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ID PMID Title PublicationDate abstract
16805753 Left and right ventricular diastolic functions in patients with rheumatoid arthritis witho 2006 Jun The aim of this study was to assess the prevalence of diastolic dysfunction of the left ventricle (LV) and of the right ventricle in patients with rheumatoid arthritis (RA) without clinically evident cardiovascular manifestations and to estimate whether there is a correlation between the duration of RA and the degree of LV diastolic dysfunction. The study included 81 patients (61 females and 20 males) with RA without clinically evident heart disease (group 1) and 40 healthy subjects (29 females and 11 males) who served as a control group (group 2). Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects. There were significant differences between patients with RA vs. control group with regard to early diastolic flow velocity (E), atrial flow velocity (A) and the E/A ratio (0.68 +/- 0.19 m/s vs. 0.84 +/- 0.14 m/s, p < 0.001; 0.73 +/- 0.15 m/s vs. 0.66 +/- 0.13 cm/s, p = 0.01; and 0.97 +/- 0.3 vs. 1.32 +/- 0.37, p < 0.001, respectively). There was significant difference between groups regarding the right ventricular early diastolic (Er)/atrial (Ar) flow velocities (Er/Ar ratio) (1.07 +/- 0.3 vs. 1.26 +/- 0.3, p = 0.002). There was a weak correlation between transmitral E/A ratio and the duration of RA (r = - 0.22, p = 0.001). Myocardial performance index (MPI) appeared to differ little in patients with RA as compared with control group (0.51 +/- 0.1 vs. 0.52 +/- 0.2, p = NS). In patients with RA without clinically evident cardiovascular disease, the left ventricular diastolic function and the right ventricular diastolic function are reduced. Left ventricular wall thickness, dimensions, systolic function and MPI were found to be normal. LV diastolic function had a weak correlation with the duration of RA.
15647422 The development of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. 2005 Feb Based on a previously developed rheumatoid arthritis MRI scoring system (OMERACT 2002 RAMRIS), the development team agreed which joints, MRI features, MRI sequences, and image planes would best illustrate the scoring system in an atlas. After collecting representative examples for all grades for each abnormality (synovitis, bone oedema, and bone erosion), the team met for a three day period to review the images and choose by consensus the most illustrative set for each feature, site, and grade. A predefined subset of images (for example, for erosion--all coronal slices through the bone) was extracted. These images were then re-read by the group at a different time point to confirm the scores originally assigned. Finally, all selected images were photographed and formatted by one centre and distributed to all readers for final approval.
16650791 Three-dimensional Doppler sonographic vascular imaging in regions with increased MR enhanc 2006 Oct OBJECTIVE: To compare three-dimensional (3D) power Doppler ultrasonography (PDUS) with contrast enhanced magnetic resonance imaging (MRI) in their capability to visualize synovial vascularity in inflamed wrists of patients with rheumatoid arthritis (RA). METHODS: Nine patients with RA showing clinically active arthritis of the wrist as determined by tenderness and swelling were examined by contrast enhanced MRI and 3D PDUS. Vascularity close to and inside the joint capsule was visualized by conventional power Doppler mode. In a region with high Doppler signal intensity (=region of interest/ROI) a 3D blood vessel tree was obtained by a free-hand sweep. 3D images were evaluated with regard to the number of blood vessels in the intra- and peri-articular region. MRI examinations were performed using a 1.5 T Scanner. In MRI, time resolved coronal contrast enhanced T1-weighted sequences with fat suppression were acquired during an 8 min period to assess tissue enhancement. Relative enhancement was calculated and compared to 3D PDUS findings. RESULTS: A 3D vascular tree consisting of peri- and intra-articular blood vessels could be demonstrated in the same anatomical ROI in which an increased gadolinium enhancement was measured by MRI in all examined RA patients. The number of penetrating vessels into the joint capsule, the number of intra-articular vessels and a semiquantitative estimation of the strength of blood flow were used to generate a 3D score for the intensity of synovial vascularity. CONCLUSION: When compared with clinical symptoms and the gold standard dynamic MRI, 3D PDUS is a reliable imaging technique for assessing synovial vascularity in inflamed wrists of RA patients.
15975964 Efficacy and safety of switching from infliximab to adalimumab: a comparative controlled s 2006 Feb OBJECTIVE: To describe the efficacy and safety of adalimumab in patients with rheumatoid arthritis (RA) who had previously discontinued infliximab treatment. METHODS: 24 patients with RA who discontinued treatment with infliximab (switchers) were treated with adalimumab (40 mg every 2 weeks, subcutaneously) for 12 months. The results were compared with those for 25 patients with RA receiving adalimumab who had not previously used an anti-tumour necrosis factor alpha inhibitor (controls). Disease activity was measured with the 28 joint count Disease Activity Score (DAS28), and clinical response with the American College of Rheumatology (ACR) 20% response criteria. RESULTS: At baseline there were no differences in demographic, clinical, and laboratory features between the two groups. After 12 months' adalimumab treatment, clinical improvement was similar in both groups. More specifically, ACR 20% response criteria were achieved by 18/24 (75%) switchers and by 19/25 (76%) subjects in the control group. Four switchers discontinued the study-two because of adverse events and two because of lack of efficacy, while three control patients discontinued the study-one because of lack of efficacy and two owing to side effects. CONCLUSION: Adalimumab is a well tolerated and effective treatment for patients with RA, even when infliximab has been discontinued.
15640269 Antibodies to citrullinated human fibrinogen (ACF) have diagnostic and prognostic value in 2005 Aug BACKGROUND: The anti-cyclic citrullinated peptide (CCP) test has a high sensitivity and specificity for rheumatoid arthritis, although CCP is not the physiological target of the autoantibodies. Citrullinated fibrin is abundant in inflamed synovium OBJECTIVE: To assess the diagnostic and prognostic value of antibodies against citrullinated fibrinogen (ACF), a soluble precursor of fibrin, in comparison with IgM-rheumatoid factor (IgM-RF) and the second generation anti-CCP test. METHODS: In 379 patients with early arthritis (258 rheumatoid and 121 undifferentiated), the sensitivity, specificity, and positive predictive value of ACF, anti-CCP, and IgM-RF for diagnosing rheumatoid arthritis were calculated. Multivariate logistic regression analysis was used to assess the diagnostic and prognostic value (radiographic progression after two years) of the tests. RESULTS: The sensitivities of the ACF, anti-CCP, and IgM-RF tests were 55.8%, 57.8%, and 44.6%, with specificities of 92.6%, 94.2%, and 96.7%, respectively. Approximately 30% of the IgM-RF negative patients were positive for ACF or anti-CCP or both. The ACF and anti-CCP test had a high agreement in early arthritis (kappa = 0.84). Of all baseline characteristics, the ACF test and the anti-CCP test were the best predictors for diagnosing rheumatoid arthritis at one year (odds ratio (OR) = 10.3 and 10.6, respectively) and for radiographic progression after two years (OR = 12.1 and 14.8). CONCLUSIONS: ACF is as sensitive as anti-CCP and more sensitive than IgM-RF in diagnosing rheumatoid arthritis in early arthritis. The ACF test is also a good predictor of radiographic progression, with a performance similar to the anti-CCP test. The ACF test and the anti-CCP test are especially valuable in IgM-RF negative arthritis.
16955242 The effect of substance P on nitric oxide release in a rheumatoid arthritis model. 2006 Jun OBJECTIVE: The inflammatory mediator substance P (SP) acts principally through the neurokinin (NK1) receptor. We assessed the influence of SP on production of NO and its possible role in the pathogenesis of rheumatoid arthritis (RA). METHODS: The effect of SP (0.1-100 nM) on concentrations of the NO metabolite, nitrite, produced by synovial fibroblasts from RA patients was studied. For comparison, the effects of TNF-alpha (0.57 pM-5.7 nM) and IL-1beta (0.57 pM-5.7 nM) were also studied. In parallel studies, footpad inflammation was induced in NK1 receptor knock-out (KO) and wild-type (WT) mice, and swelling and NO metabolite levels were measured. RESULTS: In cultured synoviocytes, SP, TNF-alpha and IL-1beta induced significantly increased nitrite concentrations. Consistent with a role for NO in SP-mediated inflammatory reactions, the plasma NO metabolite level in WT mice was significantly increased at 3 days following an injection of 10 mg/ml Mycobacterium tuberculosis, but there was no significant change in NK1 KO mice. These results were paralleled by the changes in footpad swelling in WT mice compared to NK1 KO mice. CONCLUSION: SP, like TNF-alpha and IL-1beta, induces NO in both rheumatoid synoviocytes and experimental models of inflammation. Treatments directed against SP may have important and hitherto unrecognised anti-inflammatory effects.
15906586 Association between health-related quality of life and clinical efficacy endpoints in rheu 2005 May BACKGROUND: Improvement of health-related quality of life (QoL) is increasingly recognized as a maj or treatment goal for patients with rheumatoid arthritis (RA). There are several measures of general health status and of physical functioning for assessing treatment effects on QoL in patients with RA, however, the relationship between QoL outcomes and conventional clinical efficacy endpoints is not completely understood. OBJECTIVE: To describe the association between changes in QoL and changes in other efficacy measures, among patients with RA after four weeks of treatment with etoricoxib, naproxen or placebo, and to explore differences in the association of changes in efficacy and changes in QoL parameters across treatment groups. METHODS: The study used data from 1684 patients with RA enrolled in two identical clinical trials (one US and one multinational). Patients were randomized to placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily in a 2 : 2: 1 allocation ratio. Primary efficacy endpoints were tender joint count, swollen joint count, patient global assessment of disease activity (100 mm VAS), and investigator global assessment of disease activity (0 - 4 Likert scale). QoL assessments were based on the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Survey Short Form 36 (SF-36). Mean differences between baseline and week four were calculated for each parameter studied. Linear regression analysis was performed to assess the association between changes in clinical efficacy and changes in QoL parameters, adjusted for covariates. RESULTS: The degree of association between changes in tender or swollen joint counts and changes in QoL variables was low, explaining less than 10% of the variability for most QoL variables, except bodily pain (SF-36). In contrast, changes in patient global assessment of disease activity explained 33% of the variability in the overall HAQ score, and in the physical component score (SF-36; adjusted regression models). Values for investigator global assessment of disease activity were below those for patient global assessment but above joint count measures. Results were similar between the etoricoxib, naproxen and placebo groups in the degree of association between changes in efficacy and QoL variables. CONCLUSION: Currently used efficacy endpoints are less than ideal predictors of change in QoL. There is no evidence from this study that the association between changes in CE endpoints and QoL was different across treatments. Our results highlight the need to assess both conventional efficacy measures and QoL in clinical trials of RA treatments.
16881106 Anti-cyclic citrullinated peptide versus anti-Sa antibodies in diagnosis of rheumatoid art 2006 Aug OBJECTIVE: . To compare the diagnostic value of anti-cyclic citrullinated peptide (anti-CCP) and anti-Sa antibodies in serum for prediction of rheumatoid arthritis (RA) in an outpatient clinic for connective tissue diseases and spondyloarthritides. METHODS: A cross-sectional study was carried out to analyze the presence or absence of anti-CCP and anti-Sa antibodies in the sera of 250 randomly selected patients. The disease distribution in the study was as follows: 87 patients had RA (34.8%); 90 (36%) had other connective tissue diseases (CTD); 50 (20%) spondyloarthritis; 19 (7.6%) polymyalgia rheumatica; and 4 (1.6%) juvenile idiopathic arthritis. RESULTS: Anti-CCP antibodies were detected in 63 patients with RA and in 9 patients with other illnesses [sensitivity 72.4%, specificity 94.4%, positive predictive value (PPV) 87.5%]. Anti-Sa antibodies were detected in 38 patients with RA and in 6 patients with other illnesses (sensitivity 43.6%, specificity 96.3%, PPV 86.3%). Anti-CCP and anti-Sa results were discordant in up to 47 of 87 RA patients. No relation between the presence of anti-Sa and higher or lower titers of anti-CCP antibodies was observed. CONCLUSION: The diagnostic value in RA is similar for both antibodies. However, the sensitivity of anti-CCP detection is higher than that of anti-Sa. Our results suggest that presence of anti-Sa antibodies in serum may be useful as a complementary assay when anti-CCP antibodies are negative and RA is suspected.
16126979 Nocturnal hormones and clinical rhythms in rheumatoid arthritis. 2005 Jun It is well known that some clinical signs and symptoms of rheumatoid arthritis (RA) vary within a day and between days; the morning stiffness that is observed in patients who have RA has become one of the diagnostic criteria of the disease. The circadian changes in the metabolism or nocturnal secretion of endogenous corticosteroids is certainly responsible, in part, for the time-dependent changes that are observed in the inflammatory response and related clinical symptoms. More recently, melatonin (mLT), another circadian nocturnal hormone that is the secretory product of the pineal gland, has been implicated in time-dependent inflammatory reactions, with effects that are opposite of those of corticosteroids. Therefore, altered functioning of the hypothalamic-pituitary-adrenocortical axis (reduced corticosteroid production) and of the pineal gland (increased mLT production) found in RA patients seem to be important factors in the perpetuation and clinical circadian symptoms of the disease. Consistently, human proinflammatory Th1-type cytokine production (related to mLT stimulation) exhibits a diurnal rhythmicity, with peak levels during the night and early morning, at a time when plasma cortisol (inducing Th2-type cytokine production) is lowest and mLT is highest. Reduced daily light exposure as observed in northern Europe (Estonia), at least during the winter, might explain the higher and more prolonged mLT concentrations as well as some epidemiological features that are observed in northern European patients with RA versus southern European patients.
15846592 Health-related quality of life predicts future health care utilization and mortality in ve 2005 Apr OBJECTIVE: To investigate whether health-related quality of life (HRQOL) measures predict health care utilization and mortality in a cohort of veterans with self-reported physician-diagnosed arthritis. METHODS: A cohort of veterans from the Upper Midwest Veterans Integrated Service Network (VISN) was mailed a self-administered questionnaire that was composed of the SF-36V (modified from SF-36 for use in veterans) and questions regarding demographics, current smoking status, limitation of activities of daily living (ADLs), and preexisting physician-diagnosed medical conditions, including arthritis. Within subjects reporting physician-diagnosed arthritis, we analyzed the associations between the SF-36V component summary scales (physical and mental component summary, PCS and MCS, respectively) and the occurrence of any hospitalization, number of hospitalizations, number of outpatient visits, and mortality, for the year after survey administration, using multivariable regression analyses. RESULTS: Of 34,440 survey responders who answered a question regarding arthritis, 18,464 (58%) subjects reported physician-diagnosed arthritis. Arthritic patients in the lowest tertile of PCS scores had significantly higher odds of any hospitalization (Odds ratio (OR) 1.49, 95% confidence interval (CI) [1.25-1.76]) and mortality (OR 1.69, 95% CI [1.18-2.42]), and a significantly higher number of hospitalizations/year (Rate ratio (RR) 1.09, 95% CI [1.05-1.13]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). Arthritic patients in the lowest tertile of MCS scores had significantly higher odds of any hospitalization (OR 1.20, 95% CI [1.02-1.41]), mortality (OR 2.14, 95% CI [1.56-2.94]), and a significantly higher number of hospitalizations/year (RR 1.05, 95% CI [1.02-1.09]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). CONCLUSIONS: HRQOL, as assessed by the SF-36V, predicts future inpatient and outpatient health care utilization and mortality in veterans with self-report of physician-diagnosed arthritis.
16394642 [A clinical trial of low dose methotrexate therapy in patients with rheumatoid arthritis]. 2005 Dec The efficacy and safety of MTX in active RA were evaluated based on patient medical records. The study population consisted of 460 patients with active RA who had received no prior MTX therapy and started it at our hospital between August 1998 and December 2003 (80 men and 380 women with a mean age of 59.3 years). After 24 weeks of MTX therapy, 61.3% of patients showed a 20% improvement, and 30.4% achieved a 50% improvement according to the ACR criteria. The cumulative rate of patients who continued MTX therapy for 48 weeks was 0.567. During the observation period, 260 patients (56.5%) experienced 304 adverse reactions. 52 patients (11.3%) discontinued treatment because of adverse reactions, and 10 patients (2.2%) died. The adverse reactions that occurred in at least 1% of patients were: abnormal hepatic function (31.7%), infection (6.1%), gastrointestinal symptoms (5.0%), stomatitis (3.9%), hematological abnormalities (3.5%), fracture (3.5%), malignant tumor (2.6%), interstitial pneumonia (2.0%), cerebrovascular or cardiovascular disorder (2.0%), headache (1.7%), eruption (1.3%), and alopecia (1.1%). Adverse reactions were more common in the elderly and patients with advanced stage disease. This study reaffirms the therapeutic benefit of MTX, but suggests that careful monitoring is of great importance.
16287925 Comparison of the Health Assessment Questionnaire (HAQ) and the modified HAQ (MHAQ) in pat 2006 Apr OBJECTIVES: Physical disability in patients with rheumatoid arthritis (RA) is often assessed by questionnaires. We compared the Health Assessment Questionnaire (HAQ) with the modified HAQ (MHAQ) in a cohort of RA patients across various levels of disability, and examined correlations with other measures of physical function. METHODS: Patients with RA (n = 182) completed self-report questionnaires assessing functional capacity. Instruments included the MHAQ and HAQ completed separately, as well as SF-36 and the Arthritis Impact Measurement Scales (AIMS). Scores from unadjusted and adjusted HAQ were compared with MHAQ at various disability levels. RESULTS: A clear ceiling effect with aggregation of normal scores for physical function was observed for MHAQ (23%) and HAQ (12%), but not for SF-36 (4%) or AIMS (5%). The correlations between adjusted/unadjusted HAQ and MHAQ scores were 0.85/0.88. A discrepancy in HAQ and MHAQ scores was observed in patients with high levels of disability, especially when MHAQ was compared with the adjusted final HAQ score. Adjustment of HAQ by aids or help increased the final score by an average of 0.15, and both adjusted and unadjusted HAQ scores were numerically clearly higher (mean 0.45 and 0.30, respectively) than the MHAQ score. CONCLUSION: The present findings indicate that MHAQ and HAQ may be applicable as measures of physical capacity in RA patients, but clinicians and researchers should select the appropriate instrument for the setting, and be aware of differences in scores, especially at different disability levels.
15726372 First report of supraventricular tachycardia after intravenous pulse methylprednisolone th 2005 Nov The occurrence of supraventricular tachycardia after high-dose intravenous methylprednisolone pulse therapy (HIVMPT) in a patient with active rheumatoid arthritis is described for the first time. This case report further expands the range of arrhythmias that can occur with HIVMPT. Other arrhythmias previously reported to occur after HIVMPT include atrial fibrillation, atrial flutter, junctional rhythm, and ventricular tachycardia. To the best of our knowledge, supraventricular tachycardia has not been reported previously, although severe bradycardia, hypotension, asystole, cardiovascular collapse, and sudden death have been documented. A review of the literature indicates that these case reports not withstanding, HIVMPT is generally safe, and cardiovascular toxicity is rare. However, close supervision with repeated measurements of blood pressure, electrocardiogram, and blood electrolytes is mandatory during and immediately after HIVMPT, especially for patients with pre-existing cardiovascular disease, and the lowest effective dose of methylprednisolone should be infused at a slow rate.
16511939 Gastrointestinal prophylactic therapy among patients with arthritis treated by rheumatolog 2006 Apr OBJECTIVE: To determine rates of gastroprotective agent (GPA) use among patients with arthritis treated by rheumatologists, and to determine factors associated with GPA prescription. METHODS: In a longitudinal outcome study, 11,451 patients with rheumatoid arthritis (RA) and osteoarthritis (OA) reported all medication use, ulcer history, functional status, and sociodemographic characteristics. RESULTS: GPA were used in 21-24% of all patients with RA and OA and in about 35-40% of all high risk patients. In unadjusted analyses, GPA use was similar among NSAID users and non-users. In multivariable logistic regression analyses GPA use was associated with non-specific (NS) NSAID and COX-2 NSAID, prednisone, low dose aspirin, comorbidity, Health Assessment Questionnaire functional score, age < 65 years, increased income, not smoking, and being male. Despite numerous associations, the explanatory power for GPA use was poor (area under ROC curve = 0.680). CONCLUSION: GPA are used in 35% to 40% of patients with 4 risk factors for gastrointestinal ulceration. GPA use is not increased in NS NSAID users compared to COX-2 NSAID users, and was inversely associated with socioeconomic status. GPA use does not follow the model predicted by clinical trial results with respect to NS NSAID and age, reflecting a change in the pattern of NSAID use in patients with rheumatic disease. The major determinant of GPA use appears to be physician prescribing behavior.
17106348 Using the Actigraph to measure physical activity of people with disabilities: an investiga 2006 Dec This study investigates measurement issues when using the Actigraph motion sensor to measure the physical activity of people with disabilities. Four volunteers with rheumatoid arthritis participated in the study. Activity levels were measured using the Actigraph over four consecutive weekdays. Activity counts were determined using Actigraph Standard Software. The daily percent of waking time spent at each intensity level was calculated and a weighted average calculated to determine a single daily measure of activity. The variability of measurement, over 1, 2, 3 and 4 days, was examined using these weighted and rolling averages. Activity counts were very low, with over 50% of waking time spent in the 'very low' intensity category, demonstrating a marked floor effect. Little variability (+/-0.11 counts/min) in the level of physical activity was found across 1-4 days. The limited variability (consistency across days) in combination with the floor effect indicates that a 1-day data collection period is adequate. The limitations of the Actigraph are thus related to the existing software options, which have been designed for people without rheumatoid arthritis. The Actigraph does not appear to be a sensitive measure in people performing very low physical activity.
16414969 Synovial inflammation does not change in the absence of effective treatment: implications 2006 Aug OBJECTIVES: To determine the impact on synovial histopathology of changes in clinical disease activity in the absence of effective treatment. METHODS: Twelve patients with active RA not receiving effective treatment were studied over a 14 week period. Synovial biopsy specimens obtained at baseline and week 14 were analysed by histology and immunohistochemistry. RESULTS: Over the course of 14 weeks, there was a trend towards a decrease of the DAS28, with 7/12 patients being good or moderate DAS28 responders despite the absence of effective treatment. Patients' assessment of global disease activity and swollen joint count both decreased significantly. Histologically, there was a decrease of lining layer hyperplasia and lymphoid aggregates, a similar trend for vascularity, but there was no effect on global synovial infiltration. Accordingly, there was no decrease of the cellular infiltration with T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), plasma cells (CD38), dendritic cells (CD1a, CD83), and even an increase of CD163+ sublining macrophages, with a similar trend for CD68+ sublining macrophages. The changes in DAS28 scores in these patients did not correlate with changes in histological variables, with the exception of an inverse correlation with plasma cells. Remarkably, even in the DAS28 responders, no significant changes in synovial inflammatory infiltration were noted. CONCLUSIONS: Despite variations in global disease activity, synovial inflammatory infiltration did not change significantly in the absence of effective treatment. The lack of a placebo effect on synovial markers of treatment response such as sublining macrophages can facilitate conclusive early phase trials with small numbers of patients with RA.
16906372 Altered peptide ligands control type II collagen-reactive T cells from rheumatoid arthriti 2006 We previously reported that peripheral blood mononuclear cells from HLA-DRB1*0101 Japanese patients with rheumatoid arthritis (RA) were highly reactive to 256-271 peptide of type II collagen (CII). In this report, we tried to regulate the CII reactivity of T cells from RA patients with HLA-DRB1*0101 by altered peptide ligand (APL), which is a single amino acid substitution of the T-cell epitope on CII 256-271 peptide. Antagonistic activity of 21 APLs was assessed using three different T-cell lines. Results showed that 262 (G-->A) APL of CII 256-271 exhibited antagonistic activity in all T-cell lines and it was suggested that the application of CII APL might be a new therapeutic strategy in the regulation of RA.
15996201 Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early r 2005 Aug Accumulation of plasma cells in the synovium is one of the diagnostic hallmarks in the histopathological manifestations of rheumatoid arthritis (RA). This seems to be prominent even prior to significant B cell infiltration and/or formation of lymphoid follicles in the synovium. To clarify the mechanism of early plasma cell accumulation, we examined in situ expression of chemokines and their receptors using synovial targeting biopsy specimens, which were obtained under arthroscopy from early RA patients. By immunohistochemical staining, plasma cells were found to express a chemokine receptor CXCR3, while synovial fibroblasts in the synovial sublining regions expressed its ligand, Mig/CXCL9. By reverse transcription-polymerase chain reaction (RT-PCR), using targeted lesions of synovial tissues obtained by laser capture microdissection, expression levels of Mig/CXCL9 in the synovial sublining regions were remarkably high and were likely to be associated with interferon (IFN)-gamma expression. Furthermore, cultured synovial fibroblasts were confirmed to produce Mig/CXCL9 upon stimulation with IFN-gamma. Our results indicate that in the early stage of RA, plasma cells expressing CXCR3 may be recruited directly from the circulation into the synovial sublining regions by its ligand, Mig/CXCL9, produced by synovial fibroblasts.
15986375 Retroviral gene transfer of an antisense construct against membrane type 1 matrix metallop 2005 Jul OBJECTIVE: Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed prominently in rheumatoid arthritis synovial fibroblasts (RASFs), but the specific contribution of MT1-MMP to fibroblast-mediated destruction of articular cartilage is incompletely understood. This study used gene transfer of an antisense expression construct to assess the effects of MT1-MMP inhibition on the invasiveness of RASFs. METHODS: Retroviral gene transfer of a pLXIN vector-based antisense RNA expression construct (MT1-MMPalphaS) to MT1-MMP was used to stably transduce RASFs. Levels of MT1-MMP RNA and protein were determined by quantitative polymerase chain reaction, Western blotting, and immunocytochemistry in MT1-MMPalphaS-transduced RASFs as well as in control cells, with monitoring for 60 days. The effects of MT1-MMPalphaS on the invasiveness of RASFs were analyzed in the SCID mouse co-implantation model of RA. RESULTS: MT1-MMPalphaS-transduced RASFs produced high levels of antisense RNA that exceeded endogenous levels of MT1-MMP messenger RNA by 15-fold and resulted in a down-regulation of MT1-MMP at the protein level. Inhibition of MT1-MMP production was maintained for 60 days and significantly reduced the invasiveness of RASFs in the SCID mouse model. Whereas prominent invasion into cartilage by non-transduced and mock-transduced RASFs was observed (mean invasion scores 3.0 and 3.1, respectively), MT1-MMPalphaS-transduced cells showed only moderate invasiveness (mean invasion score 1.8; P < 0.05). CONCLUSION: The data demonstrate that an antisense RNA expression construct against MT1-MMP can be generated and expressed in RASFs for at least 60 days. Inhibition of MT1-MMP significantly reduces the cartilage degradation by RASFs.
16733485 Cementless LCS rotating-platform knee arthroplasty in patients over 60 years without patel 2006 Jun BACKGROUND: The aim of this prospective paper is to present the results of a cementless LCS rotating-platform artificial knee design without resurfacing of the patella in patients over 60 years of age. MATERIAL/METHODS: In this prospective series, 234 patients were included with 251 knees. The LCS rotating-platform uncemented design was used in all cases, without replacement of the patella. Thirty-four patients were men and 200 were women. Two hundred three patients were suffering from osteoarthrosis (10 bilateral) and 31 patients (7 bilateral) from rheumatoid arthritis. Seventeen patients had a bilateral procedure. Prophylactic antibiotics and anticoagulants were also instituted to all patients. RESULTS: Forty-nine patients developed deep vein thrombosis and responded well to the applied conservative treatment. Overall results in the first 251 cementless cases at 2 to 9.8 years' follow-up (average: 5.7 years) were good to excellent in 94.4%, fair in 4.7%, and poor in 0.7%. Radiographs of the knees showed good bonding and no signs of radiolucency. The average clinical and functional Knee Society Ratings were 21.07 points and 30.95 points, respectively, preoperatively and 87.95 points and 78.56 points, respectively, at the final follow-up evaluation. CONCLUSIONS: With an average follow-up of 5.7 years, uncemented LCS rotating-platform knee joint arthroplasty without replacing the patella in patients over 60 years old was found to perform well, with encouraging clinical and radiological results and a survival rate of 98.1%.