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ID PMID Title PublicationDate abstract
20430134 Effectiveness and safety of dietary interventions for rheumatoid arthritis: a systematic r 2010 May This systematic review assesses the effectiveness and safety of dietary interventions for rheumatoid arthritis. Randomized controlled trials comparing any dietary manipulation with an ordinary diet were included. Eight randomized controlled trials with a total of 366 patients were included. One trial found that fasting, followed by 13 months on a vegetarian eating plan, might reduce pain (mean difference on a zero to 10 scale -1.89, 95% confidence interval [CI] -3.62 to -0.16). Another single trial found that a 12-week Cretan Mediterranean eating plan might reduce pain (mean difference on a 0 to 100 scale -14.00, 95% CI -23.6 to -4.37). Due to inadequate data reporting, the effects of vegan eating plans and elimination diets are uncertain. When comparing any dietary manipulation with an ordinary diet we found a higher total drop-out of 8% (risk difference 0.08, 95% CI -0.01 to 0.17), higher treatment-related drop-out of 5% (risk difference 0.05, 95% CI -0.03 to 0.14) and a significantly higher weight loss (weighted mean difference -3.24, 95% CI -4.81 to -1.67 kg) in the diet groups compared to the control groups. The effects of dietary manipulation, including vegetarian, Mediterranean, and elemental eating plans, and elimination diets on rheumatoid arthritis are still uncertain due to the included studies being small, single trials with moderate to high risk of bias. We conclude that higher dropout rates and weight loss in the groups with dietary manipulation indicate that potential adverse effects should not be ignored.
20032224 Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expre 2010 Mar OBJECTIVE: Evaluation of the efficacy of green tea extract (GTE) in regulating chemokine production and chemokine receptor expression in human RA synovial fibroblasts and rat adjuvant-induced arthritis (AIA). METHODS: Fibroblasts isolated from human RA synovium were used in the study. Regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5, monocyte chemoattractant protein (MCP)-1/CCL2, growth-regulated oncogene (GRO)alpha/CXCL1 and IL-8/CXCL8 production was measured by ELISA. Western blotting was used to study the phosphorylation of protein kinase C (PKC)delta and c-Jun N-terminal kinases (JNK). Chemokine and chemokine receptor expression was determined by quantitative RT-PCR. The benefit of GTE administration in rat AIA was determined. RESULTS: GTE (2.5-40 microg/ml) inhibited IL-1beta-induced MCP-1/CCL2 (10 ng/ml), RANTES/CCL5, GROalpha/CXCL1 and IL-8/CXCL8 production in human RA synovial fibroblasts (P < 0.05). However, GTE inhibited MCP-1/CCL2 and GROalpha/CXCL1 mRNA synthesis in RA synovial fibroblasts. Furthermore, GTE also inhibited IL-1beta-induced phosphorylation of PKCdelta, the signalling pathway mediating IL-1beta-induced chemokine production. Interestingly, GTE preincubation enhanced constitutive and IL-1beta-induced CCR1, CCR2b, CCR5, CXCR1 and CXCR2 receptor expression. GTE administration (200 mg/kg/day p.o.) modestly ameliorated rat AIA, which was accompanied by a decrease in MCP-1/CCL2 and GROalpha/CXCL1 levels and enhanced CCR-1, -2, -5 and CXCR1 receptor expression in the joints of GTE administered rats. CONCLUSIONS: Chemokine receptor overexpression with reduced chemokine production by GTE may be one potential mechanism to limit the overall inflammation and joint destruction in RA.
21143847 Increased expression of carbonic anhydrase I in the synovium of patients with ankylosing s 2010 Dec 8 BACKGROUND: One of the most distinctive features of ankylosing spondylitis (AS) is new bone formation and bone resorption at sites of chronic inflammation. Previous studies have indicated that the hyperplasia and inflammation of synovial tissues are significantly related to the pathogenic process of AS. The present study used a proteomic approach to identify novel AS-specific proteins by simultaneously comparing the expression profiles of synovial membranes from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial tissues were collected from the hip joints of patients with AS and knee joints of patients with RA or OA (n = 10 for each disease) during joint replacement surgery. Proteins extracted from the synovial tissues were separated by 2-D electrophoresis (2-DE), and the proteins with significantly increased expression in the AS samples were subjected to MALDI-TOF/TOF-MS analysis. The results were verified using western blotting and immunohistochemistry. Levels of the candidate proteins in synovial fluids from knee joints (n = 40 for each disease) were measured using ELISA. RESULTS: The proteomic approach revealed significantly increased expression of carbonic anhydrase I (CA1) in the synovial membrane of patients with AS as compared with the RA and OA tissue samples. Immunohistochemistry and western blotting analysis confirmed the findings described above. The ELISA detected a higher level of CA1 in synovial fluids from patients with AS than those with OA. The mean value of the CA1 level was also higher in AS patients as compared with RA patients. This study also detected increased expression of alpha-1-antitrypsin in the synovial tissues from AS patients, which is in agreement with other reports. CONCLUSION: In vitro experiments by other groups indicated that CA1 catalyzes the generation of HCO3- through the hydration of CO2, which then combines with Ca2+ to form a CaCO3 precipitate. Calcification is an essential step of bone formation. Substantial evidence indicates that carbonic anhydrase also stimulates bone resorption. Hence, overexpression of CA1 in the synovial tissues of AS patients may promote improper calcification and bone resorption in AS.
19463076 Ocrelizumab: a step forward in the evolution of B-cell therapy. 2009 Jul Recent advances in our understanding of B-cell dysregulation and its important link to autoimmunity have brought about a radical change in the management of autoimmune diseases. Over the past few years, encouraging data from several clinical trials of rituximab, a chimeric anti-CD20 antibody, have led to its approval for use in rheumatoid arthritis (RA). These data, regarding clinical efficacy, safety, improved patient-reported outcomes and cost-effectiveness with the use of rituximab in patients with RA, have led to the exploration of other agents targeting B-cell functions. Ocrelizumab, a novel humanized anti-CD20 antibody, has shown clinical efficacy and safety in a recently reported trial in patients with RA. Future clinical trials will help evaluate further the role of ocrelizumab in RA and its potential use in other autoimmune diseases. This review describes current understanding of B-cell therapy, the role of rituximab in the treatment of RA and the evolving role of ocrelizumab as a B-cell-targeted therapy.
20703488 [Non-TNF biologicals in the therapeutic strategy for rheumatoid arthritis]. 2010 Sep The spectrum of agents available for the treatment of rheumatoid arthritis (RA) has become more diversified: In addition to TNF-blocking agents, Abatacept, Rituximab and Tocilizumab have now become available for the treatment of RA. All three agents were approved for patients with insufficient response/intolerability to TNF-blockers; Tozilizumab and Abatacept have also been approved for TNF-naive patients with insufficient response to Methorexate.The present article clarifies the efficacy of these three substances in the treatment algorithm of RA. Current data do not suggest differences in general; therefore, individual considerations may result in patient-specific decisions as to which drug should be used after insufficient response to a TNF-blocking agent or Methotrexate. Possible arguments are discussed.
20117307 NeuFlex and Swanson metacarpophalangeal implants for rheumatoid arthritis: prospective ran 2010 Jan PURPOSE: To compare postoperative range of motion (ROM) and function in a randomized prospective trial of Swanson and NeuFlex metacarpophalangeal (MCP) joint implants. METHODS: A total of 33 patients who had rheumatoid arthritis underwent primary MCP arthroplasty of all 4 fingers in 40 hands; 20 received Swanson implants and 20 received NeuFlex implants. Exclusion criteria included diagnosis of other connective tissue disorders and previous MCP joint surgery. All participants followed the same postoperative rehabilitation protocol. The primary outcome measure was active MCP flexion. Secondary outcomes included active MCP extension, arc of motion, ulnar drift, function (Jamar grip strength and Sollerman hand function test), and the Michigan Hand Questionnaire. Patients were assessed preoperatively and 12 months postoperatively. RESULTS: Patients' mean age was 62.5 years (Swanson) and 58.1 years (NeuFlex) (p = .03). A total of 19 of 20 hands (Swanson) and 14 of 20 hands (NeuFlex) were from female patients. Preoperative active ROM was not significantly different. At follow-up, both groups demonstrated increased active extension and arc of motion (p < .001), reduced active flexion and improved ulnar deviation (p < .001), increased mean Sollerman and Michigan Hand Questionnaire domain scores (p < .001), and improved grip strength (p = .03). Active MCP flexion was significantly greater in all 4 digits of hands with NeuFlex implants compared with Swanson implants. The NeuFlex group demonstrated a greater total arc of motion in the little finger. Implant groups were not significantly different by individual digit for active MCP extension, ulnar drift, and composite flexion. Functional outcomes did not differ between groups. Patients with Swanson implants reported higher Michigan Hand Questionnaire scores in the function and aesthetics domains. CONCLUSIONS: Both implant groups obtained satisfactory clinical improvement after MCP reconstruction of the hand. The NeuFlex group demonstrated superior ROM, whereas the Swanson group had better self-reported function and aesthetics, but not objectively measured function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.
19282308 Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumat 2010 Feb OBJECTIVES: To determine whether changes in levels of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) are associated with the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and with the subsequent flare post partum. METHODS: Disease activity scores from the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study of 118 patients were available for analysis. Before conception (if applicable), at each trimester and at 6, 12 and 26 weeks post partum, levels of the autoantibodies anti-CCP, IgM-RF, IgG-RF and IgA-RF were determined. Responses in disease activity were classified according to European League Against Rheumatism (EULAR) response criteria during pregnancy and post partum, and associated with the presence or absence of autoantibodies. RESULTS: The median levels of anti-CCP and all subclasses of RF during pregnancy were stable, whereas post partum the levels of anti-CCP, IgM-RF and IgA-RF declined. A significantly higher percentage of women without autoantibodies (negative for anti-CCP and RF) improved compared with women positive for either or both autoantibodies (75% vs 39%, p = 0.01). The occurrence of a flare post partum was comparable between these groups. CONCLUSIONS: Improvement of disease activity of RA during pregnancy was not associated with changes in levels of autoantibodies during pregnancy, however, improvement may occur more frequently in the absence of anti-CCP and RF.
20592276 Immune dysregulation by the rheumatoid arthritis shared epitope. 2010 Aug 1 Rheumatoid arthritis (RA) is closely associated with HLA-DRB1 alleles that code a five-amino acid sequence motif in positions 70-74 of the HLA-DRbeta-chain, called the shared epitope (SE). The mechanistic basis of SE-RA association is unknown. We recently found that the SE functions as an allele-specific signal-transducing ligand that activates an NO-mediated pathway in other cells. To better understand the role of the SE in the immune system, we examined its effect on T cell polarization in mice. In CD11c(+)CD8(+) dendritic cells (DCs), the SE inhibited the enzymatic activity of indoleamine 2,3 dioxygenase, a key enzyme in immune tolerance and T cell regulation, whereas in CD11c(+)CD8(-) DCs, the ligand activated robust production of IL-6. When SE-activated DCs were cocultured with CD4(+) T cells, the differentiation of Foxp3(+) T regulatory cells was suppressed, whereas Th17 cells were expanded. The polarizing effects could be seen with SE(+) synthetic peptides, but even more so when the SE was in its natural tridimensional conformation as part of HLA-DR tetrameric proteins. In vivo administration of the SE ligand resulted in a greater abundance of Th17 cells in the draining lymph nodes and increased IL-17 production by splenocytes. Thus, we conclude that the SE acts as a potent immune-stimulatory ligand that can polarize T cell differentiation toward Th17 cells, a T cell subset that was recently implicated in the pathogenesis of autoimmune diseases, including RA.
20861352 Soluble CD93 induces differentiation of monocytes and enhances TLR responses. 2010 Oct 15 The cell surface protein CD93 is known to be involved in the regulation of phagocytosis and cell adhesion. Although typically membrane-bound, a soluble form of CD93 (sCD93) has recently been identified. Currently, however, the role of sCD93 in monocyte function is unknown. In the current study, we analyzed the functional effects of sCD93 on THP-1 monocytic cells and human primary monocytes. Various forms of recombinant human sCD93 were used to investigate the effects of this molecule on both human primary monocytes and a monocytic cell line, THP-1. We found that sCD93 induced differentiation of monocytes to macrophage-like cells, as evidenced by activated cell adhesion and increased phagocytic activities. In addition, this differentiation resulted in an enhanced response to TLR stimulation in terms of differentiation marker expression and proinflammatory cytokine production. Furthermore, sCD93 enhanced LPS-stimulated TNF-α production even prior to monocyte differentiation. To investigate a possible role for sCD93 in the pathogenesis of chronic inflammatory diseases, we assessed the concentration of sCD93 in synovial fluid from patients with rheumatoid arthritis and found it to be significantly increased compared with synovial fluid from patients with osteoarthritis. Together, these data revealed a function for sCD93 that may have implications in inflammation and inflammatory diseases including rheumatoid arthritis.
18635594 Multiple antibody reactivities to citrullinated antigens in sera from patients with rheuma 2009 May BACKGROUND: Autoantibodies to cyclic citrullinated peptides (anti-CCP) are present in most patients with rheumatoid arthritis (RA), and associate with HLA-DRB1 shared epitope (SE) alleles. OBJECTIVE: To investigate reactivities of anti-CCP to various citrullinated proteins/peptides, which represent potential autoantigens in RA, and to examine the relationship between such antibodies, and their association with genetic variants within HLA-DRB1 SE alleles. METHODS: Serum samples from 291 patients with established RA and 100 sex- and age-matched healthy subjects were included in this study. Sera were first analysed for presence of anti-CCP antibodies and further for IgG and IgA antibodies towards candidate autoantigens in both their native and citrullinated form including: fibrinogen, alpha-enolase peptide-1 and the C1-epitope of type II collagen (C1(III)). Antibody specificity was confirmed by cross-reactivity tests. HLA-DR genotyping was performed. RESULTS: 72% of patients with RA were anti-CCP positive. Among the candidate autoantigens examined, IgG antibodies to citrullinated fibrinogen were found in 66% of patients' sera and in 41% for both citrullinated alpha-enolase peptide-1 and citrullinated C1(III). These antibodies were mainly seen in the anti-CCP-positive patient group; they were specific for their respective antigen and displayed limited cross reactivity. IgA responses were also detected, but less frequently than IgG. Anti-CCP and anti-citrullinated protein antibodies were associated with HLA-DRB1*04 rather than with HLA-DRB1*01 alleles. CONCLUSIONS: Antibodies directed against several citrullinated antigens are present in CCP-positive RA, with many patients displaying multireactivity. All specific reactivities were primarily associated with the HLA-DRB1*04 alleles, suggesting common pathways of anti-citrulline immunity.
20485947 [Tuberculosis in rheumatoid arthritis patients: the difficulty in making the diagnosis of 2010 Mar Since the beginning of the use of anti-TNF in the treatment of rheumatoid arthritis and other inflammatory diseases, cases of pulmonary tuberculosis and extrapulmonary tuberculosis have been reported in patients receiving such treatment. In most cases, the disease develops by the time the patient has received the sixth infusion. Every patient should be evaluated for latent tuberculosis infection prior to the use of a TNF inhibitor. However, the diagnosis of latent tuberculosis infection is a challenge. The tuberculin test, which was the only test available to detect latent tuberculosis infection for nearly a century, presents a number of limitations. Tests based on the detection of the in-vitro production of IFN-gamma by mononuclear cells activated by specific antigens appear to be more accurate and have been studied in patients with rheumatoid arthritis.
18276743 Abundant expression of the interleukin (IL)23 subunit p19, but low levels of bioactive IL2 2009 Jan OBJECTIVE: Interleukin (IL)23, composed of a p19 and a p40 subunit, is suggested to play key roles in rheumatoid arthritis (RA), dependent on the promotion and proliferation of IL17-producing T helper (Th)17 cells. However, previous studies on IL23 expression in human tissues were based on the p19 subunit only. We aimed to study the expression and regulation of IL23 subunits p19 and p40 in RA compared to patients with osteoarthritis (OA). METHODS: The expression of p19 and p40 in synovial tissues was analysed by in situ hybridisation and immunohistochemistry. IL23 in RA and OA synovial fluids and sera was determined by ELISA. Toll-like receptor (TLR)-dependent induction of p19, p40 and bioactive IL23 was determined in RA synovial fibroblasts (RASF), monocytes and monocyte-derived dendritic cells (MDDCs) by real-time PCR and reverse transcriptase (RT)-PCR, Western blot and functional assays. RESULTS: The p19 subunit was abundantly expressed in RA but not in OA synovial tissues. p19 was most prominently expressed by RASF in the synovial lining layer and at the site of invasion, but no heterodimeric IL23 was detected at these sites. Correspondingly, soluble IL23 was not detectable or found at very low levels in synovial fluids and sera of patients with RA. By in vitro experiments, we confirmed that TLR-activated RASF expressed p19 but not p40, in contrast to monocytes, which produced IL23 following TLR stimulation. CONCLUSION: The TLR-dependent induction of p19 but not p40 in RASF and the abundant expression of p19 along with the low or undetectable levels of IL23 in patients with RA provides strong evidence that p19 does not necessarily indicate the presence of IL23, as has been proposed to date.
19116923 Genetic association of the major histocompatibility complex with rheumatoid arthritis impl 2009 Jan OBJECTIVE: The HLA-DRB1 locus within the major histocompatibility complex (MHC) at 6p21.3 has been identified as a susceptibility gene for rheumatoid arthritis (RA); however, there is increasing evidence of additional susceptibility genes in the MHC region. The aim of this study was to estimate their number and location. METHODS: A case-control study was performed involving 977 control subjects and 855 RA patients. The HLA-DRB1 locus was genotyped together with 2,360 single-nucleotide polymorphisms in the MHC region. Logistic regression was used to detect DRB1-independent effects. RESULTS: After adjusting for the effect of HLA-DRB1, 18 markers in 14 genes were strongly associated with RA (P<10(-4)). Multivariate logistic regression analysis of these markers and DRB1 led to a model containing DRB1 plus the following 3 markers: rs4678, a nonsynonymous change in the VARS2L locus, approximately 1.7 Mb telomeric of DRB1; rs2442728, upstream of HLA-B, approximately 1.2 Mb telomeric of DRB1; and rs17499655, located in the 5'-untranslated region of DQA2, only 0.1 Mb centromeric of DRB1. In-depth investigation of the DQA2 association, however, suggested that it arose through cryptic linkage disequilibrium with an allele of DRB1. Two non-shared epitope alleles were also strongly associated with RA (P<10(-4)): *0301 with anti- cyclic citrullinated peptide-negative RA and *0701 independently of autoantibody status. CONCLUSION: These results confirm the polygenic contribution of the MHC to RA and implicate 2 additional non-DRB1 susceptibility loci. The role of the HLA-DQ locus in RA has been a subject of controversy, but in our data, it appears to be spurious.
20959150 The increased in vitro osteoclastogenesis in patients with rheumatoid arthritis is due to 2011 Mar 1 Increases in local and systemic bone resorption are hallmarks of rheumatoid arthritis (RA). Osteoclasts are implicated in these processes and their enhanced differentiation may contribute to bone destruction. We observed that in vitro osteoclastogenesis varies among healthy individuals and hypothesized that increased osteoclastogenesis could be a marker for the presence of RA. Our objective in the present study was to determine if in vitro osteoclastogenesis from peripheral blood mononuclear cells (PBMCs) was different in patients with RA compared to healthy controls and osteoarthritis (OA) patients. Expression of CD14 in PBMCs was quantified and PBMCs were incubated for 21 days in the presence of the osteoclastogenic cytokines M-CSF and RANKL. Differentiation on cortical bone slices permitted the analysis of bone resorption while apoptotic potential was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. In vitro osteoclastogenesis was higher in PBMCs from RA patients compared to controls, and a similar increase was observed in the percentage of osteoclast precursors in RA patients. Osteoclasts from RA patients showed lower apoptotic rates than osteoclasts from healthy controls. No difference was observed in bone resorption activity between RA patients and controls. Interestingly, the difference in osteoclast number and apoptosis rate allowed the implementation of an algorithm capable of distinguishing patients with RA from controls. In conclusion, our study shows that osteoclast differentiation from PBMCs is enhanced in patients with RA, and this difference can be explained by both a higher percentage of osteoclast precursors in the blood and by the reduced apoptotic potential of mature osteoclasts.
20738421 Varying expression of four genes sharing a common regulatory sequence may differentiate rh 2011 Jan The CD28 gene is similarly down-regulated in CD4(+) lymphocytes from both healthy elderly people and patients with rheumatoid arthritis (RA) because of impaired protein-binding activity of the 'α' sequence in its promoter region. Other genes important for the CD4(+) cell function may share that sequence and may be similarly regulated and affected. We searched GenBank for possible 'α' homologues and then compared transcriptional activities of the respective genes in the CD4(+) cells of young and older healthy individuals and those with RA by real-time PCR. We show here that genes encoding one of the zinc finger proteins (ZNF334), the 'aging hormone' Klotho, the retinoid acid receptor β2 (RARβ2) and the T-cell adapter protein GRAP-2, contain sequences with various (exceeding 70%) degrees of homology to the 'α' sequence near their promoters. These genes are transcribed in human CD4(+) lymphocytes; the expressions of RARβ2, KLOTHO and ZNF334 are significantly decreased in a correlated manner in the cells of patients with RA compared with those of healthy individuals. In RA patients, the extremely reduced expression of ZNF334 does not depend on the individual's age, apparently constituting a disease-related phenomenon; whereas that of RARβ2 and KLOTHO occurs mostly in the cells of relatively younger patients, making them similar to the lymphocytes of healthy elderly in this aspect.
19248096 Specific association of type 1 diabetes mellitus with anti-cyclic citrullinated peptide-po 2009 Mar OBJECTIVE: The co-occurrence of autoimmune diseases such as rheumatoid arthritis (RA) and type 1 diabetes mellitus (DM) has been reported in individuals and families. In this study, the strength and nature of this association were investigated at the population level in a Swedish case-control cohort. METHODS: For this case-control study, 1,419 patients with incident RA diagnosed between 1996 and 2003 were recruited from university, public, and private rheumatology units throughout Sweden; 1,674 matched control subjects were recruited from the Swedish national population registry. Sera from the subjects were tested for the presence of antibodies to cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), and the 620W PTPN22 allele. Information on a history of diabetes was obtained by questionnaire, telephone interview, and/or medical record review. The prevalence of type 1 DM and type 2 DM was compared between patients with incident RA and control subjects and further stratified for the presence of anti-CCP, RF, and the PTPN22 risk allele. RESULTS: Type 1 DM was associated with an increased risk of RA (odds ratio [OR] 4.9, 95% confidence interval [95% CI] 1.8-13.1), and this association was specific for anti-CCP-positive RA (OR 7.3, 95% CI 2.7-20.0), but not anti-CCP-negative RA. Further adjustment for the presence of PTPN22 attenuated the risk of anti-CCP-positive RA in patients with type 1 DM to an OR of 5.3 (95% CI 1.5-18.7). No association between RA and type 2 DM was observed. CONCLUSION: The association between type 1 DM and RA is specific for a particular RA subset, anti-CCP-positive RA. The risk of developing RA later in life in patients with type 1 DM may be attributed, in part, to the presence of the 620W PTPN22 allele, suggesting that this risk factor may represent a common pathway for the pathogenesis of these 2 diseases.
21358248 Long-term clinical and radiological outcomes of hybrid total knee arthroplasty. 2010 OBJECTIVES: The purpose of this study was to evaluate the clinical effectiveness and radiological results of hybrid total knee arthroplasty (TKA). METHODS: This study recruited 105 patients (169 cases) who underwent hybrid TKA for osteoarthritis and rheumatoid arthritis from 1999 to 2002. Maxim (Biomet Inc., Warsaw, IN, USA) prosthesis was used, and average follow-up was 8.6 years. Radiologically, femorotibial angle was measured in a standing anteroposterior (AP) view, and a femoral flexion angle and a tibial angle were measured using the Knee Society roentgenographic evaluation and scoring system. Radiolucent lines were detected at the last follow-up. Clinically, range of joint motion and the Knee Society clinical rating system scores were evaluated. RESULTS: The femorotibial angle was improved from varus 4.5° to 6.4° at the last follow-up. The femoral flexion in an AP view at the postoperative and last follow-up was 96.5° and 95.7°, respectively, and the tibial angle was 89.1° and 88.7°, respectively. In lateral view, the femoral flexion was 2.6° and 2.7°, respectively, and the tibial angle was 88.4° and 87.8°, respectively. Total scores of radiolucencies were 4 points or less in all cases, and the average width was 1.1 mm. Flexion contracture was improved from 10.0° to 3.5°, and further flexion was increased from 110.5° to 130.4°. Knee score and function score were also enhanced from 47.6 and 46.8 preoperatively to 89.7 and 88.4 after the operation, respectively. CONCLUSION: Hybrid technique for TKA can be effective clinically and radiologically on longterm follow-up.
20112404 Periarticular bone structure in rheumatoid arthritis patients and healthy individuals asse 2010 Feb OBJECTIVE: To define the nature of structural bone changes in patients with rheumatoid arthritis (RA) compared with those in healthy individuals by using the novel technique of high-resolution microfocal computed tomography (micro-CT). METHODS: Fifty-eight RA patients and 30 healthy individuals underwent a micro-CT scan of the proximal wrist and metacarpophalangeal joints. Bone lesions such as cortical breaks, osteophytes, and surface changes were quantified on 2-dimensional (2-D) slices as well as by using 3-D reconstruction images, and exact localization of lesions was recorded. RESULTS: Micro-CT scans could detect bone lesions <0.5 mm in width or depth. Small erosions could be observed in healthy individuals and RA patients, whereas lesions >1.9 mm in diameter were highly specific for RA. Cortical breaks were mostly found along the radial sites of the metacarpal heads. No significant difference in the presence of osteophytes between healthy individuals and RA patients was found. Cortical surface changes, presumably cortical thinning and fenestration, became evident from 3-D reconstructions and were more pronounced in RA patients. CONCLUSION: Micro-CT allows exact detection of morphologic changes of juxtaarticular bone in healthy individuals and RA patients. Even healthy individuals occasionally show bone changes, but the severity of these lesions, with the exception of osteophytes, is greater in RA patients. Thus, micro-CT allows accurate differentiation among physiologic bone changes in joints and among types of pathologic bone damage resulting from RA.
20387531 [Antisynthetase (anti PL-7 antibody) syndrome presenting as a skin rash and exacerbation o 2010 Mar A 52-year-old man was admitted to our hospital for progressive dyspnea of 3 months duration and a skin rash of 4 months duration. Previously, he had been given a diagnosis of rheumatoid arthritis at age 40, then a diagnosis of interstitial pneumonia at age 46. Tacrolimus and prednisolone were begun at age 50, and 50 mg/week of etanercept was added 17 months before admission to our hospital. Due to renal dysfunction, tacrolimus was discontinued 9 months before admission. A skin rash developed 4 months before admission, and progressive dyspnea developed over the 3 months before admission. Tacrolimus was restarted at 1 mg/day and prednisolone was increased from 5 mg/day to 15 mg/day; however, neither the skin rash nor the dyspnea improved. After visiting a local physician, the patient was then referred to our institution. On presentation, skin changes such as erythema of the superior palpebrae and fingers were noted. His serum creatine phosphokinase level was elevated, but muscle strength was normal and no abnormal electromyographic and muscle biopsy findings were found. Anti-Jo-1 antibody was negative but anti PL-7 antibody was positive. The patient did not meet the diagnostic criteria of dermatomyositis/ polymyositis, so antisynthetase syndrome was diagnosed. Etanercept was discontinued and the prednisolone increased, which resulted in improvement of the interstitial pneumonia and skin rash. Antisynthetase syndrome should be considered as a differential diagnosis when skin rash and exacerbation of interstitial pneumonia are found during treatment for rheumatoid arthritis.
20112366 Could accelerated aging explain the excess mortality in patients with seropositive rheumat 2010 Feb OBJECTIVE: To determine whether the mortality pattern in patients with seropositive rheumatoid arthritis (RA) is consistent with the concept of accelerated aging, by comparing the observed mortality rates in patients with RA with the age-accelerated mortality rates from the general population. METHODS: A population-based inception cohort of patients with seropositive RA (according to the American College of Rheumatology 1987 criteria) was assembled and followed up for vital status until July 1, 2008. The expected mortality rate was obtained by applying the death rates from the general population to the age, sex, and calendar year distribution of the RA population. The observed mortality was estimated using Kaplan-Meier methods. Acceleration factors for the expected mortality were estimated in accelerated failure time models. RESULTS: A total of 755 patients with seropositive RA (mean age 55.6 years, 69% women) were followed up for a mean of 12.5 years, during which 315 patients died. The expected median survival was age 82.4 years, whereas the median survival of the RA patients was age 76.7 years. Results of statistical modeling suggested that, in terms of mortality rates, patients with RA were effectively 2 years older than actual age at RA incidence, and thereafter the patients underwent 11.4 effective years of aging for each 10 years of calendar time. CONCLUSION: The overall observed mortality experience of patients with seropositive RA is consistent with the hypothesis of accelerated aging. The causes of accelerated aging in RA deserve further investigation.