimen-specific effica 1999 Dec Changes in lifestyle are difficult for most people but necessary for those with a chronic illness, for whom changes may involve, among other adjustments, learning new behaviours and/or modifying one's lifestyle. The ease with which such changes occur depends on the person's efficacy beliefs and outcome expectations. This paper will discuss the conceptual issues related to self-efficacy: general, domain, and specific. Examples will be drawn from the health-related behaviour changes required to manage diabetes and rheumatoid arthritis. For this paper, regimen-specific or task-specific behaviour refers to the multiple tasks that the person carries out for management of their chronic illness. Confounding the issue of perceived efficacy (general, domain or specific), is the fact that compliance with all aspects of a recommended self-care regimen will not necessarily result in metabolic control for the person with type 1 diabetes mellitus, weight loss for the person with type 2 diabetes mellitus, or pain control for the arthritic person.
9171133 Endoscopic hydrostatic balloon dilation of ulcer-induced pyloric stenosis in rheumatoid ar 1997 Jun We describe a 50-year-old Japanese woman with rheumatoid arthritis who presented with near-complete gastric outlet obstruction. The patient also suffered from secondary gastrointestinal and cardiac amyloidosis. Gastroscopy revealed multiple huge gastric antral ulcers in which amyloid deposits were identified on histologic examination. The ulcers became scars after treatment with omeprazole, which cause in severe pyloric stenosis. Endoscopic hydrostatic balloon dilation under fluoroscopic guidance was performed twice for 10 min. The pyloric outlet remained sufficiently patent 22 months later.
11128925 Relationship between interleukin-6 levels in gingival crevicular fluid and periodontal sta 2000 Nov BACKGROUND: The aim of this study was to determine and compare interleukin-6 (IL-6) levels in gingival crevicular fluid (GCF) and clinical periodontal findings in patients with rheumatoid arthritis (RA) and adult periodontitis (AP). METHODS: A total of 45 patients divided into 3 groups (15 patients with RA and AP, 15 patients with AP, and 15 periodontally healthy subjects) were included in this study. Plaque index (PI), gingival index (GI), sulcus bleeding index (SBI), probing depth (PD), and attachment level (AL) values for each patient were recorded. Enzyme-linked immunosorbent assay for quantitative detection of IL-6 in each GCF sample was employed. RESULTS: No significant difference could be detected between the RA and AP groups in the mean clinical parameter data except PI. Although the mean GCF IL-6 level in the RA group was the highest, no significant difference could be found among the groups. There was only a strong negative correlation between GCF IL-6 levels and GI scores in the RA group. CONCLUSIONS: In the patients with RA, despite increased local tissue destruction potential due to autoimmunity and higher PI levels than in the AP patients, our findings suggest that medication including corticosteroid and non-steroidal anti-inflammatory drugs may decrease gingival inflammation, but the synthesis and degradation of IL-6 in gingival tissue of RA patients may be different. To our knowledge, this study is the first report determining GCF IL-6 levels in RA patients.
10728744 Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arth 2000 Mar OBJECTIVE: To examine the bone mineral density (BMD), frequency of osteoporosis, and risk factors for BMD reduction in a representative population of female rheumatoid arthritis (RA) patients ages 20-70 years. METHODS: BMD in the femoral neck, total hip, and spine L2-4 (anterior-posterior view) was measured in 394 RA patients recruited from a validated county RA register (completeness 85%) comprising 721 women ages 20-70 years. BMD was measured with dual-energy x-ray absorptiometry, and age-specific values were compared with pooled values from a European/US population of healthy subjects free from earlier fractures, chronic diseases, and medications influencing bone metabolism. A multiple linear regression model was used to determine individual predictors of BMD. RESULTS: No statistically significant differences were found in demographic, disease activity, disease severity, or health status parameters between the RA register patients in whom BMD was measured and the remaining register patients. Femoral neck BMD was significantly reduced by 4.2% in the age group 50-59 years, and by 5.0% in those ages 60-70 years. For BMD in the total hip, the significant reductions were 3.7%, 6.0%, and 8.5% in the age groups 40-49 years, 50-59 years, and 60-70 years, respectively. No significant reduction in spine L2-4 BMD was found. A 2-fold increased frequency of osteoporosis was observed in all 4 age groups of RA patients compared with the reference population, ranging from 0% to 28.6% in the femoral neck, 0% to 29.9% in the total hip, and 1.8% to 31.5% in the spine. Predictors of reduced BMD were as follows: at the femoral neck, older age, low body weight, current use of corticosteroids, greater physical disability (as measured by the modified Health Assessment Questionnaire [M-HAQ]), and presence of rheumatoid factor; at the total hip, older age, low weight, current use of corticosteroids, and higher M-HAQ disability score; and at the lumbar spine, older age, low weight, and current use of corticosteroids. CONCLUSION: Register-based prevalence data on BMD reduction in female RA patients ages 20-70 years are presented for the first time in this report, which demonstrates a 2-fold increase in osteoporosis in this representative population.
11535347 Functional and biomechanical assessment of the normal and rheumatoid hand. 2001 Oct OBJECTIVE: To assess hand function in accordance with its accepted definition and to compare the results of three different assessment techniques. DESIGN: A clinical-type assessment was used together with measurement of pinch grip and three-dimensional biomechanical trials. BACKGROUND: Traditional clinical assessment may not relate to a patient's actual hand function. If hand function is defined as "the ability to use the hand in daily activities" then it is more appropriate to measure the forces available for performing everyday tasks using biomechanical tests. METHODS: Eight female patients with rheumatoid arthritis and eight control subjects were recruited for the study. Volunteers underwent a clinical-type assessment using a six-task activity board. Lateral pinch grip of both hands was measured using a custom-built transducer. Biomechanical trials were conducted using a 6 degree-of-freedom transducer and 6-camera motion analysis. RESULTS: Functional differences between the two subject groups were apparent using all three methods of assessment. Pinch strength correlated well with the biomechanical trial data but results from the clinical-type assessment provided only a weak correlation. CONCLUSIONS: Clinical-type assessments do not give an accurate measure of hand function. Pinch strength measurements can provide a cost-effective alternative to full biomechanical analysis. RELEVANCE: Traditional functional assessment uses measurements of grip or pinch strength and range of motion together with a subjective assessment of activities of daily living. This study demonstrates that pinch strength measurements can provide an accurate measure of hand function. The results from activity-board trials do not reflect hand ability and are of limited use for hand evaluation.
9822786 Minocycline-induced cutaneous pigmentation. 1998 Oct BACKGROUND: Minocycline-induced cutaneous pigmentation is an adverse effect that may be more common than is generally realized. It is usually reported in patients undergoing chronic minocycline therapy for acne vulgaris. OBJECTIVE: The case of a 69-year-old woman taking minocycline for rheumatoid arthritis is presented, and its differential diagnosis discussed in order to characterize the clinical features of minocycline-induced cutaneous pigmentation. CONCLUSION: Patients undergoing minocycline therapy for rheumatoid arthritis may develop bluish-grey pigmentation over the legs and forearms. Cutaneous pigmentation is a well recognized adverse effect of minocycline therapy that is usually reported in young patients on chronic therapy for acne vulgaris. However, the antiinflammatory properties of minocycline have also made it useful in the management of various inflammatory conditions such as rheumatoid arthritis.1 We report the case of a 69-year-old woman who developed progressive cutaneous pigmentation, affecting mainly the legs, approximately 3 months after beginning minocycline therapy for rheumatoid arthritis.
11197306 Association of Fc gamma receptor IIIB, but not of Fc gamma receptor IIA and IIIA polymorph 1999 Sep Human Fc gamma receptor (Fc gamma R) genes form a clustered gene family on chromosome 1q21-24. Although the association of Fc gamma R polymorphisms with systemic lupus erythematosus (SLE) has been extensively studied, the results are often contradictory. In this study, Fc gamma RIIA-131H/R, Fc gamma RIIIA-176F/V and Fc gamma RIIIB-NA1/2 genotypes were determined in the Japanese patients with SLE (n = 81) or rheumatoid arthritis (RA, n = 115) as well as in healthy individuals (n = 217), and possible association with the disease was tested using case-control analysis. Unlike in other populations, significant difference was not observed in the frequencies of Fc gamma RIIA and Fc gamma RIIIA genotypes between patients with SLE and healthy individuals. However, significant difference was detected in the frequencies of Fc gamma RIIIB genotypes between SLE and healthy individuals (P = 0.008). The odds ratio [OR] of the Fc gamma RIIIB-NA2/NA2 homozygotes for the development of SLE was 2.52 (95% confidence interval [CI]: 1.33-4.79). Among the patients with SLE, individuals with NA2/2 were significantly more likely to have lupus nephritis (P = 0.007). No association was observed between any of the Fc gamma R polymorphisms and RA. Significant linkage disequilibrium was detected between Fc gamma RIIIA and IIIB, but neither between IIA and IIIA, nor between IIA and IIIB. These observations may underscore the relevance of defective immune complex handling in the pathogenesis of SLE, or may suggest the presence of primarily associated gene(s) in linkage disequilibrium with Fc gamma R genes.
9384286 Interleukin-4 inhibits secretion of interleukin-1beta in the response of human cells to my 1997 Nov Cellular activation induced by Mycobacterium bovis bacillus Calmette-Guérin (BCG) and heat shock proteins (HSP) leads to the production of proinflammatory cytokines such as interleukin-1beta (IL-1beta) and IL-6. In this study, we found that IL-4 significantly suppressed IL-1beta secretion induced by BCG and the 70- and 65-kDa HSP. When exogenous recombinant human IL-4 was added to human mononuclear cells, a dose- and time-related inhibition of the 70-kDa HSP- and BCG-induced IL-1beta secretion was observed. IL-1beta secretion was maximally inhibited at 24 h of culture, and this inhibitory effect was sustained at a later time point of culture (120 h). In addition, IL-2, another T-cell-derived cytokine acting on monocytes, had no effect on IL-1beta secretion induced by either BCG or the 70-kDa HSP, indicating that in these experiments not all cytokines could immunoregulate IL-1beta secretion. This inhibitory effect was not due to a cytotoxic effect of IL-4, since the viabilities of human mononuclear cells were comparable in the presence and absence of IL-4. IL-4 was also able to inhibit the secretion of IL-1beta by mycobacterium-stimulated cells from three rheumatoid arthritis patients. This inhibitory effect of IL-4 was reversed with a blocking anti-IL-4 antibody. Finally, IL-4 inhibited IL-6 secretion by mycobacterium-activated human cells. These results suggest that IL-4 may be important in the regulation of the immune response to mycobacterial antigens.
9189054 Long-term follow-up of 453 rheumatoid arthritis patients treated with methotrexate: an ope 1997 May A total of 453 rheumatoid arthritis (RA) patients were followed up for 35.2 +/- 27.9 months (range 3-106). The clinical parameters decreased significantly after 6 months. Twenty-eight patients were in remission (6.4%). Rheumatoid factor (RF) positivity was less common in the group of patients in remission, with a higher frequency of visits and methotrexate (MTX) onset after 65 yr. There was a significant degradation of radiographic lesions (n = 60). A total of 101 patients (23.1%) stopped MTX, for toxicity (n = 61) and failure (n = 20). The onset of MTX after 65 yr, a low number of visits and the occurrence of side-effects were predictive of MTX withdrawal. A total of 259 patients (59.3%) had side-effects. A Ritchie's index < or = 10, a lower polymorphonuclear cell count and the absence of RF were predictive of side-effects. The probability of being on MTX at 5 yr was 73%. This study confirms the high efficacy of MTX in RA.