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ID PMID Title PublicationDate abstract
18162680 Neurological recovery after occipitocervical fixation. 2007 Dec PURPOSE: To report on 14 consecutive cases of occipitocervical fixation. METHODS: Records of 8 men and 6 women aged 40 to 81 (mean, 57) years who underwent occipitocervical fixation and were followed up for a minimum of 2 years were retrospectively reviewed. Neurological grading was assessed before and after surgery using the Ranawat grade. Intra-operative somatosensory evoked potentials were monitored. RESULTS: The main indications for surgery were rheumatoid arthritis (n=6) and cervical metastasis (n=4). 77% of the patients demonstrated neurological improvement. Four out of the 5 non-ambulatory patients (Ranawat grade IIIB) regained ambulatory status postoperatively. No patient had neurological deterioration or evidence of vertebral artery or spinal cord injury. One endured a superficial wound infection and 2 had implant breakage. CONCLUSION: Although occipitocervical fixation is technically challenging and there are risks of serious neurologic or vascular complications, it remains a viable option with favourable results in patients requiring stabilisation of the craniocervical junction.
17434910 Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis. 2007 Apr Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Better understanding of its pathophysiology has led to the development of targeted therapies that have dramatically improved outcomes. The key to therapeutic success lies in identifying individuals who will have severe destructive disease as early as possible, so that effective treatment can be initiated before irreversible damage occurs. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. We discuss anti-CCP antibody testing in rheumatoid arthritis, with an emphasis on diagnostic performance, prognostic capability, and relevance to pathogenesis and new treatment paradigms in rheumatoid arthritis.
17017948 Role of nitric oxide and reactive oxygen species in arthritis. 2006 A vast amount of circumstantial evidence implicates oxygen-derived free radicals, especially reactive oxygen species and nitric oxide as mediators of inflammation and/or tissue destruction in inflammatory and arthritic disorders. The aim of the current article is to overview the recent developments in this field, as it relates to the roles of nitric oxide (NO) and reactive oxygen species in the pathogenesis of this condition. The first part of the review focuses on the biochemical impact of NO and reactive oxygen species. The second part of the review deals with the novel findings related to the recently identified regulatory roles of the inducible isoform of nitric oxide synthase (iNOS) in the expression of pro-inflammatory mediators in inflammation. Reactive oxygen species can initiate a wide range of toxic oxidative reactions. These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3phosphate dehydrogenase, inhibition of membrane sodium/potassium ATP-ase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of inflammation. Reactive oxygen species are all potential reactants capable of initiating DNA single strand breakage, with subsequent activation of the nuclear enzyme poly (ADP ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. Recently it has been demonstrated that iNOS inhibitor prevents the activation of poly (ADP ribose) synthetase, and prevents the organ injury associated with inflammation. Although the severity and duration of inflammation may dictate the timing and extent of NOS expression, it is now evident that the up-regulation of NOS can take place during sustained inflammation. Thus, induced nitric oxide, in addition to being a "final common mediator" of inflammation, is essential for the up-regulation of the inflammatory response. Furthermore, a picture of a pathway is evolving that contributes to tissue damage both directly via the formation of reactive oxygen species, with them associated toxicities, and indirectly through the amplification of the inflammatory response.
17573817 Effect of treatment with biological agents for arthritis in Australia: the Australian Rheu 2007 Sep BACKGROUND: The Australian Rheumatology Association Database (ARAD), a voluntary national registry, has been established to collect health information from Australian patients with inflammatory arthritis for the purpose of monitoring the benefits and safety of new treatments, in particular the biological disease-modifying anti-rheumatic drugs (bDMARDs). These drugs are proving to be very effective, yet little is known of their long-term effectiveness or safety. Patient registries that systematically gather data on large cohorts of unselected patients are increasingly believed to be an essential means of answering questions of the long-term effectiveness and safety of new drugs. The aim of this report is to describe the role, development and structure of ARAD and provide some preliminary data. METHODS: As of 1 August 2006, 563 patients with rheumatoid arthritis prescribed a bDMARD have been enrolled in ARAD, involving 105 rheumatologists from across Australia. RESULTS: The data collected will enable examination of multiple domains of patient responses to bDMARDs, including quality of life, health-care utilization, incidence of adverse events and the effects of therapy switching. CONCLUSION: Evidence-based information about the long-term outcome of bDMARD therapy is essential for clinicians, consumers, policy-makers, drug development companies and approval agencies, to enable better care and improved outcomes for patients with inflammatory arthritis.
18176218 Could preoperative preferences and expectations influence surgical decision making? Rheuma 2008 Jan BACKGROUND: The goals of this assessment were to elicit rheumatoid arthritis patients' expectations of metacarpophalangeal joint arthroplasty and to explore how preoperative preferences might influence patients' surgical decision making. METHODS: Rheumatoid arthritis patients who were appropriate metacarpophalangeal joint arthroplasty candidates were assessed by surgeons at three centers. Patients answered a questionnaire on expectations for metacarpophalangeal joint arthroplasty before deciding on whether to actually undergo the procedure. RESULTS: Of 56 eligible patients, 41 percent decided to have surgery, 48 percent decided against it, and 11 percent were undecided. Among the 48 patients without previous metacarpophalangeal joint arthroplasty, improving hand appearance and hand function were most often cited by patients as "very important." The nonsurgical group was more likely to be most bothered by hand weakness (32 percent versus 0 percent, p = 0.03), whereas the surgical group was more likely to be bothered by poor function (62 percent versus 23 percent, p = 0.01). The nonsurgical patients were more likely to value their own opinion as most important in the surgical decision-making process (59 percent versus 29 percent, p = 0.04). Both groups overestimated the risk of serious complications, but the surgical group was less likely to believe postoperative rehabilitation would be difficult (odds ratio, 0.2; 95% CI, 0.1 to 0.9). CONCLUSIONS: Patients who are eligible for metacarpophalangeal arthroplasty but decline surgery appear to have different baseline expectations and preferences than those who choose surgery. Patients who refuse surgery may use information differently in their decision-making process. Understanding and addressing patients' expectations and preferences preoperatively could help identify those patients who would most likely benefit from surgery.
17827184 The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis. 2008 Jul Chronic inflammatory processes are based on a sustained and tightly regulated communication network among different cells types. This network comprises extracellular mediators such as cytokines, chemokines and matrix-degrading proteases, which orchestrate the participation of cells in the chronic inflammatory process. The mirrors of this outside communication world are intracellular transcription factor pathways, which shuttle information about inflammatory stimuli to the cell nucleus. This review examines the function of one key signal transduction pathway of inflammation--the p38 mitogen-activated protein kinases (p38MAPK). The signalling pathway is considered as crucial for the induction and maintenance of chronic inflammation, and its components thus emerge as interesting molecular targets of small molecule inhibitors for controlling inflammation. This review not only summarises the current knowledge of activation, regulation and function of the p38MAPK pathway but also examines the role of this pathway in clinical disease. It gives an overview of current evidence of p38MAPK activation in inflammatory arthritis and elaborates the key molecular determinants which contribute to p38MAPK activation in joint disease.
18633125 Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical cha 2009 Jun BACKGROUND: Recent evidence suggests that distinction of subsets of rheumatoid arthritis (RA) depending on anti-cyclic citrullinated peptide antibody (anti-CCP) status may be helpful in distinguishing distinct aetiopathologies and in predicting the course of disease. HLA-DRB1 shared epitope (SE) and peptidylarginine deiminase type 4 (PADI4) genotype, both of which have been implicated in anti-CCP generation, are assumed to be associated with RA. OBJECTIVES: To elucidate whether PADI4 affects the clinical characteristics of RA, and whether it would modulate the effect of anti-CCPs on clinical course. The combined effect of SE and PADI4 on autoantibody profile was also analysed. METHODS: 373 patients with RA were studied. SE, padi4_94C>T, rheumatoid factor, anti-CCPs and antinuclear antibodies (ANAs) were determined. Disease severity was characterised by cumulative therapy intensity classified into ordinal categories (CTI-1 to CTI-3) and by Steinbrocker score. RESULTS: CTI was significantly associated with disease duration, erosive disease, disease activity score (DAS) 28 and anti-CCPs. The association of anti-CCPs with CTI was considerably influenced by padi4_94C>T genotype (C/C: OR(adj) = 0.93, p(adj) = 0.92; C/T: OR(adj) = 2.92, p(adj) = 0.093; T/T: OR(adj) = 15.3, p(adj) = 0.002). Carriage of padi4_94T exhibited a significant trend towards higher Steinbrocker scores in univariate and multivariate analyses. An association of padi4_94C>T with ANAs was observed, with noteworthy differences depending on SE status (SE-: OR(adj) = 6.20, p(adj)<0.04; SE+: OR(adj) = 0.36, p(adj) = 0.02) and significant heterogeneity between the two SE strata (p = 0.006). CONCLUSIONS: PADI4 genotype in combination with anti-CCPs and SE modulates clinical and serological characteristics of RA.
16146751 Matrix metalloproteinases: role in arthritis. 2006 Jan 1 The irreversible destruction of the cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis (RA) and osteoarthritis (OA). While cartilage is made up of proteoglycans and type II collagen, tendon and bone are composed primarily of type I collagen. RA is an autoimmune disease afflicting numerous joints throughout the body; in contrast, OA develops in a small number of joints, usually resulting from chronic overuse or injury. In both diseases, inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) stimulate the production of matrix metalloproteinases (MMPs), enzymes that can degrade all components of the extracellular matrix. The collagenases, MMP-1 and MMP-13, have predominant roles in RA and OA because they are rate limiting in the process of collagen degradation. MMP-1 is produced primarily by the synovial cells that line the joints, and MMP-13 is a product of the chondrocytes that reside in the cartilage. In addition to collagen, MMP-13 also degrades the proteoglycan molecule, aggrecan, giving it a dual role in matrix destruction. Expression of other MMPs such as MMP-2, MMP-3 and MMP-9, is also elevated in arthritis and these enzymes degrade non-collagen matrix components of the joints. Significant effort has been expended in attempts to design effective inhibitors of MMP activity and/or synthesis with the goal of curbing connective tissues destruction within the joints. To date, however, no effective clinical inhibitors exist. Increasing our knowledge of the crystal structures of these enzymes and of the signal transduction pathways and molecular mechanisms that control MMP gene expression may provide new opportunities for the development of therapeutics to prevent the joint destruction seen in arthritis.
17312152 17beta-estradiol induces IL-1alpha gene expression in rheumatoid fibroblast-like synovial 2007 Mar 1 Rheumatoid arthritis (RA) occurs four times more frequently in women than in men, although the mechanistic basis of the gender difference is unknown. RA is characterized by the overproliferation of synoviocytes producing proinflammatory cytokines such as IL-1, implicated in the pathogenesis of the disease. In this study we examined whether 17beta-estradiol (E2) induced IL-1alpha mRNA expression in the rheumatoid fibroblast-like cell line MH7A, as well as in primary synovial cells from RA patients, and investigated the underlying molecular mechanisms. E2 induced IL-1alpha mRNA expression in both cell types in an estrogen receptor-dependent manner. In MH7A cells ERalpha but not ERbeta mediated the effects of E2. Deletion and mutation analysis revealed that a GC-rich region within the IL-1alpha gene promoter was responsible for the response to E2. EMSAs showed that Sp1 and Sp3 bound to the GC-rich region and that the transcriptional activity of Sp1 was up-regulated by the treatment with E2. Sp1 and ERalpha interacted physically regardless of the presence of E2. Physical interaction was also observed between ERalpha and histone deacetylase 2 (HDAC2), and E2 induced the dissociation of HDAC2 from ERalpha. These results suggest that E2 induces the dissociation of corepressor HDAC2 from ERalpha, which leads to the augmentation of Sp1 transcriptional activity through the GC-rich region within the IL-1alpha gene promoter.
16646297 [Hydrogen sulphide water balneum effect on erythrocyte catalase activity in patients with 2006 The aim of the study was to investigate, in vitro, hydrogen sulphide water (HSW) balneum effect on erythrocyte catalase activity in patients with rheumatoid arthritis. Erythrocytes from twenty nine consecutive patients with rheumatoid arthritis (11 men, 18 women) aged 54 years were obtained. The control group comprised of 30 healthy subjects with a mean age of about 40 years. Patients with rheumatoid arthritis were subdivided into two groups twice: with active disease (18 patients) and in remission (11 patients), and secondly into patients receiving (21 subjects) and not receiving (8 subjects) non-steroidal anti-inflammatory drugs. For erythrocyte catalase activity evaluation, method of Beers and Sizer was used. Catalase activity was assessed after 5, 10, 15, and 20 minutes erythrocytes incubation with HSW. The mean baseline erythrocyte catalase activity (to) was in rheumatoid arthritis patients of about 7.79 +/- 1.39 U/gHb and was significantly higher than in the control group: 6.96 +/- 2.68 U/gHb (p < 0.05). After 5 minutes incubation with HSW (t5) erythrocyte catalase activity increased, in rheumatoid arthritis patients to 8.21 +/- 1.77 U/gHb, after 10 minutes (t10) was 8.14 +/- 2.25 U/gHb, in control group: 7.58 +/- 2.50 U/gHb and 7.68 +/- 3.22 U/gHb, respectively. However the difference was not statistically significant. After 20 minutes of incubation (t20) erythrocyte catalase activity was the highest in the patients with active rheumatoid arthritis (8.33 +/- 1.96 U/gHb) and differed significantly from the patients in remission (6.69 +/- 1.27 U/gHb) and from patients not receiving non-steroidal anti-inflammatory drugs (6.04 +/- 1.08 U/gHb). In rheumatoid arthritis patients erythrocyte catalase activity was higher when compared with control group and increased during incubation with HSW. It seems HSW balneum produce an antioxidant effect on erythrocyte status in patients with rheumatoid arthritis.
17982222 Diagnosis and treatment of latent tuberculosis infection in arthritis patients treated wit 2007 Oct Tumor necrosis factor (TNF) is essential for host defense against Mycobacterium tuberculosis, and the risk of reactivation of latent tuberculosis infection (LTBI) increases with anti-TNF therapy. This study estimated the prevalence of LTBI and evaluated the safety and completion rate of short-course therapy with isoniazid plus rifampin for 3 months to treat LTBI in a cohort of Korean arthritis patients before initiating anti-TNF therapy. We retrospectively studied the files of 112 consecutive patients to evaluate LTBI before starting anti-TNF drugs. Screening tests were performed, including a tuberculin skin test and chest radiography. LTBI treatment was indicated in 41 patients (37%). Of these, three patients refused the LTBI treatment. Of the 38 patients who underwent LTBI treatment, 36 (95%) took isoniazid plus rifampin for 3 months. Six patients (16%) showed transient elevations of liver enzymes during the LTBI treatment. Overall, 35 patients (92%) completed the LTBI treatment as planned. In conclusion, LTBI was diagnosed in one-third of Korean arthritis patients before initiating anti-TNF therapy. A high percentage of these patients completed 3 months of LTBI treatment with isoniazid plus rifampin without serious complications.
16899106 Interleukin-6: discovery of a pleiotropic cytokine. 2006 In the late 1960s, the essential role played by T cells in antibody production was reported. This led to our hypothesis that certain molecules would have to be released from T cells to effect the stimulation of B cells. This hypothesis was shown to be true. There were certain factors present in the culture supernatant of T cells that induced proliferation and differentiation of B cells. The factor that induced B cells to produce immunoglobulins was initially named B cell stimulatory factor-2. The cDNA encoding the human B cell stimulatory factor-2 was cloned in 1986. At the same time, IFN-beta2 and a 26 kDa protein in the fibroblasts were independently cloned and found to be identical to B cell stimulatory factor-2. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte stimulating factor were also proven to be the same molecule as B cell stimulatory factor-2. Various names were used for this single molecule because of its multiple biological activities, but these have all been unified and the molecule is now known as IL-6. Since the discovery of IL-6, rapid progress has been made in our understanding of IL-6 activities, the IL-6 receptor system and the IL-6 signal transduction mechanism. More importantly, it has been shown to be involved in a number of diseases such as rheumatoid arthritis and Castleman's disease. When taking into account all the accumulated basic research on the various aspects of this molecule, it appeared that blocking the activity of IL-6 was a feasible, new therapeutic approach for chronic inflammatory diseases.
16534537 [Dose adjustment in patients treated with infliximab in routine rheumatologic care in Germ 2006 Sep OBJECTIVE: Data from international observational studies show that a considerable proportion of patients use higher dosages of infliximab (INF) than the usual 3 mg every 8 weeks used in Germany for treatment of rheumatoid arthritis. The Data are, however, inconsistent and vary between countries. Using data from the German Biologics Register RABBIT we investigated: (1) how dosage of INF develops during the first year of treatment in routine care, and (2) how dosage translates into clinical effectiveness. PATIENTS: We analysed data from 344 patients who started a treatment with INF at their inclusion into the register and who were observed for the subsequent 12 months. Mean dosage at 3 months (after the loading dose) was 3.2 mg/kg body weight/infusion and 3.3 mg/kg after 1 year. If we also consider shortening the infusion intervals, the mean dosages at the start and after 1 year were 4.0 mg/kg body weight every 8 weeks. RESULTS: Patients who were treated with low dosages of up to 3 mg/kg/8 weeks showed significantly less improvement (EULAR response) than those who were treated with higher dosages. CONCLUSIONS: The data show that German rheumatologists are aware of the high costs of treatment and try to use the lowest possible dosage. However, for a certain proportion of the patients this might be insufficient.
18045808 Recent insights in the pharmacological actions of methotrexate in the treatment of rheumat 2008 Mar This review presents recent data supporting the methotrexate (MTX) mechanisms of action, which are likely to account for its anti-proliferative and immunosuppressive effects in rheumatoid arthritis (RA). The effects of MTX in vivo may be mediated by reducing cell proliferation, increasing the rate of apoptosis of T cells, increasing endogenous adenosine release, altering the expression of cellular adhesion molecules, influencing production of cytokines, humoral responses and bone formation. Several reports indicate that the effects of MTX are influenced by genetic variants, specific dynamic processes and micro-environmental elements such as nucleotide deprivation or glutathione levels. The challenge for the future will be linking biological and genetic markers relevant to the response to MTX in RA.
18594458 Atlantoaxial transarticular screw fixation with posterior wiring using polyethylene cable: 2008 Jul 1 STUDY DESIGN: A comparative retrospective study on the posterior graft union and the facet fusion in atlantoaxial transarticular screw fixation. OBJECTIVE: To evaluate the posterior graft union and the facet fusion in atlantoaxial transarticular screw fixation when a polyethylene (PE) cable was used in rheumatoid and nonrheumatoid patients. SUMMARY OF BACKGROUND DATA: In atlantoaxial transarticular screw fixation, metal wires or cables for posterior bone graft fixation can cause intraoperative or delayed spinal cord compression. PE cables do not have the risk, but there has been no comparative report. Also, a precise evaluation on the posterior graft union and the facet fusion has not been reported. METHODS: Thirty-eight patients who submitted to atlantoaxial transarticular screw fixation and posterior bone graft without any concomitant operation were followed up for more than 2 years. The posterior graft union and the facet fusion were evaluated by functional radiographs and computed tomography scans. RESULTS: Seven patients showed the posterior graft nonunion. All of them were rheumatoid patients and received PE cable wiring for posterior internal fixation. However, 5 of the 7 cases presented stable C1-C2 with the facet fusion demonstrated by functional radiographs and computed tomography scans, achieving an overall fusion rate of 95%. CONCLUSION: In atlantoaxial transarticular screw fixation, the use of PE cable and rheumatoid background are 2 of the unfavorable factors for the posterior graft union. However, atlantoaxial transarticular screws can bring the facet fusion despite the posterior graft failure in such cases.
18174675 A case of rheumatoid arthritis with acute lymphoblastic leukemia. 2007 Dec A 69-year-old male was diagnosed with rheumatoid arthritis(RA) in 1994. Good control of the RA activity had been obtained with sodium aurothiomalate (GST). However, polyarthritis reappeared in January 2003. He was examined at the Division of Rheumatology, Department of Internal Medicine, Saitama Social Insurance Hospital in August 2003. The treatment was switched from GST to salazosulfapyridine (SASP), with improvement of the polyarthritis. Subsequently, in March 2005, the patient developed fever, pancytopenia and liver dysfunction, and was admitted to Saitama Social Insurance Hospital. Since these abnormalities were suspected to be caused by SASP, this drug was stopped and prednisolone (PSL) was started at 10 mg/day. However, since the fever, pancytopenia and liver dysfunction persisted, bone marrow examination was performed and the patient was diagnosed with acute lymphoblastic leukemia (pre B cell type, L2). He was transferred to the Division of Hematology, Omiya Medical Center, Jichi Medical University, on 8(th) April, 2005 for induction chemotherapy. Although the induction therapy needed to be stopped because the patient developed dysphagia and biliary system dysfunction, complete remission (CR) was confirmed. It was difficult to restart chemotherapy in the patient because his general condition remained poor, with repeated episodes of aspiration pneumonia and newly detected stomach cancer. He was, therefore, transferred back to Saitama Social Insurance Hospital on 28(th) September, 2005. The ALL remained in CR and the RA activity had disappeared without therapy, but the patient died of pneumonia on 1(st) August, 2006.
18413439 Acute cold stress in rheumatoid arthritis inadequately activates stress responses and indu 2009 Apr OBJECTIVE: Acute stress in patients with rheumatoid arthritis (RA) should stimulate a strong stress response. After cryotherapy, we expected to observe an increase of hormones of the adrenal gland and the sympathetic nervous system. METHODS: A total of 55 patients with RA were recruited for whole-body cryotherapy at -110 degrees C and -60 degrees C, and local cold therapy between -20 degrees C and -30 degrees C for 7 days. We measured plasma levels of steroid hormones, neuropeptide Y (sympathetic marker), and interleukin (IL)6 daily before and after cryotherapy. RESULTS: In both therapy groups with/without glucocorticoids (GC), hormone and IL6 levels at baseline and 5 h after cold stress did not change over 7 days of cryotherapy. In patients without GC, plasma levels of cortisol and androstenedione were highest after -110 degrees C cold stress followed by -60 degrees C or local cold stress. The opposite was found in patients under GC therapy, in whom, unexpectedly, -110 degrees C cold stress elicited the smallest responses. In patients without GC, adrenal cortisol production increased relative to other adrenal steroids, and again the opposite was seen under GC therapy with a loss of cortisol and an increase of dehydroepiandrosterone. Importantly, there was no sympathetic stress response in both groups. Patients without GC and -110 degrees C cold stress demonstrated higher plasma IL6 compared to the other treatment groups (not observed under GC), but they showed the best clinical response. CONCLUSIONS: We detected an inadequate stress response in patients with GC. It is further shown that the sympathetic stress response was inadequate in patients with/without GC. Paradoxically, plasma levels of IL6 increased under strong cold stress in patients without GC. These findings confirm dysfunctional stress axes in RA.
17561943 Influence of rheumatoid arthritis on work participation in Australia. 2008 Mar BACKGROUND: The aim of the study was to determine the prevalence of work disability in a cohort of Australians with rheumatoid arthritis. METHODS: A cross-sectional study of a sample of 497 individuals aged 18-65 years with rheumatoid arthritis in Adelaide, South Australia, was carried out. RESULTS: Of those employed, 130 (51%) were in full-time employment (> or= 35 h per week) work and 124 (49%) were in part-time employment (average 20 h per week). Overall, the observed/expected numbers working were 254/316 (relative risk 0.8 (0.69-0.91)). Using a comparator adjusted by removing those on the disability support pension, the relative risk of the working was 0.74. The observed/expected numbers working part time in the study group were 124/89 (relative risk 1.4 (1.25-1.65)). Those who continued to work had lower Health Assessment Questionnaire scores, less morning stiffness, superior scores for patient assessed level of function, lower pain scores, lower joint counts, a lower C-reactive protein, better measures of 'patient global assessment' and higher levels of education compared with the group who had ceased work. Overall, of those working at the time of diagnosis, 20% had ceased work within 5 years and approximately 40% had ceased work by 20 years. Of those who ceased work, the mean duration from time of diagnosis to work cessation was 7 years with half the subjects who ceased work doing so within 4 years of diagnosis. CONCLUSION: Work disability associated with rheumatoid arthritis in Australia is very significant and costly. Work disability occurs relatively early in the disease and is associated with several identifiable variables, many of which may be amenable to intervention strategies.
18649124 Synthesis and evaluation of a well-defined HPMA copolymer-dexamethasone conjugate for effe 2008 Dec PURPOSE: To develop a pH-sensitive dexamethasone (Dex)-containing N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugate with well-defined structure for the improved treatment of rheumatoid arthritis (RA). METHODS: A new pH-sensitive Dex-containing monomer (MA-Gly-Gly-NHN=Dex) was synthesized and copolymerized with HPMA using reversible addition-fragmentation transfer (RAFT) polymerization. The structure of the resulting HPMA copolymer-Dex conjugate (P-Dex) was analyzed and its therapeutic efficacy was evaluated on adjuvant-induced arthritis (AIA) rats. RESULTS: P-Dex was synthesized with controllable molecular weight and polydispersity index (PDI). The Dex content can be controlled by the feed-in ratio of MA-Gly-Gly-NHN=Dex. The P-Dex used for in vitro and in vivo evaluation has a average molecular weight (M (w)) of 34 kDa and a PDI of 1.34. The in vitro drug-release studies showed that the Dex release from the conjugate was triggered by low pH. Clinical measurements, endpoint bone mineral density (BMD) test and histology grading from the in vivo evaluation all suggest that newly synthesized P-Dex has strong and long-lasting anti-inflammatory and joint protection effects. CONCLUSIONS: A HPMA copolymer-dexamethasone conjugate with a well-defined structure has been synthesized and proved to be an effective anti-arthritis therapy. It may have a unique clinical application in the treatment of rheumatoid arthritis.
17544860 Exploring acupuncturists' perceptions of treating patients with rheumatoid arthritis. 2007 Jun AIMS: To outline acupuncturists' perceptions of treating patients with rheumatoid arthritis (RA), exploring the impact of practitioner affiliation to a traditional or western theoretical base. METHODS: Qualitative study utilising Grounded Theory Method. Nineteen acupuncturists were chosen via theoretical sampling. In-depth semi-structured interviews were tape-recorded and transcribed. Field notes were also taken. Emerging categories and themes were identified. RESULTS: Inter-affiliatory differences were identified in the treatments administered and the scope and emphasis of intended therapeutic effects. Limited divergence was found between acupuncturists' perceptions of treatment outcomes. Factors perceived as impacting on treatment outcomes were identified. CONCLUSIONS: Clinical trials of acupuncture in RA may have failed to administer a treatment which reflects that administered in clinical practice. Outcome measures employed in clinical trials of acupuncture in RA, as well as established outcome indices for RA, may lack the necessary breadth to accurately assess acupuncture's efficacy. Acupuncturist affiliation has demonstrable implications for the practice and research of acupuncture.