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

ID PMID Title PublicationDate abstract
12679156 Peroral TAS-202 reduced vessel density in rats with adjuvant-induced arthritis. 2003 Apr 11 The present study was designed to investigate blood vessel density interpreted as an indirect measurement of angiogenesis following 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylamino-pyrimidine (TAS-202) treatment in a rat model of arthritis. Male Lewis rats were inoculated intradermally with Mycobacterium butyricum into the hind paw and the arthritic responses were evaluated by measuring the changes in paw volume. Both peroral TAS-202 (10 or 30 mg/kg/day) and indomethacin (1 mg/kg/day) inhibited the autoimmune phase of the arthritic response. However, while the increase in blood vessel density in the synovial tissue was significantly inhibited by TAS-202 (10 and 30 mg/kg/day), indomethacin did not exert this effect (1 mg/kg/day). These results, together with the observation that TAS-202 in combination with indomethacin or prednisolone maintained its ability to exert an antiangiogenic effect, indicate that TAS-202 may offer promise as an oral pro-drug for the treatment of rheumatoid arthritis, through its inhibitory effect on angiogenesis at the inflammation site.
12808294 Oral administration of proteoglycan isolated from Phellinus linteus in the prevention and 2003 Jun To examine whether oral administration of proteoglycan derived from Phellinus linteus, which is known as the medicinal mushroom, can prevent or treat collagen-induced arthritis (CIA) in mice as experimental model of autoimmune disease. CIA was induced by intradermal injection of type II collagen (CII) emulsified with complete freund's adjuvant (CFA) into the base of the tail (on day 7) followed by a booster injection on day 21 into the footpad. To examine the ability of proteoglycan to effect the inhibition of CIA, doses of proteoglycan were orally administered on day 0 (pre-administration) or day 28 (post-administration) at two groups. The inhibition of CIA by oral administration of proteoglycan was associated with decrease in anti-CII IgG and IgG2a antibodies (Abs) as well as varying kinds of cytokines including IL-12, TNF-alpha, and IFN-gamma. The results showed that administration of proteoglycan was followed by decrease of CIA of the mice in pre- and post-administration groups. Our findings suggest that immunomodulating proteoglycan isolated from P. linteus may be crucially involved in the prevention and treatment of autoimmune joint inflammation such as rheumatoid arthritis, although no definite role of anti-CII Abs in the human disease has been established.
15288856 Streptococcal septic arthritis in adults. A study of 55 cases with a literature review. 2004 Jul OBJECTIVES: To evaluate the rate of occurrence and characteristics of streptococcal septic arthritis. METHODS: Retrospective single-center study of patients with bacteriologically documented septic arthritis admitted to a rheumatology department over a 20-year period. RESULTS: Of 303 cases of septic arthritis, 55 (18%) were due to streptococci and 166 (55%) to Staphylococcus aureus (55%). As compared to patients with S. aureus arthritis, patients with streptococcal arthritis was more likely to be in female (56% vs. 36%, P < 0.006) and older than 60 years of age (71% vs. 58%), less likely to have comorbidities (36% vs. 56%), rheumatoid arthritis (5% vs. 19%, P < 0.01), or diabetes (2% vs. 15%, P < 0.01), and more likely to have cancer (13% vs. 7%). Involved joints and proportions of patients with arthritis in multiple joints were similar in two groups. Mortality was lower in the group with streptococcal infection (3.6% vs. 7.8%). The streptococci were distributed as follows: group A (n = 7), group B (n = 12), group C (n = 4), group D (n = 7), group F (n = 1), group G (n = 2), nongroupable (n = 14), nontypable (n = 1), and Streptococcus pneumoniae (n = 7). Groups A and B and nongroupable strains mainly affected women; group A selectively involved younger patients and group B very elderly patients. Comorbidity, most notably cancer, was common in patients with S. pneumoniae or group D streptococci. The portal of entry was often a skin lesion for groups A and B and a medical procedure for group D. Multiple joint involvement was common with groups A and B and prosthetic joint infection with groups B and C. Group A and S. pneumoniae were associated with severe systemic symptoms and extra articular foci of infection, whereas a smoldering course was more common with groups D and G and with nongroupable strains. Residual joint abnormalities were noted in half the patients, with no differences across groups. CONCLUSIONS: The features of streptococcal septic arthritis vary according to the group of the causative organism and differ from those of S. aureus arthritis.
15124251 Antibodies to tissue transglutaminase and Saccharomyces cerevisiae in ankylosing spondylit 2004 May OBJECTIVE: Subclinical gut inflammation has been described in patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Joint involvement has also been reported related to celiac disease. We investigated IgA antibodies to bovine tissue tranglutaminase (tTg) and IgA and IgG antibodies to human tTg and to Saccharomyces cerevisiae (ASCA) in patients with AS and PsA. METHODS: We evaluated the frequency of IgA antibodies to bovine tTg, and of IgA and IgG antibodies to human tTg and to ASCA in 43 patients with AS and 75 with PsA. As control groups we considered 79 patients with rheumatoid arthritis (RA) and 78 healthy blood donors. RESULTS: We detected antibodies as follows: IgA antibodies to bovine tTg in 1/43 patients with AS, 3/75 with PsA, 1/79 with RA, and in 9/78 healthy controls; IgA antibodies to human tTg in 1/43 patients with AS, 1/75 with PsA, 1/79 with RA, and in 3/78 healthy controls; IgG antibodies to human tTg in 1/43 patients with AS, 4/75 with PsA, 5/79 with RA, and in 7/78 healthy controls. IgA ASCA were confirmed in 10/43 patients with AS, 7/75 with PsA, 14/79 with RA, and in 7/78 healthy controls; IgG ASCA were present in 5/43 patients with AS, 4/75 with PsA, 8/79 with RA, and in 8/78 healthy controls. No statistically significant difference was observed in the prevalence of IgA or IgG antibodies to bovine and human tTg and in the frequency and in mean level of IgA or IgG ASCA between the studied groups or between each group and healthy controls. CONCLUSION: Our data fail to show an increased prevalence of autoantibodies associated with celiac and Crohn's disease in patients with AS and PsA.
17041972 Pain mechanisms and the rheumatic diseases. 2004 Pain is the predominant complaint of those with a rheumatological condition. This paper provides a broad overview of the current theories on the mechanisms of pain, the structure of the nervous system, and how these may relate to the sometimes seemingly incomprehensible symptoms of pain and other sensory disturbances that some rheumatology patients describe. Three case histories relating to rheumatoid arthritis, osteoarthritis and fibromyalgia are used to illustrate how this knowledge can be applied to clinical practice.
12008165 Calcitonin in reflex sympathetic dystrophy syndrome and other painful conditions. 2002 May Salmon calcitonin (especially intranasal) provides an interesting analgesic effect in a series of painful conditions including reflex sympathetic dystrophy syndrome, adhesive capsulitis, ankylosing spondylitis, rheumatoid arthritis, vertebral crush fractures and metastasis, phantom limb pain, etc. In addition, in preliminary series, calcitonin shows an unexpected benefit to vasomotor changes and peptic ulcer. Yet the experience in these conditions is limited and needs confirmation. By comparison with the injectable, the intranasal route seems particularly interesting because of less undesirable effects, and a more rapid and probably more powerful analgesia.
15488696 Pharmacoepidemiology and rheumatic disorders. 2004 Nov This article reviews the application of pharmacoepidemiology in the evaluation of drugs that are used commonly for rheumatic disorders. Data sources and methodology considerations for these studies are highlighted. The topics that are covered included the safety evaluation of nonsteroidal ant-inflammatory drugs, adverse pregnancy outcomes of pharmaceutical agents, gastroduodenal safety of alendronate, long-term beneficial effects of methotrexate for rheumatoid arthritis, and drug use study.
24728119 [Not Available]. 2002 Sep Multiple studies in osteoarthritis (OA), rheumatoid arthritis (RA), and several acute pain models indicate that the cyclooxygenase-2-specific inhibitors celecoxib and rofecoxib are equally effective as the conventional nonsteroidal antirheumatic drugs diclofenac, ibuprofen, and naproxen. Both drugs are approved for the treatment of OA and RA in a daily dosage of 2×100 mg, 1×200 mg, and 2×200 mg (celecoxib) or 1×12.5 mg and 1×25 mg (rofecoxib). In addition, rofecoxib has also been approved by the FDA for the treatment of postsurgical pain in a dosage of 50 mg. Normally celecoxib is used in a dosage of 1×200 mg for OA and 2×200 mg for RA, whereas both 12.5 and 25 mg rofecoxib are used for the treatment of OA and 25 mg for the treatment of RA. Coxibs might also be used for the treatment of seronegative spondarthritides, as is indicated by a successful study using celecoxib for the treatment of ankylosing spondylitis.
14579167 Rheumatoid-like polyarthritis as a presenting feature of metastatic carcinoma: a case pres 2003 Oct The case of a 69-year-old woman who presented with abrupt onset of rheumatoid-like symmetrical polyarthritis but who was subsequently diagnosed to have disseminated abdominal carcinomatosis is reported. The temporal relationship between the joint symptoms and the discovery of carcinoma suggested that the arthritis was a paraneoplastic manifestation of the latter. An underlying malignancy should always be looked for in elderly patients who present with explosive polyarthritis for the first time, particular if unexplained anaemia or constitutional symptoms persist after treatment.
17642657 Management of pyoderma gangrenosum--an update. 2004 Nov Pyoderma gangrenosum is a neutrophilic dermatosis with distinctive clinical manifestations. It is frequently associated with systemic diseases like inflammatory bowel disease, rheumatoid arthritis and myeloproliferative diseases. The etiopathogenesis of pyoderma gangrenosum is still not well understood. Clinically it is classified into ulcerative, pustular, bullous and vegetative types. The diagnosis mainly depends on the recognition of evolving clinical features as there are no specific investigations for the diagnosis. It is essential to exclude other infectious diseases before therapy is initiated as corticosteroids and immunosuppressant therapy are the mainstays in the treatment of this disease. Recently, drugs like tacrolimus, mycophenolate mofetil and infliximab have shown promising results in this condition. Recent concepts regarding the various types of pyoderma gangrenosum and its management are reviewed.
15141422 [Secondary vesical amyloidosis]. 2004 Mar The bladder involvement is a very unusual fact in systemic amyloidosis. The distinction of primary and systemic amyloidosis disease with bladder involvement (secondary bladder amyloidosis) is important to the urologist. Secondary amyloidosis of the bladder is a rare disease entity (approximately 20 cases published). We document a case of a woman with a large history of rheumatoid arthritis who developed severe macrohematuria. Diagnosis was done by biopsy that revealed amyloidosis, and it was confirmed with an immunohistochemical staining of the specimens that defined the process as amyloid AA (secondary amyloidosis).
15515214 Tissue transglutaminase autoantibodies in patients with IgM rheumatoid factors. 2004 Oct 31 The recent identification of tissue transglutaminase (tTG) as the autoantigen for celiac disease-associated anti-endomysial antibodies (EMA) has allowed the use of rapid immunoassay to detect the presence of autoantibodies, anti-tTG, in the serum of patients. In this study, we examined the prevalence of IgG or IgA anti-tTG in sera from patients with elevated levels of IgM rheumatoid factors, which are autoantibodies reactive with the Fc portion of IgG. We report here on four cases of anti-tTG positivity for patients with elevated IgM rheumatoid factor (RF) without evidence of celiac sprue. The study population consisted of 65 patients (26 men, 39 women; mean age, 49 years; range 4 - 92 years) with elevated RF (>20 U/ml ), and 23 healthy subjects (12 men, 11 women; mean age, 46 years; range, 21 - 54 years). IgG and IgA anti- tTG levels were detected using a commercially available ELISA kit (Immuno-Biological Laboratories, Germany). Out of 65 patients, one (1.5%) and three (4.6%) patients were positive for IgG and IgA anti-tTG antibodies, respectively, and this was a higher frequency than occurred in healthy subjects (0/23). The clinical features of the four cases positive for IgG or IgA anti-tTG were as follows: The first case (female, 63 yrs) positive for IgA anti-tTG antibody suffered from rheumatoid arthritis, type II diabetes mellitus, iron deficiency anemia and gastric indigestion without symptoms of malabsorption. She denied any gluten sensitivity on her diet. Her esophagogastroduodenoscopic biopsy showed mucosal atrophy with no elongated crypts or infiltration of inflammatory cells in the lamina propria. The remaining three cases positive for anti-tTG antibodies had interstitial pneumonia, a herniated lumbar disc, and mild scoliosis, respectively. They all denied any malabsorption symptoms or gluten sensitivity. Jejunal biopsy could not be performed in all four cases.
12794841 Blockade of parathyroid hormone-related protein prevents joint destruction and granuloma f 2003 Jun OBJECTIVE: To determine whether parathyroid hormone-related protein (PTHrP), an interleukin-1beta-inducible, bone-resorbing peptide that is produced in increasing amounts by the synovium in rheumatoid arthritis (RA), may play a role in the pathophysiology of joint destruction in RA. METHODS: PTHrP expression and the effect of PTHrP 1-34 neutralizing antibody on disease progression were tested in streptococcal cell wall (SCW)-induced arthritis, an animal model of RA. RESULTS: As has been reported in RA, while serum levels of PTHrP did not change during SCW-induced arthritis, PTHrP expression dramatically increased in the arthritic synovium. Treatment with PTHrP neutralizing antibody (versus control antibody) did not affect joint swelling in SCW-treated animals. However, PTHrP antibody significantly inhibited SCW-induced joint destruction, as measured by its ability to block increases in serum pyridinoline (a marker of cartilage and bone destruction), erosion of articular cartilage, decreases in femoral bone mineral density, and increases in the numbers of osteoclasts in eroded bone. Unexpectedly, granuloma formation at sites of SCW deposition in the liver and spleen was also inhibited by PTHrP antibody, an effect associated with significant decreases in the tissue influx of PTH/PTHrP receptor-positive neutrophils and in SCW-induced neutrophilia. In vitro, neutrophil chemotaxis was stimulated by PTHrP 1-34. CONCLUSION: These findings suggest that PTHrP, consistent with its previously described osteolytic effects in metastatic bone disease, can also be an important mediator of joint destruction in inflammatory bone disorders, such as RA. Moreover, this study reveals heretofore unknown effects of PTHrP peptides on neutrophil function that could have important implications in the pathogenesis of inflammatory granulomatous disorders.
14965306 The anti-inflammatory potential of the filarial nematode secreted product, ES-62. 2004 Filarial nematodes achieve long-term infection via modulation of the host immune system. Although human infection can result in severe pathology, the majority of infected individuals exhibit little evidence of this. Analysis of the immune response during infection indicates that the apparently healthy majority have an anti-inflammatory phenotype and it has been speculated that this may contribute to maintenance of host health. Recent data suggest that parasite-derived molecular secretions contribute to the anti-inflammatory phenotype and we have thus characterised a major filarial nematode secreted glycoprotein, ES-62. This molecule has been found to possess broad immunomodulatory activities that are in general, anti-inflammatory. It has long been recognised that several autoimmune disorders including rheumatoid arthritis (RA) exhibit reduced incidence and severity in geographic regions in which filarial nematodes are endemic. Furthermore, it has been speculated that these two observations are causally linked. However, molecular explanations for such an association have not been forthcoming. Although the aetiology of RA is unknown most data suggest that it is mediated via a pro-inflammatory immune response associated with excess cytokine production. Given that ES-62 is anti-inflammatory, we hypothesised that it might possess activity against diseases like RA. Indeed we found that subcutaneous injection of ES-62 prevented initiation of collagen-induced arthritis (CIA) and also suppressed progression of established disease. Ex vivo analyses demonstrated that these effects were due to inhibition of TNF-alpha production and reversal of collagen specific TH-1 responses. The nematode product was also found to inhibit pro-inflammatory cytokine release in vitro in synovial cells derived from RA patients. ES-62 thus represents a parasite-derived immunomodulator with significant therapeutic potential.
14513456 Shoulder arthroplasty in the young patient. 2003 Sep We reviewed the performance of 22 shoulder implant arthroplasties in 19 patients age 50 or younger at surgery. Patients were evaluated by telephone interview, written questionnaire, and radiographic examination. The average age at surgery was 38.6 years, and the average follow-up was 5.6 years. Patients were grouped by disease process (rheumatoid arthritis [RA], avascular necrosis [AVN], trauma, and hemophilic arthropathy [HA]) and type of prosthesis (total vs. hemiarthroplasty). The highest scores (best shoulder function) were seen in patients with hemiarthroplasty for HA. Patients with hemiarthroplasty for trauma and AVN scored similarly, whereas those with a hemiarthroplasty for RA scored lowest. Patients with RA who had a total shoulder arthroplasty scored higher than patients with hemiarthroplasty. When patients in our population with longer follow-up were compared with those with a shorter follow-up, no downward trends in shoulder function were seen. Accelerated deterioration of function of shoulder arthroplasties was not observed in our young patient population.
12218485 Haemophilus influenza infection complicating a total knee arthroplasty. 2002 Sep Haemophilus influenza is rarely a cause of septic arthritis in adults. It has not been reported as a cause of infection in total knee arthroplasties. Haemophilus influenza septic arthritis is a late stage, hematogenous infection. A 43-year-old woman with a history of rheumatoid arthritis was found to have Haemophilus influenza infection 3 years after the index total knee arthroplasty. The patient was treated with debridement and systemic antibiotics. At the 5-year followup, the patient was comfortable and free of clinical signs of infection. This approach was successful at eradicating infection and salvaging the total knee arthroplasty.
15182792 Outcome of patients with undifferentiated chronic monoarthritis: retrospective study of 46 2004 May OBJECTIVE: To determine the natural history of undifferentiated monoarthritis of more than 3 months' duration and to evaluate the usefulness of classic diagnostic tools for identifying factors associated with outcomes. METHOD: Retrospective study of 46 patients with undifferentiated monoarthritis of more than 3 months' duration. RESULTS: Full resolution was the outcome in 50% of cases. Rheumatoid arthritis and spondyloarthropathy were the most common diagnoses in the remaining patients. HLA-B27 status was the only significant predictor of outcome: progression to spondyloarthropathy was significantly more common (P = 0.05) among HLA-B27-positive patients. Mean time to full recovery was significantly shorter than mean time to disease progression (12 vs. 45 months, P = 0.0015). Intraarticular glucocorticoid injections were effective in over 50% of patients. Arthritis relief during the month following the injection was associated with self-limited disease. The role for magnetic resonance imaging in managing patients with undifferentiated monoarthritis remains unclear. CONCLUSION: In patients with undifferentiated monoarthritis, the likelihood of a full recovery is 50%. The only significant predictor of outcome was positive HLA-B27 status, which was associated with progression to spondyloarthropathy.
17143662 Partial tarsal arthrodesis for rheumatoid feet. 2004 Partial intertarsal joint arthrodesis was performed on 12 feet of 11 patients as a surgical treatment for planovalgus deformity of the foot and lesions of the intertarsal joints caused by rheumatoid arthritis. Single arthrodesis was performed on the talocalcaneal joint in eight feet, two of which underwent simultaneous total ankle arthroplasty, and on the talonavicular joint in two feet. Double arthrodesis was done on the talocalcaneal and talonavicular joints in one foot and on the talonavicular and calcaneocuboid joints in one foot. Screws or staples were used for fixation. Patients were followed for 2 years to 8 years 7 months (average 4 years 3 months). Osseous fusion was achieved in all feet, and satisfactory pain relief was obtained in all cases except one. We performed this surgery in patients who were relatively active, and the results indicated that arthrodesis of a small number of joints that caused pain and deformity was effective in reducing pain and correcting the deformity. We concluded that partial tarsal arthrodesis should be performed on a limited number of joints during the early stages of planovalgus deformity of the foot because more joints are found to be fixed during the advanced stages. However, progression of the osteoarthritis was found in the neighboring joints. Close follow-up observation is needed.
14757461 Prediction of lubrication regimes in wrist implants with spherical bearing surfaces. 2004 Mar The wrist joint is frequently affected by rheumatoid arthritis, resulting in wrist pain, deformity and ultimately loss of function. Artificial wrist implants have been introduced to treat the rheumatoid wrist, to attempt to alleviate pain and restore some function to the joint. The aim of this study was to predict the likely lubrication regimes that occur in wrist implants with spherical bearing surfaces. The implant was modelled as an equivalent ball-on-plane. Elastohydrodynamic lubrication theory was used to determine the minimum film thickness for the implant under different load, entraining velocity, lubricant viscosity, size of implant and material combinations. The results show that the highest film thickness is found in large implants, with high viscosity, high entraining velocity and low load. Hard-on-soft material combinations will operate with a boundary lubrication regime. Material combinations involving ceramic bearing surfaces have the potential to operate with a mixed lubrication regime.
11879240 Selective removal of circulating immune complexes from patient plasma. 2002 Feb The principle of a patient-specific immunoadsorber (PsIA) is demonstrated. Studies with model systems (HSA/anti-HSA) on immobilization, stability, and leakage form the basis for the presented fast-performance liquid chromatography (FPLC) and batch experiments, which were conducted using two different protein A adsorbers and autologous and heterologous PsIA systems. Experiments to determine the binding capacity of protein A adsorbers and PsIAs are described. In all experiments, the adsorption of plasma IgG, total protein, and C1q and C3d circulating immune complexes were measured. Plasma of patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) was investigated. Analysis was performed in both the initial plasma and the flow-through or supernatant. Results of the investigations using FPLC and batch experiments were compared. Autologous PsIA systems are suitable for the selective removal of elevated levels of circulating immune complexes in the plasma.