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ID PMID Title PublicationDate abstract
17088564 Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. 2006 Nov 14 Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression. In contrast, T cells with other antigen specificities from these patients, or autoreactive T cells from healthy individuals and disease controls, express low levels of Kv1.3 and are predominantly naïve or central-memory (T(CM)) cells. In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4. Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells. Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats. Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted.
18312075 Accuracy of pedicle screw insertion in the cervical spine for internal fixation using fram 2008 Mar OBJECT: Although transpedicular fixation is a biomechanically superior technique, it is not routinely used in the cervical spine. The risk of neurovascular injury in this region is considered high because the diameter of cervical pedicles is very small and their angle of insertion into the vertebral body varies. This study was conducted to analyze the clinical accuracy of stereotactically guided transpedicular screw insertion into the cervical spine. METHODS: Twenty-seven patients underwent posterior stabilization of the cervical spine for degenerative instability resulting from myelopathy, fracture/dislocation, tumor, rheumatoid arthritis, and pyogenic spondylitis. Fixation included 1-6 motion segments (mean 2.2 segments). Transpedicular screws (3.5-mm diameter) were placed using 1 of 2 computer-assisted guidance systems and lateral fluoroscopic control. The intraoperative mean deviation of frameless stereotaxy was < 1.9 mm for all procedures. RESULTS: No neurovascular complications resulted from screw insertion. Postoperative computed tomography (CT) scans revealed satisfactory positioning in 104 (90%) of 116 cervical pedicles and in all 12 thoracic pedicles. A noncritical lateral or inferior cortical breach was seen with 7 screws (6%). Critical malplacement (4%) was always lateral: 5 screws encroached into the vertebral artery foramen by 40-60% of its diameter; Doppler sonographic controls revealed no vascular compromise. Screw malplacement was mostly due to a small pedicle diameter that required a steep trajectory angle, which could not be achieved because of anatomical limitation in the exposure of the surgical field. CONCLUSIONS: Despite the use of frameless stereotaxy, there remains some risk of critical transpedicular screw malpositioning in the subaxial cervical spine. Results may be improved by the use of intraoperative CT scanning and navigated percutaneous screw insertion, which allow optimization of the transpedicular trajectory.
17667990 Leukocyte gene expression signatures in antineutrophil cytoplasmic autoantibody and lupus 2007 Oct Leukocytes play a major role in the development and progression of autoimmune diseases. We measured gene expression differences in leukocytes from patients that were antineutrophil cytoplasmic autoantibody (ANCA) positive, patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), and healthy donors to explore potential pathways for clinical intervention. Leukocyte gene expression profiles were determined on Affymetrix U133A/B chips in 88 autoimmune patients, 28 healthy donors, and healthy donor leukocyte cell subtypes that were activated in vitro. Comparison of gene expression in leukocytes identified differentially expressed signature genes that distinguish each donor source. The microarray expression levels for many signature genes correlated with the clinical activity of small vessel vasculitis in the ANCA patients; a result confirmed by quantitative real time-polymerase chain reaction for 16 relevant genes. Comparison with in vitro-activated leukocyte subtypes from healthy donors revealed that the ANCA signature genes were expressed by neutrophils while the SLE signature genes were expressed in activated monocytes and T cells. We have found that leukocyte gene expression data can differentiate patients with RA, SLE, and ANCA-related small vessel vasculitis. Monitoring changes in the expression of specific genes may be a tool to help quantify disease activity during treatment.
16652440 Updates from B Cell Trials: Efficacy. 2006 May Recent reports of data from ongoing trials have contributed substantially to our growing understanding of the potential effectiveness and safety of B cell targeted therapy in the treatment of rheumatic diseases. In addition, the results have addressed practical questions regarding the administration of specific agents. Phase II trials of rituximab (RTX) have provided data supporting efficacy in rheumatoid arthritis (RA), including more clearly defining the role of glucocorticoids in the treatment and exploring the doses necessary to improve the signs and symptoms of RA. The Phase IIb Dose-Ranging Assessment International Clinical Evaluation of Rituximab in RA (DANCER) trial demonstrated that a significant percentage of patients achieved clinical improvement when treated with different doses of RTX as compared with those given placebo. The Phase III Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) trial demonstrated efficacy of RTX in patients with a history of nonresponse to tumor necrosis factor inhibitors. Preliminary results of a small cohort of patients receiving RTX retreatment demonstrated efficacy with repeat administration. Phase II results of another B cell targeted therapy, anti-B lymphocyte stimulator protein, demonstrated efficacy. The efficacy of the agent, belimumab, resulted in an ACR20 response that was significantly higher in patients treated with belimumab versus placebo and in patients with RA. These findings support the hypothesis that B cells play an integral role in the pathogenesis of RA, and this report will review the efficacy results of clinical trials targeting B cells.
18540734 Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation 2008 Jun This research examined whether cognitive behavioral therapy and mindfulness interventions that target responses to chronic stress, pain, and depression reduce pain and improve the quality of everyday life for adults with rheumatoid arthritis (RA). The 144 RA participants were clustered into groups of 6-10 participants and randomly assigned to 1 of 3 treatments: cognitive behavioral therapy for pain (P); mindfulness meditation and emotion regulation therapy (M); or education-only group (E), which served as an attention placebo control. The authors took a multimethod approach, employing daily diaries and laboratory assessment of pain and mitogen-stimulated levels of interleukin-6 (IL-6), a proinflammatory cytokine. Participants receiving P showed the greatest Pre to Post improvement in self-reported pain control and reductions in the IL-6; both P and M groups showed more improvement in coping efficacy than did the E group. The relative value of the treatments varied as a function of depression history. RA patients with recurrent depression benefited most from M across several measures, including negative and positive affect and physicians' ratings of joint tenderness, indicating that the emotion regulation aspects of that treatment were most beneficial to those with chronic depressive features.
18481115 [Impact of a motivational intervention on coping with chronic pain: results of a controlle 2008 Oct BACKGROUND: For effective self-management of chronic pain changes of cognitive and behavioral attitudes are required. The readiness to change can be described within the framework of the transtheoretical model (TTM) and is facilitated through motivational interviewing. This prospective study evaluated the effectiveness of brief motivational interviewing by telephone for the variables self-efficacy, cognitive and behavioral coping and psychological strain through chronic pain over a period of 9 months. METHODS: Different questionnaires, the self-efficacy expectations (ASES-D), cognitive, behavioral coping and psychological strain through chronic pain (FESV) and the German version of the pain stages of change questionnaires (PSOCQ), the FF-STABS were distributed to 147 patients at a rehabilitation clinic (indications: fibromyalgia syndrome, rheumatoid arthritis, ankylosing spondylitis). The intervention group participants received 3 telephone calls at intervals of 2 months with a follow-up time of 9 months after first study admission. At the end of the study 91 patients were enrolled for analysis (drop out rate 38%). To evaluate the effects of treatment nonparametric-analysis for longitudinal data was used. RESULTS AND CONCLUSION: The analysis showed significant positive effects in the intervention group for cognitive coping (U-value -2.423; p=0.015 group x time-effect) and for coping with emotional strains of chronic pain (subscale anxiety: U-value -2.3618; p=0.018; subscale anger: U-value 2.8638; p=0.004; group x time-effect). No significant effects were shown for self-efficacy expectations and behavioral coping with pain. Further explorative analysis of subgroups revealed slightly better treatment effects for patients with rheumatoid arthritis and ankylosing spondylitis than for those with fibromyalgia syndrome.
17967727 Vitamin D in rheumatoid arthritis. 2007 Nov The discovery of the vitamin D receptor (VDR) in the cells of the immune system and the fact that activated dendritic cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties. VDR, a member of the nuclear hormone receptor superfamily, was identified in mononuclear cells, dendritic cells, antigen-presenting cells, and activated T-B lymphocytes. In synthesis, the most evident effects of the D-hormone on the immune system seem to be in the downregulation of the Th1-driven autoimmunity. Low serum levels of vitamin D3 might be partially related, among other factors, to prolonged daily darkness (reduced activation of the pre vitamin D by the ultra violet B sunlight), different genetic background (i.e. vitamin D receptor polymorphism) and nutritional factors, and explain to the latitute-related prevalence of autoimmune diseases such as rheumatoid arthritis (RA), by considering the potential immunosuppressive roles of vitamin D. 25(OH)D3 plasma levels have been found inversely correlated at least with the RA disease activity showing a circannual rhythm (more severe in winter). Recently, greater intake of vitamin D was associated with a lower risk of RA, as well as a significant clinical improvement was strongly correlated with the immunomodulating potential in vitamin D-treated RA patients.
17049201 Cardiovascular disease in rheumatoid arthritis. 2006 Dec Epidemiological studies have disclosed an increased mortality due to cardiovascular (CV) complications in patients with rheumatoid arthritis (RA). Patients with this disease have an increased risk of left ventricular diastolic dysfunction and congestive heart failure that is unrelated to the presence of traditional atherosclerosis risk factors or ischemic heart disease. Endothelial dysfunction, an early step in the atherogenesis process, is observed in both early and long-standing actively treated patients with RA. High-resolution B-mode ultrasound studies of the common carotid artery have shown the presence of subclinical atherosclerosis, manifested by increased carotid intima-media thickness and carotid plaques, in patients with RA. Association between HLA-DRB1*04 shared epitope alleles, in particular with HLA-DRB1*0404, and endothelial dysfunction and CV mortality has also been observed in these patients. Chronic inflammation plays a pivotal role in the mechanisms associated with atherogenesis in RA. Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine implicated in the initiation and progression of inflammation as well as in the mechanisms associated with accelerated atherosclerosis in this disease. Anti-TNF-alpha therapy has proved to be clinically effective in patients with severe RA. Recent studies have also emphasized the positive effect of anti-TNF-alpha blockade in improving endothelial dysfunction in RA patients. However, this effect seems to be transient and in line with the persistence of chronic inflammation.
18634160 Risk of development of lung cancer is increased in patients with rheumatoid arthritis: a l 2008 Sep OBJECTIVE: To investigate the occurrence of lung cancer in patients with rheumatoid arthritis (RA) in the US veteran population. Patients with rheumatic diseases appear to have an increased risk for the development of lymphoproliferative and some solid organ malignancies. METHODS: We conducted a retrospective case control study using prospectively collected data from the Veterans Integrated Service Networks (VISN) 16 Veteran Affairs (VA) database from 1998 to 2004. We studied the association of RA and lung cancer and analyzed data on 483,721 VA patients. Patients were identified by searching for the diagnoses of RA and lung cancer based on the International Classification of Diseases (ICD) codes. We identified 8768 (1.81%) patients with a diagnosis of RA (ICD code 714.0), 7280 (1.5%) patients with lung cancer (ICD code 162.0), 247 patients with lung cancer and RA, and 7033 patients with lung cancer but no RA. Logistic regression analysis was performed to adjust for age, gender, race, and tobacco and asbestos exposure. Statistical tests were conducted at a 5% level of significance. RESULTS: The diagnosis of RA was determined to have a significant association with lung cancer in this veteran population. Patients with RA are 43% (odds ratio 1.43) more likely to develop lung cancer than patients without RA, when adjusted for covariates. CONCLUSION: Our study shows a significant positive association between RA and the development of lung cancer in the veteran population. Veterans with RA have an increased incidence of lung cancer when compared to the non-RA population.
16539824 Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rhe 2006 Jan OBJECTIVE: Systemic inflammation, insulin resistance, and endothelial dysfunction have been implicated in the development of cardiovascular disease in rheumatoid arthritis (RA). Since insulin resistance can promote endothelial dysfunction and anti-TNF-alpha blockade yield a rapid improvement of endothelial function, we have sought to assess whether TNF-alpha blockade may also result in a reduction of insulin serum levels and improvement of insulin resistance in RA patients who require this therapy because of severe and refractory disease. METHODS: We recruited patients with RA seen over a period of 1 month at Hospital Xeral-Calde, Lugo, Spain, that were on treatment with anti-TNF-alpha monoclonal antibody-infliximab. Patients with diabetes mellitus or plasma glucose > 110 mg/dl were excluded. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately prior to and after infliximab infusion. RESULTS: Twenty-seven RA patients (21 women; mean age: 57.1 years; mean DAS28: 4.43) fulfilled the inclusion criteria. Dramatic reduction in the serum insulin levels and insulin/glucose index was observed following infliximab infusion. Also, a significant improvement of insulin resistance and insulin sensitivity was found. CONCLUSION: Our study confirms a rapid beneficial effect of infliximab on insulin resistance and insulin sensitivity in RA patients treated periodically with this drug. It may support the long-term use of drugs that act blocking TNF-alpha function to reduce the mechanisms implicated in the development of atherosclerosis in patients with RA.
18565258 Genetic contribution of the CD14 -159C/T dimorphism in the promoter region in Japanese RA. 2008 Mar OBJECTIVE: To study the contribution of the CD14 gene to the pathogenesis of rheumatoid arthritis (RA) in Japanese patients. METHODS: CD14 genotyping was carried out at the -159C/T dimorphic site in 97 RA patients and 104 normal subjects by the PCR-RFLP (restriction fragment length polymorphism) METHOD: HLA-DRB1 genotyping was performed by the PCR-SSCP (sequence specific conformational polymorphism) method. RESULTS: The -159C/T dimorphism is not associated with whole RA or with female RA, and the results were compatible with a previous report from Germany. The -159C/T dimorphism was not associated with rheumatoid factor (RF)-positive RA, although the -159T allele tended to be associated with RF in the German report. The -159C/T dimorphism showed no association even in RA patients with the RA-susceptibility HLA-DRB1*0405. The -159T allele was prevalent in Japanese controls. CONCLUSION: The CD14 gene is very unlikely to be genetically involved in the pathogenesis of Japanese RA.
16542359 Association of rheumatoid factor production with FcgammaRIIIa polymorphism in Taiwanese rh 2006 Apr Fcgamma receptors (FcgammaR) impact upon the development of inflammatory arthritis through immune complex stimulation and proinflammatory cytokine production. FcgammaRIIa, FcgammaRIotaIotaIotaa and FcRgammaIIIb polymorphisms were genotyped in 212 rheumatoid arthritis (RA) patients and 371 healthy control subjects using an allelic-specific polymerase chain reaction (PCR). No significant skewing in the distribution of FcgammaRIIa H/R131, FcgammaRIIIa F/V158 and FcgammaRIIIb NA1/NA2 was found between RA patients and healthy control subjects. However, a significant skewing distribution of the FcgammaRIIIa F/V158 polymorphism was observed between rheumatoid factor (RF)-positive versus RF-negative RA patients (P = 0.01). The low-affinity FcgammaRIIIa F158 allele seems to have a protective role in RF production, in comparison with the FcgammaRIIIa V158 allele (P = 0.004; OR = 0.485; 95% CI: 0.293-0.803). A high frequency of FcgammaRIIIa F/F158 was identified in RA patients with negative RF compared with RF-positive patients (for FF158 versus FV158 + VV158; P = 0.002; OR = 0.372; 95% CI: 0.194-0.713). In addition, no association was found between FcgammaRIIa H/R131, FcgammaRhoIIIa F/V158 and FcgammaRIIIb NA1/NA2 polymorphisms and other clinical parameters. The results of this study suggest that three activating FcgammaRs polymorphisms lack association with RA but FcgammaIIIa F/V158 polymorphism may influence RF production and IgG RF immune complex handling in Taiwanese RA patients.
17906572 Assessing the range of cervical rotation in patients with rheumatoid arthritis after atlan 2007 Oct 1 STUDY DESIGN: Case-series study. OBJECTIVE: To assess range of cervical rotation possible after atlantoaxial fixation in rheumatoid arthritis (RA) patients using axial CT. SUMMARY OF BACKGROUND DATA: The atlantoaxial complex is primarily responsible for rotation, and the percentage of global cervical rotation dependent on C1-C2 is 60%. Fusion of C1-C2 was expected to cause a loss of almost half the normal cervical rotation. However, some authors had reported that cervical rotation in RA patients increased after atlantoaxial fixation because of pain relief. METHODS: Nineteen consecutive patients with atlantoaxial instability secondary to RA who had undergone transarticular fixation were included in our study. Visual analog scale was used for assessment of neck pain. We recorded functional CTs to assess C1 to T1 rotation angles before surgery and 6 months after surgery. The patient actively rotated his neck toward right as far as possible, taking care that the shoulders remained in the horizontal plane. RESULTS: The average visual analog scale for neck pain decreased significantly from 7 (range, 4-9) before surgery to 3 (range, 0-5) at 6 months after surgery. The average preoperative C1-T1 rotation angles that were measured using axial CT were 80 degrees in total. C1-T1 rotation angle significantly decreased (55% decrease) after surgery, but there was no difference between right and left motion. Average subaxial rotation (C2-T1) was 31 degrees before surgery and did not increase after surgery. CONCLUSION: All 19 patients with RA and atlantoaxial instability in our study had relief of pain and a significant decrease in the C1-T1 rotation angle after atlantoaxial fixation. Subaxial rotation did not change from before to after the operation.
16855621 Microsatellite typing for DRB1 alleles: application to the analysis of HLA associations wi 2006 Oct The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for DRB1 genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 RA patients and 374 controls) and 1364 Korean individuals (744 RA patients and 620 controls), all of whom were previously genotyped for DRB1. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value >0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of DRB1*09 and DRB1*10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with rheumatoid arthritis, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility.
17404734 Transcription regulatory polymorphism -43T>C in the 5'-flanking region of SLC19A1 gene cou 2007 Sep The reduced folate carrier (RFC) protein (SLC19A1-gene) has central role in the uptake and intracellular accumulation of folates. In this respect, we investigate whether SLC19A1 genetic variations could affect rheumatoid arthritis (RA) patient response to antifolate treatment. One hundred six unrelated RA patients were enrolled in this study. Polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) was used as the screening method for genetic variants. Unusual SSCP patterns were characterized by direct sequencing of the PCR products and subsequently restriction assays were established. Western blot analysis of RFC protein was performed in respect of the identified SLC19A1 genotypes. Patient response to methotrexate (MTX) was evaluated using disease activity for 28 joint indices score, American College of Rheumatology 20% and 50% scores. No mutation was found in the SLC19A1 gene, but three polymorphic variants: the -43T>C in the 5'-flanking sequence to the ATG-transcription start site; and the 80G>A (R27H) and 696C>T (P232P) in the coding gene sequence. The wild type alleles of the three polymorphisms were in strict linkage disequilibrium. Western blot analysis revealed that the non-wild type allele of polymorphism -43T>C is associated with low RFC protein expression levels. Furthermore, the genotypic analysis of the functional polymorphic variant -43T>C revealed to be insufficient to predict patient response to MTX therapy. According to recent literature, several transport systems account for folate membrane transport. Additionally, in previous studies discrepancies have been reported to exist between the same genetic variants and their use in prediction of patient response to MTX therapy. Therefore, the present genotypic-phenotypic association study of a functional polymorphism revealed the need of a complex genotypic analysis in order to predict patient response to folate antagonists' therapy.
17530709 Targeted mast cell silencing protects against joint destruction and angiogenesis in experi 2007 Jun OBJECTIVE: Induction of arthritis with autoantibodies against glucose-6-phosphate isomerase (GPI) is entirely independent of T cells and B cells but is strictly dependent on the presence of mast cells. Here, we used this disease model to analyze whether exclusive intraarticular mast cell reconstitution is sufficient for disease induction and whether targeted mast cell silencing can prevent neoangiogenesis and joint destruction, 2 hallmarks of rheumatoid arthritis. METHODS: Ankle swelling and clinical index scores were determined after injection of either K/BxN mouse-derived serum or control serum in wild-type Kit(+)/Kit(+) mice, congenic mast cell-deficient Kit(W)/Kit(W-v) mice, or mast cell-deficient Kit(W)/Kit(W-v) mice reconstituted with mast cells, either by intraperitoneal or selective intraarticular injection. Angiogenesis was quantified in vivo by measuring activated alphavbeta3 integrin using (18)F-galacto-RGD and positron emission tomography. In addition, staining of joint tissue with hematoxylin and eosin, Giemsa, beta3, and alpha-actin was performed. The effect of mast cell stabilization by treatment with cromolyn or salbutamol was investigated in C57BL/6 or BALB/c mice. RESULTS: Comparing wild-type mice, mast cell-deficient Kit(W)/Kit(W-v) mice, and mast cell-reconstituted Kit(W)/Kit(W-v) mice, we first showed that intraarticular and intraperitoneal mast cell engraftment fully restores susceptibility to antibody-induced arthritis, angiogenesis, and alphavbeta3 integrin activation. Importantly, selective mast cell silencing with either salbutamol or cromolyn prevented alphavbeta3 integrin activation, angiogenesis, and joint destruction. CONCLUSION: Mast cell engraftment fully restores susceptibility to alphavbeta3 integrin activation, angiogenesis, and joint destruction in GPI antibody-induced arthritis. Importantly, selective mast cell stabilization prevents alphavbeta3 integrin activation, angiogenesis, and joint destruction.
17456067 Tissue Doppler imaging in the evaluation of the left and right ventricular diastolic funct 2007 May OBJECTIVE: Previous studies have reported that cardiovascular involvement in rheumatoid arthritis (RA) occurs frequently. Although ventricular functions of RA have been investigated through the standard Doppler in RA, they have yet to be investigated thoroughly by means of the relatively new and advantageous tissue Doppler imaging (TDI). The present study aims to investigate left and right ventricular functions in RA patients by means of TDI and standard Doppler echocardiography. METHODS: A total of 60 patients with longstanding RA and 40 control subjects were included in the study and their left and right ventricular functions were assessed by standard pulsed-wave Doppler echocardiography, the color M-mode flow propagation velocity, and TDI. The left ventricular TDI was achieved at four different sites (lateral, septal, anterior, and inferior walls), while the right ventricular TDI was achieved through the tricuspid lateral annulus. RESULTS: When compared with controls, the RA group showed that basal clinic and echocardiographic parameters, early (E) and late (A) diastolic velocities of atrioventricular valves, E/A ratio, and pulmonary venous Doppler parameters of these two groups were similar. It was determined that left and right ventricular E-wave deceleration times and isovolumic relaxation times of the RA patients were determined to have increased in comparison with those of the subjects in the healthy Control Group (P < 0.05). RA patients had significantly lower color M-mode flow propagation velocity (P < 0.05). While S' peak and E' peak, two of the left and right ventricular TDI parameters, were similar in both groups, A' peak, E'/A', and E/E' parameters in RA showed statistically significant differences in RA patients. CONCLUSION: A comparison between age and sex of RA patients and healthy individuals revealed that left and right ventricular TDI parameters of RA patients were impaired, which led us to conclude that both of the ventricles could have been involved.
16463431 Splitting high-dose oral methotrexate improves bioavailability: a pharmacokinetic study in 2006 Mar OBJECTIVE: To study the bioavailability of a divided higher oral dose of methotrexate (MTX), in comparison to a single dose, in adult patients with rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in 10 patients with RA taking a stable dose (25-35 mg weekly) of MTX. Separated by one week, a pharmacokinetic analysis was performed in each patient after an oral single dose, and after an equal but split dose separated by 8 hours. MTX serum concentrations were measured by a fluorescence polarization immunoassay technique. Analysis was performed by calculation of the area under the curve (AUC) by the trapezoidal rule and by means of an iterative 2-stage Bayesian population procedure, obtaining population and individual pharmacokinetic parameters. For the population analysis, data from 15 patients in our previous study comparing oral and subcutaneous administration of MTX were also used. RESULTS: The median MTX dose was 30 mg weekly (range 25-35 mg). The bioavailability of the split dose was 28% higher compared to the single dose (p = 0.007). In the population pharmacokinetic modeling, a 2-compartment model best described the serum MTX concentration versus time curves. The mean bioavailability after single-dose and split-dose MTX was 0.76 and 0.90, respectively, compared to subcutaneous administration. There was a statistically significant difference in the bioavailability of the 2 oral administration regimens (p = 0.008). CONCLUSION: The bioavailability of oral higher dose MTX in adult patients with RA can be improved by splitting the dose.
17340197 Kinetic modeling of contrast-enhanced MRI: an automated technique for assessing inflammati 2007 May In recent years, development of rheumatoid arthritis (RA) drug therapy has been more directly targeted to counteract specific mechanisms of inflammation, and it is now believed that early aggressive treatment with disease modifying drugs is important to inhibit future structural joint damage. The development of these new treatments has increased the need for methodologies to assess disease activity in RA and monitor the effectiveness of drug therapy. Unlike X-ray, which shows only structural bone damage, magnetic resonance imaging (MRI) can depict soft tissue damage and synovitis, the primary pathology of RA. Recent studies have also indicated that MRI is sensitive to pathophysiologic changes that may predate radiographic erosions and may predict future joint damage. In this study, we have developed a computer automated analysis technique for MR wrist images that provides an objective measure of RA synovitis. This method applies a two-compartment pharmacokinetic model to every voxel of a dynamic contrast-enhanced MRI (DCE-MRI) dataset and outputs resulting parametric images. The aim of this technique is to not only objectively quantify the severity of rheumatoid synovitis, but to also locally determine where areas of serious disease activity are situated through kinetic modeling of blood-tissue exchange. Preliminary results show good correlation to early enhancement rate, which has previously been shown to be a useful clinical marker of RA activity. However, the use of tracer kinetic modeling methods potentially provides more specific information regarding underlying RA physiology. This approach could provide a useful new tool in RA patient management and could substantially improve RA therapeutic studies by calculating objective biomarkers of the disease state.
19623680 Changing pattern in the prescription of biological treatment in rheumatoid arthritis. A 7- 2008 Jan OBJECTIVE: To study prescription patterns of biological treatment in rheumatoid arthritis (RA) patients in southern Sweden, a region with no formal or economic restrictions for the use of biological treatment in rheumatological diseases. Specifically, we studied conformity with the national Swedish guidelines for biologics in RA. METHODS: Rheumatologists in southern Sweden contribute to a voluntary register on the use of biologics in treating arthritis patients (the South Swedish Arthritis Treatment Group (SSATG)). This register covers .90% of all the prescriptions of biologics for arthritis patients in the region. The treatment of 1839 patients (2704 treatment occasions) was recorded in the SSATG register during 1999-2006. Baseline characteristics were analysed. RESULTS: Baseline Health Assessment Questionnaire(HAQ) scores and Disease Activity Scores (DASs)decreased significantly between 1999 and 2006, but disease activity remained high in RA patients. RA patients were treated with biologics earlier, but only 16% of the patients received biologics within 2 years of disease onset in 2006. The percentage of RA patients who were prescribed biologics after only one previous non-biological DMARD (disease-modifying anti-inflammatory rheumatic drug) was 27% in 2006. Thirty-five per cent of all RA patients changed from one biological treatment to another. CONCLUSIONS: Baseline DASs in RA patients remained high at the start of biological treatment. The national Swedish guidelines for the prescription of biologics in RA were followed. More patients with early RA were treated with biologics. The proportion of RA patients changing from one biological drug to another increased.