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ID PMID Title PublicationDate abstract
8877918 Reliability and validity of a submaximal treadmill test to estimate aerobic capacity in wo 1996 Sep OBJECTIVE: To assess reliability and validity of a single stage submaximal treadmill test to estimate aerobic capacity in women with rheumatic disease. METHODS: 30 women with rheumatic disease (rheumatoid arthritis = 19; systemic lupus erythematosus = 5; mixed connective tissue disease = 2; psoriatic arthritis = 4) performed a submaximal exercise test at a self-selected walking speed between 3.2 and 7.2 km/h on 2 occasions, and one subjective maximal exercise test with respiratory gas analysis. Estimation of aerobic capacity from the submaximal test was obtained from a regression equation using age, walking speed, and exercise heart rate. Aerobic capacity from maximal testing was determined by observed peak oxygen consumption and by estimation using test duration in a regression equation. Correlation and regression analyses were performed to assess test-retest reliability and criterion validity of the submaximal method. RESULTS: Intraclass correlation coefficient for the submaximal test was ICC = 0.97 (95% CI = 0.94-0.99). Comparison of results from the submaximal test to the maximal test using both observation and estimation methods to determine aerobic capacity ranged from r = 0.77 to 0.80, with R2 of 0.59 to 0.65. The submaximal regression model, originally developed and validated in a sample of persons without rheumatic disease, was significantly different in this sample of women with rheumatic disease. CONCLUSION: This single stage treadmill test, suitable for use in clinical and community settings, appears to be a reliable and valid method to safely assess aerobic capacity in women with rheumatic disease. There was a tendency for the submaximal method to overestimate aerobic capacity in this sample.
8233191 New Zealand general practitioner referral patterns. 1993 Nov 10 AIM: The aim of this study was to describe the referral patterns of general practitioners in New Zealand, for a defined list of medical conditions. METHODS: A postal questionnaire was sent to a random sample of 200 general practitioners, selected from the Medical Council of New Zealand list. Responses were made on five point scales to indicate general practitioners' views on the appropriateness of referral. For each medical condition, derived from An Educational Guide for General Practice, respondents also indicated favoured agencies for referral. Cluster analysis was used on an SPSSX dataset. RESULTS: A response rate of 87% (91.5% of eligible contacts) was achieved. The conditions for which referrals were least often made included mild hypertension, rheumatoid arthritis not requiring second line therapy, hypothyroidism, and obesity. Referral was common for rheumatoid arthritis requiring second line therapy, insulin dependent diabetes mellitus, altered bowel habit with rectal bleeding, multiple sclerosis, and postmenopausal bleeding. Seventy seven different referral agencies were indicated by respondents: the most common was the general physician (13% of all agencies indicated). CONCLUSIONS: Although there are a large number of conditions which are routinely managed only in general practice, general practitioners need to be able to refer patients to other health carers, even if only occasionally. There is a high degree of consensus as to the conditions for which referral is usually appropriate. They tend to be conditions requiring well defined investigation, treatment or management procedures which are commonly provided by centralised secondary or tertiary institutions.
18475526 Enhanced levels of leukotriene B(4) in synovial fluid in Lyme disease. 1993 The purpose of this study was to evaluate the potential role of LTB(4) and cysteinyl leukotrienes in Lyme disease (LD). Therefore, a total number of 34 patients divided into four groups was studied. The patients were classified as having Lyme arthritis (n = 7) or Lyme meningitis (n = 10), and as control groups patients with a noninflammatory arthropathy (NIA) (n = 7) and healthy subjects (n = 10). LTB(4) as well as LTC(4) secretion from stimulated polymorphonuclear leukocytes (PMNL) from all groups of patients showed no statistical differences. LTB(4) levels in synovial fluid were significantly increased in patients with Lyme arthritis (median 142 ng/ml, range 88-296) when compared to the control subjects with NIA (median 46 ng/ml, range 28-72) (p < 0.05). No statistical difference of urinary LTE(4) levels between all the different groups of patients was observed. These results show that cysteinyl leukotrienes do not play an important role in the pathogenesis of LD. In contrast to previous findings in rheumatoid arthritis, LTB(4) production from stimulated PMNL was not found to be increased in LD. However, the significantly elevated levels of LTB(4) in synovial fluid of patients with Lyme arthritis underline the involvement of LTB(4) in the pathogenesis of this disease.
7869300 CGP 47969A: effect on collagen induced arthritis in DBA/1 mice. 1994 Nov OBJECTIVE: CGP 47969A is a novel and potent inhibitor of cytokine biosynthesis in human and murine monocytic cells. The effect of CGP 47969A on collagen induced arthritis (CIA) in DBA/1 mice was investigated and compared to that of prednisolone. METHODS: CIA was induced by intradermal injection of type II collagen in CFA at Day 0. CGP 47969A was applied orally, 5 times/week, starting at Day 15 after immunization. Arthritic signs were recorded 3 times/week for clinical scoring and radiographic analysis was performed at the end of the experiment at Day 60. Serum amyloid P (SAP) and anticollagen antibody titers were determined by ELISA at Day 60. RESULTS: CGP 47969A dose dependently reduced the incidence of arthritis from 93% in the positive control group to 60, 40, 30 and 10% at doses of 1, 5, 25 and 60 mg/kg/day, respectively. At a dose of 120 mg/kg, CGP 47969A totally prevented the occurrence of arthritis (ED50 between 1 and 5 mg/kg). Prednisolone at 3 and 30 mg/kg reduced the arthritis incidence to 70 and 30%, respectively. CGP 47969A dose dependently inhibited the joint destruction, as measured by radiographic scoring and its potency was comparable to that of prednisolone. The elevated serum levels of the positive acute phase protein SAP in arthritic animals were completely normalized by CGP 47969A at a dose of 60 mg/kg, however, neither CGP 47969A nor prednisolone influenced the plasma levels of anticollagen antibodies (IgG). CONCLUSION: Our results demonstrate that CGP 47969A is highly effective in CIA with a potency comparable to that of prednisolone. These promising results justify the expectation that this novel antiarthritic compound now under development might also be effective in the treatment of rheumatoid arthritis in man.
1370358 Monoclonal IgM rheumatoid factors bind IgG at a discontinuous epitope comprised of amino a 1992 Jan 1 A combination of site-directed mutagenesis and exon exchange has been used to further define the structure on IgG recognized by monoclonal IgM rheumatoid factors (RFs) from patients with Waldenstrom macroglobulinemia. Most of these RFs bound IgG1, -2, and -4 but not IgG3. For these RFs, His-435 is a critical residue for binding and replacing it with arginine, the residue present in IgG3, destroys or reduces RF binding. However, additional polymorphic sequences in both the heavy-chain constant-region domains (CH) 2 and 3 are important for RF binding. Among the important residues in CH2 are amino acids 252-254 and 309-311, which are conserved among IgG isotypes and comprise two loops of amino acids on the surface of the domain. Therefore, at least three regions, two from CH2 and one from CH3, contribute significantly to the epitope recognized by the RFs. Although this epitope contains many of the same residues as the staphylococcal protein A binding site on IgG, the binding specificities of staphylococcal protein A and monoclonal RFs are not identical. Sera from patients with rheumatoid arthritis contain antibodies directed not only at this epitope but also at other sites on IgG.
8597882 Auranofin inhibits calcium uptake into opsonized-zymosan-stimulated neutrophils obtained f 1995 Nov In order to study the pharmacological action site of auranofin during the functional suppression of leukocytes, especially neutrophils, we investigated the influence of auranofin on the calcium-45 (45Ca2+) uptake into peripheral blood neutrophils and peritoneal resident macrophages isolated from normal and adjuvant-induced arthritis (AA) rats. Calcium-45 uptake into neutrophils and macrophages obtained from normal and AA rats was increased by stimulation with opsonized-zymosan, while auranofin inhibited the increase in the 45Ca2+ uptake into neutrophils, but not into macrophages. There was a tendency that auranofin more strongly inhibited the increase in the 45Ca2+ uptake into neutrophils obtained from AA rats than normal rats, but no statistically significant difference between them was observed in the inhibitory potency of auranofin. From these results, it is suggested that auranofin would show anti-rheumatic and anti-inflammatory effects by the inhibition of Ca2+ uptake into neutrophils which infiltrate into local lesions during the early and active phases of rheumatoid arthritis.
7684307 Mechanism of joint sparing in a patient with unilateral psoriatic arthritis and a longstan 1993 May The case of a 59-year-old female with a longstanding hemiplegia who developed unilateral psoriatic arthritis and unilateral psoriasis on the non-hemiplegic side only is reported. Investigations showed an erythrocyte sedimentation rate of 58 mm/h, with all classes of rheumatoid factor negative in serum and synovial fluid (SF). An inflammatory infiltrate was demonstrated in both knee joints despite the absence of clinical involvement on the hemiplegic side. In addition, while neurofilament and substance P (SP) immunoreactivity was demonstrated in both synovial specimens, conspicuously less SP was present in the clinically involved synovial membrane. Finally, SF levels of SP and IL1 beta were raised in the clinically involved knee only.
7939417 Rheumatoid-factor-reactive sites on CH2 established by analysis of overlapping peptides of 1994 Oct Polyclonal IgM rheumatoid factors (RF) from ten patients with rheumatoid arthritis (RA) isolated on IgG affinity columns were studied for their reactivity with overlapping 7-mer peptides representative of solvent accessible regions of the CH2 domains of IgG using a pin-ELISA assay. A panel of nine monoclonal RF from RA patients' B cells were studied in parallel. Four peptides SVFLFPP (239-245), KFNWYVD (274-280), NSTYRVVSV (297-305) and VLTVLHQNWL (305-314) reacted with most RF. Glycine substitution showed that tryptophanes at 277 and 313, tyrosine at 278, valines at 279 and 305, and leucine 314 represented important residues for RF reactivity. Assays using monoclonal IgM RF produced from RA synovial B cells or peripheral blood B cells frequently showed a restricted spectrum of reactivity for CH2 epitopes, which often were identical to those binding to polyclonal IgM RF. Combinations of synthetic 7-mer peptides representing RF-reactive CH2 or CH3 epitopes produced as much as 60-90% inhibition of RF binding to IgG when peptides were preincubated with RF in free solution before completion of the reaction of RF with IgG on the ELISA plate.
8896432 Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem 1996 Nov 1 Autologous stem cell transplantation with or without in vitro lymphocyte depletion has been suggested as a new treatment option for severe autoimmune diseases. We describe five patients with autoimmune diseases (CREST syndrome, myasthenia gravis and Hashimoto's thyroiditis, systemic lupus erythematosus, atopic dermatitis, and rheumatoid arthritis) who underwent autologous bone marrow (n = 1) or peripheral blood progenitor cell (n = 4) transplantation with unmanipulated grafts as treatment for the autoimmune disease in one case or as treatment for a malignant disorder with a concomitant autoimmune disorder in four cases. In all patients serological and clinical signs of the autoimmune disease recurred early or persisted. These observations should be regarded as a cautionary note concerning the efficacy of high-dose therapy followed by transplantation of unmanipulated autologous stem cells for treatment of severe autoimmune diseases.
1361318 Complement factor 2 deficiency: a clinical and serological family study. 1992 Nov Inherited complement deficiencies are associated with a variety of connective tissue diseases. A family with inherited deficiency of complement factor 2 (C2) is described in which two family members with homozygous C2 deficiency developed cutaneous vasculitis and sicca syndrome. The other family members had heterozygous C2 deficiency and each member had the HLA-A25, B18, DR2 (w15) haplotype. The mother had seropositive rheumatoid arthritis. Further studies showed the presence of cryoglobulins, antibodies against endothelial cells, and anticardiolipin antibodies.
8653465 Lymphoma in Sjögren's syndrome. From histopathology to molecular pathology. 1996 Mar A number of autoimmune diseases predispose to the development of neoplasia. A particularly well-recognized association is the development of lymphoma in Sjögren's syndrome. Although this risk has been estimated to be 44 times that of the general population, few reliable prognostic indexes exist for individual patients. Recent advances in molecular biology have improved our understanding of Sjögren's syndrome and permitted better characterization of the generalized lymphoproliferation associated with the condition. This article reviews the histopathology of the major and minor salivary gland lesions of Sjögren's syndrome and discusses advances in molecular biology that have permitted more accurate prediction of lymphoma development in this group of patients.
7983653 The polymerase chain reaction detects B cell clonalities in patients with Sjögren's syndr 1994 Aug OBJECTIVE: To investigate the usefulness of the polymerase chain reaction (PCR) to detect B cell clonal expansions in tissues where lymphoproliferative disease was suspected in the course of Sjögren's syndrome (SS). METHODS: Tissue samples from 7 patients with definite (5 cases) or probable (2 cases) SS were subjected to routine histopathologic studies, immunophenotyping, and genotypic analysis, including Southern blotting and PCR amplification of immunoglobulin heavy chain (IgH) variable-diversity-joining (VDJ) region gene rearrangements. RESULTS: Malignant lymphoma was detected in 3 cases, and myoepithelial sialadenitis in the remaining 4. B cell clonal expansion was detected in 7/7 cases by PCR, 5/7 by Southern blotting, and in no case of myoepithelial sialadenitis by kappa/lambda light chain immunophenotyping. CONCLUSION: PCR may represent a quick and powerful tool to detect B cell clonalities in SS. Such information may provide new insights into the pathogenesis of the disease and may improve the clinical approach to the patients.
8755634 Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice. 1996 Jul 15 We have recently demonstrated Fas-mediated apoptosis in the synovium, of patients with rheumatoid arthritis (RA) and suggested that it may be one factor responsible for the regression of RA. To examine whether the induction of apoptosis caused by anti-Fas mAb may play a potential role as a new therapeutic strategy for RA, we investigated the effect of anti-Fas mAb (RK-8) on synovitis in an animal model of RA, the human T cell leukemia virus type I (HTLV-1) tax transgenic mice. We report here that administration of anti-Fas mAb into mice intra-articularly improved the paw swelling and arthritis within 48 h. Immunohistochemical study and in vitro culture studies showed that 35% of synovial fibroblasts, 75% of mononuclear cells, and some of polymorphonuclear leukocytes infiltrating in synovium underwent apoptosis by anti-Fas mAb. In situ nick end labeling analysis and electron microscope analysis clearly showed that many cells in synovium were induced apoptosis by anti-Fas mAb administration. However, local administration of anti-Fas mAb did not produce systemic side effects. Results demonstrated that administration of anti-Fas mAb in arthritic joints of the HTLV-1 tax transgenic mice produced improvement of arthritis. These findings suggest that local administration of anti-Fas mAb may represent a useful therapeutic strategy for proliferative synovitis such as RA.
11856996 Immunoregulation of Proteoglycan-Induced Arthritis in Balb/c Mice. 1996 Jan Immunization of BALB/c mice with a select group of cartilage proteoglycans induces progressive polyarthritis. The pathological mechanisms of proteoglycan-induced arthritis are based on autoimmune reactions developed against the mouse self-proteoglycan. This autoimmune inflammatory animal model, which shows many similarities to human rheumatoid arthritis, has close to 100% incidence in susceptible BALB/c mice and is an excellent in vivo model for testing disease-modifying agents. The aim of this work was to study the regulatory mechanisms which control the autoimmune reactions in proteoglycan-induced arthritis, in association with the release of most important cytokines/mediators (interleukin 1 (IL-1), interleukin-2 [IL-2], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-alpha], and prostaglandin E(2)) which are believed to play key roles in inflammatory events and cartilage degredation. We have found relatively high levels of IL-1 sera and synovial-cell culture supernatants of arthritic animals, whereas IL-1 was not detected in nonarthritic control animals. Serum autoantibody and IL-1 levels seemed to be sensitive indicators of the oncoming inflammatory events in the joints, whereas autoreactive T-cell responses to mouse proteoglycan became evident only after the onset of arthritis. As proteoglycan-specific T-cell responses were mainly restricted to the joint-draining lymph nodes during the arthritic process, it is likely that the autoantigen-driven mechanism of joint inflammation became local and self-sustaining during cartilage degradation. Thus, autoimmune mechanisms seem to be essential in the "organ specificity" of inflammatory reactions, as "arthritogenic" lymphocytes migrate to and accumulate in both the lymphoid organs and the synovium. IL-1 and IL-2 are among the most important mediators in proteoglycan-induced arthritis and are able to influence autoimmune reactions and the migration of lymphocytes to the synovium.
7699656 Fatty acids and antioxidant micronutrients in psoriatic arthritis. 1995 Jan OBJECTIVE: Red blood cell (RBC) fatty acid composition and micronutrient status were investigated in patients with psoriatic arthritis (PsA), with special regard to their relationship to clinical variables. METHODS: RBC fatty acid composition, selenium status--serum selenium and RBC glutathione-peroxidase activity (GSH-Px)--plasma copper, plasma and RBC zinc, plasma vitamins A and E, and RBC thiobarbiturate reactive substances (TBARS) after H2O2 exposure as an index of susceptibility to lipoperoxidation were measured in 25 patients with PsA and in 25 sex and age matched controls. RESULTS: A significant increase in C16:0 (p < 0.01) and in total saturated fatty acids (SFA) (p < 0.05), a significant decrease in C18:2 (p < 0.05), C20:4 (p < 0.001) and omega-6 polyunsaturated fatty acids (PUFA) (p < 0.001), a lower level of serum selenium (p < 0.01) and an increased level of plasma copper (p < 0.05) were observed in patients with PsA in comparison with controls. Significant direct correlations were observed between RBC SFA and erythrocyte sedimentation rate (ESR) (r = 0.445), duration of disease (r = 0.403) and morning stiffness (r = 0.434). CONCLUSION: As in other reports for rheumatoid arthritis (RA), our results support the view that an abnormal fatty acid pattern might be a particular metabolic modification involved or associated with the pathogenesis of rheumatic diseases.
8272708 [Confronted with mono-arthritis: which tests?]. 1993 Dec 7 A monoarthritis may correspond to a localized inflammatory process or to the onset of rheumatoid disease that may later on spread over few or several of the other joints. In this article the different diagnostic and therapeutic steps to approach monoarthritis are presented. One of the first investigations consists in an analysis of the synovial fluid. It should take place before any therapeutic step is initiated and may allow to diagnose a microcrystalline or a septic arthritis. By means of a literature review monoarthritis is described as a disease, whose cause remains often undisclosed inspite of intensive investigations, whose further course, however, is often favorable.
7541811 Primary Sjögren's syndrome and psoriasis vulgaris in a case of OKT4 epitope deficiency. 1995 Apr We report a 29-year-old female OKT4 epitope deficiency patient with primary Sjögren's syndrome and psoriasis vulgaris. Immunological investigations during the prolonged clinical course of her herpes zoster revealed that she has OKT4 epitope deficiency and primary Sjögren's syndrome. She had been treated for psoriasis vulgaris for 17 years without systemic immunosuppressive therapy. Flow cytometric study revealed that her OKT4 deficiency is heterogeneous and excluded interference with the OKT4 epitope by anti OKT4 autoantibodies. The rare coexistence of primary Sjögren's syndrome and psoriasis implicates an immune disturbance due to an unusual phenotype of CD4.
8453793 Gastric involvement in primary Sjögren's syndrome. 1993 Jan Gastric involvement was investigated in twenty Italian patients with primary Sjögren's syndrome (pSS). Gastric complaints were present in 11 cases (55%) and endoscopic abnormalities in 10 (50%) including 2 cases with active duodenal ulcer. Only two patients (10%) showed moderate chronic atrophic gastritis (AG), while most (85%) had superficial gastritis (SG). No correlations were found among endoscopy, histology and gastric symptoms. Mean serum group I pepsinogen (PG I) levels were significantly higher (p < 0.01) and PG I concentrations in the fundus of the stomach were significantly lower (p < 0.05) in pSS patients than in a matched control group of dyspeptic subjects. Serum and antral gastrin levels were elevated in 3 cases with pSS (15%) including the two with AG, although the mean levels were not different from the controls. Antibodies to gastric parietal cells (PCA) were detected in two cases (10%) including 1 with AG. The present study contradicts previous reports claiming that AG with hypopepsinogenemia is a prominent feature in Sjögren's syndrome. We suggest that, at least in Italian patients, pSS is often associated with SG and high PG I levels.
8318046 Triggering and exacerbation of autoimmune arthritis by the Mycoplasma arthritidis superant 1993 Jul OBJECTIVE: It has been postulated that superantigens might play a role in the human rheumatic diseases, by activation of self-reactive T cells or by induction of autoantibodies. The Mycoplasma arthritidis superantigen MAM, which is derived from a naturally occurring murine arthitogenic mycoplasma, uses certain V beta chains of the murine T cell receptor (TCR) that have been proposed to be involved in murine collagen-induced arthritis (CIA). The present study was designed to determine whether MAM influences the course of arthritis mediated by immunization with porcine type II collagen (PII). METHODS: MAM or phosphate buffered saline (PBS) was injected locally or systemically into mice convalescing from CIA or mice suboptimally immunized with collagen. RESULTS: In contrast to PBS, MAM caused an exacerbation of arthritis in mice that were recovering from CIA. MAM also triggered arthritis onset in mice that had been suboptimally immunized with PII up to 160 days previously. Injection of MAM during the onset phase of CIA also triggered and enhanced the severity of arthritis in mice given low doses of PII. CONCLUSION: MAM can both trigger and exacerbate murine autoimmune arthritis induced by immunization with type II collagen. Since T cells bearing the same V beta TCRs as are used by MAM have been found to comprise a major portion of the activated cells in the synovial tissue of patients with rheumatoid arthritis, it is possible that superantigens similar to MAM may play a role in this human disease.
8587078 Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial. 1995 May OBJECTIVE: Psoriatic arthritis (PsA) is often poorly responsive to 2nd line antirheumatic drug therapy. Sulfasalazine has recently gained wide acceptance in the treatment of rheumatoid arthritis, and beneficial effects have also been noted in ankylosing spondylitis and reactive arthritis. We report a double blind placebo controlled study of sulfasalazine in PsA. METHODS: Twenty-four patients with active PsA were randomized to receive either sulfasalazine (3 g/day) (n = 10) or placebo (n = 14) for 8 weeks, in a double blind manner, followed by an 8 week open label crossover phase for nonresponding placebo patients. RESULTS: Compared with placebo controls, sulfasalazine treated patients were significantly improved at Weeks 4 and 8 with respect to physician (p < 0.01) and patient (p < 0.05) global assessments. Duration of morning stiffness was significantly decreased at Week 8 (p < 0.01). Clinical variables of disease activity returned to baseline after a 4 week drug washout period in 5 evaluable patients. Six patients in the placebo group crossed over to an 8 week open label phase and demonstrated significant improvements in joint scores, 50 ft walking time, and global patient assessment. Sulfasalazine treated patients also showed significant improvements in cutaneous involvement. CONCLUSION: Sulfasalazine was effective in PsA, with efficacy observed as early as the 4th week of treatment. Longterm studies are needed to determine whether such therapy can modify disease outcome.