Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
10813302 Comparison of criteria for the classification of childhood arthritis. 2000 May OBJECTIVE: To evaluate the applicability of the ILAR criteria for classification of childhood arthritis in an outpatient pediatric rheumatology clinic population, and to determine the proportion of children who met standard classification criteria, but failed to meet ILAR criteria for specific arthritides, and therefore became unclassifiable. METHODS: We reviewed the charts of 70 consecutive patients who had arthritis for at least 6 months, and attended the clinic between September and November 1997. Sixty-nine patients were categorized according to one of the traditional classifications [ACR for juvenile rheumatoid arthritis (JRA), European Spondylarthropathy Study Group (ESSG) for spondyloarthropathy, Vancouver Criteria for juvenile psoriatic arthritis (JPsA)], and the ILAR classification system. RESULTS: Sixty-one patients (88.4%) were classifiable by the ILAR system; 8 others failed to fulfill ILAR criteria for any specific category, and were assigned to the "other arthritis" category. Of the 29 patients with oligoarticular onset JRA, 6 were unclassified, 5 because of exclusions, and one because he fulfilled criteria for 2 categories. Presence of a family history of psoriasis accounted for most of the exclusions in the oligoarthritis and enthesitis related arthritis categories. All patients with polyarticular onset or systemic onset JRA were classified in the corresponding category in the ILAR system. One 9-year-old patient with spondyloarthropathy was reclassified as "other arthritis" because of exclusions. All 6 children with definite JPsA met ILAR criteria for PsA. Of 4 patients with probable JPsA, only 2 met ILAR criteria for PsA, a third was classified as rheumatoid factor negative polyarthritis, and the fourth was classified as "other arthritis" because of exclusions. CONCLUSION: The ILAR classification criteria applied to a group of children with chronic arthritis classified by traditional criteria results in reassignment of 11.6% of the patients, predominantly in the oligoarticular group. It will be important to determine the role of the presence of a family history of psoriasis in classifying these patients.
9860433 A diffuse T lymphocytic gastrointestinal mucosal infiltration associated with Sjögren's s 1998 Dec We report the case of a 45-yr-old white man, investigated for chronic diarrhea, malabsorption and weight loss associated with sicca syndrome. Endoscopic and x-ray examinations showed normal macroscopic mucosa in gastrointestinal tract (GIT). Immunohistochemistry showed diffuse polyclonal T cell lymphocytes infiltrating either epithelium and lamina propria in GIT. There was no villous atrophy in the jejunum and ileum. Corticosteroids, azathioprine, and cyclosporine failed to improve symptoms. Monthly intravenous cyclophosphamide administered over 1 yr, stopped the diarrhea and weight loss. The patient is free of symptoms up to a 5-yr follow-up.
9933332 Correlation between clinical and ultrasound assessment of the knee in children with mono-a 1999 Feb BACKGROUND: Ultrasonography of the knee is a non-invasive, readily available and low-cost tool for demonstrating peri-articular tissues. OBJECTIVE: To correlate clinical features with US findings in the detection, quantification and follow-up of inflammatory signs of the knee in children with pauci-articular juvenile rheumatoid arthritis (JRA). MATERIALS AND METHODS: US of both knees was performed in 49 patients on the same day as the clinical examination. All joints were classified into two groups by clinical criteria: group A (active disease) or group B (quiescent disease). Thirteen patients underwent one or more follow-up examinations. US was performed with a small-parts, 7.5-MHz, electronic linear probe by using a technique previously reported. Quantitative assessment of any effusion and synovial thickening was evaluated at the level of the suprapatellar bursa. Wilcoxon and Spearman tests were employed to compare US findings between the two groups and to correlate clinical and US findings within each group, respectively. RESULTS: US demonstrated significant increase of effusion and synovial thickening in group A joints. US enabled visualisation of clinically undetected popliteal cysts in three patients. Correlation between clinical and US findings was significant in group A and positive, though not significant, in group B. CONCLUSIONS: US seems to be a sensitive and reliable method for the assessment and monitoring of knee joint involvement in pauci-articular JRA.
10599333 Sjögren's syndrome. Autoimmune epithelitis. 1999 Sjögren's syndrome is a chronic autoimmune disorder characterized by mononuclear cell infiltration proximally to epithelial cells of exocrine glands. In recent years, several studies have tried to address the function of the components of the immunopathologic lesion in Sjögren's syndrome. The majority of the mononuclear infiltrating cells are CD4 positive T lymphocytes (60-70%) whereas B cells constitute one fourth of the infiltrating cells. Macrophages and natural killer cells are poorly represented in the lesion. Epithelial cells of minor salivary glands of patients with Sjögren's syndrome express proinflammatory cytokines (IL-1 beta, IL-6), protooncogenes (c-myc) and costimulatory molecules (B71, B72). The destruction of epithelial cells of Sjögren's syndrome patients is probably due to activation of several apoptotic pathways since epithelial cells express different apoptosis related molecules such as Fas, FasL, Bax, while mononuclear cells express Bcl-2, Perforin and Granzymes. Finally epithelial cells seem to exert a regenerative effort since they express trefoil proteins (pS2). The above properties give epithelial cells a significant role in the pathophysiology of the syndrome but the exact events which drive the immune system towards an autoimmune reaction remain obscure.
11204499 Hepatitis C virus infection mimicking primary Sjögren syndrome. A clinical and immunologi 2001 Jan Hepatitis C virus (HCV) infection is emerging as an extremely common and insidiously progressive liver disease that is often associated with several extrahepatic manifestations. In 1992, a possible relationship between Sjögren syndrome (SS) and patients with HCV infection was first postulated. Subsequently, several studies demonstrated that a "true" SS, with similar clinical and histologic features to those observed in primary SS, may occur in some patients with chronic HCV infection. We report the clinical and immunologic characteristics of 35 patients with chronic HCV infection and a well-documented diagnosis of SS. Compared with 60 patients with primary SS who tested negative for HCV antibodies, SS-HCV patients showed a higher mean age (65.9 yr versus 61.5 yr, p = 0.04), a lower prevalence of parotidomegaly (17% versus 47%, p = 0.004), and a higher prevalence of liver involvement (94% versus 3%, p < 0.001). Moreover, those patients with HCV-related SS showed a higher prevalence of anti-parietal cell gastric antibodies (31% versus 13%, p = 0.03), antimitochondrial antibodies (14% versus 2%, p = 0.02), cryoglobulinemia (60% versus 10%, p < 0.001), hypocomplementemia (60% versus 8%, p < 0.001), and a lower prevalence of anti-Ro/SS-A (17% versus 38%, p = 0.03). The "true" SS observed in some patients with HCV may be considered 1 of the extrahepatic manifestations of HCV, and we suggest that HCV infection can be considered as an exclusion criterion for the diagnosis of primary SS.
11354561 Still's-like disease, breast prosthesis, and collagen implants. 2001 Apr Silicone-induced connective tissue disease raises a controversial issue. We report a case of Still's disease associated with silicone and collagen implants that showed improvement on steroids, but remained steroid-dependent despite removal of the silicone implants. This observation complements four previous cases in the literature and questions the role of breast implants in the pathogenesis of Still's disease. The number of cases studied is insufficient for conclusions, but silicone-implant-associated syndrome may be confused with Still's disease. We consequently propose the use of ferritinemia and its serum glycosylated fraction level as discriminating factors. Collagen has been associated with some inflammatory diseases, but never previously with Still's disease. However, considering this observation and previous data in the literature, its role may be postulated as an exacerbating factor or a pathogenic agent.
16100693 Advances in anti-arthritic agents. 24-25 January 2000, London, UK. 2000 Apr This meeting provided an excellent overview of the field of arthritis, although most of the drugs mentioned were designed to treat rheumatoid arthritis. There was an air of excitement surrounding the event because, after a substantial period of dormancy in clinical rheumatology, there are now many promising new treatments emerging, which, it is hoped, will greatly improve the quality of life for numerous arthritis sufferers. Speakers covered topics as diverse as care for sufferers, impact of the disease, status of current treatments, and approaches for the future. The majority of the presentations were drug-oriented; the speaker generally gave a summary of their company's arthritis research program and then followed this with a case study of its lead compound.
10846730 Masticatory function in patients with juvenile rheumatoid arthritis. 2000 May PURPOSE: Children with Juvenile Rheumatoid Arthritis (JRA) rarely report temporomandibular joint (TMJ) pain, which may be due to pain avoidance mechanisms resulting in compromised masticatory function. This study examined the relationship between self-report measures of pain and dysfunction and measures of chewing performance in 44 JRA children and 34 normal controls. METHODS: The children were divided into three groups: Group 1, JRA children with temporomandibular joint disorder (TMD); Group 2, JRA children without TMD; Group 3, normal control children without TMD. Both visual and analog scales of jaw pain, ability to chew, and quality of life were administered before and after chewing tasks. Children chewed standardized portions of an artificial food for 20 cycles and expectorated the particles into a cup. This process was repeated five times. Median particle size and a broadness of particle distribution index were measured. Also, the number of chewing cycles prior to the child's first swallow for a cube of carrot was recorded. RESULTS: The broadness of particle distribution index was greater for Group 1 (P < 0.001) and Group 2 (P < 0.03) than for Group 3 with no difference in number of chews for carrot mastication among groups. Group 1 reported more pain and dysfunction before the chewing tasks than Groups 2 or 3 (P < 0.05). Interestingly, only Group 3 reported increased pain and decreased ability to chew after chewing tasks (P < 0.02). CONCLUSION: Children with JRA compromise their masticatory function as a pain avoidance mechanism. Such findings may have profound implications with regard to the nutritional status for these children.
9473382 A mixed Th1/Th2 cell cytokine response predominates in systemic onset juvenile rheumatoid 1998 Feb The immune response identified by the induction of Th1/Th2 cells plays a critical role in the pathogenesis of various inflammatory and immune disorders. We have determined that in children with systemic onset juvenile rheumatoid arthritis (JRA), peripheral blood mononuclear cells (PBMC) constitutively and after stimulation with various antigens in vitro induce a higher secretion of interleukin-4 (IL-4) and IL-10 with a characteristic deficiency of IL-2 and interferon-gamma (IFN-gamma). This cytokine pattern is a representative of a mixed Th1/Th2 cell response in JRA. The CD3/CD28 costimulatory molecule was found to be a potent inducer of IL-4 and IL-10 secretion. PBMC-derived augmented IL-10 secretion was inhibited by exogenous Th1 cell type recombinant cytokines (IL-2, IL-12, and IFN-gamma). Although IL-10 inhibits PBMC-induced proinflammatory IL-1alpha and tumor necrosis factor-alpha secretion, it had no major effect on IL-6 production. The finding of a distinctly enhanced mixed Th1/Th2 cell response cytokine (IL-4 and IL-10) pattern in JRA provides a framework for developing strategies for immunologic intervention in this rheumatic disorder in children.
10365570 Tissue inhibitor of metalloproteinases-1 and matrix metalloproteinase-3 in Japanese health 1999 Jun BACKGROUND AND METHODS: To determine the clinical values of tissue inhibitor of metalloproteinases-1 (TIMP-1) and matrix metalloproteinase-3 (MMP-3) in juvenile rheumatoid arthritis (JRA), we measured serum levels of these enzymes with rapid one-step sandwich enzyme immunoassay. Forty-one JRA patients, 48 normal healthy children (NC) and 10 Kawasaki disease (KD) patients were investigated. RESULTS: Serum TIMP-1 levels in NC corresponded to those in normal adults reported in the literature, while MMP-3 levels were lower than those in healthy children and the ratio of MMP-3/TIMP-1 decreased. The TIMP-1 levels in JRA and KD at the first clinic examination were statistically higher than those in NC (P < 0.05) and MMP-3 levels and MMP-3/TIMP-1 in JRA were significantly higher than those in NC (P < 0.0001 and 0.0005, respectively) and KD (P < 0.001 and 0.0005, respectively). In JRA, MMP-3 levels of patients with arthritis were statistically higher than those of patients without arthritis (P < 0.05) and MMP-3 levels were correlated with C-reactive protein (rs = 0.465, P < 0.05), while TIMP-1 did not (rs = 0.340). There was a positive correlation between serum levels of MMP-3 and TIMP-1 and prognosis (rs = 0.733, P < 0.05). CONCLUSION: In JRA, the serum MMP-3 level is a useful marker to evaluate joint damage, while serum TIMP-1 remains an acute phase reactant.
10553337 [Parvovirus B19 as a cause of acute arthritis]. 1999 Sep 30 Parvovirus B19 is known to cause erythema infection (fifth disease), acute and chronic arthritis, aplastic crises in chronic hemolytic anemia, chronic anemia in the immunocompromised host and hydrops fetalis. We present two patients with acute arthritis due to parvovirus infection. Both had symmetrical synovitis in wrists and ankles. Patient 1 presented with fever and rash before joint symptoms occurred; patient 2 had joint symptoms only. Arthritis due to parvovirus is usually self-limited, but may develop into a chronic disease similar to rheumatoid arthritis. Parvovirus should be considered one of the differential diagnoses while dealing with acute or chronic arthritis.
10407083 Intravenous administration of superoxide dismutase entrapped in long circulating liposomes 1999 Jul 15 Rheumatoid arthritis (RA) is a prevalent and debilitating autoimmune disease that affects the joints. RA is characterized by an infiltration of the affected joint by blood-derived cells. In response to activation, these cells generate reactive oxygen species, resulting in an oxidative stress situation. One approach to counteract this oxidative stress situation is the use of antioxidants as therapeutic agents. The free radical scavenger enzyme superoxide dismutase (SOD) may be used as a therapeutic agent in rheumatoid arthritis, but its rapid elimination from the circulation is a major limitation. Targeted delivery of SOD may overcome this limitation. In this study, the utility of PEGylated liposomes (PEG-liposomes) for targeting SOD to arthritic sites was explored. The targeting of SOD to arthritic sites following intravenous administration of both PEG-liposomes and positively charged liposomes lacking PEG but containing stearylamine (SA-liposomes) in rats with adjuvant arthritis was studied. At 24 h post injection, the blood levels of long circulating liposomes with a mean size of 0.11 micrometer and 0.20 micrometer were 8- and 3-fold higher, respectively, as compared to the SA-liposomes. The majority of SOD administered in liposomal form remains within the liposomes when they circulate in the bloodstream. The highest target uptake was observed with PEG-liposomes with a mean size of 0.11 micrometer and the lowest uptake with the SA-liposomes. These results demonstrate that SOD can be targeted to inflamed sites most efficiently via small-sized PEG-liposomes. Small-sized PEG-coated liposomes are to be preferred if prolonged circulation and enhanced localization of SOD at arthritic sites are desired.
24387018 Expression of membrane-type matrix metalloproteinases in synovial tissue from patients wit 2001 Mar Abstract We investigated the expression of membrane-type matrix metalloproteinase (MT-MMP) and matrix metalloproteinase (MMP) mRNAs in synovial tissue from patients with rheumatoid arthritis (RA, n = 5) or osteoarthritis (OA, n = 5) by Northern blot analysis. Northern analysis demonstrated strong expression of MT1-MMP, MT3-MMP, MMP-1, and MMP-3 and weak expression of MT2-MMP and MMP-8 in synovial tissue from patients with RA or OA. MT4-MMP was not detected. No significant difference was shown in the expression of MT-MMP mRNAs between RA and OA. Synovial tissue of RA or OA patients expressed MT-MMPs as well as MMPs. These results indicate that, in addition to MMPs, MT1-MMP, MT3-MMP, and probably MT2-MMP may play a role in the degradation of bone and cartilage matrix in RA and OA. Such information may provide a clue to the development of a novel therapeutic approach targeted on the prevention of joint destruction.
9375287 Skin involvement as a relevant outcome measure in clinical trials of systemic sclerosis. 1997 Nov Advances in our understanding of the pathobiology of scleroderma and the ever-increasing availability of rational candidate therapies have brought the clinical study of scleroderma to the forefront. In the 1990s, consensus measures of outcome have been developed for common disorders such as rheumatoid arthritis. With decisions founded on extensive and validated data, the clinical research community and regulatory agencies have accepted the importance of a demonstration of small degrees of change over relatively short periods of time. The current level of sophistication in scleroderma research is reminiscent of our approach to the study of rheumatoid arthritis in the early 1970s. Accessible, reproducible, and cost-effective measures of outcome are needed in scleroderma. These measures should incorporate clinical meaningfulness and be relevant to quality of life. This review discusses some of the more recent studies of outcome measures in scleroderma, some or all of which are considered relevant to both drug development and clinical care of the individual patients.
19078480 Clinical and Immunomodulatory Effect of Fun-boi, an Herbal Medicine, in Rheumatoid Arthrit 2000 Oct Crude preparations of Fun-boi (Fen-fan-ji in Chinese), a traditional anti-rheumatic herb, have been used safely over millennia. To begin to study the efficacy of Fun-boi on the disease activity and the peripheral lymphocyte subsets, we performed a 12-week, open-label trial of Fun-boi extract (a decoction of Fun-boi 10 g/day) in 29 patients with rheumatoid arthritis (RA). Most clinical and immunological variables: swollen joint count, physician's and patient's assessment, pain score and IgM rheumatoid factor, showed statistically significant improvement. Seven (24%) of the enrolled patients met the American College of Rheumatology (ACR) criteria for a 20 percent improvement in measures of disease activity (ACR20) and 3 (10%) met those for ACR50. The CD3+CD8+ lymphocytes were increased significantly. Accordingly, the CD4/CD8 ratio was decreased; however, these changes did not show any clear correlation with clinical response. Two patients (7%) experienced some minor transient adverse events. In conclusion, Fun-boi is safe and showed beneficial effect in some patients for the treatment of the relatively mild RA seen in the patients studied. Further controlled studies are indicated. Clinicians should keep an open mind about possible benefits of these still incompletely studied herbal agents.
9531826 [Large granular lymphocytic leukemia]. 1998 Mar 10 Large granular lymphocyte leukaemia (LGL leukaemia) is a rare, chronic lymphoproliferative bone marrow disease which can be considered a subtype of chronic T-cell lymphocytic leukaemia (T-CLL). We describe three patients with large granular lymphocyte leukaemia. They all suffered from chronic disease with neutropenia and relative lymphocytosis. An expansion of mature lymphocytes with the CD3+, CD8+, CD57+ immunophenotype was demonstrated in all three patients. Two patients had a history of recurring infections. Serological findings compatible with rheumatic disease were present in all three patients, and two suffered from rheumatoid arthritis. We have made a brief survey of this disease, which is characterized by relative or absolute lymphocytosis, neutropenia, and an increased risk of infection. Rheumatoid arthritis and other associated autoimmune manifestations occur frequently. Large granular lymphocyte leukaemia should be considered a possible diagnosis in patients with chronic neutropenia and relative lymphocytosis, in particular if rheumatic manifestations are also present. Flow cytometric immunophenotyping is a sensitive method in diagnosing this disease.
24383783 A case of asymptomatic acute pulmonary embolism due to deep venous thrombosis after total 2001 Dec Abstract In the field of orthopedics, acute pulmonary embolism (APE) associated with deep venous thrombosis (DVT) is a serious complication following surgery and leads to death if undetected. Although an examination for the presence of APE after surgery has been well established in other countries, there are few reports on APE after orthopedic surgery in Japan. Here, we describe a case of asymptomatic APE associated with DVT after total knee arthroplasty (TKA) in a patient with rheumatoid arthritis (RA). Because it is difficult to determine the clinical features of APE prior to the initiation of angiography, we used a perfusion lung scan, which is a useful tool for detecting asymptomatic APE. We successfully identified APE in the TKA patient with RA, and continuous intravascular infusion of a thrombolytic agent and an anticoagulant was an effective treatment in this case. Our report clearly shows that a well-established procedure for diagnosis, as well as therapeutic guidelines, are essential for detecting systemic thromboembolism in patients after orthopedic surgery.
9453836 [Enthesiopathy and bone disease during the course of inflammatory spondylarthropathies. Di 1997 Jun Our studies concerning enthesopathies during the course of spondylarthropathies show that enthesopathies are very frequent: 58% among 48 spondylarthropathies in a preliminary study. The comparison of the frequency of enthesopathies in spondylarthropathies (58%) and in Rheumatoid Arthritis (6.6%) show a highly significant difference. In our latest study enthesopathies were found in 67% among 115 spondylarthropathies. We have also described the mean locations and clinical features. They are observed early in the course of the disease. Histological studies of enthesopatic and normal enthesis were also performed. They were unable to find a specific image. Nevertheless inflammatory changes in some of our cases and in cases retrieved in the medical literature confirm the involvement of enthesis in the pathological process of spondylarthropathies. Enthesopathies represent a very good diagnostic symptom. They are the hallmark of spondylarthropathies for adults and even more for children. Furthermore, if one admits the assertion that peripheral and spinal involvement is the result of bone remodeling enthesitic lesions, then enthesopathies and osteitis, ending in ankylosis, may be considered as the fundamental pathophysiological mechanism of spondylarthropathies in contrast with erosive lesions of rheumatoid arthritis.
15775563 [Relationship between periarticular osteoporosis and osteoblast senescence in patients wit 2001 May The rate of bone formation is largely determined by the number of osteoblasts, which in turn is determined by the rate of replication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. However, the exact age-dependent changes of the cellular activity, replicative potential and life-span of osteoblasts have not so far been investigated to date. Here we present evidence that the cellular activity, telomere lengths and replicative life-span of osteoblastic cells obtained from juxta-articular bone marrow gradually decrease with the advance of donor age in patients with rheumatoid arthritis or osteoarthritis. Recently, human telomerase reverse transcriptase (hTERT) has been identified as a human teromerase catalytic subunit. We postulate that an expansion of the life-span of osteoblasts and their maintenance as differentiated bone matrix-producing cells may allow for autologus or allogenic cell and gene therapy in bone and joint diseases including osteoporosis. We therefore transfected human osteoblasts with a vector expressing hTERT cDNA, and investigated whether the replicative life-span can be expanded by the introduction of telomerase in human osteoblasts.
11064595 [Exploratory analysis of elevated C-reactive protein without leukocytosis from the clinica 2000 Aug We studied the characteristics of admitted patients who showed discrepancy between C-reactive protein(CRP) and white blood cell count(WBC). We extracted those patients from our laboratory information system by two criteria: WBC is less than 9500/microliter and either(1) CRP is more than 5.0 mg/dl, or(2) the pair of CRP and WBC is out of 95% confidence ellipse. We found 346 and 90 cases by the two criteria, respectively. They consisted of a variety of diseases, prevalent were such as pneumonia, rheumatoid arthritis, malignant lymphoma, post-operative state and so on by either criterion. There was predominance of elderly patients as a whole. The analysis of individual time courses revealed that WBC did not change in parallel with CRP in patients with rheumatoid arthritis and malignant lymphoma, while they paralleled in those with infectious diseases and post-operation states. The elevation of WBC in some patients might have been overlooked since WBC was not always to be ordered together with CRP. We need a prospective study to closely analyze serial relationship between CRP and WBC for factors leading to the discovery.