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ID PMID Title PublicationDate abstract
14761774 Heart transplantation in a patient with chloroquine-induced cardiomyopathy. 2004 Feb We present the first report of a patient who underwent heart transplantation (HT) after endomyocardial biopsy (EMB) and revealed chloroquine-induced cardiomyopathy (CIC). This patient, who was treated with chloroquine for 6 years, developed a restrictive cardiomyopathy that progressed to congestive heart failure (CHF) resistant to medical management.
15290751 Septic arthritis caused by Actinobacillus ureae in a patient with rheumatoid arthritis rec 2004 Aug Actinobacillus ureae, formerly known as Pasteurella ureae, is a rare human pathogen. We describe a case of septic arthritis and abscess formation caused by this unusual organism in a patient with rheumatoid arthritis, who was being treated with tumor necrosis factor-alpha inhibitors.
12709545 Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagno 2003 May OBJECTIVES: To evaluate the association of anti-cyclic citrullinated peptide (anti-CCP) antibodies with immunoglobulin (Ig) M and IgA rheumatoid factors (RF) in discriminating between rheumatoid arthritis (RA) and other rheumatic diseases, and to determine, in a longitudinal study, whether clinical signs of disease severity are associated with the presence of these autoantibodies at the time of patient inclusion. METHODS: The presence of these three markers was determined in 196 patients with established RA, 239 non-RA controls with various rheumatic diseases (cross-sectional study) and in 27 patients with arthritis of less than 1 yr disease duration who were subsequently followed during about 8 yr (longitudinal study). At the time of follow-up, 21 of these 27 patients had RA. They were further evaluated and several clinical variables were recorded. RESULTS: The specificity was significantly increased (from 82-90% to 98% in the cross-sectional study) when the combination of anti-CCP antibodies with IgA RF or the combination of the three serological markers was used. An association was observed between the presence of the three autoantibodies and clinical signs of disease severity (functional disability, presence of erosions and absence of clinical remission). CONCLUSIONS: The presence either of anti-CCP antibodies and IgA RF or of the three markers appears to be useful in the diagnosis of RA. Their association with clinical signs of disease severity at the time of patient inclusion suggests their potential usefulness as markers for prognosis.
14607865 Immunoglobulin G and A antibody responses to Bacteroides forsythus and Prevotella intermed 2003 Nov The objective of the present study was to investigate immunoglobulin G (IgG) and IgA antibody immune responses to Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, and Candida albicans in the sera of patients with rheumatoid arthritis (RA), the synovial fluid (SF) of patients with RA (RA-SF samples), and the SF of patients without RA (non-RA-SF samples). An enzyme-linked immunosorbent assay was used to determine IgG and IgA antibody levels in 116 serum samples from patients with RA, 52 RA-SF samples, and 43 non-RA-SF samples; and these were compared with those in SF samples from 9 patients with osteoarthritis (OA-SF samples) and the blood from 100 donors (the control [CTR] group). Higher levels of IgG antibodies against B. forsythus (P < 0.0001) and P. intermedia (P < 0.0001) were found in non-RA-SF samples than in OA-SF samples, and higher levels of IgG antibodies against B. forsythus (P = 0.003) and P. intermedia (P = 0.024) were found in RA-SF samples than in OA-SF samples. Significantly higher levels of IgA antibodies against B. forsythus were demonstrated in both RA-SF and non-RA-SF samples than in OA-SF samples. When corrected for total Ig levels, levels of IgG antibody against B. forsythus were elevated in RA-SF and non-RA-SF samples compared to those in OA-SF samples. Lower levels of Ig antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group for both IgG (P = 0.003) and IgA (P < 0.0001). When corrected for total Ig levels, the levels of IgG and IgA antibodies against B. forsythus were still found to be lower in the sera from patients with RA than in the plasma of the CTR group (P < 0.0001). The levels of antibodies against P. gingivalis and C. albicans in the sera and SF of RA and non-RA patients were comparable to those found in the respective controls. The levels of IgG and IgA antibodies against B. forsythus were elevated in SF from patients with RA and non-RA-SF samples compared to those in OA-SF samples. Significantly lower levels of IgG and IgA antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group. This indicates the presence of an active antibody response in synovial tissue and illustrates a potential connection between periodontal and joint diseases.
14593902 [Prevalence of extrahepatic illnesses in patients with chronic hepatitis b and hepatitis c 2003 Apr Chronic infections that caused by hepatitis B and C viruses, are important all of the world as a public health problem. Despite intensive control measurements, the incidences of chronic hepatitis B and C virus infections in our country are estimated as 5-7% and 3%, respectively. There are accumulating data of especially autoimmune mediated extrahepatic manifestations of hepatitis B and C virus infections, such as Diabetes Mellitus (DM), Behçet's Disease (BD), hypo- or hyper-thyroiditis and autoimmune diseases. The aim of this study was the retrospective evaluation of 400 chronic B hepatitis (CBH) and 35 C hepatitis (CCH) patients by means of the presence of extrahepatic manifestations. As a result, the positivity rates of extrahepatic manifestations detected in CBH and CCH patients were as follows respectively; 1.5% and 8.5% for DM, 1.5% and 5.7% for hypothyroiditis, 0.75% and 2.8% for hyperthyroiditis, 2% and 20% for nodular goitre, 0.25% and 5.7% for BD, 1% and 0% for systemic lupus, 1% and 5.7% for Rheumatoid Arthritis (RA), and 22% and 11.4% for iron deficiency anemia. DM, thyroid diseases and RA were the most common extrahepatic manifestations detected in both of the patient groups, while the rates of DM, BD and nodular goitre were found higher in CCH patients than CBH patients (p < 0.05). As a result, the extrahepatic manifestations should be carefully followed in patients with chronic hepatitis B and C infections, for an early diagnosis and appropriate treatment.
15529343 Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joi 2004 Nov Alkaptonuria, a rare autosomal-recessive disorder caused by mutations in the HGD gene and a deficiency of homogentisate 1,2-dioxygenase, is characterized by accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue resulting in joint disease. Certain medications have been reported to cause cutaneous hyperpigmentation resembling that of alkaptonuria. We present 5 such cases. Eighty-eight patients with a possible diagnosis of alkaptonuria were examined at the National Institutes of Health Clinical Center between June 2000 and March 2004. The diagnosis of alkaptonuria was confirmed or ruled out by measurement of HGA in the urine. Five patients with findings consistent with ochronosis, including pigmentary changes of the ear and mild degenerative disease of the spine and large joints, were diagnosed clinically as having alkaptonuria, but the diagnosis was withdrawn based on normal urine HGA levels. All 5 patients were women who had taken minocycline for dermatologic or rheumatologic disorders for extended periods. Minocycline-induced hyperpigmentation should be considered in the differential diagnosis of ochronosis. This could be of increased significance now that minocycline and other tetracyclines have been proposed as therapeutic options for rheumatoid arthritis, bringing a new population of patients with ochronosis and arthritis to medical attention with the potential, but incorrect, diagnosis of alkaptonuria.
15454123 Felty's syndrome. 2004 Oct Felty's syndrome (FS) comprises a triad of rheumatoid arthritis (RA), neutropenia and splenomegaly, occurring in less than 1% of RA patients. Clinically it is characterized by severe joint destruction contrasting with moderate or absent joint inflammation and severe extra-articular disease, including a high frequency of rheumatoid nodules, lymphadenopathy, hepatopathy, vasculitis, leg ulcers, skin pigmentation etc. Recurrent bacterial infections are mostly due to the severe, otherwise unexplained neutropenia. The cause of neutropenia lies in both decreased granulopoiesis and increased peripheral destruction of granulocytes. Recurrent infections may lead to increased mortality. Spontaneous remission of the syndrome also occurs. Over 95% of FS patients are positive for rheumatoid factor (RF), 47-100% are positive for antinuclear antibody (ANA), and 78% of patients have the HLA-DR4*0401 antigen. Some 30% of FS patients have large granular lymphocyte (LGL) expansion. LGL expansion associated with uncomplicated RA is immunogenetically and phenotypically very similar to but clinically different from FS. Neutropenia of FS can be effectively treated with disease-modifying anti-rheumatic drugs (DMARDs), the widest experience being with methotrexate (MTX). Results of treatment with granulocyte colony-stimulating factor (G-CSF) are encouraging, but there is no experience with other biological agents. Splenectomy results in immediate improvement of neutropenia in 80% of the patients, but the rate of infection decreases to a lesser degree.
12165096 Simultaneous analysis of T cell clonality and cytokine production in rheumatoid arthritis 2002 Aug In this study we examined the cytokine production by T cells and TCRVbeta subsets in peripheral blood (PB) and synovial fluid (SF) from six RA patients and PB from 10 normal subjects, using three-colour flow cytometry. In two RA subjects we assessed T cell clonality by RT PCR using TCRBV family-specific primers and analysed the CDR3 (complementarity determining region 3) length by GeneScan analysis. A high percentage of IFN-gamma- and IL-2- producing cells was observed among the PB T cells in both the RA patients and normal controls and among the SF T cells in RA patients. In contrast, the percentage of T cells producing IL-4 and IL-5 was small among PB T cells in both RA patients and normal controls and among SF T cells in RA patients. There was no significant difference in the production of IFN-gamma, IL-2 and IL-5 between the two compartments (PB and SF); however, there were significantly more IL-4-producing cells in SF. Molecular analysis revealed clonal expansions of four TCRBV families in SF of two of the RA patients studied: TCRBV6.7, TCRBV13.1 and TCRBV22 in one and TCRBV6.7, TCRBV21.3 and TCRBV22 in the second. These expansions demonstrated cytokine expression profiles that differed from total CD3+ cells, implying that T cell subsets bearing various TCR-Vbeta families may have the potential to modulate the immune response in RA patients.
12902472 Synoviocyte-mediated expansion of inflammatory T cells in rheumatoid synovitis is dependen 2003 Aug 15 Fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis elicit spontaneous proliferation of autologous T cells in an HLA-DR and CD47 costimulation-dependent manner. T cell costimulation through CD47 is attributed to specific interaction with thrombospondin-1 (TSP1), a CD47 ligand displayed on FLS. CD47 binding by FLS has broad biological impact that includes adhesion and the triggering of specific costimulatory signals. TSP1(+) FLS are highly adhesive to T cells and support their aggregation and growth in situ. Long-term cultures of T cells and FLS form heterotypic foci that are amenable to propagation without exogenous growth factors. T cell adhesion and aggregate formation on TSP1(+) FLS substrates are inhibited by CD47-binding peptides. In contrast, FLS from arthroscopy controls lack adhesive or T cell growth-promoting activities. CD47 stimulation transduces a costimulatory signal different from that of CD28, producing a gene expression profile that included induction of ferritin L chain, a component of the inflammatory response. Ferritin L chain augments CD3-induced proliferation of T cells. Collectively, these results demonstrate the active role of FLS in the recruitment, activation, and expansion of T cells in a CD47-dependent manner. Because TSP1 is abundantly expressed in the rheumatoid synovium, CD47-TSP1 interaction is proposed to be a key component of an FLS/T cell regulatory circuit that perpetuates the inflammatory process in the rheumatoid joint.
12954252 Five-year results of a new total replacement prosthesis for the finger metacarpo-phalangea 2003 Oct An unconstrained surface metacarpophalangeal joint replacement was developed with metal metacarpal and polyethylene phalangeal components, fixed by uncemented finned polyethylene plugs which allowed some metacarpal component motion. Clinical and radiological results in 13 joints in eight patients are presented after 5 years. One infection required revision at 3 months. There were no further complications. At final review there were no implant failures. Two of 13 joints showed lucency around the phalangeal component and one showed 2mm subsidence of the metacarpal component. No other adverse radiological features were observed. Seven patients had no pain and one had minor discomfort. Joint movement had improved from an arc of 27 degrees to 60 degrees and disability, assessed using the P.E.M. questionnaire, had improved from 77% to 9%.
12755791 Single value of serum transferrin receptor is not diagnostic for the absence of iron store 2003 Jun Serum transferrin receptor (sTfR) concentrations were measured in anaemic patients with rheumatoid arthritis (RA). Serum transferrin receptor concentrations were positively correlated with the percentage of hypochromic cells and negatively correlated with MCH. There was a weak correlation with serum ferritin (sFn) concentration but not with reticulocyte count. Thus, high concentrations of sTfR indicate iron-deficient erythropoiesis rather than levels of storage iron in the tissues. Patients were divided into three groups on the basis of sFn concentration: those with probable tissue iron deficiency, those with adequate iron stores and those with intermediate values of sFn which did not allow classification. The median sTfR concentration was significantly higher in the iron-deficient group than in the other two groups but because of overlap between the three groups, a single sTfR value was of limited value in determining the level of storage iron in an individual with RA.
15643572 Applications of ultrasound in arthritis. 2004 Dec The current article demonstrates some of the common sonographic features of the major arthritides. In rheumatoid arthritis, sonography shows the primary intra-articular location of the joint synovitis and bone erosion as well as any associated tenosynovitis. In early disease, this distribution can be distinguished from that of the spondyloarthropathies, in which the changes are typically centered on the entheses. These can be similarly differentiated from the chrystal arthropathies and osteoarthritis. In addition to its role in helping to make an accurate initial diagnosis, ultrasound is able to provide information as to disease activity and the efficacy of therapeutic agents.
12621815 [Adult-onset Still-disease: survey of 18 cases]. 2003 Jan 26 INTRODUCTION: Adult onset Still's disease (juvenile rheumatoid arthritis with septic appearance) is rare, leading to clinical signs similar to those seen in bacterial sepsis, lymphomas, rheumatological, or systemic autoimmune diseases. The disease can present with a fever of unknown origin, and can cause difficulties in the diagnosis. It is based upon, partly, the exclusion of other diseases and on diagnostic criteria. Its characteristic feature is the rise of acute phase proteins. Exanthemata are temporary. The basis of treatment is immunosuppression, however relapses can occur. AIM: The aim of the authors was to evaluate on the most characteristic clinical signs and laboratorical data of their patients, and to examine the revealing parameters of the course of the disease. METHOD: Retrospective epidemiological survey of the data obtained from 18 patients. RESULTS: The characteristic signs of the disease were, fever, sore throat, arthritis, joint pain, exanthemata, hepato-splenomegaly, lymphadenomegaly, pleurisy. The typical laboratorical data were: elevated CRP, low PCT, negative Waaler-Rose and ANA test, low serum iron level, leukocytosis, thrombocytosis, elevated alkalic phosphatase activity, high LDH, positive bone scintigraphy. The fever was steroid dependent. Generally, the illness was recognised after 2-3 months, and relapses were frequent. CONCLUSIONS: Still's disease has an important role in the differential diagnosis of fever of unknown origin. The diagnosis is based upon the evaluation of clinical signs and laboratorical data together. Prolonged immunosuppressive therapy is required.
12776164 Intra-articular adenoviral-mediated gene transfer of trail induces apoptosis of arthritic 2003 Jun Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that primarily affects joints. In rheumatoid joints there is extensive synovial proliferation with diseased synovium becoming highly aggressive, attaching to the articular cartilage and bone to form what is termed a pannus. The formation of active pannus is central to erosive disease and resulting joint destruction. In this study, we examined the ability to eliminate the hyperplastic synovium by adenoviral-mediated gene transfer of human TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF family that is able to induce apoptosis through interaction with receptors containing death domains, DR4 and DR5. Infection of synovial cells derived from RA patients with Ad.TRAIL resulted in significant apoptosis in three out of five lines. Moreover, primary rabbit synovial fibroblasts were also sensitive to Ad.TRAIL-mediated gene transfer. In a rabbit model of arthritis, intra-articular gene transfer of TRAIL induced apoptosis in cells within the synovial lining, reduced leukocytic infiltration and stimulated new matrix synthesis by cartilage. These results demonstrate that TRAIL can affect the viability of the cells populating the activated synovium in arthritic joints and suggest that the delivery of TRAIL to arthritic joints may represent a non-invasive mechanism for inducing pannus regression.
15529353 Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppr 2004 Nov OBJECTIVE: To investigate the molecular mechanisms of the antiarthritic effects of bee venom (BV) and melittin (a major component of BV) in a murine macrophage cell line (Raw 264.7) and in synoviocytes obtained from patients with rheumatoid arthritis. METHODS: We evaluated the antiarthritic effects of BV in a rat model of carrageenan-induced acute edema in the paw and in a rat model of chronic adjuvant-induced arthritis. The inhibitory effects of BV and melittin on inflammatory gene expression were measured by Western blotting, and the generation of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) and the intracellular calcium level were assayed. NF-kappaB DNA binding and transcriptional activity were determined by gel mobility shift assay or by luciferase assay. Direct binding of BV and melittin to the p50 subunit of NF-kappaB was determined with a surface plasmon resonance analyzer. RESULTS: BV (0.8 and 1.6 mug/kg) reduced the effects of carrageenan- and adjuvant-induced arthritis. This reducing effect was consistent with the inhibitory effects of BV (0.5, 1, and 5 mug/ml) and melittin (5 and 10 mug/ml) on lipopolysaccharide (LPS; 1 mug/ml)-induced expression of cyclooxygenase 2, cytosolic phospholipase A(2), inducible NO synthase, generation of PGE(2) and NO, and the intracellular calcium level. BV and melittin prevented LPS-induced transcriptional and DNA binding activity of NF-kappaB via the inhibition of IkappaB release and p50 translocation. BV (affinity [K(d)] = 4.6 x 10(-6)M) and melittin (K(d) = 1.2 x 10(-8)M) bound directly to p50. CONCLUSION: Target inactivation of NF-kappaB by directly binding to the p50 subunit is an important mechanism of the antiarthritic effects of BV.
12707568 Infectious complications of biologic treatments of rheumatoid arthritis. 2003 May Agents that block the action of tumor necrosis factor-alpha and recombinant interleukin-1 have been shown to be effective biologic treatment modalities in patients with rheumatoid arthritis. Given the immunosuppressive effects of tumor necrosis factor-alpha and interleukin-1 blockers, infections have emerged as possible complications of using these agents, an observation foreshadowed in prelicensure animal studies. At this time, hundreds of thousands of patients have received these drugs, and a wide variety of infectious complications has been reported, among which reactivation tuberculosis is most notable. Case reports alone, however, do not necessarily reflect a causal association between a therapeutic product and an adverse event. The authors review the infectious complications of the use of these agents as reported in the medical literature from November 2001 through October 2002.
12510361 [Combination therapy of disease-modifying antirheumatic drugs(DMARDs) in rheumatoid arthri 2002 Dec The early suppression of disease activity during the first 2 years in rheumatoid arthritis (RA) has been reported to be exclusively important to prevent joint destruction and functional decline. Since single disease-modifying antirheumatic drugs(DMARDs) therapy is still disappointing, many rheumatologists today advocated a more aggressive approach using combinations of classic DMARDs. Many clinical trials on combination therapy have been reported and most studies of combination therapy focused on the efficacy of a treatment strategy. Therefore, the possible synergistic action of combination of drugs has not been demonstrated. Among combination of therapy of classical DMARDs, only few trials demonstrated the efficacy of combination therapy. The incidence of adverse effects among 341 RA patients was investigated by our department. The incidence of adverse effect in combination therapy revealed 36.4% which was not statistically different from that in monotherapy(33.6%, p = 0.41). The recent studies on combination therapy on classical DMARDs are not encouraging, however, the combination therapy for patients with early RA, drugs utilizing immunosuppressant, biologics and other newly developed drugs will still have a chance to expect a potent efficacy for RA.
12100022 C-ANCA-positive IgG fraction from patients with Wegener's granulomatosis induces lung vasc 2002 Jul The aim of the present study was to analyse in rats the ability of C-ANCA-positive IgG fraction in triggering inflammatory response on pulmonary tissue. Wistar rats (n = 18) were injected via the the internal jugular vein with 20 mg of total C-ANCA-positive IgG fraction isolated from serum of three different Wegener's granulomatosis patients obtained before therapy. Similarly, control rats were treated with IgG fraction from two rheumatoid arthritis patients (n = 7), IgG from six normal human sera (n = 15) or saline (n = 18), respectively. Animals were sacrificed after 24h of injection for histological analysis of the lungs. Vasculitis and inflammatory infiltrate were consistently absent in rats injected with rheumatoid arthritis IgG or saline and in 14/15 of normal IgG treated animals. In contrast, marked vasculitis was observed in all 18 animals injected with C-ANCA-positive IgG fraction. The histological features were characterized by the presence of a perivascular pleomorphic cellular sheath, particularly around small vessels, endothelial adherence and diapedesis of polymorphonuclear leucocytes and presence of granuloma-like lesions. A dose-response relationship was observed between protein concentration of C-ANCA IgG sample and the intensity of the inflammatory response in the animals. In addition, IgG fraction with undetectable C-ANCA, obtained from one patient in remission after treatment, was not able to reproduce the pulmonary tissue alterations induced by its paired IgG that was positive for C-ANCA taken before therapy. The experimental model described herein may be useful to characterize more effectively the pathogenic mechanism of C-ANCA in Wegener's disease.
15319108 Usefulness of bioabsorbable thread pins after resection arthroplasty for rheumatoid forefo 2004 Jul BACKGROUND: Bioabsorbable thread pin has been used for internal fixation of bone. The results of resection arthroplasty of the lesser metatarsophalangeal (MTP) joints using internal intramedullary fixation with bioabsorbable pins have not been reported. METHODS: Resection arthroplasty of the MTP joints of the lesser toes with poly-L-lactic acid (PLLA) thread pins or Kirschner wires was performed at random in reconstruction of the 87 rheumatoid forefeet (62 patients) with a grommet-protected silicone-rubber implant insertion of the first MTP joint. Clinical symptoms, the state of radiographic changes, and complications were assessed 5-10 years (average, 7.7 years) postoperatively. RESULTS: The mean American Orthopaedic Foot and Ankle Society clinical scores at the preoperative and latest points were 31 and 91, respectively, in the operated patients with PLLA pins, while the mean scores were 32 and 82, respectively, in the operated patients with Kirschner wires. The lesser toes treated by bioabsorbable pins did not become rigid, although they were stable. Recurrent dorsal subluxation of the lesser MTP joints was visible on radiographs in three of the 46 feet with PLLA pins, while two feet had three dislocated MTP joints and one subluxated MTP joint postoperatively and recurrent dorsal subluxation of the lesser MTP joints was visible in four of the 41 feet with Kirschner wires. The postoperative hallux valgus did not progress to the preoperative level during the follow-up period in both groups. Two of the 46 feet with PLLA pins and two of the 41 feet with Kirschner wires had radiographic evidence of silicone synovitis without pathological fracture. Three patients with Kirschner wires had wire-track infection, and one patient had severe circulation disturbance of the corrected lesser toes necessitating wire removal. CONCLUSIONS: A new trial of internal fixation with bioabsorbable pins may lead to the establishment of a safe method for enhancing stability of the lesser toes after resection arthroplasty of the lesser MTP joints.
12697449 Immunoglobulin free light chains and mast cells: pivotal role in T-cell-mediated immune re 2003 Apr Immunoglobulin (Ig) free light (L)-chains have long been considered as the meaningless remnants of a spillover in the regular Ig production by B cells. The recently discovered role for Ig free L-chains in mediating hypersensitivity-like responses sheds new light on their potential role in immune responses. Ig free L-chains can sensitize mast cells, such that a second encounter with the appropriate antigen results in mast-cell activation. The possible importance of this reaction for the induction of T-cell-mediated immune reactions, leading to contact sensitivity, multiple sclerosis and rheumatoid arthritis is discussed.