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ID PMID Title PublicationDate abstract
18837751 Use of the rotational path removable partial denture concept in a Kennedy Class II patient 2008 This case report describes the treatment of a patient with Sjogren's syndrome who was missing all of the posterior teeth in the maxillary left arch. Implants were contraindicated for this patient because of a chronic sinus infection. Various removable prosthodontic options were considered, and the patient was ultimately treated very conservatively with a rotational path removable partial denture (RPD). This approach required no tooth preparation other than bonding a resin composite cingulum rest on the maxillary left canine. The use of the rotational path RPD eliminated any unsightly clasp assembly display and provided a satisfactory esthetic result. CLINICAL SIGNIFICANCE: The rotational path removable partial denture is an underutilized option for the esthetic replacement of missing teeth. It should be considered as an option in both tooth-borne and Kennedy Class II situations.
18051790 [Sjögren's syndrome with multiple bullae due to pulmonary nodular amyloidosis]. 2007 Nov We reported a case of Sjögren's syndrome with pulmonary involvement diagnosed by video-assisted thoracoscopic lung biopsy. The patient was a 54-year-old woman with antiphospholipid syndrome. Her chest radiograph and CT scan showed multiple nodules with or within cystic lesions. The thoracoscopic lung biopsy specimens revealed nodular amyloid deposits associated with bronchiolitis. The mechanism of bulla formation appeared to be a check-valve mechanism caused by the narrowing of the airway due to bronchiolitis with mononuclear cell infiltration. She has no symptoms without respiratory failure or functional impairment, therefore we are following her closely without therapy.
18260312 [A case of primary Sjögren's syndrome presenting with middle lobe syndrome complicated by 2008 Jan A 52-year-old woman was found to have abnormal shadows in her chest radiograph in a health examination. At the age of 47 middle lobe syndrome had been pointed out and Mycobacterium intracellulare had been cultured from her sputum. Chest computed tomography scans showed a coin lesion and bronchiectasis in the middle lobe. On the other hand she suffered xerostomia and had a high level of serum anti-SS-A antibody. Further examination of her eyes and mouth gave her a diagnosis of primary Sjögren's syndrome (pSS). By video-assisted thoracoscopic surgery we resected the coin lesion which contained an abscess with acid-fast bacilli, identical to Mycobacterium intracellulare. The histopathology showed lymphocytic infiltration, caseous necrosis with Langhans' giant cells, and epithelioid granulomas. We finally made a diagnosis of pSS presenting with middle lobe syndrome (MLS) complicated by nontuberculous mycobacterial disease (NTM). We discuss the mechanism by which pSS could be complicated by NTM and MLS. Clinicians should pay attention to this possible relationship, especially among middle-aged and elderly women.
17963047 Horizons in Sjögren's syndrome genetics. 2007 Jun Sjögren's syndrome (SS) is a complex polygenic autoimmune disorder. A few major genetic effects have been identified. Historically, HLA and non-HLA genetic associations have been reported. Recently, the HLA region continued to reveal association findings. A new susceptibility region has been suggested by a study of a D6S349 microsatellite marker. Among non-HLA studies, recent association of immunoglobulin kappa chain allotype KM1 with anti-La autoantibodies in primary Sjögren's syndrome confirms findings in a study from two decades ago. Meanwhile, mouse models have been employed to study the genetic contribution to salivary lymphadenitis or dry eyes and mouth. Gene transfer exploration in mouse models shows promise. The authors review the HLA and non-HLA association studies and the mouse model work that has been reported. Newly developed genomic capacity will provide, in the future, a much closer approximation of the true picture of the genetic architecture of Sjögren's syndrome.
17696265 Temporomandibular joint arthritis in juvenile idiopathic arthritis: prevalence, clinical a 2007 Sep OBJECTIVE: To perform a prospective, comprehensive, clinical, and radiological evaluation of temporomandibular joint (TMJ) involvement and its influence on craniofacial growth, in a cohort of patients with juvenile idiopathic arthritis (JIA), representing all JIA subtypes. METHODS: Clinical rheumatologic and orthodontic evaluations were performed in 100 patients with JIA [12 systemic arthritis, 24 rheumatoid factor (RF)-negative polyarthritis, 1 RF-positive polyarthritis, 39 oligoarthritis, 22 enthesitis-related arthritis, 2 psoriatic arthritis]. An orthopantomogram and lateral cephalogram were performed in 46 patients. The prevalence of TMJ arthritis was studied in relation to JIA subtype and disease characteristics; cephalometric measurements were compared to those from age- and sex-matched healthy controls. RESULTS: Whereas 55% of patients with JIA had at least one symptom/sign of TMJ arthritis, 78% of the radiographed group exhibited condylar lesions. The presence of condylar damage was not related to clinical orthodontic findings or to JIA subtype, disease activity, severity, or duration. Patients with JIA exhibited larger mandibular plane and A-nasion-B angles, larger total anterior facial height, smaller interincisal and sella-nasion-B angles, and shorter mandibular ramus lengths than their age- and sex-matched controls. Craniofacial alterations were clearly related to the presence of condylar damage, even when present at a minimal degree. CONCLUSION: Our data show that TMJ condylar damage occurs very frequently in JIA, and irrespective of JIA subtype; condylar lesions can present early, progress insidiously, and -- even at a minimal degree -- can severely alter the craniofacial profile. We propose that the followup of patients with JIA should include early and regular evaluation by an orthodontist, supplemented with radiographic TMJ imaging.
18847314 Belimumab, an anti-BLyS human monoclonal antibody for potential treatment of inflammatory 2008 Nov BACKGROUND: B lymphocyte stimulator (BLyS) is a factor determining the survival of B cells, and elevated levels in serum or locally have been observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Belimumab (LymphoStat-B), a human monoclonal antibody that inhibits BlyS, was developed for the treatment of these diseases. OBJECTIVE: To summarize preclinical development, efficacy and safety of belimumab in treatment of RA and SLE. METHODS: Articles found in a PubMed search and data presented in abstract form at international conferences up to August 2008 are described. RESULTS/CONCLUSIONS: Belimumab was well tolerated in treatment of RA over 24 weeks and SLE over 3 years. It significantly decreased rheumatoid factor (RF) levels, and modestly reduced symptoms of RA, especially in some subgroups such as patients with high disease activity, positive RF and no anti-TNF treatment experience. It also significantly reduced symptoms of SLE, and decreased anti-double-stranded DNA autoantibodies among patients with positive baseline anti-double-stranded DNA or antinuclear antibodies during a long-period treatment. These results suggest that careful patient selection is necessary to achieve optimal outcomes.
16700080 Changes in use of disease-modifying anti-rheumatic drugs in Australia over the period 1992 2006 Jul PURPOSE: Evidence is growing that early use of disease-modifying anti-rheumatic drugs (DMARDs) and combinations of these drugs provide optimal care for people with rheumatoid arthirits. The aim of this study was to describe objectively the pattern of consumption of DMARDs in the Australian community (community-based prescribing, specialist and general practitioner) 1992-2004, and to compare this with prescribing patterns reported in other countries. METHOD: Dispensing statistics from the Pharmaceutical Benefit Scheme (PBS-Australia's universal prescription subsidy scheme) were analysed and temporal trends evaluated. Drug consumption was calculated as the number of dispensed defined daily doses (DDD)/1000 inhabitants/day (WHO ATC/DDD classification 2005). RESULTS: The consumption of DMARDs in the Australian community increased steadily from 2.6 DDD/1000 inhabitants/day in 1992 to 5.5 DDD/1000 inhabitants/day. Over the period 1992-2004, methotrexate (MTX) was the most commonly used DMARD (from 0.6 to 3.0 DDD/1000 inhabitants/day). Consumption of gold (parenteral and oral) and penicillamine declined during this time. The inclusion of leflunomide on the PBS in 2000 contributed to the increase in DMARD usage. CONCLUSION: Use of DMARDs within the Australian community has increased in recent years, coinciding with the change in guidelines for therapy for rheumatoid arthritis (RA) to earlier use of DMARDs and the more common use of combinations. This study used DDD methodology to quantify trends for DMARD consumption and these trends are broadly consistent with international prescribing patterns assessed using different methodologies.
18676139 "Macromolecules to PDMS transfer" as a general route for PDMS biochips. 2009 Jan 1 "Macromolecules to PDMS transfer" technique relying on the direct entrapment of macromolecules spots during PDMS polymerisation is proposed as an alternative for the easy and simple PDMS surface modification. In the present work, the development of three different applications based on this procedure is presented as proof of the method potentialities. First, C-reactive protein (CRP) sandwich immunoassay using immobilised monoclonal anti-CRP antibodies was developed for sepsis diagnosis. The preserved integrity of the immobilised monoclonal immunoglobulin permitted the sensitive detection of free CRP in human sera (LOD=12.5 microg/L, detection ranging over two decades). Then, rheumatoid arthritis diagnosis through the rheumatoid factor (RF) detection based on rabbit immunoglobulins immobilisation allowed the detection of specific antibodies in human sera samples down to low RF levels (detection range 5.3-485 IU/mL). Finally, the "Macromolecules to PDMS transfer" procedure was used to easily and rapidly produce fibronectin-based cell culture arrays. The successful attachment of HeLa and BALB/3T3 cells was demonstrated with optical microscopy and specific staining of actin and vinculin.
18647853 Self-assessments of patients via Tablet PC in routine patient care: comparison with standa 2008 Dec OBJECTIVE: We evaluated the feasibility of electronic data capture of self-administered patient questionnaires using a Tablet PC for integration in routine patient management; we also compared these data with results received from corresponding paper-pencil versions. METHODS: Standardised patient questionnaires (FFbH/HAQ, BASDAI, SF-36) were implemented in our documentation software. 153 outpatients (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis) completed sets of questionnaires as paper-pencil and electronic versions using a Tablet PC. The quality and validity of data obtained using a Tablet PC and the capability of disabled patients to handle it were assigned; patients' experiences, preferences and computer/internet use were also assessed. RESULTS: Scores obtained by direct data entry on the Tablet PC did not differ from the scores obtained by the paper-pencil questionnaires in the complete group and disease subgroups. No major difficulties using the Tablet PC occurred. 62.1% preferred remote data entry in the future. Seven (4.6%) patients felt uncomfortable with the Tablet PC due to their rheumatic disease. CONCLUSIONS: Self-administered questionnaires via Tablet PC are a facile and capable option in patients with rheumatic diseases to monitor disease activity, efficacy and safety assessments continuously. Tablet PC applications offers directly available data for clinical decision-making improves quality of care by effective patient monitoring, and contributes to patients' empowerment.
18636673 Chronic hepatitis C infection in a patient with bone marrow hypoplasia. 2008 Jul 14 Chronic hepatitis C virus (HCV) infection is associated with multifarious extra-hepatic manifestations; the most described and discussed being mixed cryoglobulinemia which is strongly related to B-cell lymphoproliferative disorders (LPDs). We present a case of chronic HCV infection and mixed cryoglobulinemia, with minimal liver involvement. The case is a 53-year-old patient who was diagnosed as having bone marrow hypoplasia at the age of three. She received several blood transfusions to normalize her haemoglobin. At the age of 31, she was diagnosed with rheumatoid arthritis on account of her diffuse joint pain and inflammation, elevated rheumatoid factor (RF) and Raynaud's phenomenon. Twenty years later, monoclonal gammopathy of IgG Lambda (one year later, changed to IgM Kappa) was detected during a routine examination. A bone marrow biopsy showed hypoplasia, Kappa positive B-lymphocytes and low-grade malignant lymphoma cells. PCR of the bone marrow aspirate was not contributory. No treatment was initiated owing to her poor bone marrow function and she is under regular follow-up.
18353049 Juvenile idiopathic arthritis profile in Turkish children. 2008 Apr BACKGROUND: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders. Publications from different countries point to differences in the disease manifestation of JIA among different populations. The aim of the present paper was to evaluate the clinical and laboratory features of JIA in Turkish children. METHODS: A total of 196 JIA patients who fulfilled International League of Associations for Rheumatology (ILAR) diagnostic criteria were included in this retrospective study. The data collected were age, gender, age at disease onset and at diagnosis, and follow-up duration. Antinuclear antibody (ANA), rheumatoid factor (RF), and human leukocyte antigen B-27 were evaluated for each patient. RESULTS: There were 102 boys and 94 girls with a mean duration of disease of 4.1 years. The mean age at the first visit was 8.8 years, and the mean age at onset of disease was 6.8 years (range, 8 months-15 years). Polyarticular JIA was the most frequent onset type (37.2%). Other subtypes included oligoarthritis (34.2%), systemic arthritis (15.3%), psoriatic arthritis (1%), enthesitis-related arthritis (9.7%), and other arthritis (2.2%). ANA was positive in 28 patients (14.2%). Chronic uveitis occurred in two patients with oligoarthritis; and two patients with enthesitis-related arthritis had acute uveitis. Three patients (1.4%) developed amyloidosis. CONCLUSION: Compared to reports from Western countries, remarkably different features of JIA were found in Turkish children, which included higher frequency of polyarticular JIA, higher prevalence among boys, lower rate of ANA positivity and uveitis. Further studies are required to understand how genetic and environmental differences affect JIA expression.
18525086 A cluster of chilblains in Hong Kong. 2008 Jun OBJECTIVE: To report a recent clustering of chilblain cases in Hong Kong. DESIGN: Case series. SETTING: A regional hospital and a social hygiene clinic in the New Territories West, Hong Kong. PATIENTS: Patients with a clinical diagnosis of chilblains in February 2008. RESULTS: Eleven patients with chilblains were identified; seven (64%) gave an antecedent history of prolonged exposure to cold. They all presented with erythematous or dusky erythematous skin lesions affecting the distal extremities, especially fingers and toes. Laboratory tests revealed elevated antinuclear antibodies titres in two, positive rheumatoid factor in two, presence of cold agglutinins in one, and a raised anti-DNA titre (>300 IU/mL) in one. Skin biopsies were performed in six patients, four of them showed typical histopathological features of chilblains. In the patient with systemic lupus erythematosus, features of vasculitis were suspected, and in the one with pre-existing juvenile rheumatoid arthritis, there were features of livedo vasculitis. In 10 (91%) of the patients, the skin lesions had resolved when they were last assessed (at the end of March 2008), but had persisted in the patient who had pre-existing systemic lupus erythematosus. CONCLUSION: The recent clustering of chilblains was possibly related temporally to the prolonged cold weather at the end of January to mid-February. In our series, most of the patients developed chilblains as an isolated condition and resolved spontaneously within a few weeks. Laboratory tests and skin biopsies for chilblains are not necessary, unless the condition persists, the diagnosis in doubt or an underlying systemic disease is suspected.
16982003 Analog peptides of type II collagen can suppress arthritis in HLA-DR4 (DRB1*0401) transgen 2006 Rheumatoid arthritis (RA) is an autoimmune disease associated with the recognition of self proteins secluded in diarthrodial joints. We have previously established that mice transgenic for the human DR genes associated with RA are susceptible to collagen-induced arthritis (CIA) and we have identified a determinant of type II collagen (CII(263-270)) that triggers T-cell immune responses in these mice. We have also determined that an analog of CII(263-270) would suppress disease in DR1 transgenic mice. Because the immunodominant determinant is the same for both DR1 transgenic and DR4 transgenic mice, we attempted to determine whether the analog peptide that was suppressive in DR1 transgenic mice would also be effective in suppressing CIA in DR4 transgenic mice. We treated DR4 transgenic mice with two analog peptides of CII that contained substitutions in the core of the immunodominant determinant: CII(256-276) (F263N, E266D) and CII(256-270) (F263N, E266A). Mice were observed for CIA, and T-cell proliferative responses were determined. Either peptide administered at the time of immunization with CII significantly downregulated arthritis. Binding studies demonstrated that replacement of the phenylalanine residue in position 263 of the CII peptide with asparagine significantly decreased the affinity of the peptide for the DR4 molecule. In contrast, replacement of the glutamic acid residue in position 266 with aspartic acid or with alanine had differing results. Aspartic acid reduced the affinity (35-fold) whereas alanine did not. Both peptides were capable of suppressing CIA. With the use of either peptide, CII(256-276) (F263N, E266D) or CII(256-270) (F263N, E266A), the modulation of CIA was associated with an increase in T-cell secretion of IL-4 together with a decrease in IFN-gamma. We have identified two analog peptides that are potent suppressors of CIA in DR4 transgenic mice. These experiments represent the first description of an analog peptide of CII recognized by T cells in the context of HLA-DR4 that can suppress autoimmune arthritis.
17763406 Protein isoprenylation regulates secretion of matrix metalloproteinase 1 from rheumatoid s 2007 Sep OBJECTIVE: To determine whether protein prenylation (farnesyl/geranylgeranylation) regulates matrix metalloproteinase (MMP) secretion from rheumatoid arthritis (RA) synovial fibroblasts (RASFs), and whether MMP-1 secretion can be regulated by statins or prenyltransferase inhibitors via effects mediated by ERK, JNK, and NF-kappaB. METHODS: RASFs obtained from patients during elective knee replacement surgery were assessed by immunoblotting and/or enzyme-linked immunosorbent assay for secretion of MMP-1 and MMP-13 in the presence of tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), statins, the farnesyl transferase (FT) inhibitor FTI-276 and geranylgeranyl transferase inhibitor GGTI-298, and prenyl substrates (farnesyl pyrophosphate [FPP] and geranylgeranyl pyrophosphate [GGPP]). Activities of JNK and ERK were determined by phosphoimmunoblotting, and NF-kappaB activation was determined by nuclear translocation of the p65 component. RESULTS: FTI-276, but not statins, inhibited RASF secretion of MMP-1, but not MMP-13, following induction with TNFalpha (P = 0.0007) or IL-1beta (P = 0.006). Loading RASFs with FPP to promote farnesylation enhanced MMP-1 secretion. FTI-276 inhibited activation of JNK (P < 0.05) and NF-kappaB (P = 0.02), but not ERK. In contrast, GGTI-298 enhanced, while GGPP inhibited, MMP-1 secretion. FTI-276 and GGTI-298 together had no effect on MMP-1 secretion. Stimulation of RASFs with TNFalpha or IL-1beta led to increased expression and activity of FT. CONCLUSION: Protein farnesylation is required for expression and secretion of MMP-1 from RASFs, via effects on JNK and NF-kappaB. The ability of cytokines to stimulate the expression and activity of FT suggests that FT may be increased in the rheumatoid joint. In contrast, geranylgeranylation down-regulates MMP-1 expression. Statins simultaneously inhibit farnesylation and geranylgeranylation, and in consequence do not inhibit MMP-1 secretion. The ability of FTI-276 to inhibit MMP-1 secretion suggests a potential therapeutic strategy in RA.
17678599 [Functional impairment in psoriatic arthritis. Multicentric study of 343 patients]. 2007 Jul 7 BACKGROUND AND OBJECTIVE: The study is aimed at improving our knowledge about the functional impairment of the psoriatic arthritis through a multicentral series. PATIENTS AND METHOD: We have designed a transversal and multicentral study (centers of the same geographical area), including 343 patients with psoriatic arthritis. Eight medical centers have participated. Patients have been divided depending on the assistential level where they are visited. We have collected the following data: sex, age, assistential level, duration of psoriasis and arthritis, age at onset of psoriasis and arthritis, clinical form, ARA functional impairment, number of tender and swollen joints, presence of dactylitis, distal interphalangeal affection, axial involvement, ostheolisis or nail lesions, erithrocyte sedimentation rate (ESR), C-reactive protein, hemoglobine, leucocites, platelets, HLA-B27 and rheumatoid factor. RESULTS: 7.14% of the patients were significatly disabled (ARA functional class III and IV). 30.32% were patients visited in a primary assistential level, 30.90% in a secondary assistential level and 38.78% a tertiary and universitary hospital. We found statistically significant correlation between III and IV functional classes and age, assistential level, ostheolisis, corticoid treatment, ESR, leucocites, platelets and number of tender joints. CONCLUSIONS: We find a better functional capacity in our patients than in other studies. The inclusion of patients from different assistential levels instead of just patients visited in a tertiary hospital might be the cause of this difference.
16736523 Formatted anti-tumor necrosis factor alpha VHH proteins derived from camelids show superio 2006 Jun OBJECTIVE: The advent of tumor necrosis factor (TNF)-blocking drugs has provided rheumatologists with an effective, but highly expensive, treatment for the management of established rheumatoid arthritis (RA). Our aim was to explore preclinically the application of camelid anti-TNF VHH proteins, which are single-domain antigen binding (VHH) proteins homologous to human immunoglobulin V(H) domains, as TNF antagonists in a mouse model of RA. METHODS: Llamas were immunized with human and mouse TNF, and antagonistic anti-TNF VHH proteins were isolated and cloned for bacterial production. The resulting anti-TNF VHH proteins were recombinantly linked to yield bivalent mouse and human TNF-specific molecules. To increase the serum half-life and targeting properties, an anti-serum albumin anti-TNF VHH domain was incorporated into the bivalent molecules. The TNF-neutralizing potential was analyzed in vitro. Mouse TNF-specific molecules were tested in a therapeutic protocol in murine collagen-induced arthritis (CIA). Disease progression was evaluated by clinical scoring and histologic evaluation. Targeting properties were evaluated by 99mTc labeling and gamma camera imaging. RESULTS: The bivalent molecules were up to 500 times more potent than the monovalent molecules. The antagonistic potency of the anti-human TNF VHH proteins exceeded even that of the anti-TNF antibodies infliximab and adalimumab that are used clinically in RA. Incorporation of binding affinity for albumin into the anti-TNF VHH protein significantly prolonged its serum half-life and promoted its targeting to inflamed joints in the murine CIA model of RA. This might explain the excellent therapeutic efficacy observed in vivo. CONCLUSION: These data suggest that because of the flexibility of their format, camelid anti-TNF VHH proteins can be converted into potent therapeutic agents that can be produced and purified cost-effectively.
16646003 A comparison of response criteria to evaluate therapeutic response in patients with juveni 2006 May OBJECTIVE: There are no validated criteria to evaluate clinical response in juvenile idiopathic arthritis (JIA). The purpose of this study was to compare 4 sets of criteria (2 from the American College of Rheumatology [ACR] and 2 from the European League Against Rheumatism [EULAR]) for clinical response evaluation in JIA patients treated with methotrexate and/or anti-tumor necrosis factor alpha drugs. METHODS: Seventy-five patients with JIA were evaluated at baseline and after 6 months of therapy with second-line drugs. Mean age at study onset was 12.8 years (range 2-32.9 years). Diagnoses were systemic JIA (n = 16), rheumatoid factor-positive JIA (n = 5), rheumatoid factor-negative JIA (n = 9), persistent oligoarticular JIA (n = 10), extended oligoarticular JIA (n = 33), and psoriatic arthritis (n = 2). Clinical response was evaluated with the ACR Pediatric 30 criteria and the ACR 20% response criteria (ACR20), and with the EULAR Disease Activity Score (DAS) and 28-joint DAS (DAS28). Patients with EULAR criteria responses of "good" or "moderate" were classified as responders. Responders and nonresponders according to the different criteria were then compared. RESULTS: For patients younger than 16 years, Cohen's kappa varied between 0.51 and 0.72, with a good-to-excellent reproducibility index for all comparisons, except for the DAS28/ACR20 comparison. The best agreement was obtained by comparing the DAS and the ACR Pediatric 30. For patients older than 16 years, the reproducibility index was good or excellent in only 2 cases, i.e., comparing the DAS and the ACR Pediatric 30 and comparing the DAS and the DAS28 (as expected). CONCLUSION: Our study shows a good agreement overall for the different criteria tested. The highest concordance was observed between the DAS and the ACR Pediatric 30, the lowest between the DAS28 and the ACR20. Our data suggest that the ACR Pediatric 30 criteria can be used also in adult patients affected by JIA, and that the original DAS can be an alternative to the ACR Pediatric 30 in both children and young adults with JIA.
17956918 The cost-effectiveness of etanercept and infliximab for the treatment of patients with pso 2007 Nov OBJECTIVE: Tumour necrosis factor (TNF) antagonists have been shown to improve the outcomes in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We assess the cost-effectiveness of two TNF antagonists and so-called 'palliative care' for the treatment of active PsA from the perspective of the UK National Health Service (NHS). METHODS: Bayesian statistical methods were used to synthesize evidence from three Phase III trials, identified through a systematic review, and estimate the relative efficacy of etanercept, infliximab and palliative care. A probabilistic decision analytic model was then used to compare these treatments after the failure of at least two conventional disease-modifying anti-rheumatic drugs (DMARDs), following the British Society for Rheumatology (BSR) guidelines for use. The primary outcome measure, quality-adjusted life years (QALYs), was derived from utility values estimated as a function of disability measured by the Health Assessment Questionnaire (HAQ). The deterioration experienced in HAQ at treatment withdrawal (rebound) was incorporated using alternative scenarios to represent best- and worst-case assumptions. The model was extended beyond the trial duration to a 10-yr and lifetime horizon, using available evidence and expert opinion-based assumptions on disease progression. Resource utilization was based on literature, national databases and expert opinion. Prices were obtained from routine NHS sources and published literature. RESULTS: At a 10-yr time horizon, the incremental cost-effectiveness ratio (ICER) for etanercept compared with palliative care was pound sterling26 361 per QALY gained for the best-case rebound scenario, which increased to pound sterling30 628 for the worst-case. The ICERs for infliximab compared with etanercept were pound sterling165 363 and pound sterling205 345 per QALY, respectively. These findings are mainly explained by the fact that infliximab has higher acquisition and administration costs without substantially superior effectiveness compared with etanercept. Results were sensitive to estimates of rebound assumptions at withdrawal and the time horizon. CONCLUSIONS: Only results for etanercept remained within the range of cost-effectiveness estimates considered to represent value for money in the NHS by the National Institute for Health and Clinical Excellence. Further research appears most valuable in relation to the short-term effectiveness, utility parameters and assumptions regarding the effect of rebound.
16869004 A peptide from thrombospondin 1 modulates experimental erosive arthritis by regulating con 2006 Aug OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with leukocyte adhesion to and extravasation through vascular endothelium into synovial tissue. Recent evidence indicates that the thrombospondin 1 gene is up-regulated in patients with RA. We have identified a region within the TSP-1 type 3 repeats that inhibits human neutrophil elastase (HNE) and binds to human neutrophils. The present study was undertaken to investigate the therapeutic benefit of this TSP-1-derived peptide sequence and its effect on connective tissue growth factor (CTGF), a protein involved in fibrotic disorders and in neovascularization, which is a hallmark of RA. METHODS: CTGF gene and protein expression, as well as protein levels of CTGF in the synovium, after treatment with the TSP-1-derived peptide were studied in the peptidoglycan-polysaccharide animal model of erosive arthritis. RESULTS: Peptide treatment prevented joint infiltration and inflammation and was associated with reduced circulating antigen levels of HNE and TSP-1. Additionally, CTGF was up-regulated in this experimental model of RA. Treatment with the TSP-1-derived peptide was associated with down-regulation of the message and protein levels of CTGF. Immunofluorescence studies showed that the mean area fraction of CTGF immunoreactivity in the peptide-treated group of animals was significantly less than that in the untreated group. CONCLUSION: These results document a role for TSP-1 in regulating CTGF gene and protein expression in synovial tissue, suggesting a link with the disease course in this model of RA. This TSP-1-derived synthetic peptide may represent an important template for drug development in RA and other inflammatory conditions associated with neutrophil activation.
17588133 Effects and mechanisms of Paeoniflorin, a bioactive glucoside from paeony root, on adjuvan 2007 May OBJECTIVE AND DESIGN: Paeoniae alba Radix has been recognized as a valuable herb in the treatment of rheumatoid arthritis (RA) in traditional Chinese medicine. The purpose of this study was to investigate the effects of Paeoniflorin (PF), a bioactive glucoside from paeony root, on the rats with adjuvants arthritis (AA) and underlying mechanisms. MATERIALS: AA was induced by injecting Complete Freund's adjuvant (10 mg/ml) into hind paw in male Sprague-Dawley rats. TREATMENT: PF (5, 10, 20 mg/kg/d) was orally administered to the rats 14 to 20 days after injection of complete Freund's adjuvant. METHODS: Arthritis was evaluated by hind paw swelling, polyarthritis index, immune organ weights, and histological examination. Interleukin-1 (IL-1) activity was assessed by thymocyte proliferation as quantified by the 3-(4, 5-2dimethylthiazal- 2yl) 2,5-diphenyltetrazoliumbromide (MTT) assay. The content of prostaglandin E2 (PGE2) was measured by radioimmunoassay. The levels of IL-6, granulocyte macrophage colony stimulating factor (GM-CSF) and vascular epidermal growth factor (VEGF) in synovium homogenates were measured by enzyme-linked immuno-absorbent assay (ELISA) respectively. Expression of inhibitory subunits of G protein (G i) and cyclo-oxygenase-2 (COX-2) were detected by Western blotting technique. RESULTS: There were significant secondary inflammatory reactions in AA rats, which were accompanied by a decrease in immune organ weights. The administration of PF (10, 20 mg/kg/day, i. g., days 14-20) inhibited the inflammatory response and restored the weight of immune organs of AA rats. Synoviocyte proliferation of AA rats increased significantly, and the levels of IL-1, PGE2, IL-6, VEGF and GM-CSF in synovial homogenates of AA rats were also elevated compared with the normal group. The administration of PF (10, 20 mg/kg/day, i.g., days 14-20) reduced the above changes significantly. Finally, the expression of Gi1, Gi2, Gi3 and COX-2 in synovial homogenates of AA rats were also elevated. The administration of PF reduced Gi expression at doses of 10 and 20 mg/kg and decreased COX-2 expression at a dose of 20 mg/kg. CONCLUSION: PF suppresses rat AA at least partly by inhibiting abnormal proliferation of synoviocytes and the production of IL-1, PGE2, IL-6, VEGF and GM-CSF by synoviocytes and reducing Gi and COX-2 expression in synovium.