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ID PMID Title PublicationDate abstract
16819616 [Low-grade-/high-grade-synovitis: synovitis-score as a gold standard?]. 2006 Aug BACKGROUND: Synovectomy specimens represent important material submitted from the orthopedist to the pathologist. However, no consistent histopathological grading system for chronic synovitis has been established so far. PATIENTS AND METHODS: The three compartments of chronic synovitis (enlargement of lining cell layer, density of synovial stroma cells, leukocytic infiltrate) are graded semiquantitatively (from 0=absent to 3=strong), and the points for each compartment add up to the synovitis score: 0-1 = no synovitis, 2-4 = low-grade synovitis, 5-9 = high-grade synovitis. A total of 618 synovial specimens (resections n=559, biopsies n=59) from degenerative and inflammatory joint diseases were graded by two independent observers. RESULTS: Median synovitis scores when correlated to clinical diagnoses were: 1, control; 2, osteoarthritis and post-traumatic arthritis; 3, psoriatic arthritis; 5, reactive and rheumatoid arthritis. The differences between rheumatic and non-rheumatic diseases were significant (p<0.001). The correlation between the two observers was high (p<0.001). CONCLUSIONS: The proposed synovitis score enables stratification of chronic synovitis into low-grade (score 2-4) and high-grade (score >4), which is correlated to the nature of the disease (low-grade to non-rheumatic, high-grade to rheumatic), and it therefore contributes to the diagnosis of rheumatic and non-rheumatic joint diseases.
17890113 Lipid rafts in T cell signalling and disease. 2007 Oct Lipid rafts is a blanket term used to describe distinct areas in the plasma membrane rich in certain lipids and proteins and which are thought to perform diverse functions. A large number of studies report on lipid rafts having a key role in receptor signalling and activation of lymphocytes. In T cells, lipid raft involvement was demonstrated in the early steps during T cell receptor (TCR) stimulation. Interestingly, recent evidence has shown that signalling in these domains differs in T cells isolated from patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we discuss these findings and explore the potential of lipid rafts as targets for the development of a new class of agents to downmodulate immune responses and for the treatment of autoimmune diseases.
17078892 Interactions between IL-32 and tumor necrosis factor alpha contribute to the exacerbation 2006 IL-32 is a newly described cytokine in the human found to be an in vitro inducer of tumor necrosis factor alpha (TNFalpha). We examined the in vivo relationship between IL-32 and TNFalpha, and the pathologic role of IL-32 in the TNFalpha-related diseases - arthritis and colitis. We demonstrated by quantitative PCR assay that IL-32 mRNA was expressed in the lymphoid tissues, and in stimulated peripheral T cells, monocytes, and B cells. Activated T cells were important for IL-32 mRNA expression in monocytes and B cells. Interestingly, TNFalpha reciprocally induced IL-32 mRNA expression in T cells, monocyte-derived dendritic cells, and synovial fibroblasts. Moreover, IL-32 mRNA expression was prominent in the synovial tissues of rheumatoid arthritis patients, especially in synovial-infiltrated lymphocytes by in situ hybridization. To examine the in vivo relationship of IL-32 and TNFalpha, we prepared an overexpression model mouse of human IL-32beta (BM-hIL-32) by bone marrow transplantation. Splenocytes of BM-hIL-32 mice showed increased expression and secretion of TNFalpha, IL-1beta, and IL-6 especially in response to lipopolysaccharide stimulation. Moreover, serum TNFalpha concentration showed a clear increase in BM-hIL-32 mice. Cell-sorting analysis of splenocytes showed that the expression of TNFalpha was increased in resting F4/80+ macrophages, and the expression of TNFalpha, IL-1beta and IL-6 was increased in lipopolysaccharide-stimulated F4/80+ macrophages and CD11c+ dendritic cells. In fact, BM-hIL-32 mice showed exacerbation of collagen-antibody-induced arthritis and trinitrobenzen sulfonic acid-induced colitis. In addition, the transfer of hIL-32beta-producing CD4+ T cells significantly exacerbated collagen-induced arthritis, and a TNFalpha blockade cancelled the exacerbating effects of hIL-32beta. We therefore conclude that IL-32 is closely associated with TNFalpha, and contributes to the exacerbation of TNFalpha-related inflammatory arthritis and colitis.
18289056 Joint diseases and matrix metalloproteinases: a role for MMP-13. 2008 Feb The role of matrix metalloproteinases in disease has been investigated over the last two decades. A focus on this family of proteases is particularly emphasized in two major arthritides in humans, osteoarthritis and rheumatoid arthritis. Early work described the presence of multiple MMP family members in the joint of the disease state and recent advances in the development of new knockout mice and disease models have allowed investigators to directly test the role of the MMP proteases in arthritis. MMP-13 is expressed by chondrocytes and synovial cells in human OA and RA and is thought to play a critical role in cartilage destruction. The recent development of an MMP-13 knockout mouse has documented the important role for this enzyme in cartilage formation and further studies under disease conditions promise to reveal the function of this enzyme in disease pathology. This review describes a body of research that supports the development of novel selective MMP-13 inhibitors with the hope of developing these compounds in clinical trials for the treatment of arthritis.
18188533 Subcutaneous inflammation (panniculitis) in tibio-tarsal joint of rats inoculated with com 2007 Dec Complete Freund's adjuvant (CFA)-induced arthritis in rats, which presents similar features to rheumatoid arthritis, is a model widely used in aetiopathogenetic and investigational drug studies. In this model, arthritis is induced by intradermal injection of Mycobacterium tuberculosis suspended in mineral oil in the hind footpad. Although the histopathology findings in the joint are well described, the marked subcutaneous features of panniculitis that concomitantly occur in this model have received no attention. The objective of this paper is to describe the subcutaneous histopathological features in 8 Wistar rats after intraplantar injection of CFA. We studied the subcutaneous histopathological features in 8 Wistar rats after intraplantar injection of CFA in the left hind paw. The levels of subcutaneous inflammation of the animals in this study were evaluated for the histological characteristics present in the tissue and scored with 4 parameters (acute inflammation, chronic inflammation with fibrosis, subcutaneous and profound soft tissue necrosis, and the presence of giant cells, neutrophils, macrophages and lymphocytes) on days 4, 7, 11 and 15 after induction. All animals developed intense subcutaneous inflammation characteristic of panniculitis, with predominance of acute changes in the initial period, with progression to a self-perpetuating chronic fibrotic process on day 15. These observations precede the joint changes. Besides being an interesting model for better studying diseases with panniculitis, our observations bring up issues concerning the possible relations between subcutaneous and joint inflammatory changes.
19662198 Human chitinases and chitinase-like proteins as indicators for inflammation and cancer. 2007 May 3 Human Glyco_18 domain-containing proteins constitute a family of chitinases and chitinase-like proteins. Chitotriosidase and AMCase are true enzymes which hydrolyse chitin and have a C-terminal chitin-binding domain. YKL-40, YKL-39, SI-CLP and murine YM1/2 proteins possess solely Glyco_18 domain and do not have the hydrolytic activity. The major sources of Glyco_18 containing proteins are macrophages, neutrophils, epithelial cells, chondrocytes, synovial cells, and cancer cells. Both macrophages and neutrophils use the regulated secretory mechanism for the release of Glyco_18 containing proteins. Glyco_18 containing proteins are established biomarkers for human diseases. Chitotriosidase is overproduced by lipid-laden macrophages and is a major marker for the inherited lysosomal storage Gaucher disease. AMCase and murine lectin YM1 are upregulated in Th2-environment, and enzymatic activity of AMCase contributes to asthma pathogenesis. YKL proteins act as soluble mediators for the cell proliferation and migration, and are also involved in rheumatoid arthritis, inflammatory bowel disease, hepatic fibrosis and cirrhosis. Chitotriosidase and YKL-40 reflect the macrophage activation in atherosclerotic plaques. Serum level of YKL-40 is a diagnostic and prognostic marker for numerous types of solid tumors. YKL-39 is a marker for the activation of chondrocytes and the progression of the osteoarthritis in human. Recently identified SI-CLP is upregulated by Th2 cytokine IL-4 as well as by glucocorticoids. This unique feature of SI-CLP makes it an attractive candidate for the examination of individual sensitivity of patients to glucocorticoid treatment and prediction of side effects of glucocorticoid therapy. Human chitinases and chitinase-like proteins are found in tissues and circulation, and can be detected by non-invasive technologies.
19039551 Radiosynoviorthesis (RSO): influencing factors and therapy monitoring. 2008 Nov OBJECTIVE: To evaluate the effectiveness of radiosynoviorthesis (RSO) in relation to joint type and underlying disease by both self-assessment of patients and scintigraphic assessment to determine conditions under which RSO might be preferable to the sole intra-articular corticoid injection. METHODS: Radiosynoviorthesis was performed on 136 patients for 424 joints [242 small, 130 medium-sized, and 52 large joints; 313 with rheumatoid arthritis (RA) and 111 with osteoarthritis (OA)]. The success of RSO was evaluated after 12 months by patients' estimation, and in 35 patients for 157 joints additionally by two-phase bone scintigraphy. The relative change in the scintigraphic uptake was compared with the patients' estimation. RESULTS: The subjectively estimated success rates for the small, medium-sized, and large joints were 89% (215/242), 86% (112/130), and 79% (41/52), and for RA and OA 89% (280/313) and 79% (88/111), respectively. The scintigraphically determined response rates for small and medium-sized joints were 81% (86/106) and 69% (35/51), respectively. There was a mismatch between patients' assessment and scintigraphic assessments in 18% (28/157) with 6 false-negative and 22 false-positive estimations using scintigraphy as the standard of reference. CONCLUSIONS: The success of RSO is higher in patients with RA than in patients with OA. For the finger, ankle, and wrist joints in RA, RSO is so promising that we would like to advocate its preference over the sole intraarticular corticoid injection. Perfusion bone scintigraphy can be used for therapy monitoring and earlier switching to RSO by showing that other therapies have failed.
18161752 TNF-mediated inflammatory disease. 2008 Jan TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response. This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease. TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways. These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration. Vascular endothelial cells respond to TNF by undergoing a number of pro-inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis. The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis. The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases.
16876794 Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice. 2006 Aug 21 Sphingosine-1-phosophate, generated from the phosphorylation of sphingosine by sphingosine kinase enzymes, is suggested to function as an intracellular second messenger for inflammatory mediators, including formyl peptide, C5a, and Fc. More recently, a role for sphingosine kinases during inflammation has also been proposed. Here we show that sphingosine kinase 1 knockout mice exhibit normal inflammatory cell recruitment during thioglycollate-induced peritonitis and that sphingosine kinase 1-null neutrophils respond normally to formyl peptide. In the collagen-induced arthritis model of rheumatoid arthritis, sphingosine kinase 1 knockout mice developed arthritis with normal incidence and severity. Our findings show that sphingosine kinase 1 is dispensable for inflammatory responses and support the need for more extensive studies of sphingosine kinases in inflammation.
18947375 Mesenchymal stem cells in arthritic diseases. 2008 Mesenchymal stem cells (MSCs), the nonhematopoietic progenitor cells found in various adult tissues, are characterized by their ease of isolation and their rapid growth in vitro while maintaining their differentiation potential, allowing for extensive culture expansion to obtain large quantities suitable for therapeutic use. These properties make MSCs an ideal candidate cell type as building blocks for tissue engineering efforts to regenerate replacement tissues and repair damaged structures as encountered in various arthritic conditions. Osteoarthritis (OA) is the most common arthritic condition and, like rheumatoid arthritis (RA), presents an inflammatory environment with immunological involvement and this has been an enduring obstacle that can potentially limit the use of cartilage tissue engineering. Recent advances in our understanding of the functions of MSCs have shown that MSCs also possess potent immunosuppression and anti-inflammation effects. In addition, through secretion of various soluble factors, MSCs can influence the local tissue environment and exert protective effects with an end result of effectively stimulating regeneration in situ. This function of MSCs can be exploited for their therapeutic application in degenerative joint diseases such as RA and OA. This review surveys the advances made in the past decade which have led to our current understanding of stem cell biology as relevant to diseases of the joint. The potential involvement of MSCs in the pathophysiology of degenerative joint diseases will also be discussed. Specifically, we will explore the potential of MSC-based cell therapy of OA and RA by means of functional replacement of damaged cartilage via tissue engineering as well as their anti-inflammatory and immunosuppressive activities.
18408253 Non-steroidal anti-inflammatory drug use does not appear to be associated with increased c 2009 Mar OBJECTIVES: There is controversy about the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular disease (CVD) mortality. The aim of this study was to explore associations between NSAID use and mortality in patients with inflammatory polyarthritis (IP). SUBJECTS AND METHODS: A total of 923 patients with new onset (IP), recruited to the UK Norfolk Arthritis Register (NOAR) between 1990-1994, were followed up to the end of 2004. Current medication was recorded annually for the first 6 years and then every 2-3 years. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured. Logistic regression was used to calculate all cause and CVD mortality odds ratios (OR) for NSAID use at baseline and during follow-up, adjusting for gender and time-varying covariates: RF, CRP, joint counts, smoking, steroid use, DMARD use and other medication use. RESULTS: By 2004 there were 203 deaths, 85 due to CVD. At baseline, NSAIDs were used by 66% of patients. In final multivariate models, baseline NSAID use was inversely associated with all cause mortality (adjusted OR 0.62, 95% CI 0.45 to 0.84) and CVD mortality (adjusted OR 0.54, 95% CI 0.34 to 0.86). Interval NSAID use had weaker mortality associations: all cause mortality (adjusted OR 0.72, 95% CI 0.52 to 1.00), CVD mortality (adjusted hazard ratio (HR) 0.66, 95% CI 0.40 to 1.08). CONCLUSION: No excess CVD or all cause mortality was observed in NSAID users in this cohort of patients with IP. This is at variance with the literature relating to NSAID use in the general population. It is unclear whether this represents unmeasured confounders influencing a doctor's decision to avoid NSAIDs in the treatment of IP.
17435839 [Recurrent acute idiopathic pericarditis: rheumatologic therapy, autoantibodies and long t 2007 Jan OBJECTIVE: To evaluate therapy and rheumatologic aspects of recurrent acute idiopathic pericarditis (RAIP). METHODS: We studied 46 patients. We used non-steroidal anti-inflammatory drugs (NSAIDs) at high dosage. We did not start corticosteroid: if already started, we planned a very slow tapering; 37 patients (80.4%) were treated with colchicine. We also assessed the frequency of ANA, anti-SSA and Rheumatoid factor. RESULTS: With our protocol recurrences dropped from 0.46 to 0.03 attacks/patient/month (p<0.00001) within 12 months and remained at the same level (0.024) till the end of the follow-up (mean 8 years). In the 37 patients treated with colchicine recurrences dropped from 0.5 to 0.03 (p<0.0001) within 12 months, and in 9 patients not given colchicine from 0.27 to 0.045 (p<0.005). When colchicine was used the decrease was significantly higher (0.47 vs 0.23) (p<0.001). In 27 (58.7%) patients ANA were positive at a titre >1/80, in 7 (15.2%) >1/160. Rheumatoid factor was positive in 7 (15.2%) and anti-SSA in 4 (8.7%). During the follow-up 4 (8.7%) new diagnosis of Sjogren and 1 (2.2%) of Rheumatoid Arthritis were made. CONCLUSION: NSAIDs at high dosage, slow tapering of corticosteroid and colchicine are very effective in RAIP. The improvement is more dramatic in colchicine treated patients, but also other patients can achieve good control of the disease. The finding of ANA, anti-SSA and the new rheumatological diagnoses support the involvement of autoimmunity.
18821663 Work and sick leave among patients with early inflammatory joint conditions. 2008 Oct 15 OBJECTIVE: To study the occurrence of sick leave and to identify work characteristics related to sick leave in patients with early inflammatory joint conditions. METHODS: Patients with inflammatory joint conditions present for <12 months were included in this cross-sectional study. Approximately 85% of patients satisfying the criteria participated. Data collection included demographics, clinical characteristics, pain, physical functioning and mental health (Short Form 36), fatigue, and behavioral coping (Coping of Rheumatic Stressors questionnaire). Work characteristics included physical load, psychosocial load, job control, and support at work. Outcome was defined as sick leave for >2 weeks during the past 6 months. Multiple logistic regression analysis was conducted. RESULTS: Sick leave was reported by 54 (26%) of 210 employed patients, with 75% of the sick leave periods attributed to joint conditions. Of these 210 patients, 23% were classified as having rheumatoid arthritis (RA), 35% as having non-RA arthritis, and 42% as having inflammatory joint conditions without synovitis. Pain, poor physical functioning, and passive behavioral coping were related to increased sick leave, whereas diagnostic group was not. Low job control, i.e., low control over planning and pacing of activities within the job, was associated with increased sick leave (odds ratio [OR] 2.74), whereas being a supervisor (OR 0.21) and clerical work (OR 0.45) were related to reduced sick leave. CONCLUSION: Substantial sick leave in the past 6 months was reported by 26% of patients with early inflammatory joint conditions. Pain, functional limitations, and fewer opportunities to determine one's work activities were associated with the occurrence of sick leave.
19041074 Imaging: the need for standardization. 2008 Dec The five stages in the evolution of a new method or measure are discovery (by design or inadvertent), development, testing, standardization and application. However, measures may be accepted, disseminated and used before they have been formally evaluated and standardized. This chapter describes the properties of measurement in the medical sciences and the process of standardization. It includes an example of the development and standardization of a magnetic resonance imaging rheumatoid arthritis score, and ends with a matrix that can serve as a guide for systematic appraisal and standardization of outcome measures, such as imaging outcomes. Using the matrix, one can determine the gaps in knowledge and what further evaluation is needed in one or more domains or metrics.
17471822 Introduction to B-Cell disorders. 2007 Feb Healthcare professionals have a good understanding of B cells in normal immunity. Although the role of lymphocytes and the lymphoid system in lymphoma is understood, the role of B cells is less clear in several autoimmune diseases, such as rheumatoid arthritis, idiopathic thrombocytopenic purpura, and autoimmune hemolytic anemia. This article will present an overview of malignant and nonmalignant B-cell disorders. Experts hypothesize that some monoclonal antibodies can deplete the B-cell population and prevent B- and T-cell responses in autoimmune diseases. Nurses should understand the data surrounding monoclonal therapy, which are not always presented clearly. Nurses' ability to interpret data is important to their patients and colleagues.
19197840 Z-lengthening of the iliotibial band to treat recalcitrant cases of trochanteric bursitis. 2007 Jan Greater trochanteric bursitis is a relatively common presentation at hip clinics. It presents with pain around the greater trochanter. Diagnosis is usually made on clinical grounds when other hip and spinal pathologies are ruled out and there is tenderness present over the trochanteric region. Rheumatoid arthritis (1), athletic injury (2), total hip arthroplasty (3) and idiopathic disease (4) are some of the known causes of trochanteric bursitis. Treatment is mainly non-operative and expectant; however various operative interventions have been described in the literature. We present a series of 16 patients who had recalcitrant trochanteric bursitis following failed non-operative treatment and were treated with bursectomy and Z-lengthening of the iliotibial band. All 14 patients who answered the questionnaire were happy with the outcome of operation and 13/14 patients would undergo a similar procedure again. To the best of our knowledge, this is the only series in the literature describing this particular procedure for treatment of trochanteric bursitis.
18291078 [Suicidal behaviour and somatic disorders]. 2008 Feb 11 AIM: To review current knowledge on suicide and suicidal behaviour in selected somatic disorders and pain syndromes. MATERIALS AND METHODS: Available literature concerning suicide risk and cancer, neurological disorders, heart and lung disorders, bowel disorders. AIDS: Rheumatoid arthritis and pain was found by using Medline. RESULTS: There are fairly robust studies on the increased risk of suicide in a number of neurological disorders and cancers, while studies in cardiac, lung, rheumatologic disorders and others are fewer and far less robust. CONCLUSION: Suicide risk factors i.e. psychiatric disorder, previous suicide attempts, suicidal thoughts have to be considered in patients suffering from somatic disorders, especially disorders involved with an increased suicide risk.
17982568 Biological functions of interleukin-21 and its role in inflammation. 2007 Oct 22 Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, is mainly produced by activated T lymphocytes, particularly the inflammatory Th17 subset, and is believed to be a key factor in the transition between innate and acquired immunity. In the last few years, this cytokine has been shown to modulate the functions of T, B, and NK cells, as well as cells of myeloid origin. In addition, it was demonstrated that IL-21 is a potent antitumor agent, making it a promising candidate for the development of therapeutic tools. IL-21 has also been associated with different autoimmune and inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. This review will summarize the biological functions of IL-21 and its potential role in inflammation.
17803815 Fatal miliary Coccidioidomycosis in a patient receiving infliximab therapy: a case report. 2007 Sep 5 A 78-year-old white male from Iowa in the United States of America receiving the anti- tumor necrois factor (TNF) agent infliximab therapy for rheumatoid arthritis developed a cheek ulcer which failed to respond to empiric antibiotic therapy. He subsequently presented with progressive respiratory failure from miliary coccidioidomycosis which proved fatal. The patient vacationed in Arizona 6 months previously and likely contracted the organism there as Iowa is not an endemic area for coccidioidomycosis. Respiratory failure from miliary infiltration is an uncommon presentation of coccidioidomycosis. Physicians should be aware of the importance of travel history and potential for life-threatening coccidioidomycosis in patients receiving tumor necrosis factor inhibitors.
17689790 Insufficiency fracture of the acetabular medial wall. 2007 Aug Acetabular insufficiency fractures are much less common than acetabular fractures associated with trauma. They most commonly occur in postmenopausal women with a history of rheumatoid arthritis or pelvic irradiation. We present the case of a 93-year-old man with an atraumatic pelvic insufficiency fracture of the fossa acetabuli. The patient had 2 predisposing risk factors: osteoporosis and lower-extremity reconstructive surgery.