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ID PMID Title PublicationDate abstract
16246063 Novel tissue remodelling roles for human recombinant erythropoietin. 2005 Nov rHuEPO (recombinant human erythropoietin) is a haemopoietic growth factor and a primary regulator of erythropoiesis that is used for the treatment of chronic anaemia associated with RA (rheumatoid arthritis). Erythropoietin also appears to modulate a broad array of cellular processes, including progenitor stem-cell development, cellular integrity, angiogenesis and oxidative damage. These diverse activities suggest the exciting possibility of multiple roles for rHuEPO therapy in a variety of disorders other than RA, including cerebral ischaemia, myocardial infarction, chronic congestive heart failure and cancer. Thus it appears that rHuEPO may be a pleiotropic agent, capable of influencing tissue remodelling independently of its established erythropoietic role. Whereas these effects may be largely beneficial, dose-related side effects could have implications for the safe therapeutic use of rHuEPO and its illegal use as a performance-enhancing agent in endurance sports.
17802930 [Corticosteroid resistance thrombocytopenia in connective tissue disorders and vasculitis] 2006 Apr In rheumatic diseases there can appear deteriorations of the thrombocytes number in the sense of increase or decrease of this number.Thrombocytosis has 3 major causes: (1) reactive or secondary thrombocytosis; (2) family thrombocytosis and (3) clonal thrombocytosis. Thrombocytopenia, that is, decrease of the thrombocytes number below 150000/mmc is unusually in rheumatic diseases. Their mechanism of production can be central and peripheral. In the connective tissue disorders and vasculitis thrombocytopenia can has different causes: (1) decrease thrombocytes production; (2) splenic platelets sequestration; (3) peripheral platelets consumption; (4) peripheral immune mediated destruction of platelets. Thrombocytopenia is present in the following rheumatic diseases: systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Felty syndrome, vasculitis. Steroids are the conventional first line therapy for immune thrombocytopenia. Corticosteroid resistance can develop as a result of deteriorations that appear to the any level of pathway action of corticosteroids.
16235342 Acupuncture and electroacupuncture for the treatment of rheumatoid arthritis. 2005 Oct 19 BACKGROUND: Acupuncture has been used by rehabilitation specialists as an adjunct therapy for the symptomatic treatment of rheumatoid arthritis (RA). Acupuncture is a traditional Chinese medicine where thin needles are inserted in specific documented points believed to represent concentration of body energies. In some cases a small electrical impulse is added to the needles. Once the needles are inserted in some of the appropriate points, endorphins, morphine-like substances, have been shown to be released in the patient's system, thus inducing local or generalised analgesia (pain relief). This review is an update of the original review published in July 2002. OBJECTIVES: To evaluate the effects of acupuncture or electroacupuncture on the objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: A comprehensive search of MEDLINE, EMBASE, PEDro, Current Contents , Sports Discus and CINAHL, initially done in September 2001, was updated in May 2005. The Cochrane Field of Rehabilitation and Related Therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registries. Handsearching was conducted on all retrieved papers and content experts were contacted to identify additional studies. SELECTION CRITERIA: Comparative controlled studies, such as randomized controlled trials and controlled clinical trials in patients with RA were eligible. Trials published in languages other than French and English were not analyzed. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search and extracted data using pre-defined extraction forms. Consensus was reached on all the extracted data. Quality was assessed by two reviewers using a five point validated tool that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: After the updated searches were conducted, five further potential articles were identified; however, these did not meet the inclusion criteria. Two studies involving a total of 84 people were included. One study used acupuncture while the other used electroacupuncture. In the acupuncture study, no statistically significant difference was found between groups for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale for patient's global assessment (VAS G), number of swollen joints and tender joints, general health questionnaire (GHQ), modified disease activity scale (DAS) or for the decrease in analgesic intake. Although not statistically significant, pain in the treatment group improved by 4 points on a 0-100mm visual analogue scale versus no improvement in the placebo group. In the second study, using electroacupuncture, a significant decrease in knee pain was reported in the experimental group, 24 hours post treatment, when compared to the placebo group (WMD: -2.0 with 95% CI -3.6,-4.0). A significant decrease was found also at four months post-treatment (WMD -0.2, 95% CI: -0.36, -0.04) AUTHORS' CONCLUSIONS: Although the results of the study on electroacupuncture show that electroacupuncture may be beneficial to reduce symptomatic knee pain in patients with RA 24 hours and 4 months post treatment, the reviewers concluded that the poor quality of the trial, including the small sample size preclude its recommendation. The reviewers further conclude that acupuncture has no effect on ESR, CRP, pain, patient's global assessment, number of swollen joints, number of tender joints, general health, disease activity and reduction of analgesics. These conclusions are limited by methodological considerations such as the type of acupuncture (acupuncture vs electroacupuncture), the site of intervention, the low number of clinical trials and the small sample size of the included studies.
16755914 [Expression of sTNFR-IgGFc fusion gene in endothelial cell and its application in gene the 2006 May Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine, acting as a regulator of inflammation and immunity. TNFalpha plays a critical role in the pathogenesis of rheumatoid arthritis. Blocking of TNFa activity suppressed inflammatory tissue damage. In present study, the chimeric gene of soluble TNF receptor and IgG Fc fragment (sTNFR-IgG FC) was cloned into the mammalian cell expression vector pStar. When the plamid pStar/sTNFR-IgGFc-GFP was transfected into endothelial cells, a considerable expression of the sTNFR-IgG Fc fusion protein was detected. Moreover, the product in 100microL expression supernatant could completely antagonize the cytolytic effect of 1ng TNFa on L929 cells, even at 1/64 dilution. Then the plasmid was delivered into CIA-induced rheumatoid arthritis mice by tail vein injection. The expression of sTNFR-IgG Fc was detected in liver by RT-PCR. Animals in treatment group showed reduced symptoms of arthritis and more active. This treatment induced decrease of synovial incrassation and prevented the cartilage destruction of the mice RA model. These results show that tail vein injection is an effective way for gene therapy and sTNFR-IgGFc expression plasmid is potential for the treatment of rheumatoid arthritis.
16320327 Nurse-like cells from patients with rheumatoid arthritis support the survival of osteoclas 2005 Dec OBJECTIVE: To elucidate the role of nurse-like cells (NLCs) obtained from rheumatoid arthritis (RA) patients in bone loss during progressive synovial expansion. METHODS: CD14+ monocytes were cocultured with NLCs for 4 weeks and collected as NLC-supported CD14+ (NCD14+) monocytes. To determine their ability to differentiate into osteoclasts, NCD14+ monocytes were further cultured with macrophage colony-stimulating factor (M-CSF) together with RANKL or tumor necrosis factor alpha (TNFalpha). NCD14+ monocytes were also cocultured with SaOS-4/3 cells, which were shown to support osteoclastogenesis in response to parathyroid hormone (PTH). CD14+ monocytes were cocultured with SaOS-4/3 cells to elucidate how SaOS-4/3 cells and NLCs supported CD14+ monocytes for a long period. Synovial expansion adjacent to bone in RA patients was examined immunohistochemically to detect osteoclast precursors such as NCD14+ monocytes. RESULTS: NLCs supported the survival of CD14+ monocytes for 4 weeks. NCD14+ as well as CD14+ monocytes differentiated into osteoclasts in the presence of M-CSF together with RANKL or TNFalpha. NCD14+ monocytes also differentiated into osteoclasts in PTH-treated cocultures with SaOS-4/3 cells. SaOS-4/3 cells supported the survival of CD14+ monocytes for 4 weeks in the presence, but not absence, of PTH. Treatment of SaOS-4/3 cells with PTH up-regulated the expression of M-CSF messenger RNA. Neutralizing antibodies against M-CSF inhibited the NLC-supported survival of CD14+ monocytes. CD68+ monocytes and M-CSF+ fibroblast-like synoviocytes were colocalized in regions adjacent to the destroyed bone of RA patients. CONCLUSION: Our findings suggest that NLCs are involved in RA-induced bone destruction by maintaining osteoclast precursors via production of M-CSF.
15893949 Do arachidonic acid and its metabolites, secreted by rheumatoid and osteoarthritic synovia 2005 Dec AIMS: To further characterize factors secreted in vitro by osteoarthritic and rheumatoid arthritis synovial membranes that inhibit DNA synthesis by cultured human articular chondrocytes, and extend these findings to synovial fluid. MATERIAL AND METHODS: Synovial tissue, synovial fluid and articular cartilage were obtained at surgery from two patients suffering rheumatoid arthritis and two other patients suffering from osteoarthritis. Synovial tissue was incubated in DMEM, then condition media and synovial fluids were extracted with methanol. Methanol extracts and extracted residues (hyaluronic acid, proteins) were assayed for their capacity to inhibit DNA synthesis in articular chondrocytes. Methanol extracts were also fractionated by thin layer chromatography on silica-coated plates and recovered fractions similarly tested. RESULTS: All extracts exhibited strong and concentration-dependent inhibition of [3H]-thymidine incorporation. The most potent inhibition was obtained with the extracts from rheumatoid joints and the least potent inhibition was with synovial fluids. The removal of active substances with methanol leaves an inactive residue. Methanol extraction does not alter the mitogenic activity of five exogenous growth factors and two cytokines, thus suggesting that such activity is entirely due to lipids. The bulk of anti-mitotic factors extracted by methanol co-migrate when fractionated by thin layer chromatography on silica-coated plates with arachidonic acid and its lipo-oxygenase metabolites. IN CONCLUSION: Inflamed synovium produces and releases lipids, most probably arachidonic acid metabolites that inhibit cell proliferation thus limiting inflammation and pannus formation in arthritis.
16834969 [Effects of traditional Chinese medicine for invigorating spleen to resolve dampness and d 2006 Jul OBJECTIVE: To observe the clinical effects of Xinfeng Capsules (XFC), a traditional Chinese medicine for invigorating the spleen to resolve dampness and dredging collaterals, on patients with rheumatoid arthritis (RA) and anemia, and to investigate its mechanism. METHODS: Forty patients with RA and anemia were divided into three groups: XFC-treated group (n=20), Tripterygium glycosides Tablets (TGT)-treated group (n=10) and methotrexate (MTX)-treated group (n=10). The patients in each group took corresponding medicine for three months. The response rates of the three groups were evaluated after treatment. The general symptoms and specific signs and symptoms of RA were observed before and after the treatment. The indexes of blood routine examination and some other laboratory indexes such as erythrocyte sedimentation rate (ESR), and blood levels of rheumatoid factor (RF), iron, C-reaction protein (CRP), immunoglobins (Ig), complements 3 and 4, tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10) and erythropoietin (EPO) were all examined and compared before and after treatment. RESULTS: The total response rate in the XFC-treated group was similar to those both in the TGT-treated and MTX-treated groups. The effects on relieving specific symptoms of RA in the three groups were also similar. The ESR and serum levels of RF, CRP, IgG, IgA and IgM were all decreased after treatment as compared with those before treatment in the three groups, and there were no significant differences among those laboratory indexes in the three groups after treatment. The XFC displayed more obvious effects on improving the general symptoms of patients with RA and anemia, increasing the blood levels of hemoglobin, iron and IL-10, while decreasing the serum level of TNF-alpha and regulating the serum EPO level, as compared with those in the TGT-treated and MTX-treated groups. CONCLUSION: The XFC for invigorating the spleen to resolve dampness and dredging collaterals was developed on the basic principle of regulating spleen. It can obviously improve the symptoms and laboratory indicators of RA. Such effects may be related to maintaining the balance of cytokines, regulating the serum level of EPO and increasing the serum iron level in patients with RA and anemia.
15817660 Occurrence and risk factors for falls in rheumatoid arthritis. 2005 Nov OBJECTIVES: To determine the one year period prevalence of falls by age and sex in patients with rheumatoid arthritis and the influence of concurrent medical treatment and disability on the occurrence of falls in this group. METHODS: A consecutive series of rheumatoid patients aged 35 years and over, attending hospital outpatient clinics at Hope hospital, Salford, were asked to complete an interview assisted questionnaire which asked about the occurrence and number of falls in the previous 12 months. SUBJECTS: who took part were asked about current treatment with antihypertensive agents, diuretics, sedatives or hypnotics, antidepressants, and a history of previous hip/knee surgery. They also completed the health assessment questionnaire (HAQ). Logistic regression was used to determine the association between these variables and falls in the previous 12 months. RESULTS: 253 men and women, mean age 62 years, were studied, and 84 (33%) reported falling in the previous year (36% of women and 26% of men). Of these, 52% had fallen on more than one occasion. There was no important increase in the frequency of falls with age. After adjusting for age and sex, those who had fallen in the previous year were more likely to report taking antidepressant treatment (odds ratio (OR) = 2.09) and to have impairment in both walking (OR = 1.37) and rising (OR = 1.41). The HAQ score was higher in those who reported a fall than those who did not, though the difference was not statistically significant. CONCLUSIONS: In this hospital based survey, one in three patients with rheumatoid arthritis reported falling in the previous 12 months. Falls were associated with self reported impairment in lower limb function.
17158431 Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients wi 2006 Dec BACKGROUND: Tumor necrosis factor (TNF) is an important mediator of cachexia, and its blockade prevents catabolism in animal models. However, little evidence shows that anti-TNF therapy is effective in treating cachexia in humans. OBJECTIVE: The main aim of this study was to investigate the effect of etanercept, a synthetic soluble TNF receptor, on body composition in patients with early rheumatoid arthritis (RA). DESIGN: Twenty-six patients were randomly assigned to 24 wk of treatment with etanercept or methotrexate; the latter is the first-line therapy for RA. Body composition, physical function, disease activity, systemic inflammation, and the circulating insulin-like growth factor (IGF) system were measured at baseline (week 0) and at follow-up (weeks 12 and 24). Twelve patients in each treatment group (9 F, 3 M) completed the study. RESULTS: Overall, no important changes in body composition were observed, despite a transient increase in IGF-I at week 12 (P < 0.01). However, the secondary analysis of those patients (6/treatment group) who gained weight during follow-up showed a significant effect of etanercept on the composition of the weight gained: 44% of weight gained in the etanercept group was fat-free mass, as compared with only 14% in the methotrexate group (P = 0.04). Etanercept and methotrexate were equally effective in controlling the disease and improving physical function. CONCLUSIONS: Anti-TNF therapy with etanercept is not superior to that with methotrexate for the treatment of rheumatoid cachexia over a period of 6 mo. However, TNF blockade seems to normalize the anabolic response to overfeeding and, if these findings are confirmed, may be useful in conditions characterized by anorexia and weight loss.
16738952 Inhibition of IL-1, IL-6, and TNF-alpha in immune-mediated inflammatory diseases. 2006 Jun Blockade of cytokines, particularly of tumour necrosis factor alpha (TNF-alpha), in immuno-inflammatory diseases, has led to the greatest advances in medicine of recent years. We did a thorough review of the literature with a focus on inflammation models in rodents on modified gene expression or bioactivity for IL-1, IL-6, and TNF-alpha, and we summarized the results of randomized controlled clinical trials in human disease. What we have learned herewith is that important information can be achieved by the use of animal models in complex, immune-mediated diseases. However, a clear ranking for putative therapeutic targets appears difficult to obtain from an experimental approach alone. This is primarily due to the fact that none of the disease models has proven to cover more than one crucial pathogenetic aspect of the complex cascade of events leading to characteristic clinical disease signs and symptoms. This supports the notion that the addressed human immune-mediated diseases are polygenic and the summation of genetic, perhaps epigenetic, and environmental factors. Nevertheless, it has become apparent, so far, that TNF-alpha is of crucial importance in the development of antigen-dependent and antigen-independent models of inflammation, and that these results correlate well with clinical success. With some delay, clinical trials in conditions having some relationship with rheumatoid arthritis (RA) indicate new opportunities for blocking IL-1 or IL-6 therapeutically. It appears, therefore, that a translational approach with critical, mutual reflection of simultaneously performed experiments and clinical trials is important for rapid identification of new targets and development of novel treatment options in complex, immune-mediated, inflammatory diseases.
15322815 The relationship between arthritis and human parvovirus B19 infection. 2005 Nov In order to evaluate the role of human parvovirus B19 in the etiopathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), synovial fluid and blood specimens were collected at 1-month intervals from 20 patients with early synovitis (ES) and 31 with RA. Blood specimens were also collected from 25 patients with SLE, 25 with osteoarthritis (OA) as the diseased control group, and 50 healthy blood donors (HBD) as the healthy control group. Detection of B19 IgM and B19 IgG were performed by enzyme-linked immunosorbent assay from serum specimens, and B19 DNA was detected by polymerase chain reaction from synovial fluid samples. B19 IgM, B19 IgG, and B19 DNA were found in the three patients of the ES group. Subsequently, two of them were diagnosed with RA and one with SLE. B19 DNA was also detected in the synovial fluid of eight patients in the RA group. Of them, all were positive for B19 IgG and half were positive for B19 IgM. B19 IgM was not detected in either of the control groups. To define the role of B19 in the etiopathogenesis and prognosis of undiagnosed arthritis and other chronic inflammatory diseases such as RA and SLE, we need broader serial and prospective studies based on clinical and laboratory collaboration. In conjunction with case reports, these studies would also serve to detect other possible factors in the etiopathogenesis of chronic inflammatory diseases.
15936131 Grading of radiographic osteolytic changes after silastic metacarpophalangeal arthroplasty 2005 Aug The purpose of this study was to compare the incidence of radiographic osteolysis following insertion of 89 Swanson and 126 Sutter metacarpophalangeal implants in rheumatoid arthritis patients. The mean follow-up time in the two groups of patients was 57 (40-80) and 55 (36-79) months, respectively. This paper proposes a new method of classifying radiographic osteolysis. The remarkable number of osteolytic changes seen in the bones adjacent to MCP prostheses in this study would suggest that silastic prostheses should only be used when other surgical alternatives cannot be used and that long-term control by radiography be maintained after implantation of silicone prostheses into the MCP joint. In all grades of our classification, osteolysis was more frequent in the Sutter than in the Swanson group in this study, suggesting that use of the Sutter rather than the Swanson implant is questionable.
16960935 Intranasal administration of recombinant human cartilage glycoprotein-39. A phase I escala 2006 Sep OBJECTIVE: To investigate safety and tolerability and pilot efficacy of repeated single doses of Org39141 in patients with active rheumatoid arthritis (RA). Org 39141 is recombinant human cartilage glycoprotein-39, intended to induce mucosal tolerance upon intranasal administration. METHODS: RA patients with moderate disease activity were treated for 4 weeks and followed for another 8 weeks. The trial had a sequential cohort design: RA patients in the first cohort received 4 intranasal doses (one per week) of either 25 microg Org 39141 or placebo; in subsequent cohorts, treatment with 125microg, 625 microg, or 3125 microg Org39141 was compared to placebo. Safety was evaluated by means of reporting adverse events, standard laboratory testing, and nose examination. The primary efficacy endpoint was RA disease activity as measured by the Disease Activity Score 28 (DAS28). RESULTS: A total of 36 patients were randomized. Org39141 was well tolerated, and no severe or serious adverse events (AE) were reported. In the pooled placebo group, a decrease in DAS28 was observed, but to a lesser extent than in the Org 39141 treatment groups. After 4 weeks of treatment, the mean decrease in DAS in the 625 microg Org 39141 treatment group (-24%) was statistically (p = 0.02) and clinically (EULAR criteria) significantly larger than in the pooled placebo group (-3%). Once-weekly intranasal treatment with Org39141 was well tolerated, and no serious or severe AE were reported. A trend towards efficacy was observed. Our results are encouraging for further clinical development of Org39141.
15731289 Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthriti 2005 Aug BACKGROUND: Leptin regulates food intake and modulates immunity and inflammation. A positive feedback mechanism has been described between tumour necrosis factor (TNF) and leptin, and it has been suggested that leptin potentiates inflammation in patients with rheumatoid arthritis (RA). OBJECTIVE: To assess whether inflammation correlates with leptin concentrations in patients with RA, and whether anti-TNF treatment modulates leptin concentrations in these patients. METHODS: Leptin, IL6 and CRP were measured (at baseline and after 2 weeks of treatment) in the blood of 31 patients with RA starting either anti-TNF treatment or placebo, and in 18 healthy controls. RESULTS: In patients with RA, plasma leptin concentrations at baseline correlated inversely with the degree of inflammation as assessed by C reactive protein (CRP; r(s)(2) = 0.21, p<0.01) or interleukin (IL) 6 concentrations (r(s)(2) = 0.22, p<0.008). Mean (SD) leptin concentrations did not differ between patients with RA and controls (6.0 (4.6) v 4.2 (2.8) ng/ml in men; 15.1 (7.9) v 13.4 (5.2) ng/ml in women). Short course anti-TNF treatment for 2 weeks did not modify leptin concentrations, despite significant reduction of CRP and IL6. CONCLUSION: A significant inverse correlation between inflammation and leptin concentrations was found in patients with active RA, although plasma leptin concentrations did not significantly differ from those in healthy controls. This suggests that active chronic inflammation may lower plasma leptin concentrations. Two weeks' treatment with anti-TNF did not change plasma leptin concentrations and longer treatment may be needed to see an effect on leptin.
15642153 Interleukin-7 deficiency in rheumatoid arthritis. 2005 Interleukin-7 (IL-7) is a stromal factor that is crucial for the development of T lymphocytes in humans and mice, and also B lymphocytes in mice. IL-7 can act as a T cell growth factor as well as a critical anti-apoptotic survival factor. The essential non-redundant role of this cytokine for T cell development in vivo is indicated by the phenotype of murine knockout models as well as by humans with a T-B+NK+ form of severe combined immunodeficiency (SCID) resulting from mutations in IL-7 receptor alpha chain. IL-7 deficiency has now been found in patients with rheumatoid arthritis, a finding that relates not only to the T-lymphocyte status in this disease but also to the ability of patients with rheumatoid arthritis to recover from therapy-induced lymphopenia.
16194739 Outcome of Copeland surface replacement shoulder arthroplasty. 2005 Sep We report the outcome of humeral head surface replacement hemiarthroplasty performed at our institution using the Copeland prosthesis. We followed 56 shoulders (52 patients) for a mean of 34.2 months (range, 24-63 months). Two were lost to follow-up, and there were six deaths unrelated to the shoulder surgery. Preoperative diagnoses in the remainder were osteoarthritis (20), rheumatoid arthritis (26), rotator cuff tear arthropathy (1), and post-traumatic arthrosis (1). The mean age was 68 years. Constant scores for the whole group improved from a mean preoperative score of 16.4 (range, 8-36) to 54.0 (range, 20-83) at last follow-up (P < .05). Three cases underwent subsequent arthroscopic subacromial decompression for impingement symptoms. One case required revision for aseptic loosening to a stemmed implant. Contained, nonprogressive osteolysis was seen in 2 cases. One periprosthetic humeral neck fracture was managed successfully nonoperatively. These results are comparable to those obtained with a modern stemmed hemiarthroplasty and are similar to Copeland's own series.
16460255 Periodontal and hematological characteristics associated with aggressive periodontitis, ju 2006 Feb BACKGROUND: Periodontitis shares several clinical and pathogenic characteristics with chronic arthritis, and there is some degree of coexistence. The aims of this study were to elucidate whether patients with localized aggressive periodontitis (LAgP), generalized aggressive periodontitis (GAgP), juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA) share periodontal and hematological characteristics distinguishing them from individuals free of diseases. METHODS: The study population consisted of white adults (or=4 mm, CAL>or=2 mm, and ABL>or=2 mm compared to controls. The percentage of sites with CAL>or=2 mm significantly correlated with the levels of IgM-RF and IgA-RF. Missing teeth in JIA and RA patients were not lost due to periodontitis. Patients with GAgP showed higher levels of leukocytes, including neutrophils, and CRP compared to controls. In part, JIA and RA patients showed similar results. CONCLUSIONS: Young adults with RA may develop periodontal destruction, and these patients require professional attention. Both differences and similarities in periodontal and hematological variables were seen in individuals with periodontitis, JIA, and RA.
15550533 Cost effectiveness of adalimumab in the treatment of patients with moderate to severe rheu 2005 Jul BACKGROUND: Societal decision makers increasingly emphasise their need for evidence based economic analyses to make reimbursement decisions. OBJECTIVE: To analyse the cost utility of adalimumab, on both incremental cost and incremental quality adjusted life years (QALYs), versus traditional disease modifying antirheumatic drugs and the other tumour necrosis factor (TNF) antagonists suitable for submission to the Swedish LFN (Pharmaceutical Benefit Board). METHODS: Swedish unit costs and treatment guidelines from a lifetime perspective were implemented. A mathematical model, incorporating data from seven trials, simulated the experiences of 10 000 hypothetical patients with moderate to severe rheumatoid arthritis (RA). The primary outcome measure-QALYs-was derived from utility values calculated from a relationship between the Health Assessment Questionnaire (HAQ) Disability Index (DI) and Health Utility Index-III (HUI-3) from adalimumab trial results. The model followed the progression of HAQ-DI through a number of treatments in a sequence accounting for mortality, drug and monitoring costs, and other direct costs. RESULTS: When using ACR50 as a response threshold for determining successful treatment, adalimumab plus methotrexate showed the greatest number of QALYs gained (2.3 from one study and 2.1 from the pooled results of two trials). The etanercept plus methotrexate strategy yielded QALY gains similar to the pooled adalimumab results. Except for the infliximab strategy, the costs results were between 35 000 and 42 000, a range normally considered cost effective in other European countries. CONCLUSION: Adalimumab appears to be cost effective for the treatment of moderate to severe RA. The results suggest that adalimumab is at least as cost effective as other TNF antagonists.
16535997 [Correlation between bronchoalveolar lavage and lung function in patients with systemic sc 2005 Dec Fibrous alveolitis (FA), or diffuse interstitial fibrosis, is used as a term for diseases in patients suffering from some kind of systemic connective tissue (SCT) disorder and lung fibrosis. FA is not unusual in clinical practice in patients with SS and rheumatoid arthritis (RA) and can be found in the definitive fibrosis phase of the disease; the early detection of FA is of great importance. The aim of this study was to determine whether there was a correlation between certain lung function parameters and cellular components of BAL in patients with SS and RA. Lung function (LF) and BAL examination was carried out in all 20 SS patients and 38 RA patients. LF was evaluated via spirometry, flow volume curves, the lung transfer factor for carbon monoxide (DLco), and the coefficient of transfer factor (K/DLco), as well as body plethysmography and blood gas analysis. A differential number of cells were taken in all BAL samples. Normal cellular components of lavage were found in 19 patients (50%). Ly-alveolitis was found in 10 patients (4 with SS and 6 with RA) (26%), and N-alveolitis in 9 patients (8 with SS and 1 with RA) (23.7%). An increased percentage of CD8+T lymphocytes in relation to CD4+T lymphocytes, and a decreased level of CD4+/CD8+ was found through BAL. Restrictive ventilation disorder was discovered in 6 patients (15.7%), TLC values were reduced in 6 patients (15.7%), and K/DLco was decreased in 5 patients. DLco was normal in 20 patients (53%) and reduced in 18 patients (47%). We discovered a significant correlation between DLco and cellular components (neutrophile or lymphocyte) present in BAL, but there was no significant correlation between other lung function parameters. Analysis of BAL and DLco examination can be considered to be suitable parameters of interstitial lung changes in SS and RA patients.
17043048 The differential expression of corticosteroid receptor isoforms in corticosteroid-resistan 2007 Apr OBJECTIVE: A proportion of patients with rheumatoid arthritis (RA) fail to respond adequately to corticosteroid (CS) therapy. Using an in vitro CS sensitivity bioassay, we have subdivided RA patients into steroid-sensitive (SS) and -resistant (SR) subgroups and this correlates with clinical responses to CS therapy. CSs exert their effects via the CS receptor (CR), which exists as two main isoforms, CRalpha and CRbeta. CRbeta can function as a negative inhibitor of CRalpha. We have hypothesized that steroid resistance in RA patients is due in part to a relative over-expression of the CRbeta. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from SS and SR RA patients. CRalpha and CRbeta mRNA expression was determined by quantitative real time polymerase chain reaction (qRT-PCR). The ratio of CRbeta/CRalpha mRNA expression was determined. CRalpha and CRbeta protein expression by PBMCs was analysed by flow cytometry. RESULTS: qRT-PCR analysis showed a trend towards higher expression of both CRbeta and basal CRbeta/CRalpha ratio in SR RA patients. Stimulation of PBMCs in vitro with concanavalin-A induced a significantly higher CRbeta mRNA expression, and CRbeta/CRalpha ratio in SR RA patients compared with SS patients, which was not inhibited by hydrocortisone. Flow cytometry showed that the percentage of PBMCs staining for CRbeta protein was significantly lower in the SS RA group (SS 43.3 +/- 14.8% vs SR 88.6 +/- 8.6%; P < 0.0010). The mean intensity of fluorescence CRbeta staining was higher in the SR RA patients (P < 0.001). CONCLUSION: We show for the first time that CRbeta is over-expressed in SR RA patients and that hydrocortisone fails to inhibit concanavalin-A stimulated increase in CRbeta mRNA in SR RA patients. This mechanism may contribute in part to the CS hyporesponsiveness seen in some RA patients.