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ID PMID Title PublicationDate abstract
15565393 Debilitating diarrhoea and weight loss due to colitis in two RA patients treated with lefl 2005 Feb Diarrhoea and weight loss are frequently reported adverse events in rheumatoid arthritis (RA) patients receiving the disease-modifying antirheumatic drug (DMARD) leflunomide. According to the available literature these side effects occur mostly during the first 6 months of treatment, are rather mild and rarely lead to treatment withdrawal. In this report, we describe the clinical, endoscopic and histologic findings in two RA patients with severe diarrhoea and important weight loss more than 12 months after starting treatment with leflunomide. In both cases the symptoms were caused by colitis, but one had ulcerative and the other microscopic colitis. Despite treatment with budesonide the complaints only improved after withdrawal of leflunomide, making a causal relationship between this drug and the pathogenesis of colitis probable. The heterogeneous histopathological findings in these two patients, however, do not allow us to draw any definitive conclusions about the mechanism by which leflunomide causes diarrhoea and weight loss in RA patients. We conclude that persistent diarrhoea or weight loss in patients taking leflunomide can be more serious than what is previously reported in the literature. In such cases leflunomide treatment should be stopped and an endoscopic examination of the colon is recommended. Given the long half-life of this drug a washout procedure with cholestyramine should be considered whenever the problem is severe or persistent.
15234492 Risk factors in carpal tunnel syndrome. 2004 Aug We have undertaken a large case-control study using the UK General Practice Research Database to quantify the relative contributions of the common risk factors for carpal tunnel syndrome (CTS) in the community. Cases were patients with a diagnosis of CTS and, for each, four controls were individually matched by age, sex and general practice. Our dataset included 3,391 cases, of which 2,444 (72%) were women, with a mean age at diagnosis of 46 (range 16-96) years. Multivariate analysis showed that the risk factors associated with CTS were previous wrist fracture (OR=2.29), rheumatoid arthritis (OR=2.23), osteoarthritis of the wrist and carpus (OR=1.89), obesity (OR=2.06), diabetes (OR=1.51), and the use of insulin (OR=1.52), sulphonylureas (OR=1.45), metformin (OR=1.20) and thyroxine (OR=1.36). Smoking, hormone replacement therapy, the combined oral contraceptive pill and oral corticosteroids were not associated with CTS. The results were similar when cases were restricted to those who had undergone carpal tunnel decompression.
12840047 Customized molecular phenotyping by quantitative gene expression and pattern recognition a 2003 Jul Description of the molecular phenotypes of pathobiological processes in vivo is a pressing need in genomic biology. We have implemented a high-throughput real-time PCR strategy to establish quantitative expression profiles of a customized set of target genes. It enables rapid, reproducible data acquisition from limited quantities of RNA, permitting serial sampling of mouse blood during disease progression. We developed an easy to use statistical algorithm--Global Pattern Recognition--to readily identify genes whose expression has changed significantly from healthy baseline profiles. This approach provides unique molecular signatures for rheumatoid arthritis, systemic lupus erythematosus, and graft versus host disease, and can also be applied to defining the molecular phenotype of a variety of other normal and pathological processes.
11816264 Effect of hemodialysis on leflunomide plasma concentrations. 2002 Jan OBJECTIVE: To report on the influence of hemodialysis on the disposition of leflunomide in a woman with end-stage renal disease. CASE SUMMARY: A 65-year-old white woman with a history of diabetes, end-stage renal disease, rheumatoid arthritis, vasculitis, and leg ulcers was admitted to the hospital with a flare in the symptoms of joint pain and vasculitis. Prior to admission, she had been treated for rheumatoid arthritis with methotrexate 7.5 mg once a week. Due to adverse effects from methotrexate and continuing painful joints, leflunomide was considered as a therapeutic alternative. A loading dose of 100 mg was followed two days later by a daily dose of 10 mg. The active metabolite of leflunomide (A771726) was measured before and after hemodialysis and between hemodialysis sessions over a period of 80 days. Pre- and post-hemodialysis concentrations were compared for 17 sessions during this time. Based on the initial measured concentrations, the leflunomide dose was increased to 20 mg/d for several weeks before being reduced to 15 mg due to elevated liver enzymes. DISCUSSION: Although renal pathways are responsible in part for excretion of A771726, the concentrations achieved in this patient at doses of 10-20 mg/d were at the low end of the range reported in the literature. It was shown that pre- and post-hemodialysis concentrations of A771726 did not differ significantly. Thus, the low concentrations of A771726 were not a result of the hemodialysis. CONCLUSIONS: Steady-state concentrations of A771726 in plasma were not affected by hemodialysis or renal impairment. Reduction of the dose of leflunomide in patients with chronic renal failure undergoing hemodialysis does not appear to be required.
15638042 The effect of taurine chloramine on pro-inflammatory cytokine production by peripheral blo 2004 Nov OBJECTIVE: Pro-inflammatory cytokines play a critical role in the pathogenesis of RA. A natural oxidant, TauCl exerts anti-inflammatory activities. Here, the effects of Tau and TauCl on key pro-inflammatory cytokines--IL-1beta, IL-6 and TNF-alpha production by LPS-triggered peripheral blood mononuclear cells (PBMCs) isolated from RA and OA patients and healthy blood donors--were examined. METHODS: PBMCs were stimulated with LPS (24 h) in the presence of Tau or TauCl (200-400 microM). Cytokine production was measured in culture supernatants (secreted) and cells lysates (cell-associated) using specific ELISAs. RESULTS: Production of the secretedforms of IL-1beta and IL-6 was inhibited by TauCl with IC50 approximately equal to 250 microM and 300-400 microM respectively, in all investigated groups. In all cultures of PBMCs TauCl raised the TNF-alpha production at the low concentration (200 mM), while at the higher concentration (400 microM) either reduced it (55% of RA, 70% of OA patients and 55% of healthy donors) or exerted no effect (remainder of patients). Interestingly, Tau did not significantly affect any cytokine production. CONCLUSION: TauCl at high concentrations down-regulates pro-inflammatory cytokine production. However, the impact of TauCl on TNF-alpha production by PBMCs from RA is more limited than in cells isolated from OA patients.
15642146 Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphop 2005 We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3-4 months. Both cohorts produced naive T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort.
11880552 Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglyc 2002 Mar Polyphenolic compounds from green tea have been shown to reduce inflammation in a murine model of inflammatory arthritis, but no studies have been undertaken to investigate whether these compounds are protective to joint tissues. We therefore investigated the effects of catechins found in green tea on cartilage extracellular matrix components using in vitro model systems. Bovine nasal and metacarpophalangeal cartilage as well as human nondiseased, osteoarthritic and rheumatoid cartilage were cultured with and without reagents known to accelerate cartilage matrix breakdown. Individual catechins were added to the cultures and the amount of released proteoglycan and type II collagen was measured by metachromatic assay and inhibition ELISA, respectively. Possible nonspecific or toxic effects of the catechins were assessed by lactate output and proteoglycan synthesis. Catechins, particularly those containing a gallate ester, were effective at micromolar concentrations at inhibiting proteoglycan and type II collagen breakdown. No toxic effects of the catechins were evident. We conclude that some green tea catechins are chondroprotective and that consumption of green tea may be prophylactic for arthritis and may benefit the arthritis patient by reducing inflammation and slowing cartilage breakdown. Further studies will be required to determine whether these compounds access the joint space in sufficient concentration and in a form capable of providing efficacy in vivo.
14714042 [Treatment with etanercept in chronic polyarthritis]. 2003 Sep 25 BACKGROUND: In randomised trials, treatment with anti-tumour necrosis factor alpha drugs has been shown to be efficacious for patients with rheumatoid arthritis. We analysed the effectiveness and toxicity of etanercept treatment in our day-to-day rheumatology practice at the University Hospital of Northern Norway. MATERIAL AND METHODS: Patients with active polyarthritis who had failed at least three different disease-modifying anti-rheumatic drugs including methotrexate and/or combination therapy were consecutively included in an open study when they started etanercept therapy (25 mg twice per week subcutaneously). During follow up we noted the number of swollen and tender joints, took visual analogue scores (0-100 millimetre) for pain and global well-being, administered the Modified Health Assessment Questionnaire, performed laboratory tests, and took note of side effects. RESULTS: Between April 1999 and July 2001, etanercept treatment was initiated in 71 patients. An ACR-20 response (20% improvement according to American College of Radiology criteria) occurred in 57% of patients after one month of treatment and in 70 % after three months, ACR-50 response in 24% and 42%, and ACR-70 response in 6% and 20%. While half of all patients reported side effects, only five patients (7%) discontinued treatment because of them. INTERPRETATION: Etanercept is effective therapy for many patients with severe chronic polyarthritis in clinical practice. Short-term side effects occur more frequently than reported and seem less frequent with concomitant methotrexate therapy. Long-term side effects are still unknown and require close monitoring.
15367748 Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis. 2005 Jan OBJECTIVES: The aim of the study was to assess the role of extracellular cytochrome c as an inducer of joint inflammation and to examine its levels in sera and synovial fluids of rheumatoid arthritis (RA) patients. METHODS: Mice were injected intra-articularly with different doses of cytochrome c and joints were evaluated histopathologically and immunohistochemically 3 and 10 days later. In addition, mouse spleen cells were stimulated with different concentrations of cytochrome c, followed by assessment of NF-kappaB activation and cytokine production. Sera and synovial fluid from RA patients and sera from healthy individuals were assessed with respect to cytochrome c levels by an enzyme-linked immunoassay technique. RESULTS: Histopathological signs of arthritis were evident in 75% of animals following intra-articular injection of cytochrome c. Synovitis was characterized by influx of Mac-1+ cells. In vivo depletion of neutrophils and monocytes led to abrogation of arthritis. Stimulation of mouse spleen cells in vitro with cytochrome c resulted in activation of NF-kappaB and release of proinflammatory cytokines and chemokines. Cytochrome c levels in RA patients' sera were significantly lower than in healthy controls. Further, cytochrome c levels in synovial fluid were significantly lower than in corresponding blood samples. CONCLUSIONS: Our findings demonstrate that extracellular cytochrome c displays direct proinflammatory properties mediated by activation of NF-kappaB and causing neutrophil and monocyte triggered inflammation. We hypothesize that decreased levels of cytochrome c in RA patients reflect consumption of this molecule in the synovial tissue, decreasing apoptosis and shifting the balance towards inflammation.
12096221 Methotrexate in the treatment of rheumatoid arthritis. I. In vitro effects on cells of the 2002 Jul OBJECTIVE: Low-dose methotrexate (MTX) is often used in the treatment of rheumatoid arthritis (RA). To be effective, treatment must be long-term, and there are concerns that MTX may impair bone formation in a population already predisposed to osteoporosis. The purpose of this investigation was to determine the direct effects of MTX at clinically relevant doses on the growth and differentiation of human cells of the osteoblast (bone-forming) lineage. METHODS: Cells derived from the marrow stroma (BMSC) and trabecular surfaces [human bone-derived cells (HBDC)] of adult ribs were cultured in the absence or presence of MTX (1-1000 nM). To promote the differentiation and further maturation of cells of the osteoblast lineage, one half of the cultures were treated additionally with 10 nM dexamethasone (Dx). RESULTS: In cultures of BMSC, treatment with MTX (+/-Dx) did not affect the total number of colonies that formed or the expression of the developmental markers STRO-1 and alkaline phosphatase (AP). At concentrations > or =10 nM, however, there was a statistically significant reduction in the number of cells harvested at the end of primary culture. In cultures of HBDC, treatment with MTX (in the presence of Dx) did not affect cell number or the expression of AP. CONCLUSIONS: At concentrations > or =10 nM, treatment with MTX inhibits the proliferation of primitive marrow stromal cells, but not their ability to undergo osteogenic differentiation. The proliferation and further maturation of cells of the osteoblast lineage is not affected by treatment with MTX. These findings are reassuring for clinicians using MTX in the treatment of RA.
15517632 Proinflammatory cytokine profiles in sera and pathological tissues of patients with active 2004 Nov OBJECTIVE: To investigate concentrations of proinflammatory cytokines in the sera and their mRNA expression in biopsy specimens of evanescent rash and synovitis from patients with active untreated adult onset Still's disease (AOSD). METHODS: We measured serum levels of interleukin 6 (IL-6), IL-8, and tumor necrosis factor (TNF-alpha) by immunochemiluminescence method and serum IL-18 levels by ELISA in 50 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. Multivariate analysis was used to evaluate the correlation between serum cytokine levels and disease activity and clinical features of AOSD. We also evaluated the expression of cytokine transcripts by real-time quantitative polymerase chain reaction in biopsy specimens of evanescent rash and synovitis from 12 patients with active untreated AOSD. RESULTS: Significantly higher levels of IL-6, IL-8, IL-18, and TNF-alpha in sera were found in patients with active untreated AOSD compared to healthy controls. Serum levels of IL-6 and IL-18 correlated well with clinical activity score of AOSD patients. Multiple logistic regression analysis showed that serum IL-6 level was a possible predictor for the occurrence of evanescent rash (p = 0.0593), serum IL-8 level was a significant predictor of persistent arthritis, and serum IL-18 level predicted occurrence of liver dysfunction. The levels of mRNA expression of IL-6, IL-18, and IL-8 were significantly higher in the biopsy tissue of Still's rash from AOSD patients compared with those in controls. Levels of mRNA expression of IL-18, IL-8, and TNF-alpha were significantly higher in the synovial membranes of AOSD patients compared with those in osteoarthritis controls. Significantly lower levels of TNF-alpha and IL-8 were found in the sera and in the synovial membranes of AOSD patients compared with those in RA patients. AOSD patients who had a chronic articular course had significantly higher levels of serum IL-8 compared with those who had a monocyclic systemic course. CONCLUSION: Significantly higher levels of IL-6, IL-8, IL-18, and TNF-alpha were seen in both sera and pathological tissues of patients with active AOSD. The associations between levels of cytokine profile and distinct clinical manifestations and various patterns of disease course suggest the heterogeneity of pathogenesis in AOSD.
15548126 Longitudinal analysis of the use of etanercept versus infliximab determined from medical c 2004 Nov OBJECTIVE: To describe the dosing of etanercept and infliximab for the treatment of rheumatoid arthritis (RA). METHODS: Adult patients with a diagnosis of RA who were treated with either etanercept or infliximab between 1999 and 2002 were selected from 16 rheumatology practices in the western and southeastern United States. Patients with a terminal illness or those receiving a tumor necrosis factor (TNF)-alpha inhibitor for an indication other than RA were excluded. Data were collected through a review of the patient medical records. Data collected on each patient included demographics, concurrent disease-modifying antirheumatic drug therapy, TNF-alpha inhibitor dose, frequency, duration of TNF-alpha inhibitor therapy, and discontinuation of TNF-alpha inhibitor therapy. RESULTS: A total of 244 patients were included in the evaluation (etanercept only [n=128; 52%], infliximab only [n=89; 36%], both [n=27; 11%]). The mean age of these patients was 55.1+/-13.3 years, 54.9+/-13.5 years, and 52.8+/-14.0 years, respectively; the mean duration of RA was 13.3 +/- 8.8 years, 13.4+/-8.0 years, and 14.0 +/- 9.9 years, respectively. Female patients constituted 70% of the sample. Health maintenance organization insurance was the most common form of medical insurance (45.8%), followed by Medicare (22.3%). The mean duration of follow-up for etanercept and infliximab treatment was 29.3+/-14.1 months and 14.8+/-6.9 months, respectively. Among patients who were still receiving therapy at the time of review, the mean initial and last etanercept doses were 25.0 mg versus 25.8 mg (P=0.16); the mean initial and last infliximab doses were 3.38 mg/kg versus 4.51 mg/kg (P<0.001). CONCLUSION: The dosing of etanercept and infliximab therapy was consistent with the approved labeling of both medications.
12585788 Provider volume and other predictors of outcome after total knee arthroplasty: a populatio 2003 Feb INTRODUCTION: Because of rationing of the limited pool of health care resources, access to total knee arthroplasty (TKA) is limited, but investigation of variables that predict complications, length of hospital stay, cost and outcomes of TKA may allow us to optimize the available resources. The objective of this study was to examine the effect of various factors on complication rates after TKA in patients managed in Ontario. METHODS: Patients who had undergone an elective TKA between 1993 and 1996, as captured in the Canadian Institute for Health Information (CIHI) database, formed the study cohort. The CIHI dataset was used to obtain information regarding in-hospital complications, hospital length of stay, revision rates, infection rates and mortality. Generalized estimating linear or logistic regression equations were used to model outcomes as a function of age, gender, comorbidity, diagnosis and provider volume. RESULTS: During the study period, 14,352 patients in Ontario underwent TKA. Mortality at 3 months was associated with patient age, gender and comorbidity. There was no association between provider volume and mortality or the infection rate. Higher revision rates at 1 and 3 years were significantly associated with lower patient age and low hospital volume (p < 0.05). Hospitals in which fewer than 48 TKA procedures were done per year (< 40th percentile) had 2.2-fold greater 1-year revision rates than hospitals performing more than 113 TKAs annually (> 80th percentile). Complications during admission were associated with increased patient age and comorbidity, and higher hospital volume. Longer hospital stay was associated with female gender, increasing patient comorbidity and age, and lower provider volume. Surgeons who performed fewer than 14 TKAs annually (< 40th percentile) kept patients in hospital an average of 1.4 days longer than surgeons performing more than 42 TKAs annually (> 80th percentile). CONCLUSIONS: Patient variables significantly affect the rate of complications. Age, sex and comorbidity were significant predictors of complications, length of hospital stay and mortality after TKA. Although low surgeon volume was related to longer hospital stay, there was no association between surgeon volume and complication rates. The increased early revision rate for low-volume hospitals demands further study.
12868201 [Coxibs: highly selective cyclooxygenase-2 inhibitors. Part II. Side effects]. 2003 Apr Slow, time-dependent, irreversible, highly selective inhibitors of COX-2 such as celecoxib, etoricoxib, rofecoxib and valdecoxib, so-called coxibs, are a new group of drugs widely used in rheumatology as well as in other fields of medicine. The tolerability of these drugs is at least equivalent to that of commonly used non-selective COX inhibitors (e.g. diclofenac, ibuprofen, naproxen). The unquestionable superiority of selective COX-2 blockade includes a low risk of gastrointestinal side effects. However, similarly to the other COX inhibitors, coxibs must be carefully administered to patients with coexistent liver and renal disease, generalised atherosclerosis, ischaemic heart disease, and to the elderly and children. Pregnancy and lactation require precise monitoring of adverse effects on the fetus, neonate and infant, or discontinuation of therapy with the drug.
15153537 Stroma cell-derived factor 1alpha mediates desensitization of human neutrophil respiratory 2004 Jun 1 Classical chemoattractants such as fMLP or the complement factor C5a use G protein (Gi)-coupled receptors to stimulate both chemotaxis and production of reactive oxygen species (respiratory burst, RB) by polymorphonuclear leukocytes (PMN). The chemokine stroma cell-derived factor 1alpha (SDF1alpha) and its Gi-coupled receptor, CXCR4, regulate leukocyte trafficking and recruitment to the synovial fluid of rheumatoid arthritic patients (RA-SF). However, the role of SDF1alpha in the RB is unknown and was studied in this work in vitro with healthy PMN in the absence and presence of RA-SF. In healthy PMN, SDF1alpha failed to stimulate the RB, even though the p38 mitogen-activated protein kinase was activated to a similar level as in fMLP-stimulated PMN. In contrast, the SDF1alpha-mediated calcium transients and activation of phosphatidylinositol 3-kinase/Akt were partially deficient, while p44/42 mitogen-activated protein kinases were not activated. SDF1alpha actually desensitized weakly the fMLP-mediated RB of healthy PMN. This cross-inhibitory effect was amplified in PMN treated with RA-SF, providing a protection against the exacerbation of RB induced by C5a or fMLP. This SDF1alpha beneficial effect, which was prevented by the CXCR4 antagonist AMD3100, was associated with impairment of C5a- and fMLP-mediated early signaling events. Thus, although SDF1alpha promotes leukocyte emigration into rheumatoid synovium, our data suggest it cross-desensitizes the production of oxidant by primed PMN, a property that may be beneficial in the context of arthritis.
15172851 Association of rheumatologic disease with preeclampsia. 2004 Jun OBJECTIVE: To determine whether maternal rheumatologic disease is associated with an increased risk of adverse obstetric or neonatal outcomes. METHODS: Using an institutional database, we identified all women with diagnosed rheumatologic disease (n = 114) who delivered a baby at our institution during a 33-month period. We compared the incidence of adverse obstetric and neonatal outcomes among these women with the incidence among women without rheumatologic diseases (n = 18,534). RESULTS: Women with rheumatologic diseases were more likely to have preeclampsia than women without rheumatologic disease (8.8% versus 2.3%, P <.001) Women with rheumatologic diseases were also at increased risk of preterm delivery (15.2% versus 7.8%, P =.002) and small-for-gestational-age infants (8.0% versus 3.1%, P =.001) compared with women without rheumatologic disease. CONCLUSION: The finding that women with rheumatologic diseases are at increased risk of adverse obstetric outcomes suggests a need for heightened clinical vigilance and further research into the common pathophysiologic correlates. LEVEL OF EVIDENCE: II-2
15476200 Expression of mitogen-activated protein kinase phosphatase 1, a negative regulator of the 2004 Oct OBJECTIVE: Mitogen-activated protein kinases (MAPKs) are activated by proinflammatory stimuli. MAPK phosphatases (MKPs), in particular MKP-1, have been identified as endogenous negative regulators of MAPK activation. Since MAPKs are known to be important in rheumatoid arthritis (RA) synoviocyte activation, this study assessed the expression, regulation, and function of MKP-1 in RA. METHODS: MKP-1 expression was measured by Western blotting (WB) and real-time polymerase chain reaction (PCR). RA fibroblast-like synoviocytes (FLS) were treated with interleukin-1beta (IL-1beta), tumor necrosis factor alpha, fetal calf serum, and dexamethasone. Expression of MAPKs in RA FLS was analyzed by WB using phosphospecific antibodies, while IL-6 expression was assessed by real-time PCR. RESULTS: MKP-1 protein and messenger RNA were detected in cultured RA FLS. IL-1beta rapidly up-regulated MKP-1, coinciding with reciprocal down-regulation of ERK, JNK, and p38 MAPK phosphorylation. Dexamethasone rapidly and sustainably up-regulated MKP-1, and this also coincided with down-regulation of ERK, JNK, and p38 MAPK phosphorylation. In addition, dexamethasone augmented IL-1beta-induced up-regulation of MKP-1, and this was associated with inhibition of ERK, JNK, and p38 MAPK phosphorylation and IL-6 expression. Dexamethasone had no effect on the phosphorylation of upstream kinases such as MEKK-3/6. In the presence of glucocorticoid (GC) receptor antagonist RU 486, the dexamethasone-mediated up-regulation of MKP-1 was impaired. Moreover, inhibition of MKP-1 expression impaired dexamethasone-mediated inhibition of MAPK phosphorylation. CONCLUSION: This study demonstrates the expression of MKP-1 in RA FLS. Cytokine and GC regulation of MKP-1 may be important in determining the magnitude of the inflammatory response in RA that is mediated via MAPKs. The effects of GCs in RA may be mediated, in part, via GC receptor-dependent up-regulation of MKP-1.
15163279 Aceclofenac in the management of inflammatory pain. 2004 Jun Aceclofenac (Almirall Prodesfarma SA) is an oral NSAID that is effective in the treatment of painful inflammatory diseases and has been used to treat > 75 million patients worldwide. It has proved as effective as diclofenac, naproxen and piroxicam in patients with osteoarthritis, diclofenac, ketorolac, tenoxicam and indomethacin in patients with rheumatoid arthritis and tenoxicam, naproxen and indomethacin in patients with ankylosing spondylitis. It also provides effective analgesia in other indications, such as dental or gynaecological pain, lower back pain and ear, nose and throat indications. Aceclofenac appears to be particularly well-tolerated amongst the NSAIDs, with a lower incidence of gastrointestinal adverse effects. This good tolerability profile results in a reduced withdrawal rate and hence greater compliance with treatment.
17474576 [An assessment of the epidemiological situation concerning cardiovascular diseases in the 2002 The paper aims at indicating the disadvantageous epidemiological situation concerning cardiovascular diseases, which constitutes the most important health problem in the Lodz region. At the end of 1999, 2,652,999 people inhabited the Lodz voivodeship. In 1999, 32,572 died, including 15,773 (48.43%) due to cardiovascular diseases. Therefore, the mortality rate concerning this group of diseases amounted to 593 out of 100,000 inhabitants of the voivodeship. It was higher among females than males (603 compared with 581). Cardiovascular diseases caused 43.35% of male deaths and 54.03% of female deaths. At the end of 2001, the Lodz voivodeship had 2,632,879 inhabitants. Out of 31,007 deaths, 14,977 (48.30%) were caused by cardiovascular diseases. Therefore, the mortality rate for this group of diseases amounted to 569 out of 100,000 in 2001. It is worth noting that the rate was higher among females than males (585 compared with 551) again. 42.32% of males and 55.01% of females that died lost their lives because of cardiovascular diseases. The number of deaths was calculated according to ten groups of these diseases as defined by the ICD-10. Our paper contains a detailed presentation of the mortality rates because of cardiovascular diseases by sex and by age in the Lodz voivodeship.
15082469 A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a 2004 Sep OBJECTIVE: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). METHODS: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. RESULTS: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%). CONCLUSIONS: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone.