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ID PMID Title PublicationDate abstract
14572623 Autoantibodies to serotonin in serum of patients with psychiatric disorders. 2003 Nov 1 Antibodies to serotonin in serum were investigated by ELISA in patients with paranoid schizophrenia (N=27), schizoaffective psychosis (N=38), depression (N=67), Alzheimer's disease (N=21), chronic alcoholism (N=43), rheumatoid arthritis (N=25), and multiple sclerosis (N=16), and in healthy volunteers (N=60). Increased antibody reactivity to serotonin was found in schizoaffective psychosis, chronic alcoholism, and rheumatoid arthritis. Decreased antibody reactivity to serotonin was found in multiple sclerosis and depression. These anti-serotonin antibodies belong to the class of so-called natural autoantibodies. Alterations of these natural autoantibodies could indicate a disturbance to the immune system. It is possible that these antibodies could also influence receptor function. Autoantibodies to neurotransmitters in a wide spectrum of psychiatric disorders have not previously been reported.
12729115 The role of the posterior cruciate ligament in total knee replacement. 2003 Apr We randomised 129 knees which were to be replaced using a standard posterior-cruciate-ligament (PCL)-retaining cemented total knee replacement into two groups. In one the PCL was retained in the normal way and in the other it was resected. They were well matched, with a predominance of women, and a mean age of 67 years. There was no statistically significant difference in the Hospital for Special Surgery scores at a mean of 57 months (56 to 60) between the two groups although 21 patients (24 knees) were lost to follow-up. Relief from pain, correction of deformity, range of movement, stability and strength were comparable in both. Radiological assessment showed femoral rollback in approximately 20% of knees with a slightly higher incidence in the PCL-resected group. There was no significant loosening detected in either group at review at two years. At five years, one knee in the PCL-retained group had been revised because of infection and one patient in each group was awaiting revision for loosening. Our findings have shown no significant difference in the five-year results for a PCL-retaining total knee replacement if the PCL is excised or preserved. This suggests two important points. First, the PCL is not functional in most patients with a total knee replacement even when retained. Secondly, patients with an excised PCL show a good result with a PCL-retaining implant, thereby questioning the need for a posterior stabilised design in such a situation.
12056297 [Technique and value of arthrosonography in rheumatologic diagnosis. 2: Ultrasound diagnos 2002 Apr The clinical investigation of the hips in patients with rheumatic diseases is often equivocal. Thus, ultrasonography of this region is very relevant for rheumatologists. We suggest following standard scans: 1) anterior longitudinal scan to detect synovitis of the hip joint, iliopectineal bursitis, irregularities of the bone surface in osteoarthritis, Perthes' disease, and erosions due to inflammatory disease, 2) anterior transverse scan to evaluate these structures in an additional dimension, 3) lateral longitudinal scan of the hip joint with the same objective as the above mentioned scans; 4) lateral longitudinal scan, and 5) lateral transverse scan of the greater trochanter to diagnose trochanteric bursitis and bone irregularities due to enthesiopathy, and 6) dorsal oblique scan (optional) to diagnose hip joint effusions and pannus that localize in the dorsal region. Rotation of the joint is necessary to detect small effusions. The transducers should have a medium frequency of 5 to 7.5 MHz. In obese or muscular patients, 3.5 MHz transducers may be necessary to increase penetration. The anterior distance between the bone and the joint capsule of the hip joint is > or = 7 mm in probable and > or = 8 mm in definite synovitis or effusions. Synovitis or effusions are probable if the difference between right and left hip is > or = 2 mm, and they are definite if the difference is > or = 3 mm.
12852704 Valdecoxib: a review. 2003 Mar BACKGROUND: Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, naproxen, and related agents are nonselective inhibitors of both cyclooxygenase-1 (COX-1) and COX-2, which catalyze prostaglandin synthesis. This inhibition accounts not only for the analgesic, anti-inflammatory, and antipyretic effects of these agents, but also for side effects such as gastric mucosal damage and renal toxicity. Substantial evidence suggests that sparing COX-1 is advantageous for gastric safety. OBJECTIVE: This article reviews available information on the new COX-2-selective inhibitor valdecoxib, including its clinical pharmacology, pharmacokinetics, adverse effects, potential drug interactions, and contraindications and warnings. Results of clinical trials of efficacy and tolerability are summarized. METHODS: Articles for inclusion in this review were identified through searches of PubMed and MEDLINE (1966-December 2002) and International Pharmaceutical Abstracts (1970-December 2002). Search terms included valdecoxib, Bextra, COX-2-selective inhibitors, coxibs, and selective cyclooxygenase inhibitors. The reference lists of identified articles were reviewed for additional publications. Product information was also obtained from the manufacturer of valdecoxib. RESULTS: Fourteen clinical studies involving > 4000 patients have been conducted. Valdecoxib was significantly more effective than placebo in the treatment of adult rheumatoid arthritis, osteoarthritis, pain associated with primary dysmenorrhea, and postoperative pain. Valdecoxib was comparable to naproxen for the treatment of rheumatoid arthritis in 1 study and equivalent to naproxen for the treatment of osteoarthritis in other studies. Three studies found valdecoxib comparable to naproxen sodium for the relief of moderate to severe pain due to primary dysmenorrhea, and others found valdecoxib comparable to oxycodone plus acetaminophen and significantly more effective than rofecoxib for the relief of pain associated with dental surgery (P < 0.05). Four safety studies and 2 reviews of clinical trials documented lower rates of endoscopic gastroduodenal ulcer formation with valdecoxib compared with ibuprofen, naproxen, and diclofenac (P < 0.001 to P < 0.05). Valdecoxib did not inhibit platelet function (bleeding time and platelet aggregation) in healthy adults or in the elderly. Due to the risk of potentially serious skin and allergic reactions, patients who are allergic to sulfa-containing drugs should not take valdecoxib. The drug should be discontinued immediately if rash develops. CONCLUSIONS: In clinical trials, valdecoxib was effective for the treatment of osteoarthritis, rheumatoid arthritis, and moderate to severe pain associated with primary dysmenorrhea. As with the other COX-2-selective inhibitors (celecoxib and rofecoxib), valdecoxib appears to produce less gastrointestinal toxicity than conventional nonselective NSAIDs, although some of the relevant clinical studies have been published only as abstracts. Use of valdecoxib should be reserved for patients at risk for NSAID-induced gastrointestinal problems.
12924499 Fibrillary glomerulonephritis with hypocomplementemia. 2003 Aug A 59-year-old man was referred for evaluation of nephrotic syndrome. The patient was diagnosed to have rheumatoid arthritis and had been treated for 10 years. Renal biopsy showed mesangial proliferation with small nodular formations, which were determined as fibrillary deposits (average diameter: 20 nm) by electromicroscopy. Congo-red stain was negative. The laboratory findings revealed hypocomplementemia and lambda type of Bence-Jones protein in urine without other systemic diseases including multiple myeloma. Immunosuppressive therapy did not attenuate the nephrotic-range proteinuria. Such a case of fibrillary glomerulonephritis with hypocomplementemia is rare.
15580154 Adalimumab: human recombinant immunoglobulin g1 anti-tumor necrosis factor monoclonal anti 2004 Fall Tumor necrosis factor (TNF) is a proinflammatory cytokine that is involved with normal inflammatory and immune responses and with the pathogenesis of chronic inflammatory medical conditions, such as rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, and Crohn's disease. The newest therapies for these inflammatory conditions include the TNF biologic response modifiers infliximab, etanercept, and adalimumab. Adalimumab is a human recombinant immunoglobulin G1 anti-TNF monoclonal antibody. As monotherapy, or in combination with methotrexate or other traditional disease-modifying antirheumatic drugs, adalimumab can produce improvements in the signs and symptoms associated with rheumatoid arthritis and can slow progression of the joint destruction. The adverse effect profile of adalimumab seems to be comparable to that of etanercept. Adalimumab also seems to be useful in the treatment of psoriasis, psoriatic arthritis, and Crohn's disease; however, none of these indications are approved by the US Food and Drug Administration, and the optimal dosing regimen for these indications has not been established.
15165294 Pneumonia due to Cryptococcus neoformans in a patient receiving infliximab: possible zoono 2004 Jun The use of humanized antibody against tumor necrosis factor alpha (TNF-alpha) may increase the risk of various opportunistic infections, including tuberculosis and fungal infections. We report a case of cryptococcal pneumonia in a patient who was taking infliximab for rheumatoid arthritis. A temporally related exposure history raised the possibility that our patient acquired the infection from his pet cockatiel. It seems prudent to advise patients receiving infliximab to avoid exposure to pet avian excreta.
15478159 Comprehensive assessment of clinical outcome and quality of life after total shoulder arth 2004 Oct 15 OBJECTIVE: To explore the physiometric and psychometric properties of clinical, generic, and condition-specific assessment instruments. To describe patients' outcome after total shoulder arthroplasty. METHODS: Forty-three patients were assessed in a 5-6-year cross-sectional catamnesis. RESULTS: With regard to shoulder joint stability, pain, general physical health, and mental health, the patients showed scores comparative to normative scores. Significant functional limitation was evidenced by low mean scores on the specific function scales (e.g., Disability of the Arm, Shoulder and Hand questionnaire score = 64.0, normative score = 86.6). There were high correlations among the joint-specific scales (up to 0.93) and moderate correlations between these and the generic and clinical scales. Factor analysis identified 3 different assessment domains. CONCLUSION: The patients' quality of life (QOL) was high and not affected by impairment in some specific functional abilities. Physical QOL, mental QOL, clinical assessment, condition-specific measures, and generic measures were identified as separate domains, all of which are required for a comprehensive and sophisticated assessment in practical clinical routine.
15050886 Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the lite 2004 Apr 5 Anemia is a common comorbidity in individuals with rheumatoid arthritis (RA). In fact, anemia of the type characterized by low serum iron concentrations in conjunction with adequate iron stores is frequently associated with RA and has served as a model for anemia of chronic disease. A systematic search of the scientific literature published since January 1966 identified 19 articles that reported findings on either the prevalence of anemia in patients with RA or outcomes for patients with anemia and RA. Ten articles addressed the prevalence of anemia in patients with RA. Estimates of the prevalence of mild anemia ranged between 33% and 60%; however, the 2 studies that examined demographics in patients with RA did not identify subpopulations at particular risk for anemia. Twelve articles assessed the impact of the resolution of anemia on symptoms and quality of life (QOL) in patients with RA. For many of the parameters assessed-including swollen, painful, and tender joints, pain, muscle strength, and energy levels-a positive correlation was observed between improvement of symptoms and the resolution of anemia. In addition, 2 studies reported a significant improvement in QOL scores in patients with RA who experienced a response to treatment for anemia. These results suggest that (1) patients with RA who have anemia are likely to have more severe joint disease and (2) if the anemia is successfully treated, the joint disease will likely respond to treatment as well. Whether improvements in QOL and/or joint symptoms occur with improvement of anemia, independent of other signs of an overall response to RA therapy, remains to be determined.
11961974 [A critical evaluation of side effect data on COX-2 inhibitors]. 2002 Feb 20 BACKGROUND: Celecoxib and rofecoxib have been used in Norway since 2000. These cyclooxygenase 2 inhibitors (COX-2 inhibitors) have no better clinical efficacy than older non-steroid anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis or osteoarthritis, but may possibly lead to a lower incidence of upper gastrointestinal ulcers. MATERIAL AND METHODS: Published and unpublished clinical data on side effects were examined and interpreted. The aim was to evaluate the general safety of these new drugs compared with older NSAIDs. RESULTS: The incidence of side effects is addressed in two large published studies comparing COX-2 inhibitors with other NSAIDs. Only rofecoxib showed an unequivocal lower incidence of complicated upper gastrointestinal ulcers. However, the incidence of serious side effects was significantly higher in the rofecoxib group. In the other study there was a trend towards more serious side effects in the celecoxib group. INTERPRETATION: The available clinical data do not suggest that COX-2 inhibitors are safer drugs than other NSAIDs.
14566967 Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of hum 2003 Dec This study addresses mechanisms by which interleukin-1beta (IL-1beta) regulates human chondrocyte apoptosis induced by a combination of the anti-CD95 antibody CH-11 and the proteasome inhibitor (PSI). The effect of IL-1beta on apoptosis varied among tissue samples. IL-1beta either enhanced (16/22 samples) or inhibited (6/22 samples) DNA fragmentation and caspase-3 processing. The protective effect of IL-1beta was abrogated by the nitric oxide (NO) synthesis inhibitor N-monomethyl-l-arginine (L-NMMA) while apoptosis stimulation was not affected. The NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl penicillamine (SNAP) blocked DNA fragmentation, and this was associated with partial inhibition of caspase-3 processing. Pyrrolidine dithiocarbamate (PDTC), a scavenger of reactive oxygen species (ROS) blocked apoptosis induction by CH-11/PSI as well as the enhancement by IL-1beta. The pro-apoptotic effects of IL-1beta were also abrogated by the p38 inhibitor SB 202190. In conclusion, IL-1beta augments CH-11/PSI induced apoptosis in the majority of chondrocyte samples. The pro-apoptotic effect of IL-1beta is not dependent on NO. In contrast, the anti-apoptotic effect of IL-1beta observed in a minority of samples is partially NO-dependent.
12233895 Influence of Helicobacter pylori eradication therapy on the occurrence of gastrointestinal 2002 Sep OBJECTIVE: To evaluate the effect of eradication treatment of Helicobacter pylori and the influence of H. pylori status on the incidence of gastrointestinal (GI) events in rheumatic patients receiving longterm conventional nonsteroidal antiinflammatory drug (NSAID) therapy combined with omeprazole. METHODS: Patients (n = 919) requiring longterm NSAID therapy entered this multicenter, open label, parallel group study. H. pylori positive patients were randomized to receive either eradication therapy (omeprazole 20 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg bid for 7 days) or no therapy. Both these groups and the H. pylori negative patients were given omeprazole, 20 mg once daily, along with NSAID for the study duration (5-8 weeks). Treatment failure (primary outcome variable) was defined as the occurrence of severe GI event (symptomatic ulcer, bleeding, perforation) or dyspepsia leading to discontinuation of NSAID therapy, unscheduled consultation, or upper GI tract endoscopy. RESULTS: Treatment failure was recorded in 9/294 (3.06%) infected patients receiving eradication therapy, 8/219 (3.65%) infected patients receiving omeprazole alone, and 5/391 (1.28%) H. pylori negative patients (p > 0.05). H. pylori eradication did not appear to influence the incidence and severity of dyspeptic symptoms in infected patients. CONCLUSION: Our results do not support the use of H. pylori eradication therapy in rheumatic patients receiving conventional NSAID along with omeprazole.
15149282 Effects of pro- and anti-inflammatory cytokines and nitric oxide donors on hyaluronic acid 2004 Sep The aim of the present study was to investigate the effects of (i) the pro-inflammatory cytokines IL (interleukin)-1beta, TNF-alpha (tumour necrosis factor-alpha), IFN-gamma (interferon-gamma) and anti-inflammatory cytokines IL-4 and IL-13, and (ii) NO (nitric oxide) donors on HA (hyaluronic acid) production by synovial cells from patients with rheumatoid arthritis. Synovial cells obtained from five patients with rheumatoid arthritis were incubated for 24 h without or with IL-1beta, TNF-alpha, IFN-gamma, or with this mixture for 24 h plus IL-4 or IL-13 for the last 6 h. The same cells were also incubated for 3-24 h without or with SNP (sodium nitroprusside) or SNAP (S-nitroso-N-acetyl-DL-penicillamine). HA secretion was determined by an immunoenzymic assay based on HA-specific binding by proteoglycan isolated from bovine cartilage. IL-1beta, TNF-alpha and IFN-gamma alone or in combination stimulated HA synthesis, whereas IL-4 and IL-13 dose-dependently inhibited HA production induced by Th1 cytokines. HA production was significantly increased by the presence of 1 mM SNP after 6 and 12 h (maximal effect). HA production was significantly increased by the presence of 0.01 and 0.1 mM SNAP after 12 h of incubation, and cells treated with 1 mM SNAP showed a maximal HA production after 24 h of incubation. In conclusion, the present study provides data concerning the regulatory role of pro- and anti-inflammatory cytokines and NO donors on HA metabolism in rheumatoid synovial cells and may help in understanding the pathophysiology of rheumatoid arthritis.
12404034 [Sodium gold thiosulfate therapy: an open, viewed, multicenter trial in rheumatoid arthrit 2002 Jul OBJECTIVE: To evaluate if parenteral gold-therapy with Sodium gold thiosulfate is effective and safe for the treatment of rheumatoid arthritis we began an open, multicenter trial. METHODS: 126 rheumatoid arthritis patients were treated with Sodium gold thiosulfate for two years. Efficacy, quality of life, progression of joint damage, inflammatory parameters and side effects were evaluated. RESULTS: Gold salts reduced joint inflammation and improved subjective and objective symptoms, quality of life and activity of illness within 6 months. Side effects appeared in 13,8% of all cases and regressed, promptly, when gold therapy stopped. The poor efficacy caused the interruption and the change from the gold therapy to others disease-modifying anti-rheumatic drugs (DMRDs) in 17,8 % of the patients. CONCLUSIONS: The follow-up showed Sodium gold thiosulfate was effective in Rheumatoid Arthritis and the survival in therapy was of 77,8% to one year and of 68,4% to two years.
12887102 Natural autoantibodies to TCR public idiotopes: potential roles in immunomodulation. 2003 Mar Autoantibodies directed against variable domain epitopes of the alpha/beta T cell receptor (TCR) occur in sera of man, mouse and other vertebrates. Here, we focus upon autoantibodies expressed in human rheumatoid arthritis (RA) and systemic erythematosus (SLE) with parallel studies involving collagen induced arthritis (CIA) in mice transgenic for human HLA-DR conferring resistance or susceptibility to autoimmune disease. We report specificity characterization of polyclonal and monoclonal IgM and IgG autoantibodies from SLE and for IgM monoclonal autoantibodies of RA patients. The data suggests that autoantibodies directed against "public" idiotopes present in the first complementarity determining region (CDR1) and the third framework (FR3) of the Vbeta gene products are generated in response to over-production of autodestructive T cells bearing particular Vbeta gene products and function to modulate (downregulate) the expression of these T cells. Since antibodies of these specificities are present in polyclonal IgG immunoglobulin (IVIG) preparations used for therapeutic purposes, the immunomodulatory effects of antibodies directed against TCR variable domains may account, at least in part, for the efficacy of IVIG preparations in therapy of autoimmune diseases and in the prevention of graft versus host reactions.
12932295 Mactinin: a modulator of the monocyte response to inflammation. 2003 During inflammatory processes, monocytes leave the blood stream at increased rates and enter inflammation tissue, where they undergo phenotypic transformation to mature macrophages with enhanced phagocytic activity. alpha-Actinin, a cytoskeletal protein, is present in focal adhesion complexes and left in the microenvironment as a result of cell movement. Mactinin, a 31 kDa amino-terminal fragment of alpha-actinin, is generated by the degradation of extracellular alpha-actinin by monocyte-secreted urokinase. We have previously demonstrated that mactinin promotes monocyte/macrophage maturation. We now report that 0.5-10 nM mactinin has significant chemotactic activity for monocytes. Mactinin seems to be present in inflammatory arthritis synovial fluid, because affinity-purified antisera reacted with a protein of the expected molecular mass in various types of arthritis fluids that were immunoaffinity-purified and subjected to Western analysis. Thus, six of seven samples from patients with psoriatic arthritis, reactive arthritis, gout, or ankylosing spondylitis contained mactinin at levels that are active in vitro. Initially, mactinin was not found in affinity-purified rheumatoid arthritis samples. However, it was detectable after the dissociation of immune complexes, suggesting that it was complexed to anti-microfilament auto-antibodies. In addition, mactinin was found in the lavage fluid from the arthritic knee joints of rabbits with antigen-induced arthritis and was absent from the contralateral control knee fluids. We conclude that mactinin is present in several types of inflammatory arthritis and might modulate mononuclear phagocyte response to inflammation.
12794366 [Influence of glucocorticoids on bone mineral density in rheumatoid arthritis and seronega 2003 Glucocorticoids are commonly used for treatment of rheumatoid arthritis and seronegative spondyloarthropathies. The aim of this study was to investigate the influence of the glucocorticoids for the bone mineral density of patients with chronic autoimmune arthritides, to evaluate the importance of the duration and dosage of the treatment, and to compare with well-known risk factors for osteoporosis: age and sex of patients, duration of menopause, length of the arthritis-related functional insufficiency. One-hundred-eighty-eight rheumatoid arthritis and 97 seronegative spondyloarthropathies patients were investigated. Bone mineral density was examined by the method of dual energy x-ray absorptiometry (Hologic QDR 4500 W) in the vertebral bodies of the lumbar spine and the hip. Relative risk of glucocorticoids for development of osteopenia and osteoporosis was moderate, less significant than the impact of patient's age. Negative influence of glucocorticoids on the bone mineral density was related with cumulative dose and duration of the treatment. In rheumatoid arthritis patients it was more significant, than in cases of seronegative spondyloarthropathies. Diminishing of the bone mineral density was more important in the lumbar spine, the changes in hip mineralization were less expressed in both diseases.
15585509 TNF-alpha neutralization in cytokine-driven diseases: a mathematical model to account for 2005 Mar OBJECTIVES: Neutralization of TNF-alpha with either monoclonal antibodies or soluble receptors, although not curative, has significant clinical benefit in patients with rheumatoid arthritis (RA). In contrast, blockade of TNF-alpha has little clinical benefit in the majority of patients with systemic inflammatory response syndrome (SIRS) in spite of the identification of TNF-alpha as a key factor in its pathology. It is not clear why there is such a significant difference in the responses to TNF-alpha neutralization in these two conditions. Here we use mathematical modelling to investigate this discrepancy. METHODS: Using the known pharmacokinetic and pharmacodynamic properties of TNF-alpha-blocking biological agents, we constructed a mathematical model of the biological actions of soluble(s) TNFR2, Etanercept and Infliximab. RESULTS: Our model predicts that all three inhibitors, but especially Etanercept, are effective at controlling TNF-alpha levels in RA, which we propose is a condition in which TNF-alpha production and inhibition are in equilibrium. However, when free TNF-alpha drops to a low level, as can occur in SIRS, which we propose is a non-equilibrium condition, the sequestered TNF-alpha can act as a slow-release reservoir, thereby sabotaging its effectiveness. CONCLUSIONS: These results may explain the effectiveness of TNF-alpha blockade in the equilibrium condition RA and the ineffectiveness in the non-equilibrium condition SIRS.
15331191 Interstitial lung disease in the patient who has connective tissue disease. 2004 Sep Interstitial lung disease is a common complication of many of the connective tissue diseases. Because the prognosis, degree of reversibility, and optimal therapy differs for each disease presentation, a thorough knowledge of the pulmonary presentations of each connective tissue disease is important. Additionally, the challenge of finding the patient who has occult connective tissue disease in an interstitial lung disease clinic is discussed.
15576416 Raised serum APRIL levels in patients with systemic lupus erythematosus. 2005 Jul OBJECTIVE: To determine whether serum levels of a proliferation-inducing ligand (APRIL) are raised in patients with systemic lupus erythematosus (SLE) and correlate with autoantibody titres or disease activity, or both. METHODS: Serum samples from 48 patients with SLE, 41 normal healthy subjects, and 21 patients with rheumatoid arthritis (RA) were assayed for APRIL by enzyme linked immunosorbent assay. Medical charts were retrospectively reviewed for autoantibody titres and immunoglobulin levels. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index. RESULTS: The APRIL levels in the serum samples from patients with SLE were significantly higher than in those from healthy controls and those from patients with RA. Serum APRIL levels did not correlate with serum IgG and IgM levels, but had a tendency to correlate with anti-double stranded DNA antibody titres. Moreover, serum APRIL levels correlated significantly with musculoskeletal manifestations among patients with SLE when assessed by the BILAG index. CONCLUSION: APRIL may be an important factor in raised autoantibody titres and musculoskeletal disease in patients with SLE. Patients with raised serum APRIL levels may be ideal candidates for therapeutic targeting of APRIL.