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ID PMID Title PublicationDate abstract
20301228 Teaching medical students about chronic disease: patient-led teaching in rheumatoid arthri 2010 Mar OBJECTIVES: To evaluate the effectiveness of patient-led teaching compared with doctor-led teaching, regarding the impact of chronic disease (rheumatoid arthritis [RA]). METHODS: A set of learning objectives regarding the impact of RA on patient and family was designed. Students (n = 42) attached to the academy for their musculoskeletal diseases module were randomized to teaching either by a doctor or a patient. Outcome was assessed using a knowledge test, feedback forms and qualitative written interview. RESULTS: In the knowledge test, the groups performed equally. The patient-taught group scored 24.5 +/- 3.5 (max 35); the doctor-taught group scored 24.6 +/- 4.1 (p > 0.05; NS). Feedback was completed by 40/42 students. Mean scores for the overall grading of teaching (1-5, where 1 = worst, 5 = best) were: patient teaching 4.36 (95% confidence interval [CI] 4.11, 4.61); doctor teaching 3.69 (95% CI 3.52, 3.92).The difference between the average scores was 0.42 (p = 0.005). Qualitative feedback showed recurring themes that students appreciated the personal nature of the patient's teaching, enabling them to understand the impact of the disease on patients and their families. The doctors' teaching was also appreciated, particularly the interactive style and opportunity to participate in role play. CONCLUSIONS: We have demonstrated that our patient was at least as good as a doctor at teaching about the impact of chronic disease on patients. Furthermore, this experience is valued by students who appreciate the personal insight that a patient can offer.
20303765 The Bi-Surface total knee arthroplasty: minimum 10-year follow-up study. 2010 Aug The Bi-Surface Knee System (Japan Medical Material, Kyoto, Japan), which has a unique ball-and-socket joint and whose femoral component is made from alumina ceramic, was designed to improve deep knee flexion and long-term durability after total knee arthroplasty. The purpose of this study was to review the clinical results of a minimum 10-year follow-up. Between 1989 and 1997, 507 total knee arthroplasties were carried out in 371 patients. Forty three patients (56 knees) were lost to follow-up. The mean age of the patients at operation was 68.5 years, and the patients were followed up for a mean of 11.7 years. The knees were evaluated on the basis of Knee Society knee score and functional score, radiographs, and Kaplan-Meier survivorship analysis. The knee score was improved from 38.9+/-17.4 points preoperatively to 93.3+/-7.8 points at the latest follow-up (p<0.001). The functional score was improved from 34.9+/-19.3 points to 52.7+/-24.1 points (p<0.001). The mean range of flexion was improved from 118.7+/-21.7 degrees to 124.2+/-20.8 degrees (p<0.001). The critical angle, which means the border to gain more range of flexion postoperatively, was 130.1 degrees. Kaplan-Meier survivorship at 10-year was 95.9% with any operation or radiographic failure as the end point. The corresponding rate was 97.4% with revision of any component as the end point. No ceramic component fracture occurred. The present study demonstrates that good range of flexion was maintained for a long time after total knee arthroplasty with excellent durability. The Bi-Surface Knee System appears to have achieved its design objectives.
20432974 [A case of pulmonary nontuberculous mycobacteriosis aggravated during treatment with etane 2010 Apr A 81-year-old woman with rheumatoid arthritis (RA) was admitted to our hospital because of a productive cough and bloody sputum. She had been treated with etanercept, a tumor necrosis factor (TNF) antagonist, for 9 months before admission. A chest CT scan on admission showed small nodules, bronchiectasis and consolidations in bilateral lung fields. A diagnosis of pulmonary nontuberculous mycobacteriosis (NTM) was established by positive cultures for Micobacterium intracellulare both in her sputum and bronchial secretions obtained by bronchoscopy. It has been reported that bacterial pneumonia, tuberculosis (TB) and pneumocystis pneumonia (PCP) occur during treatment with etanercept or infliximab. However, there were few reports of NTM in post-marketing surveys of etanercept or infliximab in Japan. As pulmonary is NTM related to treatment with etanercept or infliximab and may progress rapidly with few drugs effective against NTM, we should be aware of pulmonary NTM as well as TB and PCP in the treatment of RA with etanercept or infliximab.
19327242 The development of trigeminal neuralgia related to auricular chondritis in a patient with 2009 Jan Cranial neuropathy is an uncommon manifestation of relapsing polychondritis (RPC). Optic neuropathy is the most common type of cranial nerve involvement in RPC. Until now, trigeminal neuralgia (TN) has been reported with different rheumatic diseases, however, there is no reported case of TN associated with RPC. We here present a case of RPC with TN. A 57 year-old female patient previously diagnosed with rheumatoid arthritis (RA) and RPC presented us with polyarthritis, auricular and nasal chondritis, and TN. Cranial MRI and MRI angiography of the brain did not show any pathology. The patient partially responded to RA therapy; and carbamazepine and etanercept were administered. RA-related joint findings, her chondritis and TN symptoms improved completely with etanercept. We presume that the TN was caused by compression of the trigeminal nerve from inflammation or ischemia secondary to vasculitis.
19254680 Attentional biases in chronic pain associated with rheumatoid arthritis: hypervigilance or 2009 Mar There is evidence that pain patients demonstrate attentional biases toward some pain-related stimuli (eg, sensory words) and not others (eg, affective words). However, whether individuals in chronic pain caused by rheumatoid arthritis (RA) also demonstrate this bias has not been investigated. Further, within the pain literature, whether these biases reflect hypervigilance or difficulty disengaging from stimuli remains contentious. The present study aimed to determine (a) whether RA patients demonstrate an attentional bias to sensory pain words; and (b) whether this bias is a result of hypervigilance or failure to disengage from the stimuli. RA patients showed a bias toward sensory words and away from threat-related words. The effect for sensory words resulted from slowed performance on incongruent trials (ie, difficulty disengaging), whereas the bias away from threat words resulted from faster responses on incongruent trials (ie, avoidance of threat). The pattern of attention biases in RA patients is very similar to those found in patients with chronic pain. At least in RA, attentional biases appear to be related to a failure to disengage from pain-related words rather than hypervigilance. PERSPECTIVE: There is continued debate about whether these biases are caused by hypervigilance toward pain stimuli or difficulty disengaging from pain stimuli. This study shows that in a group of RA patients, attentional biases toward pain are caused by difficulty disengaging rather than hypervigilance.
20391510 Low-dose aspirin in the primary prevention of rheumatoid arthritis: the Women's Health Stu 2010 Apr OBJECTIVE: Low-dose aspirin may reduce the risk of developing rheumatoid arthritis (RA) through its effect on cyclooxygenase activity and its antioxidant pathways. Previous randomized trial data have demonstrated a beneficial effect of low-dose aspirin in reducing other inflammatory diseases, such as asthma and colorectal adenomas, but no trial has evaluated the role of aspirin in RA prevention. METHODS: The Women's Health Study is a randomized, double-blind, placebo-controlled trial conducted between 1992 and 2004 designed to evaluate the risks and benefits of low-dose aspirin (100 mg every other day) and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health care professionals age > or =45 years throughout the US. After excluding women with RA at baseline, 39,144 women were evaluated for the present study. A definite diagnosis of RA was assessed during followup by self-report and confirmed using a connective tissue disease screening questionnaire, followed by a medical record review by a rheumatologist for American College of Rheumatology criteria. RESULTS: During an average followup of 10 years, 106 women developed definite RA (48 women in the aspirin group and 58 in the placebo group). There was a nonsignificant risk for RA (relative risk [RR] 0.83, 95% confidence interval [95% CI] 0.56-1.21; P = 0.33) associated with aspirin. There were 64 seropositive RA cases (60%) and 42 seronegative RA cases (40%). Aspirin also had no significant effect on either seropositive RA (RR 1.0, 95% CI 0.61-1.63) or seronegative RA (RR 0.62, 95% CI 0.33-1.15). CONCLUSION: One hundred milligrams of aspirin taken every other day was not associated with a significant reduction in the risk of developing RA among women in a randomized, double-blind, placebo-controlled trial.
20975635 Cardiovascular risk profile in systemic lupus erythematosus and rheumatoid arthritis: a co 2010 Jul OBJECTIVE: Premature atherosclerosis is well-documented both in Systemic Lupus Erythematosus (SLE) and in Rheumatoid Arthritis (RA) patients, but cardiovascular (CV) risk is particularly high in lupus women. Although conventional CV risk factors do not fully explain the excessive risk in inflammatory diseases, they remain major contributors to atherosclerosis. The aim of the present study was to investigate whether CV risk factors are differentially associated with SLE and RA. METHODS: One hundred women with SLE, 98 with RA and 102 controls matched on age and without overt CV or renal disease were assessed for the presence of Framingham (hypertension, hypercholesterolemia, low HDL, diabetes, smoking) and other CV risks (atherogenic index of plasma (AIP), insulin resistance, obesity, central obesity, metabolic syndrome, uric acid, sedentarism, hypothyroidism and family history of premature CV disease). RESULTS: Modifiable CV risk factors are highly prevalent and occur more frequently in SLE and RA than in age-matched controls. Some differences in Framingham risk factors were found between SLE and RA, with hypertension being more common in young lupus women, hypercholesterolemia more frequent in RA and low HDL-C more frequent in SLE. However, the estimated 10-year Framingham CHD risk or the Reynolds Risk Score was comparable in both diseases. Although hypercholesterolemia was more frequent in RA, lupus women display a more atherogenic lipid profile, with significantly lower HDL-C levels (56.5±16 mg/dl versus 63.7±18; p=0.005), and more cases above the high risk cutpoints for cholesterol/HDL-C (14% versus 4.1%; p=0.01) and for AIP (15% versus 6.1%; p=0.03). Also, uric acid levels are higher in SLE women (4.8±1.5 mg/dl) than in RA (4.1±1.1 mg/dl), p=0.001. On the other hand, insulin resistance is significantly higher in women with RA as compared with SLE (median HOMA-IR 3.5 [6.4]) versus 0.72 [2.5]; p<0.0001) and the difference remained significant after adjustment for BMI and corticosteroids. CONCLUSIONS: Cardiovascular risk profile is distinct in SLE and RA women and the contribution of traditional CV risk factors to atherogenesis may be different in these two diseases. Prospective studies are necessary to understand how the control of modifiable risks can improve CV outcome in different inflammatory settings.
20100793 Cost-utility of different treatment strategies after the failure of tumour necrosis factor 2010 Apr OBJECTIVE: To evaluate the cost-utility of different treatment strategies in severe RA after TNF-inhibitor failure. METHODS: The cost-effectiveness of treatment strategies was compared in a group of hypothetical Finnish RA patients. Initially, the patients received either best supportive care (BSC) or one of the following treatments before BSC: adalimumab (ADAL), abatacept (ABAT), etanercept (ETAN), infliximab (INFL) or rituximab (RTX). Further treatments were added to the most cost-effective strategy in a stepwise manner. The analysis was performed on an Excel-based Markov state transition model using the probabilistic approach. The clinical outcomes related to treatments were estimated from published clinical trials. The gained quality-adjusted life-years (QALYs) were estimated based on Health Utilities Index (HUI-3) and disease severity scores (HAQ). The resource use and costs were obtained from the Finnish treatment practice, one published study, the Finnish Unit Cost list and Finnish Medicine Tariffs. RESULTS: Treatment with RTX was more effective and less costly than treatment with ADAL, ABAT or ETAN after TNF-inhibitor failure. An additional QALY gained with RTX costs 30,248 euros compared with BSC. The incremental cost-effectiveness ratios (ICERs) are 50,941, 50,372, 36,121 and 67,003 euros per QALY gained for adding ADAL, ETAN, INFL and ABAT to the RTX strategy, respectively. According to the cost-effectiveness acceptability frontier (CEAF), only BSC or treatments with RTX or RTX followed by INFL should be considered after TNF-inhibitor failure, if willingness to pay is between 0 and 50,000 euros per QALY gained. CONCLUSIONS: Treatment with RTX is a cost-effective treatment strategy in RA patients in Finland.
19370182 [The mediterranean diet model in inflammatory rheumatic diseases]. 2009 Jan The Mediterranean diet is based on a pattern of eating closely tied to the Mediterranean region, which includes Greece and southern Italy. Essentially, the traditional diet emphasizes foods from plant sources, limited meat consumption, small amounts of wine and olive oil as the main fat source. The beneficial effects of the Mediterranean diet has been proven not only to cardiovascular diseases but also for diabetes, obesity, arthritis and cancer. Its anti-inflammatory and protective properties are linked to the large presence of omega-3 polyunsaturated fatty acids, vitamins, but especially to the constituents of extra virgin olive oil: oleic acid, phenolic compounds olecanthal, a new recently discovered molecule, with natural anti-inflammatory properties. It has been shown that the Mediterranean diet can reduce disease activity, pain and stiffness in patients with inflammatory arthritis and may thus constitute a valuable support for patients suffering from these diseases.
20213086 [Hermann Lebert (1813-1878): natural scientist, spa doctor, histopathologist and clinician 2010 Jul H. Lebert was in many ways an extraordinary personality. He began is career as a scientist performing experimental research in botany and zoology. After a short period as a spa doctor--work he approached on a scientific basis--he performed one of the first microscopic tissue analyses, as well as writing two significant works with a wealth of pictures on pathophysiology and histopathology, thereby paving the way for cellular pathology. In addition to general problems relating to inflammation, he concentrated on tumors and tuberculosis. He was one of the first to recommend pre-operative histology, making him a pioneer of biopsy diagnostics.As a clinician he worked in nearly all areas of internal medicine, including neurology, and published a large number of monographs, of which the first German monograph on acute articular rheumatism was one. Rheumatology played a considerable role in both his histopathological and clinical activities.Of particular interest is the fact that Lebert frequently travelled between Switzerland, France and Germany and was applauded in all three as a great scientist, as awards from both Napoleon III and the Prussian King Friedrich Wilhelm IV can testify.
20504106 The efficacy and safety of golimumab in the treatment of arthritis. 2010 Jul IMPORTANCE OF THE FIELD: Twenty-five years ago, rheumatoid arthritis (RA) was a relentless disease, treated symptomatically because of the lack of effective, well tolerated medications which could halt disease in most patients. The introduction of methotrexate, sulfasalazine and leflunomide, and aggressive treatment, changed the prognosis of RA in the 1990s. Biologic therapies have dramatically changed the long-term prognosis of patients with rheumatoid and psoriatic arthritis and ankylosing spondylitis. AREAS COVERED IN THIS REVIEW: Unfortunately, no one single agent is fully effective in every patient. For this reason, another agent, golimumab (GLM), a TNF-alpha inhibitor (TNF-I) was developed. The basis of this review is all peer-reviewed manuscripts on GLM in the treatment of RA, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) found in Pub Med. and Medline from 2000 to 2010 and abstracts presented at the major rheumatology congresses within the past five years. WHAT THE READER WILL GAIN: This review describes the efficacy and safety of GLM and should enable an understanding of the benefit-risk profile of GLM in the treatment of RA, PsA and AS. TAKE HOME MESSAGE: GLM is effective and has a safety profile similar to other TNF-I in the treatment of RA, AS and PsA.
20721724 The usefulness of neutrophil CD64 expression in the diagnosis of local infection in patien 2010 Jul BACKGROUND: The diagnosis of local infection in patients with rheumatoid arthritis (RA) is frequently difficult because clinical signs and symptoms and laboratory test results of local infection are also observed in arthritis of active RA. The need for a specific marker of infection is high in RA patients. The usefulness of neutrophil CD64 expression (CD64) to diagnose local musculoskeletal infection (local infection) and discriminate local infection from RA-related inflammation in RA patients was examined. METHODS: CD64 was measured by a quantitative method using flow cytometry in 61 RA patients in whom local infection was suspected, and the usefulness of CD64 was examined by comparing the findings with clinical results. RESULTS: There were 25 patients with local infection and 36 patients without infection. The median CD64 value the patients with local infection was 3148 molecules/cell (interquartile range [IQR], 2140-6231) and that of the patients without infection was 1106 molecules/cell (IQR, 804-1464) with a statistically significant difference (P < 0.0001). In contrast, no significant difference between the groups was observed in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count. The area under the curve of CD64 calculated by receiver operating characteristic curve analysis was larger than that of CRP, ESR, or WBC count, suggesting that CD64 has superior ability to discriminate of infection compared to these other markers. When the cutoff value of CD64 was set at 2000 molecules/cell, the sensitivity and specificity of CD64 for the detection of local infection in RA patients were 76.0% and 94.4%, respectively. CONCLUSIONS: CD64 is a useful marker in RA patients to discriminate local infection from RA-related inflammation.
19721349 [Clinical features in patients with polymyalgia rheumatica]. 2009 Aug Polymyalgia rheumatica (PMR) is an inflammatory disease of unknown etiology affecting elderly patients and characterized by muscle pain and morning stiffness in proximal areas (pelvic and shoulder girdles and neck). It is sometimes difficult to distinguish PMR from rheumatoid arthritis (RA), or vasculitis. In the present study, we examined the clinical characteristics of the patients diagnosed with PMR in our hospital retrospectively. There were 44 patients with the median age of 71s. Eighty percent of the patients were in their 60s or 70s, and 3 patients (6.8%) were in there 50s or younger. There was no sex preponderance in frequency. Fifteen patients (34%) presented with both proximal and distal muscle pain. Arthritis occurred in 16 patients (36%), the half of which was monarthritis or oligoarthritis, and was more involved in wrist or knee joint. Only 3 patients had temporal arteritis (TA) complicated with PMR. Mean of maximum serum CRP was 8.18 mg/dl, and rheumatoid factor and anti-CCP antibodies were positive in 2 patients and a patient, respectively. There was no patient positive for ANCA. Serum MMP-3 levels tended to be higher in female patients. Median of maximum prednisolone (PSL) dose used for the treatment was 0.195 mg/kg of body weight daily. No patient needed any immunosuppressants. In the 26 patients we had a chance to follow, there were no patients who developed RA 6 months after the initial diagnosis. Progression from PMR to RA was reported, and mean period between the diagnosis of PMR and RA was one to 5 years.
19062243 [Pneumocystis pneumonia among patients with systemic diseases]. 2009 Feb The termPneumocystis carinii is now reserved for the animal form of the disease, for humans Pneumocystis jiroveci is appropriated. Incidence of pneumocystis pneumonia (PCP) among patients with systemic rheumatic diseases varies from 0.2% for rheumatoid arthritis to up 12% for Wegener's granulomatosis. Clinical and radiological presentation of pneumocystis pneumonia among non-VIH patients is often difficult to diagnose and the installation can be abrupt. Most of cases of PCP occur during the first 3 months following the beginning of immunosuppressant agents. Mortality during PCP is high with an average of 40% of death, rising 60% in case of mechanical ventilation. Prophylaxis of PCP is needed (without support by randomised studies) for patients with Wegener's granulomatosis, in case of cyclophosphamide or high-dose of methotrexate use except for rheumatoid patients, if a simultaneous treatment by corticosteroids and immunosuppressant agent is required, if a prolonged corticosteroid treatment (> 2 months) is used with dose of prednisone-equivalent > 16mg per day or > 20mg per day > 1month associated with one or more risk factors of PCP among advanced age, denutrition or deep lymphopenia. The best prophylaxis of PCP is cotrimoxazole.
20868571 Vitamin D modulates peripheral immunity in patients with Behçet's disease. 2010 Jul BACKGROUND AND OBJECTIVES: There is little knowledge about clinical and immunological variables associated with vitamin D insufficiency in inflammatory diseases. We sought to investigate disease variables associated with vitamin D levels in patients with Behçet's disease (BD) and its interaction with inflammatory responses. METHODS: One hundred and sixty BD patients (102 patients in active stage) were enrolled in a study assessing the relationship between serum vitamin D concentrations and disease activity. As control diseases we studied 22 Rheumatoid arthritis (RA) and 30 multiple sclerosis (MS) patients. Serum concentrations of vitamin D were assayed with a radioimmunoassay kit. To assess the correlation between inflammatory mediators, immune cell expression and vitamin D, 20 active BD patients and 18 healthy controls were investigated: T-cell subsets and Treg cells were quantified by flow cytometry. Th1/Th2 ratio and Th17 were studied by intracytoplasmic cytokines expression (IFN-γ, IL-4, IL-10 and IL-17). RESULTS: Decreased levels of vitamin D were observed in active BD patients compared to patients in the inactive stage and to healthy controls (p=0.0246; p=0.0001). A low significant difference was observed between inactive BD and healthy controls (p=0.004). Active BD expressed higher vitamin D levels than RA (p=0.007) and MS (p=0.044) patients (p=0.0238). In active BD, vitamin D levels were correlated with CRP and ESR. Serum levels of vitamin D correlated positively with the number of Treg cells (r=0.640; p=0.0024). The IFN-γ/IL-4 ratio (Th1/Th2) was inversely correlated with serum 25(OH)D levels (r=-0.599; p=0.0053). CONCLUSIONS: Active BD was associated with lower serum Vitamin D levels. Our results showed that low levels of vitamin D were associated with a decrease in Treg cells and a skewing of the Th1/Th2 balance towards Th1. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in BD patients. As suggested in other inflammatory/autoimmune diseases, vitamin D may modulate inflammatory mediators.
20494473 The novel anti-rheumatic compound Rabeximod impairs differentiation and function of human 2011 Jan Rabeximod (9-chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo[2,3-b]quinoxaline) is a synthetic compound that is currently being developed for the treatment of rheumatoid arthritis (RA). Here, we investigated the effects of Rabeximod on the functionality of human antigen-presenting cells (APCs) of myeloid origin. Different subsets of professional APCs were generated from human monocytes in vitro and simultaneously treated with different doses of Rabeximod. Although Rabeximod had no effect on the differentiation of monocytes into anti-inflammatory macrophages (AI-MÏ•s), this compound impaired monocyte differentiation into monocyte-derived dendritic cells (MDCs) and pro-inflammatory allostimulated macrophages (Allo-MÏ•s). MDCs that were treated with Rabeximod resulted in a significant decrease in their ability to pinocytose antigens, while no effect was exerted by the drug on the ability of Allo-MÏ•s and AI-MÏ•s to phagocytose. Furthermore, we observed a significant reduction in the allostimulatory ability of MDCs and Allo-MÏ•s after treatment with Rabeximod, although this compound did not affect the low immunostimulatory capacity of AI-MÏ•s. Conversely, the effect of Rabeximod in influencing cytokine secretion by APCs appeared to be limited. In conclusion, Rabeximod impairs differentiation of monocytes into different pro-inflammatory APCs, leading to impaired immunostimulatory abilities of these cells. Our observations shed light on the cellular mode of action and the immunomodulatory effect of Rabeximod.
20808295 The yin and yang of regulatory T cells and inflammation in RA. 2010 Oct Rheumatoid arthritis (RA) is characterized by chronic inflammation leading to joint destruction. Regulatory T (T(REG)) cells are potent suppressors of autoimmunity, but are not capable of controlling every aspect of the inflammatory reaction. We have found that T(REG)-cell function is abnormal in patients with RA, and that a distinct population of T(REG) cells with potent suppressive properties is induced after therapy with inhibitors of tumor necrosis factor. In this Review, we discuss the mutual interactions between the opposing forces of T(REG) cells and inflammation in the context of RA. Therapeutic approaches that enhance T(REG)-cell function whilst controlling inflammation are likely to be the most effective strategies for restoring immune tolerance in patients with this disease.
20337546 The association of luteinizing hormone and follicle-stimulating hormone with cytokines and 2010 Mar OBJECTIVES: Disease activity in rheumatoid arthritis (RA) varies substantially during periods when luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels change, for example during pregnancy, postpartum, and menopause. We wanted to investigate whether small fluctuations in these hormones could be associated with similar fluctuations in cytokines and disease activity in RA. METHODS: Disease activity markers, serum LH, FSH, and 24 cytokines were assessed on days 1 and 8 in 20 RA patients (median age 58 years, six males) and 19 controls (median age 56 years, six males). RESULTS: Percentage changes in LH and FSH correlated positively with percentage changes in key proinflammatory cytokines such as tumour necrosis factor (TNF)alpha (LH r = 0.737, p = 0.0007; FSH r = 0.680, p = 0.001) and interleukin (IL)-1beta (LH r = 0.515, p = 0.050; FSH r = 0.749, p = 0.0008). Similar correlations were observed with IL-2, IL-2R, IL-8, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and eotaxin, but not with the anti-inflammatory cytokine IL-10, in RA and not in controls. Percentage changes in LH, FSH, and cytokines were not correlated with percentage changes of several disease activity markers but were correlated positively with cross-sectional levels of disease activity markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Visual Analogue Scale (VAS) pain, VAS global (physician/patient), and the modified Health Assessment Questionnaire (MHAQ)]. CONCLUSIONS: The significant associations between percentage changes in LH and FSH and percentage changes in key cytokines and several cross-sectional markers of disease activity may indicate that LH and FSH influence crucial points of the cytokine cascade in RA. This may help to explain, partially, why disease activity initiates or worsens during periods of increased LH and FSH, such as the postpartum period and the menopause.
18772190 Reversible changes in serum immunoglobulin galactosylation during the immune response and 2009 Aug OBJECTIVES: Improved DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology was used to monitor the changes in the galactosylation status of serum immunoglobulins during the immune response and therapy of autoimmune arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in susceptible DBA/1 mice and the undergalactosylation status (UGS) of serum immunoglobulins was determined using the improved DSA-FACE technology. Prophylactic intravenous tolerisation with type II collagen as well as semitherapeutic treatment with dexamethasone (DEX) were performed and UGS was analysed. Next, the serum immunoglobulin glycosylation profiles of patients with rheumatoid arthritis (RA) and spondyloarthropathy (SpA) were studied and changes in the UGS scores during anti-tumour necrosis factor (TNF)alpha therapy followed. RESULTS: In the longitudinal CIA study, the undergalactosylation state of immunoglobulins was found to be significantly correlated with the clinical arthritis scores. Upon collagen-specific tolerisation as well as glucocorticoid semitherapeutic treatment, improvement of the clinical arthritis scores correlated with decreased levels of UGS. It was also demonstrated that withdrawal of DEX was associated with an increased UGS score. Interestingly, reversibility in the UGS was also shown during treatment of patients with RA and SpA with anti-TNFalpha. CONCLUSIONS: These findings demonstrate that the UGS of serum immunoglobulins changes during the disease course of CIA and that this UGS is inhibited by antigen-specific and antigen-independent treatment procedures. The observation that Ig galactosylation is a reversible process is also documented during treatment of patients with RA and SpA with anti-TNFalpha.
19758219 Role for CaMKII inhibition in rheumatoid arthritis: effects on HIF-1-induced VEGF producti 2009 Sep BACKGROUND AND AIMS: The present study was designed to investigate the effects of a novel CaMKII inhibitor SMP-114, which was effective in a collagen-induced arthritis model in rats, on rheumatoid synovial fibroblasts. METHODS: Rheumatoid synovial fibroblasts (RSF) were cultured under pro-inflammatory (IL-1beta stimulation) and hypoxic conditions. Protein and mRNA expression of HIF-1alpha and the effects of inhibitors of the CaMKII-, PI3K-, and ERK pathway on VEGF and IL-6 production were analyzed. RESULTS: Stimulation under hypoxic conditions induced higher expression of HIF-1alpha and VEGF mRNA than treatment with either IL-1beta or hypoxia alone. However, incubation with a specific CaMKII inhibitor did not result in reduced VEGF production in RSF. CONCLUSIONS: CaMKII activation has been reported to be involved in HIF-1alpha stabilization, but incubation with SMP-114, a specific CaMKII inhibitor, had no effect on HIF-1-induced VEGF production by rheumatoid synovial fibroblasts.