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ID PMID Title PublicationDate abstract
16864918 Efficacy and safety of leflunomide alone and in combination with methotrexate in the treat 2006 Aug BACKGROUND: Rheumatoid arthritis patients who develop refractoriness are left with no alternatives other than leflunomide and costly biological response modifiers. Leflunomide, though effective, was associated with adverse events and has not been extensively studied in the Indian population. AIMS: Determination of safety and efficacy of leflunomide alone and if not useful, in combination with methotrexate in patients refractory to conventional disease-modifying agents. SETTING AND DESIGN: Open labeled clinical trial with leflunomide [100 mg, OD x 3 days followed by 20 mg, OD x 6 months], if no improvement at three months, combined with methotrexate [5-7.5 mg, OD x 3 months] at a tertiary care hospital. MATERIALS AND METHODS: The primary endpoint in the improvement in EULAR criteria and secondary endpoints were patient and physician global evaluation, incidence of remission and biochemical and clinical adverse events. STATISTICAL ANALYSIS: Chi square test or Fisher's exact test and parametric and non-parametric repeat measure ANOVA were used for analysis. RESULTS: Among 84 patients who were included in the study, leflunomide showed improvement and remission in 52 [62%] and 6 [7%] in six months, by intention to treat analysis. Adverse events were observed in 15, discontinuation in 5 and 24 dropped out. With combination in 11 patients, there was improvement and remission in nine [91%] and one [9%] after three months. Adverse events were observed in six and one discontinued. CONCLUSIONS: If regular monitoring of hepatic function and hematological parameters are performed, leflunomide is an effective and safe drug in the Indian population in resistant rheumatoid arthritis patients, especially if used alone.
16283863 Economic burden of patients with anemia in selected diseases. 2005 Nov OBJECTIVE: To examine the economic impact of patients with anemia in selected diseases. METHODS: A retrospective cohort design was used to estimate the differences in costs between anemic and nonanemic patients. The analysis used administrative claims data (1999-2001) from a US population to assess direct costs and disability and productivity data (1997-2001) to estimate indirect costs. Adult patients with a diagnosis of rheumatoid arthritis (RA), inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cancer, or congestive heart failure (CHF) were identified. Costs were estimated using a generalized linear model, adjusting for age, sex, comorbidities, and disease severity. The adjustment variables for disease severity were based on ICD-9, HCPCS, or pharmacy codes. These costs were projected to a 1-million-member, similar population. RESULTS: The percentage of anemia patients varied among conditions (6.9-26.1%); the CKD population had the highest prevalence. CKD anemic patients incurred the greatest average annual direct costs ($78,209), followed by CHF ($72,078) and cancer ($60,447). After adjusting for baseline characteristics including severity, the difference in direct costs between anemic and nonanemic patients decreased for all diseases; CHF patients incurred the greatest adjusted cost difference between anemic and nonanemic ($29,511), followed by CKD ($20,529) and cancer ($18,418). Unmeasured severity and coding bias may account for a portion of the differences in the adjusted cost. CONCLUSION: Anemia may substantially increase health-care costs at a level that is economically very relevant, despite the fact that these patients may comprise only one tenth of the overall anemic population.
15498849 Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates angiogenesis. 2005 Mar 15 The 4A11 antigen is a unique cytokine-inducible antigen up-regulated on rheumatoid arthritis (RA) synovial endothelial cells (ECs) compared with normal ECs. Previously, we showed that in soluble form, this antigen, Lewis(y)-6/H-5-2 (Le(y)/H) or its glucose analog, 2-fucosyl lactose (H-2g), induced the expression of EC intercellular adhesion molecule-1 (ICAM-1) and leukocyte-endothelial adhesion through the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. Currently, we show that H-2g induces release of EC angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), an effect inhibited by decoy nuclear factor kappaB (NFkappaB) oligodeoxynucleotide (ODN). JAK2 and phosphoinositide-3 kinase (PI3K) are 2 upstream kinases of NFkappaB activated by H-2g, as confirmed by an inhibitor of kappa B kinase (IKKbeta) assay. In vitro, H-2g induces vascular sprouting in the rat aortic ring model, whereas blockade of JAK2, PI3K, or NFkappaB inhibits sprouting. Likewise, in the in vivo mouse Matrigel plug angiogenesis assay, chemical inhibitors and antisense or decoy ODNs of JAK2, PI3K, or NFkappaB decrease angiogenesis, confirming the importance of these pathways in H-2g-induced EC signaling. The critical role of Le(y)/H involvement in angiogenesis and its signaling pathways may provide new targets for therapy of diseases characterized by pathologic neovascularization.
16112980 Gene therapy for the treatment of musculoskeletal diseases. 2005 Jul Research into the orthopaedic applications of gene therapy has resulted in progress toward managing chronic and acute genetic and nongenetic disorders. Gene therapy for arthritis, the original focus of research, has progressed to the initiation of several phase I clinical trials. Preliminary findings support the application of gene therapy in the treatment of additional chronic conditions, including osteoporosis and aseptic loosening, as well as musculoskeletal tumors. The most rapid progress is likely to be in tissue repair because it requires neither long-term transgene expression nor closely regulated levels of transgene expression. Moreover, healing probably can be achieved with existing technology. In preclinical studies, genetically modulated stimulation of bone healing has shown impressive results in repairing segmental defects in the long bones and cranium and in improving the success of spinal fusions. An increasing amount of evidence indicates that gene transfer can aid the repair of articular cartilage, menisci, intervertebral disks, ligaments, and tendons. These developments have the potential to transform many areas of musculoskeletal care, leading to treatments that are less invasive, more effective, and less expensive than existing modalities.
16207341 Reconstitution of the adult B cell repertoire after treatment with rituximab. 2005 B cells play diverse and fundamental roles in the pathogenesis of autoimmune diseases. Consequently, therapeutic targeting of B cells is gaining prominence in our clinical armamentarium for an ever expanding array of autoimmune and neoplastic disorders. Therefore, it is of great importance to understand the mechanism of action of B cell depletion. Given that the ideal consequence of B cell depletion would be the subsequent re-establishment of immunologic tolerance, a detailed analysis of the properties of the emerging repertoire will be required. The results presented by Rouzière and coworkers in their study of rheumatoid arthritis patients shed some light on this question and are discussed in this commentary.
16234431 Heme oxygenase 1 (HO-1) regulates osteoclastogenesis and bone resorption. 2005 Dec Heme oxygenase 1 (HO-1) plays an important role in vascular disease, transplantation, and inflammation. In animal models of acute and chronic inflammation, induction of HO-1 has anti-inflammatory and cytoprotective properties. Since inflammation is an important trigger of osteoclastogenesis, we hypothesized that HO-1 might influence osteoclastogenesis. We investigated the effects of induction of HO-1 on osteoclast formation in vitro and in vivo. Furthermore, we addressed the role of HO-1 in inflammatory bone loss in humans. When HO-1 was induced by hemin in vitro, a significant dose-dependent inhibition of osteoclastogenesis was observed. Up-regulation of HO-1 was mediated by activation of MAPK and primarily prevented differentiation of osteoclast precursors to osteoclasts, whereas it did not affect mature osteoclasts. Anti-osteoclastogenic properties of hemin were based on a down-regulation of c-fms, RANK, TRAF-6, and c-fos. In addition, induction of HO-1 inhibited TNF-triggered osteoclast differentiation in vitro as well as LPS-driven inflammatory bone loss in vivo. Furthermore, HO-1 induction suppressed osteoclastogenesis and bone destruction in a TNF-mediated arthritis. In line, assessment of synovial tissue from rheumatoid arthritis patients revealed that osteoclasts are usually HO-1 negative. Moreover, serum levels of bilirubin, a metabolite of HO-1, were elevated in rheumatoid arthritis patients without bone damage, suggesting HO-1 affects bone loss in humans. In summary, these data indicate that HO-1 negatively regulates osteoclastogenesis, leading to a positive net balance of bone.
16877461 A clinical trial of specialist footwear for patients with rheumatoid arthritis. 2007 Feb OBJECTIVES: The structural and functional changes in the RA foot often affect the patient's gait and mobility, impacting on the patient's quality of life. Successful management of these foot pathologies and resultant problems can involve the provision of specialist therapeutic footwear. The aim of the study was to evaluate the value of a new footwear design based on patients' opinions compared with a traditional footwear design. METHOD: A total of 80 patients with RA of 5 yrs or more duration, foot deformity, difficulty in being able to obtain suitable retail footwear and self-reported foot pain were recruited. Patients were randomly assigned to either an intervention group (new design) or the control group (traditional design). Patients completed two specific health-related quality of life scales (Foot Health Status Questionnaire and the Foot Function Index) at baseline and after 12 weeks. RESULTS: Only 36 patients completed the trial. Ten refused the footwear outright and 34 withdrew from the study after the footwear was supplied, due to either non-footwear related problems or reasons related to the footwear. Both the specific health-related quality of life scales demonstrated significant improvement from baseline to week 12 with the intervention group (P < 0.05). There was no significant difference in both specific health-related quality of life scales after week 12 with the traditional group (P > 0.05). CONCLUSIONS: Improvement in pain and patient satisfaction with the new design of footwear for patients with RA over the traditional design indicates the importance of patient involvement in the design process and throughout the process of supplying and monitoring the footwear. The fact that the new-design shoe was based on patients' involvement in the design process in a previous study may be the most important factor in its success. In order to meet the clinical goals of this footwear the patients need to wear them, and to achieve this the patients' requirements need to be acknowledged.
16216670 Analysis of a GT microsatellite in the promoter of the foxp3/scurfin gene in autoimmune di 2005 Aug The aim of this study was to assess the possible association of the functional (GT)(n) microsatellite polymorphism in the FOXP3 gene with predisposition to several autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease, and celiac disease. We analyzed a case-control cohort composed of 231 SLE patients, 293 RA patients, 528 inflammatory bowel disease (354 Crohn's disease patients and 260 UC patients) patients, 103 celiac disease patients, and 274 healthy controls ethnically matched. Genotyping of (GT)(n) microsatellite was performed by polymerase chain reaction (PCR)-based method combined with fluorescent technology. We found no evidence for association of this polymorphism between controls and these autoimmune disease patients. Additionally, no differences in the genotype and allele distribution were found when patients were stratified according to clinical manifestation. The (GT)(n) microsatellite of the FOXP3 gene may not play a relevant role in the susceptibility to SLE, RA, inflammatory bowel disease, and celiac disease in our population.
16380754 [Anti-TNFalpha treatment in patients with rheumatoid arthritis and anti-Ro/SSA antibodies] 2005 Dec OBJECTIVE: To analyse clinical efficacy, onset of new autoantibodies or symptoms of autoimmune disease in patients affected by rheumatoid arthritis with anti-Ro/SSA treated with anti-TNFalpha agents. METHODS: Six anti-Ro/SSA positive subjects with RA were studied every six months until 24th month of treatment in order to detect ANA titer (IFI), anti-dsDNA (Farr), anti-cardiolipin and anti-beta2glycoprotein I (ELISA), anti-ENA (CIE). The titre of anti-Ro/SSA were analysed by ELISA. Four patients were diagnosed as overlap RA/SS. RESULTS: Six female patients (mean age 58 ys, SD 9.8 ys), with long-standing RA (mean 7 ys, range 5-22 ys) were treated with anti-TNFalpha agents for a mean of 31 months (SD: 20.4 m): 4 with Infliximab and 2 with Etanercept. All the patients showed a significant reduction of DAS until 24th month (p < 0.006) with stability of sicca symptoms. The titer of ANA and anti-Ro/SSA was stable, while 4 subjects developed anti-dsDNA at low titer within 6-12 months. One patient withdrawn the treatment, because of lupus-like features; another one, with HCV hepatitis, interrupted Etanercept because of elevation of liver enzymes. No anticardiolipin or antibeta2GPI antibodies were detected. One subject with RA-SS also presented a primary biliary cirrhosis: clinical and histological features of cholangitis remained stable during Etanercept treatment. CONCLUSIONS: Anti-TNFalpha treatment showed good efficacy and safety in anti-Ro/SSA positive patients with RA. Anti-ds-DNA antibodies at low titer appeared in most patients while the onset of lupus-like disease could be considered a rare event also in RA patients with a rich autoimmune repertoire.
17195360 [Preliminary data concerning cross-reacting anticardiolipin antibodies as potential inhibi 2006 May In analyzed synovial fluids, suspected for endotoxin presence, the presence of endotoxin done was proved by LAL-test in 21 synovial fluids /42%/ and in 12 of 20 /60%/ the presence of endotoxin inhibiting substances /IS/ was proved. Because many parameters /like presence CIC, anti-LPS, KDO/ indicates that in the group of LAL-negative /IS/ - positive synovial fluids the presence of endotoxin is very possible, IS have been removed /by heating to 100 degrees C/ and after that the endotoxin activity was shown in about 27% of synovial fluids. Additional analysis of the Cohn fraction /prepared by ammonium sulfate precipitation/ confirmed the presence in the gamma and alpha and beta fractions a weak IS activity /in a dose dependent manner. No IS activity, have been shown yet in the fraction of affinity purified aCl antibodies.
15759949 Laboratory testing in the rheumatic diseases: a practical review. 2005 Feb Laboratory testing for the rheumatic diseases can allow for rapid diagnosis and appropriate management, while false-positive tests can lead to inappropriate management and unnecessary concern for the patient. An evaluation of laboratory testing for rheumatic illnesses is discussed, including the well-known acute phase proteins, the use of ANA in screening, and the newer antibodies which may potentially allow for an earlier diagnosis. A thorough history and examination are arguably the best screening tests. Clinicians should be judicious in their use of laboratory testing, and should only do so in an attempt to further refine the diagnosis.
16631753 Biology of vascular endothelial growth factors. 2006 May 22 Angiogenesis is the process by which new blood vessels are formed from existing vessels. The vascular endothelial growth factors (VEGFs) are considered as key molecules in the process of angiogenesis. The VEGF family currently includes VEGF-A, -B, -C, -D, -E, -F and placenta growth factor (PlGF), that bind in a distinct pattern to three structurally related receptor tyrosine kinases, denoted VEGF receptor-1, -2, and -3. VEGF-C and VEGF-D also play a crucial role in the process of lymphangiogenesis. Here, we review the biology of VEGFs and evaluate their role in pathological angiogenesis and lymphangiogenesis.
17133607 A novel autoantigen to differentiate limited cutaneous systemic sclerosis from diffuse cut 2006 Dec OBJECTIVE: To investigate the presence and clinical significance of autoantibodies against the interferon-inducible gene IFI16 in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and other autoimmune diseases. METHODS: Immunohistochemical analysis was used to evaluate the expression of IFI16 in skin biopsy specimens obtained from patients with SSc and patients with SLE. Levels of antibodies against IFI16 in sera from 82 patients with SSc and 100 patients with SLE were determined by enzyme-linked immunosorbent assay. Other autoimmune diseases such as primary Sjögren's syndrome (SS), rheumatoid arthritis (RA), chronic urticaria, and hepatitis C virus (HCV) infection were also examined. RESULTS: Expression of IFI16 was greatly increased and was ubiquitous in all layers of the epidermis and in the dermal inflammatory infiltrates of lesional skin from both patients with SLE and patients with SSc. Patients with SLE, those with primary SS, and those with SSc exhibited significantly higher anti-IFI16 IgG antibody levels compared with normal controls (for SLE, P < 0.002; for primary SS, P < 0.001; for SSc, P < 0.0005). Anti-IFI16 titers above the ninety-fifth percentile for control subjects were observed in 26% of the patients with SLE, 50% of those with primary SS, and 21% of those with SSc (28% of patients with limited cutaneous SSc [lcSSc] versus 4% of patients with diffuse cutaneous SSc [dcSSc]). In contrast, the prevalence of anti-IFI16 was 4% in patients with RA, 5% in those with chronic urticaria, and 13% in those with HCV infection. CONCLUSION: The results of this study provide evidence that an IFN-inducible gene, IFI16, may be involved in the pathophysiologic mechanisms of connective tissue disorders such as SSc. Moreover, a strict correlation with lcSSc was also demonstrated, thus providing a novel tool in the differential diagnosis of lcSSc from dcSSc.
17052183 Phosphoinositide 3-kinase signalling and FoxO transcription factors in rheumatoid arthriti 2006 Nov Although the mechanisms leading to the induction of RA (rheumatoid arthritis) are poorly understood, improper activation, proliferation, survival and retention of neutrophils, macrophages, lymphocytes and other leucocytes contribute to perpetuation of inflammation and eventual joint destruction through activation of stromal fibroblast-like synoviocytes. Fundamental studies in developmental biology, cellular biology and immunology have established critical roles for PI3K (phosphoinositide 3-kinase) signal transduction pathways in cellular chemotactic responses, proliferation, apoptosis and survival. Despite profound alteration of these cellular processes in RA, involvement of PI3K signalling pathways in this chronic inflammatory disease, and their assessment as potential therapeutic targets, has until recently received scant attention. This review highlights recent advances in our understanding of PI3K signalling pathways, in particular regulation of FoxO (forkhead box O) transcription factors, and their relevance to RA.
16755991 [Polymorphism of gene promotor region for MMP-2 in rheumatoid arthritis]. 2006 Apr INTRODUCTION: Matrix metalloproteinase (MMP) belonging to family of zinc-dependent endopeptidases participates in remodelling of extracellular matrix in many physiological and pathological processes including rheumatoid arthritis (RA). Rheumatoid arthritis is a chronic autoimmune inflammatory multi-systemic disease characterized, among others, by degradation of hyaline articular cartilage and escalated angiogenesis. As a matter of fact, these processes may by influenced by MMP. On the other hand, MMP can suppress inflammation by degrading biologically active molecules like cytokines, chemokines or growth factor receptors. Increased levels of MMP-2 (gelatinase A) are observed in serum and synovial fluid of patients with RA. Gene polymorphism for MMP-2 can affect susceptibility to development and/or severity of RA. METHOD: The aim of the study was to prove possible association of polymorphisms in gene promotor region for MMP-2 (-1575 G/A, -1306 C/T, -790 T/G, -735 C/T) with RA. We worked with 101 patients with RA who met reviewed diagnostic criteria of ACR (1987) for RA, and suffer from RA for at least 2 years. Control group consisted of 101 healthy volunteers of similar age and gender distribution. RESULTS: RA patients and control group did not differ in genotype distributions or frequencies of alleles of polymorphisms -1575A/G, -1306C/T and -735 C/T. Significant difference was observed between RA patients and control group in allelic frequencies of polymorphism -790 T/G MMP-2 (T allele -0.70 vs. 0.66, Pa = 0.013). Also, a tendency of GG genotype growth was noted in RA patients (Pg = 0.053). Significant difference in allelic frequencies was also observed between men with RA and men from control group (T allele -0.80 vs. 0.61, Pa = 0.025). Haplotype of GCGC polymorphisms -1575 G/A, -1306 C/T, 790 T/G, -735 C/T was more frequent in RA patients (Pcorr = 0.016; OR = 0.09; confidence interval 0.00-0.65), whereas GCTC haplotype was noted more frequently in control group (Pcorr = 0.017; OR = 1.8; confidence interval 1.17-2.70). CONCLUSION: The results indicate the association between polymorphisms in gene promotor region for MMP-2 and susceptibility to development of RA.
16613915 Undergraduate musculoskeletal examination teaching by trained patient educators--a compari 2006 Nov BACKGROUND: To compare the core hand and knee examination skills gained by undergraduates taught either by trained patient educators (PEs) or by doctors. METHODS: A total of 50 final year medical students were randomized to receive training from PEs or doctors. Group A were taught hand examination by a PE with rheumatoid arthritis, and knee examination by a PE with osteoarthritis. Group B was taught hand and knee examination by a consultant rheumatologist plus an untrained patient with appropriate signs. All students were taught an established core skills set in small group workshops. Students then undertook two validated objective structured clinical examination (OSCE) stations with two blinded assessors. Pre- and post-teaching questionnaires established the students' self-reported levels of skills (SRS) and a student evaluation of teaching (SET). The study was analysed as an equivalence trial. A mean difference in OSCE scores of 10% was assumed to be of educational significance. RESULTS: Although the SET scores of both groups were high, the doctor-led group received higher scores. Aside from this, the two student groups did not differ significantly. There were no significant differences in mean hand OSCE (mean difference = 0.88, P = 0.28, 95% CI = -0.73 to 2.49) or knee OSCE (mean difference = 0.28, P = 0.7, 95% CI = -1.19 to 1.75) scores. Both the upper and lower confidence intervals for each mean difference fell within the 10% range (-2.8 to 2.8 for the hand, and -2.5 to 2.5 for the knee) and equivalence was assumed. CONCLUSIONS: Adequately trained PEs can deliver clearly structured undergraduate skills, teaching with equivalent learning outcomes to those of rheumatology consultants. PEs are a valuable development to augment musculoskeletal education in the face of expanding student numbers.
17166737 MIF production by dendritic cells is differentially regulated by Toll-like receptors and i 2006 Oct Macrophage migration inhibitory factor (MIF) is clearly associated with rheumatoid arthritis (RA) disease severity. However, the regulation of MIF during the course of RA has not been subjected to similar scientific scrutiny. The aim of our study was to investigate the role of various Toll-like receptors (TLRs) and inflammatory mediators on MIF production by dendritic cells (DCs) in healthy controls and RA patients. DCs were cultured from 12 healthy donors and 12 RA patients. Triggering via TLR mediated pathways was achieved using various TLR specific ligands alone or in combination: Pam3Cys for TLR2, LPS and recombinant extra domain A containing fibronectin for TLR4 and Poly(I:C) and R848 for TLR3 and TLR7, respectively. In addition, iDCs from healthy controls were incubated with various cytokines, RANKL and CD40L for 48 h. MIF levels were measured using an ELISA assay. Stimulation of DCs by TLR4 ligands resulted in higher MIF production compared to immature DCs from healthy controls (p<0.002) and RA patients (p<0.002). DCs from RA patients produced higher MIF levels than healthy controls both at the immature stage (p<0.04) as well after full maturation via TLR2 (p<0.04) and TLR4 (p<0.001) triggering. Incubation with TLR3 and TLR7 ligands resulted in a significantly decreased secretion of MIF in RA patients and controls. Simultaneous incubation of TLR4 with either TLR3 or TLR7 ligands resulted in a decrease of MIF secretion when compared to TLR4 stimulation alone. The secretion of MIF increased when DCs were stimulated with TNF-alpha, RANKL and CD40L. The secretion of MIF by dendritic cells is differentially regulated by TLRs. In addition, TNF-alpha, RANKL, and CD40L augment MIF production by DCs and thus play a potential role in the amplification of the inflammatory loop in RA.
15833145 The evolving clinical profile of abatacept (CTLA4-Ig): a novel co-stimulatory modulator fo 2005 Abatacept (CTLA4-Ig) is a novel fusion protein designed to modulate the T cell co-stimulatory signal mediated through the CD28-CD80/86 pathway. Clinical trials have provided preliminary evidence of the efficacy of this compound in the treatment of rheumatoid arthritis. This review describes the molecular and biologic bases for the use of abatacept in rheumatoid arthritis and summarizes the current clinical data on its safety and effectiveness in this disease.
15910559 Systemic autoimmune diseases co-existing with chronic hepatitis C virus infection (the HIS 2005 Jun OBJECTIVES: To describe the clinical and immunologic characteristics of a large series of patients with systemic autoimmune diseases (SAD) associated with chronic hepatitis C virus (HCV) infection. METHODS: We analysed 180 patients diagnosed with SAD and chronic HCV infection seen consecutively at our centres during the last 10 years. The clinical and immunological patterns of disease expression were compared with 180 SAD-matched patients without chronic HCV infection. RESULTS: A total of 180 HCV patients fulfilled the classification criteria for the following SAD: Sjogren's syndrome (n = 77), systemic lupus erythematosus (n = 43), rheumatoid arthritis (n = 14), antiphospholipid syndrome (n = 14), polyarteritis nodosa (n = 8) and other SAD (n = 24). One hundred and thirty (72%) patients were female and 50 (28%) male, with a mean age at SAD diagnosis of 50 years. The main immunologic features were antinuclear antibodies in 69% of patients, cryoglobulinaemia in 62%, hypocomplementaemia in 56% and rheumatoid factor (RF) in 56%. Compared with the SAD-matched HCV-negative group, SAD-HCV patients presented a lower prevalence of females (P = 0.016), an older age at SAD diagnosis (P = 0.039) and a higher prevalence of vasculitis (P < 0.001) and neoplasia (P < 0.001). Immunologically, SAD-HCV patients presented a lower prevalence of antinuclear (P = 0.036), anti-extractable nuclear antigen (P = 0.038) and anti-DNA (P = 0.005) antibodies, and a higher frequency of RF (P = 0.003), hypocomplementaemia (P < 0.001) and cryoglobulins (P < 0.001). CONCLUSIONS: In comparison with an SAD-matched HCV-negative population, SAD-HCV patients were older and more likely to be male, with a higher frequency of vasculitis, cryoglobulinaemia and neoplasia. This complex pattern of disease expression is generated by a chronic viral infection that induces both liver and autoimmune disease.
15911212 Disease-modifying antirheumatic drug use in the elderly rheumatoid arthritis patient. 2005 Aug During the 10-year period since the last review was done by Gardner and Furst, studies have furthered our knowledge of use of disease-modifying antirheumatic drugs (DMARDs) in the elderly rheumatoid arthritis (RA) patient. This article will briefly review the clinical pharmacology of human as they age, and detail the effects of aging on the specific pharmacokinetics and responses to commonly used DMARDs. There has been some progress in understanding the elderly RA patient, however, there is insufficient data for much confidence in DMARDs effects in the elderly.