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ID PMID Title PublicationDate abstract
8990964 Exercise in the prevention and treatment of chronic disorders. 1996 Nov The Defense Women's Health Research Initiative commissioned a review of the literature of women's health issues. This was performed and published by the Institute of Medicine. In this publication it was noted that health promotion and disease prevention in women should be an area of high priority for military medicine. This article details some of the ways in which exercise may make substantial contributions to this goal. The available evidence indicates that there is an inverse association between physical activity and a variety of chronic diseases. Moreover, physical activity appears to influence psychological well-being. Aerobic exercise is the mode most frequently studied, and appears to confer positive changes, but other forms of exercise may prove to be equally beneficial. However, the appropriate duration, intensity, and frequency of the exercise have not been determined for any of these chronic health problems and must be considered before global recommendations can be offered. Efforts to promote physical activity within the community, schools, and homes must be initiated to achieve the goals set forth in Healthy People 2000, so the health of our women can improve. Future studies will be required to identify mechanisms whereby physical activity confers benefit.
8013714 Lamellar keratoplasty in the management of inflammatory corneal ulceration and perforation 1994 Corneal ulceration and perforation may occur in the course of several systemic and ocular inflammatory conditions. These serious complications may respond to systemic immunosuppression and conjunctival surgery, but tectonic keratoplasty is sometimes required. We report on 10 cases of corneal ulceration (of which 8 suffered perforation) in patients with rheumatoid arthritis, Stevens-Johnson syndrome and Mooren's ulceration which were treated by lamellar keratoplasty. Our microsurgical technique for lamellar keratoplasty benefited from the use of viscoelastic agents, cyanoacrylate adhesive and an adjustable stepped diamond knife. These recent advances have made this procedure as easy to perform as a penetrating keratoplasty. Lamellar keratoplasty virtually eliminates the risk of graft rejection and reduces the risk of perforation in the event of a subsequent exacerbation of the melting process. Surgery preserved the globe in all 10 cases, and the pre-operative visual acuity was maintained or improved in all but 1 case. Six patients achieved a visual acuity of 6/60 or better. Concomitant systemic immunosuppression was used in 6 cases and a subsequent penetrating keratoplasty performed in 3 cases. Lamellar keratoplasty provides a valuable method of preserving the integrity of the globe and maintaining useful vision in these difficult cases.
8258726 Engraftment of human synovium into severe combined immune deficient mice. Migration of hum 1993 Dec 15 To determine the feasibility of using the C.B-17 scid/scid (severe combined immune deficient, SCID) mouse as a recipient of human synovial xenografts, we have engrafted human synovium under the renal capsule of SCID mice, and determined synovial graft survival and histologic characteristics 4 to 7 wk after tissue implantation. Both normal and inflammatory synovial tissue grew well in SCID mice and maintained histologic and phenotypic components of the fresh synovial tissue before implantation. However, the number of T cells in synovial grafts decreased after implantation. To determine whether leukocytes could migrate to human synovial xenografts, either allogenic or autologous PBMC were injected in the peritoneum of SCID mice bearing synovial xenografts. We found that 7 days after i.p. injection of autologous or allogeneic PBMC, injected T cells had selectively migrated to human synovial grafts and to SCID mouse lymph nodes. Our data demonstrate that normal and inflammatory human synovial tissues will grow in SCID mice and serve as recipients for autologous and allogenic peripheral blood human T cells injected i.p. into engrafted mice.
1622417 Connective tissue activation. XXXV. Detection of connective tissue activating peptide-III 1992 Jul OBJECTIVE: To determine whether extracts of unincubated osteoarthritis (OA) and rheumatoid arthritis (RA) synovial tissue contain connective tissue activating peptide-III (CTAP-III) isoforms and prostaglandin E2 (PGE2), and whether such extracts have growth-promoting activity, and to determine whether binary combinations of CTAP-III with other cytokines reported to be present in synovial tissue lead to synergistic, additive, or inhibitory effects on growth. METHODS: Acid-ethanol extracts of human synovium were examined for growth-promoting activity by measuring formation of 14C-glycosaminoglycan (14C-GAG) and 3H-DNA in synovial cell cultures; PGE2 was measured by enzyme immunoassay, and CTAP-III isoforms were identified by Western blotting of extracted proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Growth-promoting activity of CTAP-III and other cytokines was tested in synovial cultures treated with the agonists singly and in binary combination, by measuring changes in synthesis of 14C-GAG and 3H-DNA. RESULTS: Platelet-derived CTAP-III and a cleavage isoform with the electrophoretic mobility of CTAP-III-des 1-15/neutrophil-activating peptide-2 (NAP-2) and PGE2 were found in biologically active extracts of synovial samples from patients with RA and OA. Five growth factors (recombinant epidermal growth factor [rEGF], recombinant interleukin-1 beta [rIL-1 beta], basic fibroblast growth factor [bFGF], PGE1, and PGE2) in binary combination with CTAP-III showed synergism in stimulating GAG synthesis; two (recombinant platelet-derived growth factor type BB [rPDGE-BB] and recombinant transforming growth factor beta [rTGF beta]) had an additive effect. In combination with CTAP-III, rEGF and rPDGF-BB had a synergistic effect in promoting DNA synthesis, rTGF beta and rbFGF had an additive effect, and rIL-1 beta, PGE1, and PGE2 were antagonistic. CONCLUSIONS: The results suggest that, in addition to endogenous factors, CTAP-III and other platelet-derived cytokines may play roles in regulating synovial cell metabolism in RA and OA, and that combinations of growth factors may be more significant than single agents in amplification or suppression of important cell functions.
7689976 Generation of substance P carbamate in neutral aqueous solution. Relevance to inflammatory 1993 Aug 30 High-field proton (1H) nuclear magnetic resonance (NMR) spectroscopy has been employed to evaluate the formation of substance P carbamate in aqueous solution. Equilibration of substance P with physiologically relevant concentrations of bicarbonate (2.50 x 10(-2) mol.dm-3) at pH 7.00 generated a new multiplet signal centred at 4.13 ppm in its NMR spectrum, characteristic of the alpha-proton of peptide carbamate species. High-field 1H NMR spectroscopy also demonstrated that the model dipeptide, Arg-Gly, formed a carbamate in neutral aqueous solutions containing 2.50 x 10(-2) mol.dm-3 HCO3-. The physiological significance of these results is discussed in view of the central roles of vasoactive neuropeptides in human joint diseases and the hypercapnic environment of the inflamed rheumatoid joint.
1418017 Antibodies in rheumatoid synovial fluids bind to a restricted series of protein antigens i 1992 Sep OBJECTIVE: By searching the synovial fluid of patients with rheumatoid arthritis (RA) for antibodies that react to protein antigens in synovial tissue, we sought to identify putative antigens present in RA synovial tissue that might drive the pathologic immune response believed to be responsible for the joint inflammation. METHODS: Synovial tissue was homogenized in sodium dodecyl sulfate polyacrylamide gel buffer, electrophoresed, and analyzed by immunoblotting. RESULTS: Antibodies from synovial fluids of patients with RA bound to several proteins in rheumatoid synovial tissues, including a series of low (27.5-, 29-, and 30-kd), middle (43- and 53-kd), and high (140-, 164-, and 182-kd) molecular weight proteins. Most of these antigens were also detected in normal synovial tissue, and the high molecular weight proteins were also present in normal dermal, muscle, and liver tissues. The low and middle molecular weight proteins were detected in some, but not all, of the other normal tissues and in Jurkat cell lysates. Antibodies to the low and high series of proteins were present in all rheumatoid synovial fluids tested, but were generally absent from synovial fluids from patients with other arthritic diseases. CONCLUSION: These results show that antibodies in synovial fluids consistently react to several proteins in RA and normal synovial tissues. These antigens are possibly the same antigens provoking the T cell response in RA; therefore, understanding the mechanism of the immune response against these proteins will likely lead to important insight into the etiology of RA.
1414042 [AA-amyloidosis in inflammatory rheumatic diseases. A report of clinical experiences]. 1992 Jul A review of the literature on rheumatic diseases with secondary amyloidosis and our diagnostic and therapeutic experiences in 33 own cases were reported. The place of subcutaneous fat biopsy in the diagnosis of secondary amyloidosis was shown included our own results and the corresponding literature. We saw amyloidosis type AA mostly in patients with high disease activity and progressive stage. There is no sure relationship to the duration of the disease. The renal involvement is clinical most significantly and also most frequently. The renal amyloidosis type AA can be influenced therapeutically however only in normal or unimportant restricted renal function. The therapeutic success is not depended on the choice of the long acting antirheumatic drug. The results were discussed in respect with the current literature.
10138701 A decision analysis model in the evaluation of NSAIDs in a managed care setting: a case st 1994 Nov The objective of this study is to utilize a clinical trial based on a decision-analysis model to assess the economic benefit of a lower incidence of gastrointestinal lesions in elderly patients with osteoarthritis receiving nabumetone therapy compared with ibuprofen alone and in combination with misoprostol. An arthritic population of an HMO (> 60 yr of age) was applied to the decision analysis based on the HMO's nonsteroidal anti-inflammatory drug and antiulcer usage and acquisition costs. Results indicate the potential for a decrease in overall medical resource utilization through the use of nabumetone in elderly patients with rheumatoid and osteoarthritis. Based on this information, nabumetone has been added to the HMO formulary as a second-tier agent with a repeat of the analysis scheduled in one year to verify the economic benefits and modify prescribing guidelines accordingly.
8856611 A phase I/II open label study of the safety and efficacy of an anti-ICAM-1 (intercellular 1996 Aug OBJECTIVE: Previous work suggested the potential utility of therapy with a monoclonal antibody (Mab) to intercellular adhesion molecule-1 (ICAM-1; CD54) in patients with longstanding rheumatoid arthritis (RA). Immunomodulatory interventions, including adhesion receptor directed therapies, might be expected to have greater efficacy in patients with less established or less aggressive disease. Therefore, we assessed the efficacy and safety of an anti-ICAM-1 Mab in patients with early RA. METHODS: An open label study of a 5 day infusion of an anti-ICAM-1 Mab in 10 patients with early or indolent RA was conducted. These patients were defined as having previously used < or = 1 disease modifying antirheumatic drug. RESULTS: Based on composite criteria, 7/10 patients had a marked or moderate response to therapy at one month of followup. Clinical benefit was sustained through 2 months for 5/10 patients and 3/10 had extended benefit (11, 8, and > 7 months). Clinical benefit was more likely to be obtained in patients with subacute onset of disease than in those with a fulminant onset. CONCLUSION: A single course of therapy with an anti-ICAM-1 Mab was associated with clinical improvement in a group of patients with early or indolent RA to an extent apparently greater than previously observed in patients with longstanding, aggressive RA.
1386297 Analysis of T cell receptors in rheumatoid arthritis: the increased expression of HLA-DR a 1992 Aug The phenotypic characteristics of peripheral blood T cells, isolated from 37 rheumatoid arthritis (RA) patients and 17 healthy controls were determined with special emphasis on gamma delta+ T cells and CD4-CD8- alpha beta+ T cells. Two- and three-colour automated flow cytometry analyses were performed using a panel of MoAbs directed against differentiation antigens and T cell receptor molecules. The results demonstrated: (i) no significant difference between the percentages of CD4-CD8- alpha beta+ T cells in patients and controls; (ii) a significant decrease of the gamma delta+ T cell level in the peripheral blood of RA patients relative to controls; (iii) phenotypic abnormalities of circulating gamma delta+ T cells in RA patients suggestive of an activation status in vivo. These abnormalities included a significant reduction in the density of the T cell differentiation antigen CD3 and an increase in the expression of HLA-DR antigen. The level of circulating HLA-DR+/gamma delta+ T cells was significantly higher in patients with active disease. HLA-DR+/gamma delta+ T cells were also present in the synovial fluid obtained from three patients with an active disease. In addition, preliminary experiments showed that the activated gamma delta+ T cells were predominantly V delta 1. Taken together, these data support the involvement of gamma delta+ T cells in the pathogenesis of RA.
1542871 DPB1 polymorphism in rheumatoid arthritis: evidence of an association with allele DPB1 040 1992 Jan HLA-DP polymorphism was examined in 71 rheumatoid arthritis patients and 148 controls, using dot-blot analysis with 14 synthetic oligonucleotide probes specific for the variable region of the DPB1 second exon. The DPB1 0401 allele was found to be significantly more frequent in RA patients than in controls (77.46% vs 55.40%, p less than 0.002, pc less than 0.03, relative risk value: 2.74). An association between DPB1 0401 and seropositivity for rhumatoid factors was also observed: 44 of the 55 seropositive RA patients were DPB1 0401 (p less than 0.001). Analyzing the HLA DPB1 alleles frequencies in 57 HLA-DR-typed RA patients did not show any linkage between the DPB1 0401 and the DR4 specificities. Furthermore, the DPB1 0401 homozygous frequency was increased in DR4-negative RA patients. Our findings suggest an independent role of the DPB1 0401 allele in the genetic susceptibility to RA.
9045528 [Gastroduodenal tolerance and clinical effectiveness of therapy with lonazolac-calcium in 1996 Most undesired side effects in therapy with non-steroidal antiinflammatory drugs (NSAID) mainly effect the gastric and duodenal mucosa. The radioimmunological determination of pepsinogen A and C (pepsinogen group I and II) is qualified for inclusion of the functional and morphologic state of the gastroduodenal mucosa. By determination of the pepsinogens group A and C the influence and the gastroduodenal compatibility of the non-steroidal antiinflammatory drug lonazolac Ca (LCa) [Irritren] were examined in a dosage of 600 mg/d during a 2-weeks therapy. 31 patients with various painful rheumatic diseases and 10 healthy probands as a control group were examined. The results show that the treatment with LCa did not significantly effect mean and median of pepsinogen A- and -C levels in serum. Only in 3.7% of the cases a contemporary increase of pepsinogen A and C occurred, which could be estimated as a beginning superficial gastritis. In addition the beneficial clinical efficacy of LCa was documented by a significant decrease of a tripartite pain score from 2.1 to 1.4. The results point to a very good proportion of clinical efficacy and gastroduodenal side-effects of LCa.
8406274 [Mofebutazone--evaluation of possible interaction with glibenclamide]. 1993 Aug 20 METHODS: In an open clinical trial involving 20 patients, the question was investigated as to whether the administration of 3 x 300 mg mofebutazone daily resulted in any clinically relevant changes in blood sugar levels in diabetics treated with glibenclamide. RESULTS: Fluctuations observed, both in mean and individual values, were within the range of those regularly seen in diabetics. This was shown by both weekly measurements and a comparison of daily profiles. A comparison of the daily blood sugar profile prior to and after three weeks of mofebutazone, revealed the following mean figures (+/- STD): prior to mofebutazone 12.30 hours 155.5 (+/- 23.2) mg/dl, 16.30 hours 147.2 (+/- 22.0) mg/dl; after 3 weeks of mofebutazone: 12.30 hours 162.7 (+/- 20.0) mg/dl, and 16.30 hours 151.7 (+/- 17.7) mg/dl. No side effects occurred, and no patient left the study prematurely. The laboratory parameters also studied showed no remarkable changes, either in mean values or in individual figures.
1616355 Determination of cytokines in synovial fluids: correlation with diagnosis and histomorphol 1992 Jun In a study aimed at correlating cytokine levels in synovial fluid with the pathology of rheumatoid arthritis (RA), tumour necrosis factor alpha, interleukin 1 beta and interferon gamma were immunoassayed in 27 patients with RA, 16 patients with other arthritides, 23 with osteoarthritis, 13 patients with trauma, and 18 patients at necropsy without inflammatory disease and not known to have had joint disease (median 27 hours after death). The results for interleukin 1 beta clearly show higher cytokine levels in patients with RA and other arthritides than in patients with osteoarthritis, trauma, or the patients at necropsy. Interferon gamma levels in patients with osteoarthritis and the patients at necropsy, however, were significantly greater than in patients with RA, and tumour necrosis factor alpha levels were also greater in the patients at necropsy compared with patients with RA. This study also correlated histomorphological patterns of synovitis and indicators of local inflammatory activity with synovial fluid cytokine levels, showing, for example, a positive association of interleukin 1 beta titre and a negative association of interferon gamma titre with ulcerogranulomatous synovitis (itself associated with RA). Taken together, these results extend and strengthen data suggesting a possible part played by increased synovial fluid levels of interleukin 1 beta in joint destruction in RA, but provide no evidence for increases in levels of tumour necrosis factor alpha or interferon gamma affecting the disease pathology.
8668877 Multiple-outcome meta-analysis of clinical trials. 1996 Mar 15 When several clinical trials report multiple outcomes, meta-analyses ordinarily analyse each outcome separately. Instead, by applying generalized-least-squares (GLS) regression, Raudenbush et al. showed how to analyse the multiple outcomes jointly in a single model. A variant of their GLS approach, discussed here, can incorporate correlations among the outcomes within treatment groups and thus provide more accurate estimates. Also, it facilitates adjustment for covariates. In our approach, each study need not report all outcomes nor evaluate all treatments. For example, a meta-analysis may evaluate two or more treatments (one 'treatment' may be a control) and include all randomized controlled trials that report on any subset (of one or more) of the treatments of interest. The analysis omits other treatments that these trials evaluated but that are not of interest to the meta-analyst. In the proposed fixed-effects GLS regression model, study-level and treatment-arm-level covariates may be predictors of one or more of the outcomes. An analysis of rheumatoid arthritis data from trials of second-line drug treatments (used after initial standard therapies prove unsatisfactory for a patient) motivates and applies the method. Data from 44 randomized controlled trials were used to evaluate the effectiveness of injectable gold and auranofin on the three outcomes tender joint count, grip strength, and erythrocyte sedimentation rate. The covariates in the regression model were quality and duration of trial and baseline measures of the patients' disease severity and disease activity in each trial. The meta-analysis found that gold was significantly more effective than auranofin on all three treatment outcomes. For all estimated coefficients, the multiple-outcomes model produced moderate changes in their values and slightly smaller standard errors, to the three separate outcome models.
8485910 Synovial fluid antigen-presenting cell function in rheumatoid arthritis. 1993 May We have previously demonstrated enhanced synovial fluid (SF) antigen-presenting cell (APC) function in inflammatory arthritis patients selected on the basis of marked SF mononuclear cell (MNC) responsiveness to reactive arthritis-associated bacteria (Clin Exp Immunol 1990; 79:189-94). In this study we have assessed whether similarly enhanced synovial APC function is present in other inflammatory arthritis patients by using two assay systems to study 18 rheumatoid arthritis patients whose MNC responsiveness had not been determined in advance. We demonstrate that rheumatoid SF APC are much more potent than peripheral blood (PB) APC in stimulating the responses of autologous PB T cells to a range of recall antigens. In addition, SF APC are shown to be efficient stimulators of the antigen-specific responses of MHC-compatible, cloned T cells. Enhanced synovial APC function is thus likely to be a general feature of inflammatory arthritis and may play an important role in its pathogenesis.
7533685 Structural characterization of peptides that bind synovial fluid antibodies from RA patien 1995 Apr Phage epitope library technology has become a powerful tool for identifying determinants recognized by homogenous antibodies. Screening of human sera or fluids with random peptide phage libraries is a novel approach that can dissect common features at the amino acid level in individuals infected by the same etiological agent(s). In this study we have analyzed the specificity of antibodies in synovial fluids (SF) obtained from patients with rheumatoid arthritis (RA). We found that a high proportion of the peptides binding SF antibodies differ from those binding serum antibodies, suggesting that synovial B cells are expanded as a result of local antigen stimulation. When all the selected phages (enriched library) that bind the SF antibodies from a seropositive RA patient were further screened by the use of different SF antibodies with or without rheumatoid factor activity, we identified common SF antibody specificities (IRRSETPRA, RRRVRNSDT, PVSSTRGNM). Antibodies against these common specificities are also found in SF from other RA patients. Taken together, the present results open the possibility of defining the entire set of synovium antibody specificities and also common SF specificities between RA patients.
7635977 Somatic mutation and CDR3 lengths of immunoglobulin kappa light chains expressed in patien 1995 Aug Immunoglobulin secretion by plasma cells infiltrating synovial membranes is a prominent feature of RA. Previous analyses of a cDNA library generated from synovium of RA patient BC revealed immunoglobulin kappa light chain transcripts with extensive somatic mutation, frequent N region addition, and unexpected variation in the lengths of CDR3 regions which form the center of the antigen binding site. To determine if these characteristics are present in other individuals, we performed reverse transcription-polymerase chain reaction amplification and sequenced > or = 10 V kappa-containing amplicons from nine tissue samples: synovia of three individuals with long-standing RA (including patient BC), PBLs of two of these individuals, and PBLs or splenocytes of four normal individuals. Increased levels of somatic mutation in PBLs appeared to correlate with increased age, which may reflect accumulation of circulating memory cells and/or decreased bone marrow production of naive B lymphocytes. Two of three RA synovial samples and both RA PBL samples exhibited increased proportions of clones with unusual CDR3 lengths. Enrichment for these antibody binding sites could be due to abnormal regulation of the emerging repertoire or to selection for B lymphocytes bearing antibodies of unusual specificity, and may play a role in the pathogenesis of RA.
1622416 A controlled study of the prevalence of cognitive dysfunction in randomly selected patient 1992 Jul OBJECTIVE: To investigate the prevalence of cognitive dysfunction in randomly selected patients with systemic lupus erythematosus (SLE). METHODS: Randomly selected, ambulatory patients with SLE (n = 49) or with rheumatoid arthritis (RA) (n = 40) completed neuropsychological tests. These included Associate Learning, Switching Attention, Continuous Performance, Associate Recall, Hand-Eye Coordination, Pattern Comparison, Pattern Memory, the Stroop Color and Word Test, and the Symptoms Checklist-90R. Results were evaluated by multiple linear regression analysis. RESULTS: SLE patients had poorer performance than RA patients on the test of attention (P = 0.002) and tests of visuospatial ability (P = 0.03) and P = 0.04), independent of age, education, or steroid use. The conservative level of statistical significance, adjusting for multiple comparisons, was 0.005. SLE patients reported more symptoms of cognitive difficulty. CONCLUSION: Cognitive dysfunction is common in ambulatory SLE patients as measured by standardized tests and is a cause of distress and impaired functioning. Self-reported cognitive difficulty appears to correlate with objective performance.
8717105 Quantitative photometrical assessment of iron deposits in synovial membranes in different 1996 We investigated 86 synovial membranes from patients suffering either from rheumatoid arthritis (RA) or osteoarthritis (OA). Iron deposits in the synovial membrane were stained by the Prussian blue reaction, and the amount of stained iron was quantitatively assessed by microscope photometry. We found a statistically significant increase in iron deposits in the synovial membrane of RA patients when compared to OA patients. The amount of iron deposits correlated with the histological subtype of synovitis, those presenting with more exudative and proliferative features showing greater amounts of iron deposits. We also observed an inverse correlation between the haemoglobin concentration and erythrocytes in the serum and the amount of iron in the synovial membrane. From our data we concluded that iron deposits in the synovial membrane can contribute by several mechanisms, including activation of oxygen radicals, to the chronic inflammatory reaction in RA synovitis.