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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17914133 Preliminary evidence shows that folic acid fortification of the food supply is associated 2007 Oct BACKGROUND: Fortification of the diet with folate has been used in the United States since 1997 to prevent neural tube defects in newborn babies. However, an increase in dietary folate intake could theoretically reduce the effectiveness of the anti-folate medication, methotrexate (MTX) in treating rheumatoid arthritis (RA) and other inflammatory diseases. OBJECTIVE: To investigate whether dietary fortification with folic acid interferes with MTX function in patients with RA. METHODS: We computed MTX dose per patient per year for the years 1988 to 1999 and plotted these against time, comparing the overall mean MTX dose before and after 1997, when dietary fortification with folic acid was instituted in the USA. Thirty-six subjects met eligibility criteria. RESULTS: Mean annual MTX dose was stable between 1988 and 1996 (12.4 +/- 4.0mg), but then rose linearly from 1997 to 1999 (16.6 +/- 5.1 mg, p < 0.001). CONCLUSIONS: This preliminary study suggests that folic acid supplementation may contribute to higher MTX dosing in patients with RA.
19259548 Bruton's tyrosine kinase as a drug discovery target. 2008 Sep Bruton's tyrosine kinase (Btk) is an important mediator in multiple signal transduction pathways. Fifteen years of research have revealed a complex role for Btk in hematopoietic cells. These studies suggest that Btk may be a promising target for therapeutic intervention for several complicated diseases. Inhibitors targeting the Btk kinase domain have been developed and show clear beneficial effects in animal models of rheumatoid arthritis, lymphoma and other diseases. Here, an overview of these studies is presented with an emphasis on results stemming from medicinal chemistry research.
17520171 Pericarditis: a rare complication of methotrexate therapy. 2007 Dec Serositis is a rare complication of methotrexate (MTX) administration. We report a 60-year-old man with rheumatoid arthritis who developed pericarditis after taking his weekly MTX dose, which recurred within hours after 2 subsequent weekly MTX doses. Pericarditis has not recurred after discontinuance of MTX over 3 years ago. We conclude that he had MTX-induced pericarditis, based on the close temporal relationship between MTX ingestion and manifestations of pericarditis on three distinct occasions because of the previous reports of MTX-induced pericarditis and because pericarditis has not recurred after MTX withdrawal.
18394459 Cardiovascular outcomes in male veterans with rheumatoid arthritis. 2008 Apr 15 In men with rheumatoid arthritis (RA), the confounding effect of adverse cardiovascular risk profile on the independent association of RA disease activity score (DAS) and major adverse cardiovascular events (MACEs) continues to be debated. The aim was to analyze the association of RA DAS with MACEs in a prospective cohort of men with RA enrolled in the VARA Registry at the Dallas site from January 2003 to October 2006. All subjects met American College of Rheumatology criteria for RA. All events were obtained by reviewing patient clinical data. DAS was categorized as low, 0 to 3.2; moderate, 3.2 to 5.09; and high, > or =5.1. Of 282 men (mean age 66 +/- 11.1 years), 231 had valid DASs (150, low; 60, moderate; and 21, high DAS) and were followed up for 4.4 +/- 2 years. Ninety-two subjects (32.6%; 95% confidence interval 27 to 38) experienced an MACE, a composite end point of death (9 patients; 10%), acute coronary syndrome (38 patients; 42%), coronary revascularization (47 patients; 49%), new-onset heart failure (37 patients; 40%), and stroke (15 patients; 16%). DAS was a significant predictor of MACEs (hazard ratio 1.31, 95% confidence interval 1.1 to 1.6, p = 0.01) independent of traditional risk factors. Compared with patients with low or moderate DASs, patients with high DASs had a lower mean event-free period (35 and 30 vs 19 years, respectively; p = 0.03). In conclusion, in a population of male US veterans aged >50 years, (1) patients with RA were at high risk of MACEs, and (2) RA DAS was a significant predictor of MACEs independent of traditional cardiovascular risk factors.
17937473 Leflunomide-associated infections in rheumatoid arthritis. 2007 Nov OBJECTIVE: To determine the prevalence of severe infections in patients with rheumatoid arthritis (RA) prescribed leflunomide in North Canterbury, New Zealand. METHODS: A case-note audit of all Christchurch Hospital patients with RA prescribed leflunomide between 2002 and 2006 was performed. The criterion for severe infection was inpatient hospitalization. Relevant reports to the national Pharmacovigilance Centre were also examined. RESULTS: Since January 2002, 171 patients with RA have commenced taking leflunomide. Ninety-nine of 171 (57.9%) patients were also prescribed prednisone. Combination disease modifying antirheumatic drug therapy was common, with 82/171 (48.0%) taking methotrexate (MTX), 15/171 (8.8%) hydroxy-chloroquine, 11/171 (6.4%) sulfasalazine, and 8/171 (4.7%) anti-tumor necrosis factor therapy. Eleven patients developed infection requiring hospitalization while taking leflunomide including: lower respiratory tract infections (3), cellulitis (2), disseminated herpes zoster (2), probable TB liver (1), abdominal sepsis (1), mycotic aneurysm (1) and gastroenteritis (1). Nine of the 11 patients were also taking corticosteroids or corticosteroids with MTX. The 171 patients were treated for a total of 4005 months, giving an incidence for severe infection of 3.30/100 patient-years (95% CI 1.65-5.90). Patients at increased risk were those with severe disease and taking concomitant MTX and corticosteroids. The NZ Pharmacovigilance Centre has received 7 additional reports of severe infections in patients with RA taking leflunomide. Reported cases include probable pulmonary TB (1), pneumocystis pneumonia (1), other pulmonary infection (2), and septicemia (3) including a case of infective endocarditis. Four occurred in combination with MTX, one with adalimumab. All 5 patients were also taking -corticosteroids. CONCLUSION: We believe this observed rate of serious infection is acceptable in the context of optimally treating active RA. Patients with severe disease and taking combination MTX and corticosteroids are at greatest risk. In our experience, once established, infections may rapidly progress in patients with RA taking leflunomide, and early cholestyramine washout is strongly recommended.
18578966 In vivo segmental motion of the cervical spine in rheumatoid arthritis patients with atlan 2008 May OBJECTIVE: The dynamic mechanism underlying cervical spine involvement in rheumatoid arthritis (RA) remains unidentified. The purpose of the current study was to determine the in vivo cervical segmental motion in RA patients with atlantoaxial subluxation (AAS) using a patient-based three-dimensional magnetic resonance imaging (MRI) computer model. METHODS: Healthy volunteers and RA patients with AAS (all females, n=10) underwent MRI examination of the cervical spine. Each vertebral body from the occipital bone (Oc) to the first thoracic vertebra (T1) was reconstructed from slices of T2-weighted sagittal MR images in the neutral, flexion, and extension positions. Using volume merge methods, each reconstructed vertebral body was virtually rotated and translated. Rotational segmental and translational segmental motions were obtained in three major planes. RESULTS: Overall, the axial translational motions in the RA group were lower than those in the healthy volunteers; however the axial translational motion at only C1-C2 during flexion was at the same level as that in the healthy volunteers and was greater on the bottom side than that at other intervertebral levels. The frontal rotational motions at C1-C2 during extension were greater in the RA patients than those in the healthy volunteers (p<0.05). CONCLUSION: The atlantoaxial joints in the RA patients with AAS showed great frontal rotational motion during extension and great axial translation on the bottom side during flexion. The current noninvasive MRI-based method could be useful in evaluating the 3-D dynamic mechanism underlying cervical involvement in RA in vivo.
18057530 Circulating VEGF as a biological marker in patients with rheumatoid arthritis? Preanalytic 2008 BACKGROUND: Soluble vascular endothelial growth factor (VEGF) is a promising biomarker in monitoring rheumatoid arthritis (RA), but studies of pre-analytical and biologic variability are few. METHODS: VEGF was measured by ELISA methods in serum and plasma from healthy persons and RA patients. Pre-analytical factors were investigated. A reference interval for VEGF was established in serum and plasma from 306 healthy persons. Diurnal, day-to-day, week-to-week, long-term variability, and impact of exercise were evaluated. RESULTS: Delayed processing time, room temperature, low centrifugal force and contamination of plasma with cellular elements lead to significant increases in VEGF levels, whereas storage for up to 2 years at -80 degrees C or up to 10 freeze/thaw cycles did not affect VEGF levels. Serum VEGF levels were 7-10 fold higher than plasma VEGF levels. Reference intervals for VEGF (plasma: 45 pg/ml (range: non-detectable to 352); serum: 328 pg/ml (53-1791)) were independent of gender and age. Short- and long-term biologic variability included diurnal variation (sampling should take place after 7 AM) and impact of exercise (increased VEGF immediately after bicycling normalised within 1 hour). CONCLUSIONS: Pre-analytical factors and biologic variability including diurnal variation and impact of exercise should be accounted for in future studies that include circulating VEGF as a biological marker.
18276736 Novel lymphocyte-independent mechanisms to initiate inflammatory arthritis via bone marrow 2008 Mar OBJECTIVE: In a large-scale ENU (N-ethyl-N-nitrosourea) mouse mutagenesis programme, we previously have identified and characterized a novel mutation Ali18 that causes inflammatory arthritis like lesions in peripheral joints. In this study, we analysed the immune system of Ali18 mice to understand mechanisms underlying the spontaneous inflammation. METHODS: Humoral and cellular components of the immune system were phenotyped by ELISA and flow cytometry. The contribution of the immune system for phenotype expression was analysed in disease transfer experiments. The involvement of the adaptive immune system was investigated in Ali18;Rag1 double mutants and the influence of environmental factors was analysed in Ali18 mice reared under germ-free conditions. RESULTS: Bone marrow cells from Ali18 mice were able to transfer the disease phenotype to naïve wild-type recipients suggesting that cellular components of the reconstituted immune system were sufficient to induce arthritis. Ali18 mice revealed abnormal leucocyte populations including lymphocytes and granulocytes, as well as increased plasma IL-5 and IgE levels. Ali18;Rag1 double homozygous mutants, which lack mature lymphocytes, still developed arthritis, suggesting that the phenotype is independent of the adaptive immune system. In addition, the arthritis phenotype appeared to be independent from environmental conditions as demonstrated in mice reared under germ-free conditions. CONCLUSIONS: The Ali18 mutation induces inflammatory arthritis through bone marrow-derived cells. However, non-pro-inflammatory cytokine cascades and mature lymphocyte independent-mechanisms are crucial for initiation and progression of the phenotype. Ali18 mice may thus represent a model to study mechanisms involved in seronegative arthritis induced by cells of the innate immune system.
18677051 [Daily practice using the guidelines for prevention and treatment of osteoporosis. Use of 2008 Aug A number of clinical risk factors that provide information on fracture risk over and above that given by BMD have been defined. WHO proposed FRAX (fracture risk assessment tool) in which the fracture probability could be calculated by the use of risk factors with or without BMD. The proposed independent risk factors are age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake, secondary osteoporosis, and rheumatoid arthritis. Management algorithms in postmenopausal women based on an health analysis have been proposed in several countries including UK, Sweden, Germany, USA and Canada.
17983149 Collagen-induced arthritis in mice. 2007 Collagen-induced arthritis in mice has been widely used to address questions of disease pathogenesis and to validate therapeutic targets for human rheumatoid arthritis. Arthritis is normally observed about 3 wk after immunization with autologous or heterologous type II collagen in complete Freund's adjuvant and susceptibility to the disease is strongly associated with major histocompatibility complex class II genes. The development of collagen-induced arthritis is associated with strong T- and B-cell responses to type II collagen and the chief pathological features of the disease include a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, pannus formation, cartilage degradation, erosion of bone and fibrosis. Proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin--1beta, are abundantly expressed in the arthritic joints of mice with collagen-induced arthritis and, as in human rheumatoid arthritis, blockade of these molecules is effective in reducing the severity of disease.
17210617 Analysis of the thiol status of peripheral blood leukocytes in rheumatoid arthritis patien 2007 Apr Although the exact etiology of rheumatoid arthritis (RA) remains unknown, there is increasing evidence that reactive oxygen species and a pro-oxidant/antioxidant imbalance are an important part of the pathogenesis of joint tissue injury. Flow cytometry was used to evaluate the thiol status [surface-thiols and intracellular glutathione (iGSH)] of leukocytes from RA patients and controls. Levels of surface-thiols and iGSH of leukocytes from RA patients were significantly lower than of leukocytes from controls. CD53, a glycoprotein of the tetraspanin superfamily, which coprecipitates with the GSH recycling enzyme gamma-glutamyl transpeptidase, was elevated significantly on leukocytes from RA patients compared with leukocytes from controls. Surface-thiols and GSH play important roles in redox buffering of cells, providing protection from oxidative stress. The chronic inflammation of RA has been associated with oxidative stress, which is shown to cause a decline in the levels of cellular antioxidant sulfhydryls (R-SH). As antioxidant-protective levels also decline with age, the problem is compounded in older RA patients, who did have fewer R-SH. Chronic stress can also have an effect on telomere lengths, determining cell senescence and longevity. Although telomeres shorten with increasing age, our flow cytometry studies indicate that accelerated shortening in telomere lengths occurs with increasing age of RA patients, suggesting premature cellular aging. The paradox is that lymphocytes from RA patients are believed to resist apoptosis, and we suggest that the elevated expression of CD53, which results from the increased oxidative stress, may protect against apoptosis.
16762148 Fibroblast-like synoviocytes from patients with rheumatoid arthritis are more sensitive to 2006 Mar OBJECTIVE: Fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) show characteristics of transformation. Because the chicken anemia virus protein, apoptin, induces apoptosis solely in transformed cells, it was investigated whether FLS from patients were more sensitive to apoptin-induced apoptosis than FLS from normal joints obtained from trauma patients. METHODS: FLS were transduced with maltose-binding protein (MBP)-apoptin recombinant protein or MBP as a control protein by microinjection. After 24 hours, cells were fixed and stained with immunofluorescence to detect apoptin or MBP and the number of dead cells was assessed. Furthermore, phosphorylation of apoptin was analysed in FLS from patients with RA and from trauma patients by in vitro kinase assay. RESULTS: FLS from patients with RA were significantly more sensitive to apoptin-induced apoptosis than FLS from trauma patients (p = 0.0263). Furthermore, MBP-apoptin induced more apoptosis than MBP in RA FLS (p = 0.004). No phosphorylation of apoptin was observed in FLS from patients with RA. DISCUSSION: FLS from patients with RA are more sensitive to apoptin-induced apoptosis than normal FLS, which is consistent with a transformed phenotype of these cells. However, given the lack of phosphorylation of apoptin in RA FLS the mechanism of action of apoptin seems to differ between tumour cells and RA FLS. This study indicates that apoptin may help to identify a new therapeutic pathway against hyperplasia of the synovium and joint destruction in RA.
17414533 Risk factors associated with the cumulative survival of low-dose methotrexate in 273 Japan 2007 Apr BACKGROUND: Methotrexate (MTX) has become the most commonly prescribed disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). In the Western countries, the MTX dosage is safely increased to a maximum of 25 mg/wk until a significant response is observed. On the contrary, in Japan, MTX has been approved only as a second-line agent, and the approved maximum MTX dosage is only 8 mg/wk. This suboptimal dosage may affect MTX survival in Japanese RA patients. OBJECTIVES: To study risk factors associated with the cumulative survival of MTX in Japanese RA patients. METHODS: Data on 273 patients (male 44, female 229) with RA treated with MTX between January 1, 2000 and September 30, 2004 in our center were studied. RESULTS: Two hundred seventy-three patients were followed for 437 person-years of MTX exposure. Mean MTX dosage was 5.5 +/- 1.9 mg/wk. The cumulative MTX survival probability after 5 years was 61.9%. Univariate Cox regression analysis showed a significant correlation between MTX survival probability and use of fewer previous DMARDs, higher dose of MTX, inclusion of folate supplementation, and shorter disease duration. In the multivariate Cox regression model, use of fewer previous DMARDs remained significantly related to MTX survival. Reasons for discontinuation included adverse effects in 34 patients (12.5%) and inefficacy in 6 patients (2.2%). CONCLUSIONS: Cumulative survival was the same or slightly better than those in reports from Western countries, with less withdrawals reported due to adverse events or inefficacy. Whether these results are due to different MTX needs in Japanese or to acceptance of less clinical efficacy will require further studies. The use of fewer previous DMARDs was associated with longer MTX survival.
17666451 Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthr 2008 Mar BACKGROUND: HLA-DRB1 shared epitope (HLA-SE), PTPN22 and CTLA4 alleles are associated with cyclic citrullinated peptide (CCP) and rheumatoid arthritis (RA). OBJECTIVE: We examined associations between HLA-SE, PTPN22, CTLA4 genotypes and RA phenotypes in a large cohort to (a) replicate prior associations with CCP status, and (b) determine associations with radiographic erosions and age of diagnosis. METHODS: A total of 689 RA patients from the Brigham RA Sequential Study (BRASS) were genotyped for HLA-SE, PTPN22 (rs2476601) and CTLA4 (rs3087243). Association between genotypes and CCP, rheumatoid factor (RF) erosive phenotypes and age at diagnosis were assessed with multivariable models adjusting for age, sex and disease duration. Novel causal pathway analysis was used to test the hypothesis that genetic risk factors and CCP are in the causal pathway for predicting erosions. RESULTS: In multivariable analysis, presence of any HLA-SE was strongly associated with CCP+ (odds ratio (OR) 3.05, 95% CI 2.18-4.25), and RF+ (OR 2.53, 95% CI 1.83-3.5) phenotypes; presence of any PTPN22 T allele was associated with CCP+ (OR 1.81, 95% CI 1.24-2.66) and RF+ phenotypes (OR 1.84, 95% CI 1.27-2.66). CTLA4 was not associated with CCP or RF phenotypes. While HLA-SE was associated with erosive RA phenotype (OR 1.52, 95% CI 1.01-2.17), this was no longer significant after conditioning on CCP. PTPN22 and CTLA4 were not associated with erosive phenotype. Presence of any HLA-SE was associated with an average 3.6 years earlier diagnosis compared with absence of HLA-SE (41.3 vs 44.9 years, p = 0.002) and PTPN22 was associated with a 4.2 years earlier age of diagnosis (39.5 vs 43.6 years, p = 0.002). CTLA4 genotypes were not associated with age at diagnosis of RA. CONCLUSIONS: In this large clinical cohort, we replicated the association between HLA-SE and PTPN22, but not CTLA4 with CCP+ and RF+ phenotypes. We also found evidence for associations between HLA-SE, and PTPN22 and earlier age at diagnosis. Since HLA-SE is associated with erosive phenotype in unconditional analysis, but is not significant after conditioning on CCP, this suggests that CCP is in the causal pathway for predicting erosive phenotype.
17593860 Sex influences on the penetrance of IL-1beta and IL-1RN genotypes for rheumatoid arthritis 2007 May Polymorphism (variable number of tandem repeats) in the second intron of the interleukin-1 receptor antagonist (IL-1Ra) gene and two single nucleotide polymorphisms at positions -511 and +3954 of the IL-1beta gene may be associated with an increased risk of rheumatoid arthritis (RA). This study used sex stratification to investigate a correlation of the three genetic polymorphisms with the risk of RA, on patients with RA and healthy controls. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were performed. The frequencies of the IL-1beta+3954 allele and genotype in female patients were significantly different compared with the controls; but in males, only the frequency of the IL-1beta+3954 allele was different. The frequency of the IL-1RN genotype in patients was not statistically different compared with the controls; however, the frequency of IL-1RN allele in female patients was different. The association of the three polymorphisms with the susceptibility to RA appears to be significantly affected by gender.
17278016 Long-term safety study of iguratimod in patients with rheumatoid arthritis. 2007 We conducted a 52-week clinical study of iguratimod in 394 Japanese patients with rheumatoid arthritis to evaluate the long-term safety of the drug. Iguratimod was administered orally at a daily dose of 25 mg for the first 4 weeks and 50 mg for the subsequent 48 weeks. Some of the patients continued the treatment for 100 weeks for their benefit. The cumulative incidence of adverse events for 100 weeks was 97.6%. The cumulative incidence of adverse reactions was 65.3%; unfavorable symptoms and signs (excluding abnormal laboratory data changes) accounted for 33.2% of the reactions, and abnormal laboratory data changes accounted for 50.4%. The continued treatment rate was 66.8% at week 28 and 53.6% at week 52. For reference, the American College of Rheumatology (ACR) 20 response rate was calculated for the patients who had assessable disease activity, who did not violate the study protocol, and who continued the study treatment at weeks 28 and 52. The rate was 46.9% at week 28 and 41.0% at week 52. To use iguratimod safely for a long time, patients should be observed closely for adverse reactions such as increased hepatic enzymes.
17690887 Central nervous system involvement as a major manifestation of rheumatoid arthritis. 2008 Jan A 58-year-old woman with an 8-year history of seropositive rheumatoid arthritis was admitted with right hemiparesis, history of seizures, fever, weight loss and headaches. Her blood tests revealed the presence of rheumatoid factor, elevated C-reactive protein and anti-cyclic citrullinated peptide antibodies (>200 RU/ml). Examination of cerebrospinal fluid demonstrated pleocytosis (118 cells/mm(3), predominantly lymphocytes) with elevated protein level (58 mg/dl); cultures were negative. Magnetic resonance imaging findings were suggestive for meningoencephalitis. Short course of high-dose corticosteroids and cyclophosphamide led to clinical improvement. Rheumatoid vasculitis was probably responsible for neurological symptoms.
17159887 Genomic DNA pooling for whole-genome association scans in complex disease: empirical demon 2007 Jan A pragmatic approach that balances the benefit of a whole-genome association (WGA) experiment against the cost of individual genotyping is to use pooled genomic DNA samples. We aimed to determine the feasibility of this approach in a WGA scan in rheumatoid arthritis (RA) using the validated human leucocyte antigen (HLA) and PTPN22 associations as test loci. A total of 203 269 single-nucleotide polymorphisms (SNPs) on the Affymetrix 100K GeneChip and Illumina Infinium microarrays were examined. A new approach to the estimation of allele frequencies from Affymetrix hybridization intensities was developed involving weighting for quality signals from the probe quartets. SNPs were ranked by z-scores, combined from United Kingdom and New Zealand case-control cohorts. Within a 1.7 Mb HLA region, 33 of the 257 SNPs and at PTPN22, 21 of the 45 SNPs, were ranked within the top 100 associated SNPs genome wide. Within PTPN22, individual genotyping of SNP rs1343125 within MAGI3 confirmed association and provided some evidence for association independent of the PTPN22 620W variant (P=0.03). Our results emphasize the feasibility of using genomic DNA pooling for the detection of association with complex disease susceptibility alleles. The results also underscore the importance of the HLA and PTPN22 loci in RA aetiology.
16488162 Effects of arginine-vasopressin and parathyroid hormone-related protein (1-34) on cell pro 2006 Jul OBJECTIVE: Both arg-vasopressin (AVP) and parathyroid hormone-related protein (PTHrP) may act as proinflammatory hormones. In addition, they have been suggested to be involved in the pathophysiology of rheumatoid arthritis (RA). We therefore investigated the effects of AVP and PTHrP (1-34) on cell proliferation and secretion of the glycoprotein YKL-40 in human chondrocytes derived from healthy subjects as well as from patients with RA or osteoarthritis (OA). METHOD: Primary cultures of human chondrocytes were incubated with AVP (1-100 pmol/l) or PTHrP (1-34) (0.1-100 nmol/l). Cell proliferation was measured as [3H]thymidine incorporation. Intracellular cAMP and YKL-40 in cell medium were determined by commercially available kits. RESULTS: AVP and PTHrP (1-34) increased proliferation in chondrocytes derived from healthy donors as well as from RA and OA patients. PTHrP (1-34), but not AVP, increased intracellular levels of cAMP. PTHrP (1-34) did not change the amount of YKL-40 in chondrocytes from healthy subjects or patients with OA. AVP tended to decrease the secretion of YKL-40 from healthy chondrocytes. Both PTHrP (1-34) and AVP increased YKL-40 secretion from RA chondrocytes. In contrast, AVP decreased the secretion of YKL-40 in chondrocytes from patients with OA. CONCLUSION: AVP and PTHrP (1-34) stimulated proliferation in human chondrocytes derived from healthy subjects as well as from patients with RA or OA. However, the effects of AVP and PTHrP (1-34) on YKL-40 secretion varied depending on the origin of the chondrocytes.
19026127 Behçet's syndrome patients have high levels of functional disability, fatigue and pain as 2008 Jul OBJECTIVE: Current tools for assessing Behçet's syndrome (BS) do not include patient-reported outcomes such as functional disability, pain or fatigue. We examined various outcome measures using the multi-dimensional Health Assessment Questionnaire (MDHAQ) and compared them between BS patients with and without arthritis. We also compared the results to those for patients with rheumatoid arthritis (RA), the disease in relation to which the MDHAQ has been most thoroughly studied. METHODS: We conducted a comparative review of BS and early RA patients being followed at the New York University Hospital for Joint Diseases (NYU HJD) and the Behçet's Syndrome Center. All patients completed an MDHAQ at each visit, which included functional disability, pain, morning stiffness, fatigue, and patient and physician global assessments of disease activity. A chart review for BS manifestations and treatments was also carried out. All patient evaluations reported here represent the baseline values at first visit. RESULTS: 129 patients with BS and 116 with early RA were surveyed. BS patients had similar pain levels and physician global assessment of disease activity to the RA patients and higher functional disability, fatigue and patient assessments of global disease activity. Among BS patients, those with arthritis had significantly higher scores for all the outcome measures examined except the physician global assessment of disease activity. CONCLUSION: Using the MDHAQ could reveal previously under-recognized problems in BS, as was observed in this survey of BS patients with arthritis. Such information might be helpful in the management of patients with BS.