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ID PMID Title PublicationDate abstract
17502830 Validation of the associations between single nucleotide polymorphisms or haplotypes and r 2007 Jun BACKGROUND: For prevention of joint destruction in rheumatoid arthritis, optimal management of therapy with disease-modifying antirheumatic drugs is essential. Pharmacogenomic evidence, if reliable, may be incorporated in the treatment of rheumatoid arthritis to achieve a more efficient activity control with minimized adverse events. METHODS: We conducted retrospective studies to validate our previous three different results about the association between adverse events or efficacy of two different disease-modifying antirheumatic drugs and genomic variations. Association between single nucleotide polymorphisms in N-acetyltransferase 2 gene (NAT2) and adverse events by sulfasalazine and association between C677T or A1298C in 5,10-methylenetetrahydrofolate reductase gene (MTHFR) and responses to methotrexate were examined. RESULTS: Patients without the wild-type haplotype at NAT2 were more likely to suffer from overall adverse events [n=186, P=0.001, relative risk (RR) 3.31, 95% confidence interval (CI) 1.76-6.22] and severe adverse events (P=0.015, RR 24.6, 95% CI 2.37-254.53) by sulfasalazine. Patients with the T allele at C677T in MTHFR were more susceptible to overall adverse events (n=156, P=0.003; RR 2.4, 95% CI 1.29-4.55) while patients with the C allele at A1298C were less likely to be treated with a higher dose (>6 mg/week) of methotrexate in one year of treatment (n=159, P=0.008, RR 1.84, 95% CI 1.12-3.01). In all three association studies, the results were essentially the same as previously reported. CONCLUSION: As three studies on the associations between genomic variations and adverse events or efficacy of two different disease-modifying antirheumatic drugs were replicated, the usefulness of the tests is worth being tested in clinical practice.
17998177 The results of primary Birmingham hip resurfacings at a mean of five years. An independent 2007 Nov We report an independent prospective review of the first 230 Birmingham hip resurfacings in 212 patients at a mean follow-up of five years (4 to 6). Two patients, one with a loose acetabular component and the other with suspected avascular necrosis of the femoral head, underwent revision. There were two deaths from unrelated causes and one patient was lost to follow-up. The survivorship with the worst-case scenario was 97.8% (95% confidence interval 95.8 to 99.5). The mean Harris hip score improved significantly (paired t-test, p < 0.05) from 62.54 (8 to 92) pre-operatively to 97.7 (61 to 100) at a mean of three years (2.1 to 4.3), then deteriorated slightly to a mean of 95.2 (47 to 100) at a mean of five years. The mean flexion improved from 91.5 degrees (25 degrees to 140 degrees) to 110.4 degrees (80 degrees to 145 degrees) at a mean of three years with no further improvement at five years (111.2 degrees; 70 degrees to 160 degrees). On radiological review at five years, one patient had a progressive lucent line around the acetabular component and six had progressive lucent lines around the femoral component. A total of 18 femoral components (8%) had migrated into varus and those with lucent lines present migrated a mean of 3.8 degrees (1.02 degrees to 6.54 degrees) more than the rest. Superolateral notching of the femoral neck and reactive sclerosis at the tip of the peg of the femoral component were associated with the presence of lucent lines (chi-squared test, p < 0.05), but not with migration of the femoral component, and are of unknown significance. Our results with the Birmingham hip resurfacing continue to be satisfactory at a mean follow-up of five years.
17036857 [Clinical reasoning and decision-making in practice. A man with inexplicable joint pain an 2006 Sep 23 A 52-year-old man presented with polyarthritis and was negative for rheumatoid factor, anti-CCP and ANA. He was treated with low-dose methotrexate, the drug of first choice in rheumatoid arthritis. The arthritis disappeared, but the patient developed fever, progressive dyspnoea, appetite loss and weight loss. Upon hospital admission his medication was stopped and community-acquired pneumonia was diagnosed. The fever persisted despite antibiotic treatment. The tentative diagnosis of rheumatoid arthritis was changed to systemic lupus erythematosus, based on the change in clinical condition that could not be explained by polyarthritis and seroconversion to ANA- and anti-dsDNA-positive. The patient was treated with high-dose steroids and azathioprine and remained in remission for more than 1 year after treatment. The ANA test remained strongly positive, whereas anti-dsDNA was no longer detectable. This case stresses the limited value of classification criteria for the diagnosis of rheumatoid arthritis. To differentiate between rheumatoid arthritis and systemic lupus erythematosus, tests for autoantibodies against citrullinated peptides can be used. To differentiate between systemic lupus erythematosus and infection, tests for anti-dsDNA antibodies, antinuclear antibodies, C-reactive protein and complement can be used.
16845649 Peripheral neuropathy associated with leflunomide: is there a risk patient profile? 2007 Jan PURPOSE: (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms. METHOD: All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses. RESULTS: One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range = 27-81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p = 0.0006), more often diabetic (30% vs. 2.9%, p = 0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p = 0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). CONCLUSION: Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory.
17665487 Minimal disease activity, remission, and the long-term outcomes of rheumatoid arthritis. 2007 Aug 15 OBJECTIVE: To determine the prevalence of minimal disease activity (MDA) and remission in patients with rheumatoid arthritis (RA), to assess the effect of anti-tumor necrosis factor (anti-TNF) therapy on MDA, and to determine the extent to which MDA status improves long-term outcomes. METHODS: Using the Patient Activity Scale (PAS) as a surrogate, we assessed the prevalence of MDA and remission in 18,062 patients with RA using the newly developed Outcome Measures in Rheumatology Clinical Trials (OMERACT) criteria for MDA. RESULTS: MDA was noted in 20.2% of 18,062 patients and persistent MDA, operationally defined as having MDA during >or=2 consecutive 6-month observation periods, occurred in 13.5% of 7,433 patients followed longitudinally. Disease activity at remission levels was noted in 7%. Among patients with MDA, 82% received disease-modifying antirheumatic drugs or biologic agents. Following anti-TNF initiation, the cumulative probability of achieving MDA at 2 and 6 years was 4.1% and 7.6%, respectively, and persistent MDA probabilities were 2.7% and 4.5%, respectively. Regardless of RA duration, patients with MDA had substantially better outcomes, including a 10-fold reduction in work disability and an approximately 2-fold reduction in total joint replacement and mortality. CONCLUSION: Remission remains uncommon in RA, and the prevalence of new remission in community practice is substantially lower than noted in published trials of biologic therapy. On average, persons with MDA appear to have persistently mild RA. This might be the effect of milder RA and/or more effective treatment in early RA. The PAS had satisfactory levels of agreement with the full MDA criteria and appears suitable for use in clinical and epidemiologic research.
17684286 Rheumatoid lung disease. 2007 Aug 15 Rheumatoid arthritis (RA) is a common, functionally disabling disease with genetic and environmental contributors. It occurs in approximately 1% of the population and adversely affects quality of life, functional status, and survival. Beyond its impact on the joints, pulmonary involvement occurs regularly and is responsible for a significant portion of the morbidity and mortality. Although pulmonary infection and/or drug toxicity are frequent complications, lung disease directly associated with the underlying RA is more common. The airways, vasculature, parenchyma, and pleura can all be involved, with variable amounts of pathologic inflammation and fibrosis. The true adverse clinical impact of the most important of these directly associated disorders, RA-associated interstitial lung disease (RA-ILD), has only recently begun to reveal itself. Our knowledge of the underlying pathobiology and the impact of our current immunomodulatory and biologic therapies on the lung disease are less than incomplete. However, what is clear is the importance of progressive lung fibrosis in shortening survival and impairing quality of life in RA as well as in other connective tissue diseases. The impact of historically available and newer biologic therapies in altering the outcome of RA-ILD is unknown; translational studies focused on the pathobiology and clinical studies focused on the treatment of RA-ILD are needed.
16635271 Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a G 2006 The functional single-nucleotide polymorphism (SNP) of the gene PTPN22 is a susceptibility locus for rheumatoid arthritis (RA). The study presented here describes the association of the PTPN22 1858T allele with RA in a German patient cohort; 390 patients with RA and 349 controls were enrolled in the study. For 123 patients, clinical and radiographic documentation over 6 years was available from the onset of disease. Genotyping of the PTPN22 1858 SNP was performed using an restriction fragment length polymorphism PCR-based genotyping assay. The odds ratio to develop RA was 2.57 for carriers of the PTPN22 1858T allele (95% confidence interval (CI) 1.85-3.58, p < 0.001), and 5.58 for homozygotes (95% CI 1.85-16.79). The PTPN22 1858T allele was significantly associated not only with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) positive RA, but also with RF and anti-CCP negative disease. The frequency of the PTPN22 1858T allele was increased disproportionately in male patients (53.8% compared to 33.0% in female patients, p < 0.001), and the resulting odds ratio for male carriers was increased to 4.47 (95% CI 2.5-8.0, p < 0.001). Moreover, within the male patient population, the rare allele was significantly associated with the HLA-DRB1 shared epitope (p = 0.01). No significant differences in disease activity or Larsen scores were detected. The results provide further evidence that the PTPN22 1858T allele is associated with RA irrespective of autoantibody production. The increased frequency of the risk allele in male patients and its association with the shared epitope indicate that the genetic contribution to disease pathogenesis might be more prominent in men.
15975971 Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced 2006 Feb BACKGROUND: Rheumatoid arthritis (RA) is associated with increased morbidity and mortality attributable to accelerated atherosclerosis and cardiovascular events. OBJECTIVE: To determine the role played by endothelial progenitor cells (EPC) in the defence system against arteriosclerosis. METHODS: The number and function of EPC in 13 young patients with RA with low disease activity (DAS28 3.5 (0.3)) and 13 healthy control subjects was studied. Endothelial function was investigated by agonist-induced, endothelium dependent vasodilatation measured by the forearm blood flow technique. Migratory activity and adhesion of EPC to tumour necrosis factor alpha (TNFalpha) activated mature endothelial cells and components of the extracellular matrix were tested in vitro. Putative precursor populations (CD34(+), CD34(+)/CD133(+), and CD34(+)/KDR(+) haematopoietic stem cells) were measured by flow cytometric analysis. RESULTS: Acetylcholine-induced, endothelium dependent vasodilatation was reduced by about 50% in patients with RA, indicating endothelial dysfunction, whereas endothelium-independent vasodilatation in response to glyceryl trinitrate was at control level. Significantly reduced numbers of EPC were found in the patients compared with controls. Migratory activity of EPC was decreased in patients with RA. Adhesion to mature endothelial cells after activation with TNFalpha was enhanced only in controls. The adhesion to matrix proteins and the number of putative precursor cell lineages was comparable in both groups. CONCLUSION: Endothelial dysfunction in patients with RA with low grade inflammation is associated with a reduced number and partial dysfunction of EPC. Further studies are needed to explore whether interventions that potentially ameliorate the number and function of EPC also improve endothelial function in these patients.
18668597 Evaluation of the effect of anti-tumor necrosis factor agent use on rheumatoid arthritis w 2008 Aug 15 OBJECTIVE: To examine the role of anti-tumor necrosis factor (anti-TNF) agents in predicting work disability in subjects with rheumatoid arthritis (RA). METHODS: We studied 953 subjects with rheumatologist-diagnosed RA from a US cohort using a nested, matched, case-control approach. Subjects provided data on medication usage and employment every 6 months for 18 months, were employed at baseline, and were age <65 years at last followup. Cases were subjects who were not employed at followup (n = 231) and were matched approximately 3:1 by time of entry into the cohort to 722 controls who were employed at followup. Risk of any employment loss, or loss attributed to RA, at followup as predicted by use of an anti-TNF agent at baseline was computed using conditional logistic regression. Stratification on possible confounding factors and recursive partitioning analyses were also conducted. RESULTS: Subjects' mean age was 51 years, 82% were female, 92% were white, and 72% had more than a high school education. Nearly half (48%) used an anti-TNF agent at baseline; characteristics of anti-TNF agent users were similar to nonusers. In the main analyses, anti-TNF use did not protect against any or RA-attributed employment loss (odds ratio [95% confidence interval] 1.1 [0.7-1.6] versus 0.9 [0.5-1.5]). However, a protective effect was found for users with disease duration <11 years (odds ratio [95% confidence interval] 0.5 [0.2-0.9]). In recursive partitioning analyses, age, RA global severity, and functional limitation played a much greater role in determining employment loss than anti-TNF agent use. CONCLUSION: Anti-TNF agent use did not protect against work disability in the main analyses. In stratified analyses, their use was protective among subjects with shorter RA duration, whereas in nonparametric analyses, age and disease factors were the prominent predictors of work disability.
17678823 Quantitative measures of rheumatic diseases for clinical research versus standard clinical 2007 Aug No single measure can serve as a 'gold standard' for the diagnosis, prognosis, and monitoring of patients with rheumatic diseases. Therefore, pooled indices of several measures have been developed for patient assessment. Quantitative measures and indices in rheumatology have been used primarily in clinical trials and other clinical research, but not in standard clinical care. Indeed, most standard rheumatology care is conducted without quantitative data other than laboratory tests, which often are uninformative. Some measures used in research have been adapted for standard care. The classical 66/68-joint count with graded scoring for swelling, tenderness, pain on motion, limited motion, and deformity has been shortened for clinical care to a 28-joint count, scored only as 'Yes' or 'No' for swelling or tenderness. Patient questionnaires designed for clinical research can be lengthy, with complex scoring, so that information is not available to help guide clinical decisions. By contrast, patient questionnaires designed for standard care, such as a simple one-page, multi-dimensional health assessment questionnaire (MDHAQ), are short, save time, are easily scored, and are useful in all rheumatic diseases to monitor patient status at each visit and document changes over long periods. More attention to measures for use in standard care could improve care and outcomes for patients with rheumatic diseases.
18606636 Genetic and molecular basis of quantitative trait loci of arthritis in rat: genes and poly 2008 Jul 15 Rheumatoid arthritis (RA) is an autoimmune disease, the pathogenesis of which is affected by multiple genetic and environmental factors. To understand the genetic and molecular basis of RA, a large number of quantitative trait loci (QTL) that regulate experimental autoimmune arthritis have been identified using various rat models for RA. However, identifying the particular responsible genes within these QTL remains a major challenge. Using currently available genome data and gene annotation information, we systematically examined RA-associated genes and polymorphisms within and outside QTL over the whole rat genome. By the whole genome analysis of genes and polymorphisms, we found that there are significantly more RA-associated genes in QTL regions as contrasted with non-QTL regions. Further experimental studies are necessary to determine whether these known RA-associated genes or polymorphisms are genetic components causing the QTL effect.
17870034 Comorbidities in rheumatoid arthritis. 2007 Oct Rheumatoid arthritis (RA) is often characterized by the burden of swollen joints, pain, and decreased physical function, but less understood are the many manifestations of additional health conditions that are associated with RA and its treatments. First brought to light with observations of increased mortality in RA, studies noted the increased rates of cardiovascular and infection events. The chronic, debilitating, autoimmune nature of RA affects the patient directly or indirectly in almost all organ systems, from cardiovascular problems and infections to depression and gastrointestinal ulcers. On average, the established RA patient has two or more comorbid conditions. It should be the responsibility of the rheumatologist to take these and the risk of additional conditions into account when treating the patient. This chapter reviews important comorbidities in patients with RA, their prevalence, and their relation to RA.
18039580 IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? 2008 Feb Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis. Data from experimental arthritis indicate IL-17 receptor signaling as a critical pathway in turning an acute synovitis into a chronic destructive arthritis. The identification of six IL-17 family members (IL-17A-F) may extend the role of this novel cytokine family in the pathogenesis of chronic destructive joint inflammation. Whether the successful anti-IL-17A cytokine therapy in murine arthritis can be effectively translated to human arthritis need to be tested in clinical trials in humans. Interestingly, IL-17A and IL-17F are secreted by the novel T helper subset named Th17. This novel pathogenic T cell population induces autoimmune inflammation in mice and is far more efficient at inducing Th1-mediated autoimmune inflammation in mice than classical Th1 cells (IFN-gamma). In addition to IL-17A and IL-17F, Th17 cells are characterized by expression of IL-6, TNF, GM-CSF, IL-21, IL-22 and IL-26. Th17 cells have been established as a separate lineage of T helper cells in mice distinct from conventional Th1 and Th2 cells. Whether this also applies to human Th17 and whether RA is a Th1 or a Th17 mediated disease is still not clear. This review summarizes the findings about the role of IL-17 in arthritis and discusses the impact of the discovery of the novel Th17 cells for arthritis. Further studies are needed to unravel the role of Th17 cells and the interplay of IL-17 and other Th17 cytokines in the pathogenesis of arthritis and whether regulating Th17 cell activity will have additional value compared to neutralizing IL-17A activity alone. This might help to reach the ultimate goal not only to treat RA patients but to prevent the development of this crippling disease.
16935912 Selective costimulation modulation using abatacept in patients with active rheumatoid arth 2007 Feb OBJECTIVE: To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE). METHODS: Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE. RESULTS: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections. CONCLUSION: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.
16855168 Effects of anti-TNF-alpha treatment on lipid profile in patients with active rheumatoid ar 2006 Jun Cardiovascular morbidity and mortality appear to be increased in rheumatoid arthritis (RA), which might be due to increased prevalence of risk factors for cardiovascular disease, such as an accelerated progression of atherosclerosis. Patients with active RA frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Tumor necrosis factor-alpha (TNF-alpha), a pivotal proinflammatory cytokine implicated in the pathogenesis of atherosclerosis in RA, may be involved in the development of the altered lipid profile observed in active RA. Our aim was to investigate the effects of anti-TNF-alpha treatment in combination with methotrexate (MTX) and corticosteroid therapy on lipid profile in patients with active RA. In this prospective study 34 consecutive RA patients were included (all women, mean age 51.6 +/- 7.9 years, range 46-72 years) with active (defined as Disease Activity Index 28 joint score [DAS-28], of at least 3.2) and refractory RA, in stable treatment with MTX (7.5-10 mg/week) and prednisone (7.5-10 mg/day) for 3 months. All patients received TNF-alpha blockers (n = 16, etanercept 25 mg twice weekly; n = 14, infliximab 3 mg/kg on 0, 2, 6, and every 8 weeks thereafter; and finally, n = 4, adalimumab 40 mg every other week). Total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), triglycerides (TG) and lipoprotein (a) [Lp(a)] levels and the atherogenic index (ratio cholesterol/HDL cholesterol) were measured at base line, and at 16 and 24 weeks. Results were as follows: The DAS-28 was 6.9 +/- 2.1 at base line and decreased to 4.6 +/- 1.8 after 16 weeks, and further to 4.1 +/- 1.3 after 24 weeks (both, P < 0.01). Following anti-TNF-alpha treatment, the mean levels of total cholesterol were 168 +/- 24 mg/dL at base line and increased to 188 +/- 28 mg/dL at 16 weeks (P < 0.01), and 197 +/- 26 mg/dL at 24 weeks (P < 0.001). However, also the mean levels of HDL cholesterol were significantly higher than basal values after 16 and 24 weeks of treatment (34 +/- 12 mg/dL versus 36 +/- 18 mg/dL [P < 0.05] and 38 +/- 14 mg/dL [P < 0.01], respectively). TG and Lp(a) levels, as well as the atherogenic index were not significantly changed. Interestingly, variations in disease activity were significantly and inversely correlated with HDL cholesterol levels. IN CONCLUSION: Short anti-TNF-alpha treatment was associated with a significant increase of both total cholesterol and HDL cholesterol levels, and correlated with decreased disease activity. The atherogenic index showed no changes during the study. Therefore, anti-TNF-alpha treatment might affect lipid profile in RA patients.
18509240 Application of fluorescence polarization immunoassay for determination of methotrexate-pol 2008 May Rheumatoid arthritis (RA) is a chronic disease characterized by the painful joints, inflammation, uncontrolled proliferation of synovial tissue and multisystem comorbidities. Weekly low-dose methotrexate (MTX) has been established as effective treatment in RA patients. MTX is converted to gamma-glutamyl polyglutamates, an active form of MTX, through the action of folylpolyglutamate synthetase in the cells. MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) may be useful as a therapeutic marker of RA. However, the previously reported methods for the quantification of MTX and MTX-PGs in RBCs are impractical for clinical use due to time-consuming, laborious and high cost. We attempted to apply a method with the commercially available fluorescence polarization immunoassay (FPIA) kit. We found that anti-MTX monoclonal antibody showed the reactivity to 4-amino-10-methylpteroylheptaglutamic acid (MTX-PG(7)) as equal to MTX. Good agreement was observed in the concentration-response curves between MTX and MTX-PG(7) spiked samples. Accordingly, the anti-MTX monoclonal antibody for FPIA appeared to show the equal reactivity to MTX and MTX-PGs. The recoveries of MTX and MTX-PG(7) from RBCs were 99.0% and 94.1%, respectively. Furthermore, we determined total MTX-PGs concentrations in RBCs of 71 patients with RA treated with weekly pulse MTX. Total MTX-PGs concentrations in 70% of the patients were found to be more than 50 nM that is the lower limit of MTX-PGs concentration in RBCs for expected therapeutic outcome. The routine measurement of total MTX-PGs concentration in RBCs might be useful for prediction about therapeutic outcome of MTX in RA patients.
17313014 [Professor ZHANG Ji's clinical experience]. 2006 Dec Professor ZHANG Ji has unique experience on therapeutic methods for rheumatoid arthritis, ankylosing spondylitis and obstinate facial palsy. (1) In acupuncture and moxibustion, he adopts the Governor Vessel and etiological analysis and differentiation, local acupuncture three step acupoint selection for treatment of rheumatoid arthritis; and supplementing the liver and kidney and strengthening the Governor Vessel and tonifying yang for ankylosing spondylitis; and dispelling wind and removing dampness, and dredging channels and activating the collaterals for obstinate facial palsy. (2) In Chinese drugs, on the basis of 50 year's clinical practice, he summarizes recipes Guanjie No. I and No. II. Modified Guanjie No. I is mainly used for treatment of rheumatoid arthritis, and modified Guanjie No. II mainly for ankylosing spondylitis, and Qianzheng Powder combined with drugs for clearing away heat and toxic substances are used for treatment of obstinate facial palsy.
17929140 Pancytopenia, including macrocytic anemia, associated with leflunomide in a rheumatoid art 2007 A female rheumatoid arthritis patient was admitted for productive cough and general fatigue that had gradually developed after leflunomide therapy. Side effects including severe hypoxia, thrombocytopenia, lymphocytopenia, and macrocytic anemia with schistocytes (probably drug-induced megaloblastic anemia) were noted. Leflunomide-eliminating cholestyramine therapy successfully treated all conditions excluding severe hypoxia, which occurred owing to deteriorating interstitial pneumonia and complicated bacterial pneumonia following antibiotic treatment. This is a rare case of leflunomide-associated multiple hematopoietic impairments.
17426837 Blood serum DNA in patients with rheumatoid arthritis is considerably enriched with fragme 2006 Sep We previously hypothesized that the sequence of transcribed region of human ribosomal repeats is selectively accumulated in circulating extracellular DNA due to its increased resistance to double-strand breaks caused by accumulation of single-chain breaks produced by nucleases. The contents of rDNA in blood serum DNA and in DNA from leukocytic nuclei both in healthy donors and in patients with rheumatoid arthritis were compared using dot hybridization method. By the content of non-methylated CpG-repeats, transcribed region of rDNA is identical to bacterial DNA, which is characterized by potent immunostimulatory effect. The transcribed region of rDNA (13.3 kb) contains more than 200 CpG-motifs capable of interacting with TLR9 receptors, which are the mediators of the cell immune response to the action of CpG-rich DNA fragments. The data suggest that DNA from dead cells circulating in the peripheral blood is enriched with sequences possessing potent immunostimulatory properties.
18194658 HPLC-based analysis of serum N-glycans on a 96-well plate platform with dedicated database 2008 May 1 We present a robust, fully automatable technology platform that includes computer software for the detailed analysis of low femtomoles of N-linked sugars released from glycoproteins. Features include (i) sample immobilization in 96-well plates, glycan release, and fluorescent labeling; (ii) quantitative HPLC analysis, including monosaccharide sequence, linkage, and arm-specific information for charged and neutral glycans; (iii) automatic structural assignment of peaks from HPLC profiles via web-based software that accesses our database (GlycoBase) of more than 350 N-glycan structures, including 117 present in the human serum glycome; and (iv) software (autoGU) that progressively analyzes data from exoglycosidase digestions to produce a refined list of final structures. The N-glycans from a plate of 96 samples can be released and purified in 2 or 3 days and profiled in 2 days. This strategy can be used for (i) identification and screening of disease biomarkers and (ii) monitoring the production of therapeutic glycoproteins, allowing optimization of production conditions. This technology is also suitable for preparing released glycans for other analytical techniques. Here we demonstrate its application to rheumatoid arthritis using 5 microl of patient serum.