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ID PMID Title PublicationDate abstract
14510338 Effect of minocycline and tetracycline on immunological responses in experimental animals. 2002 Nov In recent years, there has been an increase in the use of antibiotics, primarily tetracycline anlogues, like minocy cline to treat rheumatoid arthritis. However, the mechanism of action of these analogues is not clearly defined. The present study investigates the effects of minocycline and tetracycline on some immunological parameters in Wistar rats and Swiss albino mice. Haemagglutination (HA) titre was employed as parameter of humoral immune response and % leukocyte migration inhibition (% LMI) and footpad thickness tests were used as measures of cell mediated immune response. Both minocycline and tetracycline significantly improved humoral immune response in rats as indicated by an increase in anti-SRBC antibody titre. In the LMI test, depending on the time period of drug administration, there was an increase or a decrease in the % LMI. When drugs were administered on days 1-7 after sensitization, both the compounds caused a significant increase in % LMI. However, the % LMI was significantly decreased when the drugs were administered on days 7-13 of sensitization, indicating variable effects of these agents on the Immune mechanism depending on the time of administration in relation to the development of immune responsiveness. Both minocycline as well as tetracycline produced a significant decrease in the paw volume in the footpad-thickness test which indicates a decrease in lymphokine production/release. The present study thus shows that minocycline and tetracycline exhibit immunomodulatory properties, which may contribute significantly to their beneficial effects in rheumatoid arthritis.
12901949 Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases. 2003 Aug Roles for Toll-like receptors (TLRs) are emerging in conditions such as sepsis syndrome, systemic lupus erythromatosis, rheumatoid arthritis and asthma, suggesting that the selective targeting of TLRs might be useful therapeutically. TLRs are defined by the presence of extracellular leucine-rich repeats and an intracellular Toll/interleukin-1 receptor domain, and play a role in host defence and inflammation. Signalling pathways activated by TLRs show remarkable similarity to those activated by the pro-inflammatory cytokine interleukin-1 (the receptor for which also has a Toll/interleukin-1 receptor domain), although adaptor proteins specific for certain TLRs are starting to emerge (e.g. Mal and Trif). The common signalling pathways used by all members of the TLR superfamily are being targeted, with drugs that block nuclear factor-kappaB and p38 mitogen-activated protein kinase in clinical development for diseases such as rheumatoid arthritis and psoriasis. As we learn more about TLR signal transduction, more options are presenting themselves for pharmacological targeting.
12680625 Anti-transglutaminase antibodies and the serological diagnosis of coeliac disease. 2003 Tissue transglutaminase (tTG) has recently been identified as the antigenic target recognised by anti-endomysial antibodies in patients with coeliac disease. In this study, an enzyme-linked immunosorbent assay (ELISA) is used to measure IgA, IgG and IgM antibodies to tTG in patients with coeliac disease and a variety of other inflammatory disorders; and is compared to the standard immunofluorescence test used to detect endomysial antibodies (EMA). In the samples tested, 3% control sera (n=146), 83% EMA-positive sera (n=29), 9% patients with Graves' disease (n=94), 12% antimitochondrial antibody-positive sera (n=53), 11% rheumatoid arthritis patients (n=53) and 22% systemic lupus erythematosus (SLE) patients (n=46) were positive for anti-tTG antibodies. In contrast, none of the controls, 1% of patients with Graves' disease, 2% antimitochondrial antibody-positive sera, 2% rheumatoid arthritis patients and none of the SLE patients were positive for EMA. Measurement of IgG or IgM antibodies to tTG was much less reliable than IgA anti-tTG antibody for the serological diagnosis of coeliac disease. The addition of calcium to the coating buffer improved the assay characteristics of the anti-tTG ELISA. However, the IgA anti-tTG ELISA, with and without calcium, performed less well than the standard EMA test used for the serological diagnosis of coeliac disease. In particular, the anti-tTG ELISA gave a higher rate of non-specific positive reactions.
12089491 Clinical outcome of radiosynoviorthesis: a meta-analysis including 2190 treated joints. 2002 Jul A variety of indications for radiosynoviorthesis have been reported in literature, but the clinical outcome differs and depends on the primary disease and the pre-existing degenerative changes. This metaanalysis was carried out to establish groups for radiosynoviorthesis based on clinical outcome with respect to primary disease, clinical stage and the pre-existing degenerative changes. The literature search was carried out using the MEDLINE search term 'radionuclide synovectomy'. Based on reports in the literature we determined groups for radiosynoviorthesis for clinical use. Our literature list comprised 2190 joints that were treated with radiosynoviorthesis. The overall response rate for all treated joints was 72.5+/-17%. The mean improvement rate for the treated joints in rheumatoid arthritis was 66.7+/-15.4%. For osteoarthritis the success rate was 56+/-11%, with better results in case of minimal radiological changes. Radiosynoviorthesis in patients with changes according to Steinbrocker I and II was successful in 72.8+/-12.3%, and in 64+/-17.3%, respectively. Steinbrocker III and IV had a mean success rate of 52.4+/-23.6%. In the case of haemophilia and Willebrand's disease a reduction of joint bleedings and factor usages after radiosynoviorthesis was evident in 91+/-4.3%. In patients with pigmented villonodular synovitis radiosynoviorthesis was successful in 77.3+/-25.3%. It is concluded that radiosynoviorthesis provides better results in rheumatoid arthritis than in osteoarthritis. Minimal or moderate changes according to Steinbrocker stages I and II respond better to radionuclide therapy than do stages III and IV. Deformed or unstable joints might fail treatment and therefore surgical interventions should be considered. Close cooperation with orthopaedists and rheumatologists is necessary to consider radiosynoviorthesis in each patient to ensure optimal medical care.
15563243 Temsirolimus: CCI 779, CCI-779, cell cycle inhibitor-779. 2004 Wyeth (formerly American Home Products) is developing temsirolimus [Cell cycle inhibitor-779, CCI 779], an ester analogue of sirolimus, for the treatment of cancer, multiple sclerosis and rheumatoid arthritis. Temsirolimus binds to the cytosolic protein, FKBP, which subsequently inhibits mTOR (mammalian target of rapamycin). Inhibition of mTOR blocks a number of signal transduction pathways that suppress translation of several key proteins regulating the cell cycle. These effects lead to a cell cycle block at the G1 phase. In animal models of human cancers, temsirolimus inhibited the growth of a diverse range of cancer types even when an intermittent dosing schedule was used. The compound also appears to have potential for the blockade of inflammatory responses associated with autoimmune and rheumatic diseases by inhibiting T-cell proliferation. On 11 March 2002, American Home Products changed its name and the name of its subsidiary Wyeth-Ayerst to Wyeth. During the first half of 2004, Wyeth initiated ongoing recruitment into a US phase III trial comparing orally administered temsirolimus plus letrozole versus letrozole alone as first-line treatment among approximately 1200 postmenopausal women with advanced breast cancer. The multicentre, randomised, double-blind, placebo-controlled trial is estimated to last 34 months. All subjects will have the option of participating in the long-term follow-up phase of the trial that involves follow-up every 3 months until disease progression; the primary endpoint is overall progression-free survival. In August 2004, the US FDA granted temsirolimus fast-track status for the first-line treatment of poor-prognosis patients with advanced renal cell carcinoma. Previously in March 2002, temsirolimus received fast-track status from the FDA for the treatment of renal cell carcinoma in patients who failed to respond to interleukin-2 treatment. Wyeth intends to file a NDA for temsirolimus for this indication by 2006. Researchers from Wyeth presented the findings from a preclinical study of temsirolimus at the 67th Annual Scientific Meeting of the American College of Rheumatology and the 38th Annual Meeting Association of Rheumatology Health Professionals (ACR/ARHP-2003) [Orlando, FL, USA; October 2003]. The aim of this study was to determine the effect of temsirolimus on lymphocyte proliferation and cytokine production. Since lymphocytes and cytokines are significantly involved in the pathogenesis of rheumatoid arthritis, temsirolimus could have disease-modifying antirheumatic drug (DMARD) activity against rheumatoid arthritis via the inhibition of these factors. According to Wyeth's investor presentation in June 2004, the patent covering temsirolimus is due for expiry in 2014.
12353217 Induction of microsomal prostaglandin E synthase in the rat brain endothelium and parenchy 2002 Oct 21 Although central nervous symptoms such as hyperalgesia, fatigue, malaise, and anorexia constitute major problems in the treatment of patients suffering from chronic inflammatory disease, little has been known about the signaling mechanisms by which the brain is activated during such conditions. Here, in an animal model of rheumatoid arthritis, we show that microsomal prostaglandin E-synthase, the inducible terminal isomerase in the prostaglandin E(2)-synthesizing pathway, is expressed in endothelial cells along the blood-brain barrier and in the parenchyma of the paraventricular hypothalamic nucleus. The endothelial cells but not the paraventricular hypothalamic cells displayed a concomitant induction of cyclooxygenase-2 and expressed interleukin-1 type 1 receptors, which indicates that the induction is due to peripherally released cytokines. In contrast to cyclooxygenase-2, microsomal prostaglandin E synthase had very sparse constitutive expression, suggesting that it could be a target for developing drugs that will carry fewer side effects than the presently available cyclooxygenase inhibitors. These findings, thus, suggest that immune-to-brain communication during chronic inflammatory conditions involves prostaglandin E2-synthesis both along the blood-brain barrier and in the parenchyma of the hypothalamic paraventricular nucleus and point to novel avenues for the treatment of the brain-elicited disease symptoms during these conditions.
17143664 Clinical characteristics of Mycobacterium tuberculosis infection among rheumatoid arthriti 2004 To evaluate the clinical characteristics of Mycobacterium tuberculosis infection in rheumatoid arthritis (RA) patients, we examined the clinical manifestations and radiography/computed tomography (CT) findings in RA patients with tuberculosis (RA+/TB+). A total of 1121 tuberculosis patients were admitted to our hospital from 1995 to 2003, with the RA patients among them comprising 1.8% (20 cases; 9 men and 11 women). This is approximately three times as high as the prevalence of RA in the entire population in Japan. In addition, the RA+/TB+ patients were older and had a longer history of RA than the 140 outpatients in our RA clinic who did not have tuberculosis (RA+/TB-). Half of the RA+/TB+ patients had no symptoms (e.g., cough, sputum, pyrexia), and their tuberculosis was detected accidentally by radiography/CT. The positive rates of the bacilli in the smear and culture of the sputum from the RA+/TB+ patients were lower than those from 143 patients randomly selected from among 1091 tuberculosis patients without any collagen disease including RA (RA-/TB+). The RA+/TB+ patients had a higher incidence of extrapulmonary tuberculosis (30%), including four cases (20%) of miliary tuberculosis, an incidence seven times higher than among the general population of tuberculosis patients. Among 14 cases of pulmonary tuberculosis patients with RA, bilateral lesions and non-cavitary lesions were found in 71.4% and 64.3%, respectively, which tended to be a higher incidence than in the RA-/TB+ patients. The mortality rate and sputum conversion time of the RA+/TB+ patients were no different from those of the RA-/TB+ patients. The prevalence of tuberculosis in RA patients is expected to increase after introduction of anti-cytokine therapy in Japan, and careful observation should be done to avoid this complication in RA patients.
15103245 Long-term risks associated with biologic response modifiers used in rheumatic diseases. 2004 May PURPOSE OF REVIEW: The introduction of tumor necrosis factor-alpha antagonists in 1998 has had a significant impact on the treatment of rheumatoid arthritis. However, as use of these agents has increased worldwide, infrequent adverse events that were not apparent in pivotal controlled clinical trials required for registration have emerged. RECENT FINDINGS: These adverse events include serious infections, particularly tuberculosis, which may be atypical in presentation. Concern regarding increased risk of lymphoma has also emerged, although it remains unclear whether the risk exceeds that observed in other rheumatoid arthritis patients with comparable disease activity. Development of a systemic lupus erythematosus-like syndrome, which typically abates after discontinuation of the drug, is another rare complication that was further reported during the past year. Finally, additional cases of congestive heart failure and demyelinating syndromes (including cases resembling progressive multifocal leukoencephalopathy) have been reported that appear to be related to the tumor necrosis factor-alpha antagonists. SUMMARY: Additional postmarketing surveillance of these and other serious adverse events is necessary to determine the true risk of their occurrence, and whether a reassessment of the overall risk-benefit of tumor necrosis factor-alpha antagonists will be required.
14710506 Burden of major musculoskeletal conditions. 2003 Musculoskeletal conditions are a major burden on individuals, health systems, and social care systems, with indirect costs being predominant. This burden has been recognized by the United Nations and WHO, by endorsing the Bone and Joint Decade 2000-2010. This paper describes the burden of four major musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, osteoporosis, and low back pain. Osteoarthritis, which is characterized by loss of joint cartilage that leads to pain and loss of function primarily in the knees and hips, affects 9.6% of men and 18% of women aged > 60 years. Increases in life expectancy and ageing populations are expected to make osteoarthritis the fourth leading cause of disability by the year 2020. Joint replacement surgery, where available, provides effective relief. Rheumatoid arthritis is an inflammatory condition that usually affects multiple joints. It affects 0.3-1.0% of the general population and is more prevalent among women and in developed countries. Persistent inflammation leads to joint destruction, but the disease can be controlled with drugs. The incidence may be on the decline, but the increase in the number of older people in some regions makes it difficult to estimate future prevalence. Osteoporosis, which is characterized by low bone mass and microarchitectural deterioration, is a major risk factor for fractures of the hip, vertebrae, and distal forearm. Hip fracture is the most detrimental fracture, being associated with 20% mortality and 50% permanent loss in function. Low back pain is the most prevalent of musculoskeletal conditions; it affects nearly everyone at some point in time and about 4-33% of the population at any given point. Cultural factors greatly influence the prevalence and prognosis of low back pain.
24387647 Adrenocorticotropic hormone response to hypoglycemic stress was preserved by a single bedt 2004 Sep Abstract We have studied the effect of low-dose prednisolone administered before sleep on the hypothalamic-pituitary-adrenal axis and the symptoms of patients with rheumatoid arthritis (RA). Plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels were measured in the basal state and after hypoglycemic stress induced by the insulin tolerance test in 21 patients receiving prednisolone at 3-5 mg daily. The patient's global assessment of their disease activity scores on a 100-mm visual analogue scale (VAS) and self-reporting of their functional status using the health assessment questionnaire (HAQ) were evaluated. While both the cortisol and the ACTH responses were impaired dose-dependently in patients treated with prednisolone, the ACTH response was maintained in patients treated with a single daily 3-mg dose of prednisolone before sleep. There was an inverse correlation between the extent of the ACTH response and disease activity as revealed by the VAS (r = 0.521, P < 0.05). There was also a weak correlation between VAS and the self-rating depression scale (SDS) (r = 0.443), especially when only patients with an HAQ score > 10 were included in order to exclude any possible contribution of the limitations in the activities of daily living to the SDS score (r = 0.859, P < 0.05). These results suggest that a single daily low dose (3 mg) of prednisolone administered before sleep maintains the ACTH response in RA patients, and patients with a good ACTH response appear to be less depressed and have milder symptoms.
19861810 The significance of elevated serologic markers of celiac disease in children with juvenile 2003 May AIM: The aim of this study is to determine the frequency of celiac disease (CD) in a group of children with juvenile rheumatoid arthritis (JRA) and determine the correlation between the presence of the serologic markers and the histological diagnosis of CD. PATIENTS AND METHODS: Forty-two children (24 females) with JRA, aged between 5-15 years underwent study of serologic markers for CD (gliadin-IgA, gliadin-IgG, reticulin and endomysium-IgA antibodies). Endoscopic intestinal biopsy was performed in patients who had positive serologic markers for CD. The diagnosis of CD was based on the classic finding of villous atrophy and crypt hypertrophy. RESULTS: Eighteen patients (42.8%) had serologic markers for CD; ten of them with a systemic form, five with a polyarticular form and three with a pauciarticular form of JRA. Levels of AGA -IgG were high in 14 patients (77.8%), four patients (22.2%) had high levels of AGA-IgA and seven patients (38.9%) had anti-endomysium antibodies (AEA). One patient had anti-reticulin antibodies (ARA) 5.5%. Sixteen patients underwent intestinal biopsy; in only one patient with AEA antibodies (2.38%), biopsy revealed typical finding of CD. The patient with CD showed improvement in both growth parameter as well as articular symptoms after starting gluten-free diet CONCLUSION: Our study shows that the screening for silent CD among children with JRA may be useful. Those patients with AEA need further follow up since these antibodies are quite sensitive and specific for CD.
17143693 Cartilage oligomeric matrix protein in serum and synovial fluid of rheumatoid arthritis: p 2004 This study examined the serum and synovial fluid concentrations of cartilage oligomeric matrix protein (COMP) in relation to the evolution of joint cartilage damage and the requirement for surgery in 125 patients with rheumatoid arthritis (RA). We compared the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and matrix metalloproteinase-3 (MMP-3) levels with COMP levels determined by specific enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups: (1) patients with least erosive disease (LES); (2) patients with more erosive disease (MES); and (3) patients with mutilating disease (MUD). In addition, synovial fluid samples were collected from patients undergoing arthroscopic synovectomy of the knee joint (ASS) and total knee arthroplasty (TKA). Serum COMP levels correlated with the ESR (P < 0.0001, r = 0.374, n = 125) and the CRP level (P = 0.0014, r = 0.281, n = 125). COMP levels did not correlate with the MMP-3 level (P = 0.182, r = 0.114, n = 125). The COMP levels of the LES group were significantly lower than those of the MES or MUD groups. Lastly, synovial fluid COMP levels in the TKA group were higher than in the ASS group. Therefore, these findings suggest that serum and synovial fluid COMP levels in patients with RA may reflect cartilage destruction and are correlated with the ESR and the CRP level, which are indicators of the acute-phase response.
15745292 Pericardial tamponade and large pericardial effusions: causal factors and efficacy of perc 2004 In 50 patients treated from January 1998 through March 2002 for pericardial effusion and tamponade, we retrospectively investigated the efficacy of percutaneous placement of an indwelling pericardial catheter guided by 2-dimensional echocardiography and fluoroscopy. We also investigated causation. In 80% of the patients, we were able to determine specific causes through clinical, serologic, and cytologic investigation: cancer in 15 patients, chronic renal failure in 11, systemic lupus erythematosus in 2 rheumatoid arthritis in 2, Dressler syndrome in 2, tuberculosis in 1, blunt chest trauma in 1, purulent pericarditis in 1, and probably viral pericarditis in 5. No specific cause could be determined in 10 patients (20%). We did not observe any complication due to the procedure. Two patients died during hospitalization. After hospitalization, 9 patients with metastatic cancer died within 3 months. A 2nd percutaneous drainage procedure was required in 2 cancer patients. Recurrence of pericardial effusion and tamponade and the requirement of pericardiectomy occurred in 2 patients with perfusion of unknown cause and in 1 patient with perfusion due to rheumatoid arthritis. Histologic examination of pericardial tissue in patients with idiopathic disease showed fibrinous pericarditis but no causal factor. In the group with idiopathic pericardial effusion, 2 patients with multiple mediastinal lymphadenopathy underwent mediastinal exploration; biopsy revealed nonspecific lymphadenitis and fibrinous pericarditis. In patients with large pericardial effusions and tamponade, the specific cause was in most cases already known or obtained by initial clinical and laboratory investigation. Sufficient cardiac decompression was achieved by percutaneous pigtail catheter drainage.
24570156 Bone density in osteoarthritic femoral heads removed at joint replacement surgery - quanti 2002 Jan Objective. To determine if there is a change in bone density in osteoarthritic femoral heads removed at joint replacement surgery and to compare bone density in different arthropathies. Materials and methods. All femoral heads removed at joint replacement surgery at St. Michael's Hospital were examined in the Laboratory of Bone and Joint Pathology, intact as received, following sectioning in the coronal and sagittal planes by fine-detail, low-energy radiology with high-resolution, single-emulsion film. Sections were submitted for histomorphology and the study was undertaken to determine quantitatively, with the computer-assisted system, the bone density of the femoral heads. Results. Values in non-weight-bearing areas of cases of rheumatoid arthritis, fracture, and some zones of osteoarthritis were below normal values. The interesting feature was that the cortex at the calcar of the neck tended to show a greater porosity than expected for cortical bone in all cases. There was difference in density, with statistical significance in comparing weight-bearing zones of osteoarthritis versus fracture, and in osteonecrosis versus fracture, in both weight-bearing and non-weight-bearing zones. There was a strong statistically significant difference in P values between the weight-bearing and non-weight-bearing areas of patients with osteoarthritis and a relatively nonsignificant difference in patients with rheumatoid arthritis. There also was a statistically significant difference between weight-bearing and non-weight-bearing areas in the patients with fractures. Conclusion. The study demonstrated the static morphologic and morphometric variables in surgically resected femoral heads at the time of total hip arthroplasty. Obviously, this data is not a measure of outcome but must be regarded as a potential indicator of implant/host bone relationship with morphologic and morphometric implications. One can only speculate that assessment of bone density/porosity can be a predictor of long-term outcome.
11908942 The influence of HLA-DR4 (0401) on the immune response to type II collagen and the develop 2002 Mar Rheumatoid arthritis (RA) is an autoimmune disease that is genetically associated with the MHC class II molecule HLA-DRbeta1*0401 (DR4). In order to determine if this MHC can influence the immune response to the candidate autoantigen type II collagen (CII), we have studied collagen induced arthritis (CIA) resistant C57BL/6 mice, made transgenic (Tg) for human DR4. These DR4 Tg mice exhibited a strong T cell proliferative response to CII and its DR4 restricted peptide p261-273 after immunization with these antigens that was not seen in the C57BL/6 wild type mice. DR4 Tg mice also exhibited an increase in IFN-gamma production in response to CII, indicating the activation of Th1 cells. While these Tg mice produced IgM anti-CII antibodies, they failed to produce a detectable level of IgG2a (Th1 type) anti-bCII antibody and did not develop CIA. This study shows that a Th1 type T cell response to CII can be established in CIA non-susceptible mice by introducing the human transgene, DR4. This T cell response, however, is not sufficient to induce an antibody isotype switch to IgG2a, nor is it sufficient for the induction of CIA. These results may help to explain why many individuals expressing HLA-DRbeta1*0401 do not develop RA.
12086159 Familial occurrence of autoimmune diseases and autoantibodies in a Caucasian population of 2002 May To determine the prevalence of autoimmune diseases and autoantibodies in relatives of Caucasian patients with systemic lupus erythematosus (SLE) we questioned 118 patients for the prevalence of autoimmune diseases in their relatives. Multicase SLE families were selected for further investigation: assessment of the presence of antinuclear antibodies (ANA), thyroid antibodies and IgM rheumatoid factor (IgM-RF). Thirty-three patients reported the presence of 50 autoimmune diseases in 43 relatives. Twenty-two diagnoses could be either confirmed (n=14) or refuted (n=8). SLE clustered significantly within families of SLE patients. Multiple sclerosis and rheumatoid arthritis also seemed to cluster within families of lupus patients. The prevalence of ANA (24%) and thyroid antibodies (44%) in 29 relatives of multicase SLE families was raised (P<0.05). In conclusion, the prevalence of autoimmune diseases is raised in relatives of Caucasian SLE patients. Also, the prevalence of autoantibodies is raised in relatives of multicase SLE families, both suggesting genetic influences in the pathogenesis of the disease. These findings support the genome-wide screening of SLE patients to unravel factors responsible for genetic susceptibility to SLE.
15461549 Etanercept in psoriasis. 2004 Oct Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European populations. Several lines of evidence have demonstrated the correlation between elevated levels of TNF and psoriasis, suggesting that interfering with the inflammatory effects of TNF may help resolve psoriatic lesions. The biological agent, etanercept, is a fully human soluble TNF-receptor fusion protein with proven efficacy in the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, and psoriatic arthritis. In several well-controlled clinical trials, etanercept showed sustained efficacy in reducing the signs and symptoms of psoriasis in patients with moderate-to-severe disease. With the exception of injection site reactions, adverse event rates were similar to placebo and did not increase across higher doses. No opportunistic infections, including tuberculosis, were reported. From analysis of the available clinical trials, etanercept appears to be an effective and well-tolerated agent for the treatment of moderate-to-severe psoriasis.
15040077 [Effects of TNF-alpha receptor blocking peptide on adjuvant arthritis in rats]. 2003 Dec AIM: To study the effects of TNF receptor blocking peptide on adjuvant arthritis in rats. METHODS: The model of rat adjuvant arthritis was induced by injection of complete Freund's adjuvant. The TNF receptor blocking peptide was injected locally in the ankle. The ankle swelling, the pathologic changes in the ankle joint and the expression of IL-1 beta mRNA and TNF-alpha mRNA by peritoneal macrophages (RT-PCR) were observed. RESULTS: The model of rat adjuvant arthritis induced by injection of complete Freund's adjuvant was similar to human rheumatoid arthritis. The treatment with TNF receptor blocking peptide for 10 days resulted in complete inhibition of joint swelling, a decrease in infiltration of inflammatory cell into joint tissue, an obvious alleviation of inflammatory pathological damages and an apparent decline of TNF-alpha mRNA and IL-1 beta mRNA of peritoneal macrophages of rats. CONCLUSION: The TNF receptor blocking peptide can protect the joint from inflammatory damage induced by adjuvant arthritis by suppression of TNF-alpha and IL-1 production, thereby alleviating the pathological injury of joint and controlling effectively the clinic course of arthritis.
15200217 Total ankle replacement. 2004 Apr 29 patients underwent 30 Scandinavian Total Ankle Replacements (STAR) by a single surgeon, over a four year period (1997 to 2001). There were 12 primary osteo arthritic patients with 6 post traumatic. The mean age of these 18 patients was 73. Eleven patients had rheumatoid arthritis and these had a mean age of 58 years at the time of surgery. One patient had bilateral replacements giving a total of 30 prostheses inserted. On review dorsiflexion had increased from a mean of 7 to 11 degrees while plantar flexion from 15 to 24 degrees. The American Orthopaedic Foot and Ankle hindfoot score was 95 (maximum 100) and the Kofoed ankle score revealed 17 excellent, 5 good and 4 fair. No patients had radiological evidence of loosening. Our intermediate term result for the STAR (W. Link GmbH & Co., Hamburg, Germany) ankle replacement has yielded 90% excellent and good functional outcomes in a mixed osteo arthritic and rheumatoid population which mirrors the results of those published from Scandinavia.
12723989 Autoantibodies to low-density-lipoprotein-receptor-related protein 2 (LRP2) in systemic au 2003 We previously reported that autoantibodies (autoAbs) to the main epitope on CD69 reacted to its homologous amino acid sequence in low-density-lipoprotein-receptor-related protein 2 (LPR2), a multiligand receptor for protein reabsorption. In this study, we have investigated the prevalence, autoepitope distribution, and clinical significance of the autoAbs to LRP2 in patients with systemic autoimmune diseases. Using six recombinant proteins (F2-F7) for LRP2 and one for CD69, we detected autoAbs to LRP2 in sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus, Behçet's disease, systemic sclerosis, and osteoarthritis and then mapped autoepitopes by Western blotting. The autoAbs to LRP2 were detected in 87% of the patients with rheumatoid arthritis, 40% of those with systemic lupus erythematosus, 35% of those with systemic sclerosis, 15% of those with osteoarthritis, and 3% of those with Behçet's disease. Multiple epitopes on LRP2 were recognized by most of the anti-LRP2+ serum samples. All of the tested anti-CD69 autoAb+ samples reacted to LRP2-F3 containing the homologous sequence to the main epitope of CD69; however, only 38% of the anti-LRP2-F3+ samples reacted to CD69. Clinically, the existence of the autoAbs to LRP2-F4, -F5, and -F6 correlated with the presence of proteinuria in RA. This study revealed that LRP2 is a major autoantigen in RA. The autoAbs to LRP2 are probably produced by the antigen-driven mechanism and the autoimmunity to LRP2 may spread to include CD69. The anti-LRP2 autoAbs may play pathological roles by inhibiting the reabsorbing function of LRP2.