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ID PMID Title PublicationDate abstract
17235556 Preliminary evaluation in rheumatoid arthritis activity in patients treated with TNF-alpha 2007 May Methotrexate (MTX) is a first-line disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA). Leflunomide (LEF) and the biologic agents entered the arsenal of DMARDs in 1998. Therapeutic properties of new drugs are still under survey. The purpose of this study was to evaluate and compare the efficacy of MTX, LEF and a biologic agent (TNF-alpha blocker) combined with MTX in reducing disease activity in RA. Seventy-eight patients with active RA underwent a 24-week treatment with MTX 15 mg/week (30 pts), LEF 20 mg/day (30 pts) or a TNF-alpha blocker (etanercept 25 mg 2x weekly or infliximab 3 mg/kg in the week 0, 2, 6 and every 8 weeks thereafter) plus MTX 15 mg/week (18 pts). Only patients with RA resistant to MTX were included in groups receiving LEF or a biologic agent. During follow-up, patients' characteristics, disease characteristics, and clinical and laboratory data were registered. RA activity was evaluated using the ESR, tender and swollen joint counts, the duration of morning stiffness, disease activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment efficacy was demonstrated with ACR 20, 50 and 70 criteria. All groups revealed statistically significant improvement in all disease activity parameters measured. The percentage improvements were similar in groups treated with MTX and LEF and--except for VAS--significantly greater in the group treated with a biologic agent. Disease activity assessed by DAS 28 decreased significantly in all groups: the results were comparable in groups treated with MTX and LEF and significantly more prominent in the group treated with a TNF-alpha blocker. The ACR 20, 50 and 70 improvements amounted, respectively: 100, 50 and 7% in MTX group 87, 60 and 13% in LEF group and 100, 83 and 50% in a biologic agent group. The study revealed equal effectiveness of MTX and LEF in reducing disease activity in rheumatoid arthritis. The efficacy of a TNF-alpha blocker combined with MTX was higher than that of each conventional DMARDs, especially with regard to ACR 70 criteria (considerable improvement after treatment). LEF was equally effective as MTX in patients unable to continue MTX treatment due to the drug's ineffectiveness.
17017313 Comparison of costs associated with the use of etanercept, infliximab, and adalimumab for 2006 Sep A retrospective study of health plan costs related to rheumatoid arthritis (RA) revealed that etanercept was associated with the lowest drug and outpatient costs to the health plan than infliximab and adalimumab. Compared with etanercept, infliximab was related to 55% higher postindex RA-related monthly total health care costs paid by the health plan, based on adjusted analyses (95% confidence interval, 1.47-1.64). Patients receiving adalimumab had 12% higher costs (95% confidence interval, 1.04-1.21). The study showed the average dispensing dose increase was greatest for infliximab (17.4%) and least for etanercept (4.1%).
16643793 [Effects of PMA on CD147 expression in cultured THP-1 cells and monocytes of RA patients]. 2006 May AIM: To investigate the expression of CD147 both on cellular membrane and in culture supernatant of in vitro cultured THP-1 cells and monocytes of RA patients before and after stimulation with phorbol myristate acetate (PMA). METHODS: Human peripheral blood monocytes (HPBMs) were segregated from RA patients by adherent culture method. After the HPBMs and THP-1 cells were stimulated with PMA, the expression rate and expression intensity of CD147 on THP-1 cells and HPBMs of RA patients were determined by flow cytometry. The soluble CD147 levels in culture supernatant of in vitro cultured THP-1 cells and HPBMs were quantified by double antibody Sandwich ELISA. RESULTS: The soluble CD147 in the supernatant of cultured THP-1 cells and HPBMs was detectable before PMA stimulation. Both cells showed high CD147 expression. After PMA stimulation, soluble CD147 level in the supernatant of THP-1 cells increased. CD147 expression on THP-1 cells firstly increased then decreased and kept stable for several days. CD147 expression on HPBMs of RA patients decreased, but CD147 level in the culture supernatant of HPBMs of RA patients increased and kept stable for 2 days. CONCLUSION: CD147 molecule can be shed from the membrane of THP-1 cells and HPBMs of RA patients, or it can be directly secreted into the culture supernatant from the two kinds of cells. PMA can up-regulate the level of soluble CD147.
18178098 Structure-function relationships in the IL-17 receptor: implications for signal transducti 2008 Feb IL-17 is the defining cytokine of a newly-described "Th17" population that plays critical roles in mediating inflammation and autoimmunity. The IL-17/IL-17 receptor superfamily is the most recent class of cytokines and receptors to be described, and until recently very little was known about its function or molecular biology. However, in the last year important new insights into the composition and dynamics of the receptor complex and mechanisms of downstream signal transduction have been made, which will be reviewed here.
17688564 The constancy of work-related empowerment. 2007 Sep OBJECTIVE: This study describes experiences of work empowerment among staff members at the Rheumatism Foundation Hospital in Helsinki, Finland. METHODS: The data were collected on two occasions in 2004 and 2005 using a structured questionnaire with background variables and items concerning verbal, behavioural and outcome empowerment. The questionnaires were sent to all (n1=115, n2=112) members of multidisciplinary teams at the Rheumatism Foundation Hospital, with the exception of physicians, departmental secretaries and administrative personnel. The response rate at both data collections was 58%. The data were analysed by statistical methods. RESULTS: No statistically significant differences were seen in work empowerment between the two data collections. Perceptions of work-related empowerment were relatively strong. CONCLUSIONS: Work-related empowerment appears to be relatively constant and independent of changes in the organization. Indeed there is good reason to ask whether work empowerment is primarily a function of the individual employee's strengths and competencies.
16890406 Regulatory T cells in patients with systemic lupus erythematosus. 2006 Sep Regulatory T cells have an important role in the control of self-reactivity, and in the pathogenesis of autoimmune inflammatory conditions. The aim of this work was to perform a quantitative and functional analysis of regulatory T cells in patients with systemic lupus erythematosus (SLE). We studied twenty-three patients with SLE (19 active, 4 inactive), and twenty-seven healthy subjects as well as fifteen patients with rheumatoid arthritis (RA). The following cell subsets were analyzed in peripheral blood mononuclear cells by flow cytometry: CD4+CD25+, CD4+CD25(bright), CD4+Foxp3+ (Treg cells), CD8+CD28- (Ts cells), CD4+IL-10+ (Tr1 cells), and CD4+TGF-beta+ (Th3 cells). In addition, the in vitro suppressive activity of CD4+CD25+ lymphocytes was tested. We found no significant differences in the levels of all regulatory cell subsets studied in SLE patients compared to controls and RA patients. However, a defective regulatory function of CD4+CD25+T cells was observed in a significant fraction (31%) of patients with SLE. Our data indicate that although approximately one third of patients with SLE show an abnormal immunosuppressive function of Treg lymphocytes, their levels of the different regulatory T cell subsets in peripheral blood are not significantly different from those found in controls.
18436720 Monomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured b 2008 Jun BACKGROUND: SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis. METHODS: We used SELDI-TOF MS to analyze serum samples from patients with various forms of inflammatory arthritis. Several protein profiles were collected on different Bio-Rad Laboratories ProteinChip arrays (CM10 and IMAC-Cu(2+)) and were evaluated statistically to select potential biomarkers. RESULTS: SELDI-TOF MS analyses identified several calgranulin proteins [S100A8 (calgranulin A), S100A9 (calgranulin B), S100A9*, and S100A12 (calgranulin C)], serum amyloid A (SAA), SAA des-Arg (SAA-R), and SAA des-Arg/des-Ser (SAA-RS) as biomarkers and confirmed the results with other techniques, such as western blotting, immunoprecipitation, and nano-LC-MS/MS. The S100 proteins were all able to significantly differentiate samples from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from those of patients with inflammatory bowel diseases used as an inflammatory control (IC) group, whereas the SAA, SAA-R, and SAA-RS proteins were not, with the exception of AS. The 4 S100 proteins were coproduced in all of the pathologies and were significantly correlated with the plasma calprotectin concentration; however, these S100 proteins were correlated with the SAA peak intensities only in the RA and IC patient groups. In RA, these S100 proteins (except for S100A12) were significantly correlated with the serum concentrations of C-reactive protein, matrix metalloproteinase 3, and anti-cyclic citrullinated peptide and with the Disease Activity Score (DAS(28)). CONCLUSIONS: The SELDI-TOF MS technology is a powerful approach for analyzing the status of monomeric, truncated, or posttranslationally modified forms of arthritis biomarkers, such as the S100A8, S100A9, S100A12, and SAA proteins. The fact that the SELDI-TOF MS data were correlated with results obtained with the classic calprotectin ELISA test supports the reliability of this new proteomic technique.
16936330 Consistent patterns of expression of HLA class I free heavy chains in healthy individuals 2006 Nov OBJECTIVES: Major histocompatibility complex class I (MHC-I) proteins exist at the cell surface in antigen presenting forms and as beta2m-independent free heavy chains (FHCs). FHCs have been implicated in spondyloarthritis, but little is known about their expression in healthy individuals. We studied FHC expression on various human cell types, comparing spondyloarthropathy patients with healthy and rheumatoid arthritis (RA) patient controls. METHODS: MHC-I expression was analysed by flow cytometry. FHC levels were normalized for overall MHC-I to generate a relative expression level. Relative FHC levels were analysed for peripheral blood and trophoblast samples from healthy volunteers, RA and spondyloarthropathy patients. Macrophages and dendritic cells were cultured in vitro to analyse changes following activation. Peripheral blood leucocytes from patients with ankylosing spondylitis (AS) and RA were treated with inflammatory stimuli and subsequent alterations in their relative FHC levels were analysed. RESULTS: We found consistent patterns of differential relative FHC expression across lymphocyte subpopulations and particularly high expression on extravillous trophoblast. FHCs were present at higher levels in a reactive arthritis (ReA) population than in healthy controls and RA patients; differences not merely due to the presence of Human Leucocyte Antigen (HLA) B27. Treatment of leucocytes from arthritic patients with bacterial lipopolysaccharide resulted in significant up-regulation of FHC compared with an HLA B27+ control population. CONCLUSIONS: Our findings define normal levels and tissue expression of FHCs, and support the hypothesis that disregulation of heavy chain expression may play a pathogenic role in spondyloarthropathy.
17132692 CD95-Mediated control of anti-citrullinated protein/peptides antibodies (ACPA)-producing p 2007 Apr OBJECTIVE: Serum anti-citrullinated protein/peptides antibodies (ACPA) are a valuable diagnostic parameter that might be involved in rheumatoid arthritis (RA) pathogenesis. CD95-dependent apoptosis is defective in RA synovium. The present study explores the occurrence of ACPA IgG, and the CD95-mediated control of ACPA IgG-secreting plasma cells (PC) in RA patients. METHODS: Mononuclear cells (MC) were purified from synovial fluid (SF) and peripheral blood (PB) of 15 RA patients. PC capable of secreting ACPA IgG were detected in MC cultures. ACPA IgG present in serum and SF, and PB and SF MC culture supernatant was measured by ELISA. CD95, CD27 and CD138 expression was examined on RA PC identified as CD19(low) CD38(high) cells by flow cytometry. CD95-ligation was obtained by treatment of cultured MC with the anti-CD95 Ab CH11. Apoptotic PC were identified as Annexin-V+. RESULTS: ACPA IgG level was found higher in patients' SF than in their serum. PC were detectable in SF and PB, and exhibited high CD95 and CD27 expression. In contrast, SF, but not PB, PC expressed elevated levels of CD138. SF, but not PB, PC actively secreted ACPA IgG in cultures, in a linear fashion for at least 14 days, and CD95-ligation markedly reduced this activity and provoked PC apoptosis. CONCLUSIONS: The results suggest that RA synovium is a prominent site for ACPA IgG formation and for the accumulation of ACPA IgG-secreting PC exhibiting prolonged survival, probably due to RA defective CD95-mediated control.
17100544 Comparison of hormone transfer to pleural and synovial exudates. 2006 Jun OBJECTIVES: Local effects of hormones on immune and connective tissues could play some role in the development of local inflammation processes. The aim of this study was to investigate the levels of selected hormones in pleural exudates of patients with pleurisy and lung tumours, and compare these levels with hormone concentration in knee synovial fluid. SUBJECTS AND METHODS: Eleven patients with pleural exudate (mean age 62+/-3) and l9 subjects with rheumatoid arthritis (of the same mean age) participated in the observations. Plasma, pleural exudates and synovial fluid levels of cortisol, prolactin, aldosterone, testosterone, 17-beta-estradiol, dehydroepiandrosterone, progesterone, insulin and C-peptide were determined by specific radioimmunoassay. RESULTS: It was noted that all estimated hormones are transferred into pleural exudates and synovial fluid. Higher levels of dehydroepiandrosterone and C-peptide were observed in pleural exudates as compared to plasma. The concentrations of testosterone, prolactin and estradiol in males were lower in exudates as compared to plasma. Mean levels of cortisol, aldosterone, progesterone and insulin in plasma were similar to these found in pleural exudates. The comparison of hormone levels in pleural exudates and synovial fluid showed that the levels of cortisol, progesterone and dehydroepiandrosterone tended to be higher in the exudates as compared to synovial fluid. However, the levels of insulin, testosterone and estradiol in exudates were lower than these in inflammatory synovial fluid from patients with rheumatoid arthritis. CONCLUSIONS: This study showed the presence of hormones in pleural exudates. The differences in hormone concentrations in pleural exudates and synovial fluid were observed suggesting a specificity of hormone transfer from plasma to these exudates.
17417984 Effects of celecoxib on human chondrocytes--enhanced production of chemokines. 2007 Jan OBJECTIVE: The purpose of this study was to examine the effects of a selective cyclooxigenase-2 (COX-2) inhibitor (celecoxib) comparing diclofenac. METHODS: Using chondrocytes derived from cartilage of non-arthritic (NA) subjects or patients with osteoarthritis (OA) or rheumatoid arthritis (RA), we examined the effects of celecoxib on incorporation of 3H-thymidine and 35S-sulfate, apoptosis, and production of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1a and nitric oxide (NO). RESULTS: Celecoxib and diclofenac tended to reduce 3H-tymidine incorporation of chondrocytes. Celecoxib induced apoptosis in a dose-dependent manner, but to a lesser degree than diclofenac. Celecoxib inhibited proteoglycan synthesis (indicated by 35S-sulfate incorporation) in NA chondrocytes, but not in OA and RA chondrocytes. Celecoxib increased interleukin-1 (IL-1)-induced production of RANTES and MIP-1alpha by chondrocytes and decreased IL-1-induced NO production by chondrocytes, whereas it did not affect MMP production. CONCLUSION: Celecoxib had both beneficial and adverse effects on chondrocytes. RA, OA and NA chondrocytes showed different responses. Interestingly, celecoxib enhanced the production of chemokines.
17028862 The incidence of new onset congestive heart failure and heart failure exacerbation in Vete 2007 Feb The objective of this study was to evaluate the incidence of new onset or worsening congestive heart failure in Veteran's Affairs (VA) patients who have received infliximab, etanercept, or adalimumab, and to compare mortality rates in these patients to control populations. We enrolled three groups of patients for this retrospective study: TNF-alpha group (n = 103), a rheumatoid arthritis (RA) control group (n = 100), and a control group without RA (n = 100). All patients at our VA facility who had received at least one dose of the TNF-alpha antagonists were included in the TNF-alpha group. Admissions for CHF did not differ between the three groups: TNF-alpha 7 (6.7%), RA control 8 (8%), non-RA control 7 (7%); P = 0.940. Mortality rates were not significantly different: TNF-alpha 4 (3.8%), RA control 7 (7%), non-RA control 11 (11%); P = 0.147. Our study showed no difference between the three groups in either CHF exacerbation or mortality.
19002471 [The pro-inflammatory immunological memory : twist1 as a marker for chronically activated 2008 Dec State-of-the-art immunosuppressive therapies, though efficient in the treatment of rheumatic inflammatory disorders, in most cases do not provide a cure. Complete immunablation and the associated deletion of the reactive immunological memory followed by reconstitution of the "healthy" immune system from stem cells results in a therapy-free remission in many patients suffering from rheumatic diseases. Chronically activated T helper (Th) lymphocytes seem to play a critical role in this reactive pathogenic memory. We have shown that the transcription factor twist1 is specifically expressed in chronically activated, inflammatory Th cells. Twist1 as a biomarker for such Th cells enables the identification and elucidation of the role of Th cells in chronic inflammation and opens new therapeutic options for the targeted manipulation of the pathogenic, reactive memory, such as the targeted deletion of twist1 expressing pathogenic Th cells.
17502359 Low-dose glucocorticoid therapy decreases risk for treatment-limiting infusion reaction to 2007 Nov BACKGROUND AND OBJECTIVE: Treatment-limiting infusion reactions to infliximab have not been fully explained in rheumatoid arthritis patients. Our main objective is to investigate the role of daily oral glucocorticoids use on such reactions. METHOD: Forty-three patients with immediate-type infusion reactions were identified in a large registry-based cohort. These patients were then compared with the entire cohort (n = 639) and, in a separate analysis, to a nested matched control group (n = 43). The following base-line variables were compared: use of oral glucocorticoids, health-assessment questionnaire, 28-joint count-based disease activity score, duration of disease and number of failed disease-modifying antirheumatic drugs. RESULTS: The proportion of infusions associated with infusion reactions decreased significantly during the study period (p = 0.0024). Fifty per cent of the patients in the cohort were treated with daily low-dose glucocorticoids at baseline. 15/326 (4.6%) patients had an infusion reaction as compared with 28/324 (8.6%) of patients without glucocorticoid treatment (p = 0.057). In the matched comparison, 15/43 (35%) of the cases were on low-dose glucocorticoids as compared with 27/43 (64%) of the controls (p = 0.017). The use of low-dose glucocorticoids was associated with a significantly lower risk for a treatment-limiting infusion reactions in a Kaplan-Meier analysis (p = 0.04). The number needed to treat to prevent a treatment-limiting infusion reaction was 25 (95% CI: 13 to 527) in the cohort. CONCLUSION: The use of daily low-dose glucocorticoids is associated with a lower risk for treatment-limiting infusion reactions to infliximab. Overall, treatment-limiting infusion reactions have become significantly less common during the past 5 years.
16303818 Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage from pat 2006 Apr OBJECTIVES: To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells. METHODS: Human articular cartilage specimens were obtained from joints from RA and osteoarthritis (OA) patients and normal joints (controls). Transcript levels of MCP-4 in cartilage were determined by real-time polymerase chain reaction. Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast-like synoviocytes (FLS) were treated with various concentrations of recombinant MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay. RESULTS: The gene expression of MCP-4 was significantly higher in cartilage from RA patients than in that from OA patients (P = 0.00902) and in normal cartilage (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients (mean 94.7 +/- 37.6 pg/ml) was significantly higher than in serum from OA patients (mean 49.2 +/- 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 +/- 23.9 pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid from RA patients (mean 247.2 +/- 161.2 pg/ml) was also significantly higher than in that from OA patients (mean 29.6 +/- 50.5 pg/ml, P = 0.000019). Moreover, MCP-4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner. CONCLUSIONS: MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and activates the proliferation of rheumatoid synovial cells, thereby leading to joint destruction in RA.
18771370 Gingivitis and periodontitis are related to repeated high levels of circulating tumor necr 2008 Sep BACKGROUND: Several studies have indicated a relationship between rheumatoid arthritis and periodontal disease. The aim of this study was to investigate the association between the circulating proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, prostaglandin E(2), serotonin, rheumatoid factor, and periodontitis in patients with rheumatoid arthritis. METHODS: Nineteen patients, 17 women and two men, with rheumatoid arthritis were included. These patients had been examined repeatedly (average of three times) with regard to inflammatory markers and mediators from blood samples. Their teeth, excluding third molars, were examined with regard to number, clinical attachment level (CAL), probing depth (PD), and gingival bleeding on probing (BOP). Assessment of furcation involvement and increased tooth mobility was also made. All patients were non-smokers. Thirty healthy individuals, 20 women and 10 men, were included as a reference regarding TNF-alpha. RESULTS: Patients with high levels of time-averaged TNF-alpha from repeated plasma samples had a higher frequency of BOP as well as increased CAL and PD compared to those with low levels. CONCLUSION: Gingivitis and periodontitis are related to high levels of circulating TNF-alpha in patients with rheumatoid arthritis.
16859540 Statin-induced expression of CD59 on vascular endothelium in hypoxia: a potential mechanis 2006 Hypoxia, which leads to dysfunctional cell metabolism, and complement activation both play central roles in the pathogenesis of rheumatoid arthritis (RA). Recent studies have reported that mice deficient for the complement-inhibitory protein CD59 show enhanced susceptibility to antigen-induced arthritis and reported that statins have anti-inflammatory effects in RA. We hypothesized that the anti-inflammatory effect of statins in RA relates in part to their ability to increase CD59 expression in hypoxic conditions and therefore to reduce complement activation. Flow-cytometric analysis showed that CD59 expression on endothelial cells (EC) was unaffected by atorvastatin in normoxia (21% O2), whereas in hypoxic conditions (1% O2) an up to threefold dose-dependent increase in CD59 expression was seen. This effect of hypoxia was confirmed by treatment of EC with chemical mimetics of hypoxia. The upregulation of CD59 protein expression in hypoxia was associated with an increase in steady-state mRNA. L-Mevalonate and geranylgeraniol reversed the response, confirming a role for inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and geranylgeranylation. Likewise, inhibition by NG-monomethyl-L-arginine and NG-nitro-L-arginine methyl ester confirmed that CD59 upregulation in hypoxia was nitric oxide dependent. The expression of another complement-inhibitory protein, decay-accelerating factor (DAF), is known to be increased by atorvastatin in normoxia; this response was also significantly enhanced under hypoxic conditions. The upregulation of CD59 and DAF by atorvastatin in hypoxia prevented the deposition of C3, C9 and cell lysis that follows exposure of reoxygenated EC to serum. This cytoprotective effect was abrogated by inhibitory anti-CD59 and anti-DAF mAbs. The modulation of EC CD59 and DAF by statins under hypoxic conditions therefore inhibits both early and late complement activation and may contribute to the anti-inflammatory effects of statins in RA.
16479241 Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy. 2006 Mar 188Re is a radionuclide in which there is widespread interest for therapeutic purposes because of its favourable physical characteristics. Moreover, it can be eluted from an on-site installable 188W/188Re generator, which has a useful shelf-life of several months. Most of the clinical experiences gained with 188Re concern the use of 188Re-1,1-hydroxyethylidenediphosphonate (188Re-HEDP) for bone pain palliation in patients suffering prostate cancer. The maximum tolerated activity was 3.3 GBq 188Re-HEDP and if the platelet count exceeded 200 x 10(9) l(-1), the administration of 4.4 GBq appeared safe. Evidence for repeated administrations of 188Re-HEDP rather than single injections was established. In general, pain palliation occurs in 60-92% of patients with only moderate transient toxicity, mainly related to changes in blood counts. Also in haematology, radioimmunotherapy by means of 188Re might play a role by selectively targeting the bone marrow in patients undergoing conditioning prior to haematopoetic stem cell transplantation. The feasibility of such an approach was proven using a Re-labelled monoclonal antibody directed toward the CD66-antigen. More recently, encouraging safety data on locoregional treatment of primary liver tumours using 188Re-labelled lipiodol were reported. The normal organs at greatest risk for toxicity are the normal liver and the lungs. About 50% of the patients reported mild and transient side effects, mainly consisting of low grade fever, right hypochondrial discomfort or aggravation of pre-existing liver impairment. Besides the applications in oncology 188Re-based therapies have also been pioneered for benign condition such as prevention of re-stenosis following angioplasty and for radiosynovectomy in cases of refractory arthritis.
17846778 Etanercept and adalimumab treatment in patients with rheumatoid arthritis and spondyloarth 2008 Jan In the present study, we determined from a single-center data the treatment continuation, discontinuation and reasons for discontinuation in the patients with active rheumatoid arthritis (RA) or spondyloarthropathies (SpA) who were treated with etanercept or adalimumab. All RA and SpA patients, who were treated with etanercept (n = 53) or adalimumab (n = 43) as their first biological treatment according to national guidelines in the Center for Rheumatic Diseases, Tampere University Hospital during the years 1999-2005, were analyzed at baseline and after 1-year treatment. The treatment was regarded ineffective if the clinical response was lower than ACR50 in RA or the reduction of BASDAI was lower than 50% or 2 cm in SpA. After 1 year, the continuation rate was 74% with etanercept and 60% with adalimumab. Mean prednisolone dose among continuers was diminished by 52% in etanercept-treated patients and by 44% in adalimumab-treated patients. During 1-year follow-up, 14 (26%) of the etanercept-treated patients and 17 (40%) of the adalimumab-treated patients discontinued the medication. Eleven patients were regarded as poor responders, seven in etanercept group and four in adalimumab group. Adverse events (mainly infections and injection reactions) caused six discontinuations in etanercept-treated group and 11 discontinuations in adalimumab-treated group. Etanercept was discontinued due to other adverse event in two patients: in one patient due to adenocarcinoma of ovary and in one patient due to drug-related leukopenia. One patient treated with adalimumab developed clinical and immunological features of systemic lupus erythematosus (SLE). In the present study, etanercept and adalimumab treatments were started in patients who had active RA or SpA despite ongoing treatment with combinations of traditional disease modifying antirheumatic drugs (DMARDs). Thirty-nine (74%) patients and twenty-six (60%) patients achieved at least 50% response when etanercept or adalimumab was added to their earlier DMARD treatment. Adverse events (mainly infections and injection reactions) were in line with previous reports. Three rare adverse events were reported: one patient with ovarial carcinoma, one with leukopenia and one with features of drug-induced SLE.
16609887 Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induce 2006 Nov The goal of this investigation was to study the protective effects of thymoquinone (TQ) and methotrexate (MTX) on collagen-induced arthritis (CIA) in rats. On day 0 under ether anesthesia, the experimental groups were immunized with 0.5 mg native chick collagen II (CII) solubilized in 0.1 M acetic acid and emulsified in Freund's incomplete adjuvant. Control rats were gavaged with vehicle, whereas CII was administered intradermally. In addition, arthritis treated with TQ group received TQ (10 mg kg(-1) bw by gavage once a week for 3 weeks starting on day 0); and arthritis treated with MTX group received MTX (MTX was suspended in corn oil and administered by gavage at 1 mg kg (-1) bw once a week for 3 weeks starting on day 0). A significant decrease in the incidence and severity of arthritis by clinical and radiographic assessments was found in recipients of therapy, compared with that of controls. The MTX treatment significantly (P<0.01) decreased the elevated serum NO, urea and creatinine in arthritic rats. Likewise, TQ treatment was also able to reduce significantly (P<0.05) serum NO, urea and creatinine levels, but to lesser extent than MTX. The histopathologic abnormalities are consistent with the hydropic epithelial cell degenerations and moderate tubular dilatation in the some proximal and distal tubules. The severity of the degenerative changes in most of the shrunken glomerules and vascular congestion were also observed in arthritic animals. Preventive treatment of TQ and especially MTX significantly inhibited kidney dysfunction and this histopathologic alterations. These studies indicate that TQ can be used similar to MTX as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.