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ID PMID Title PublicationDate abstract
16546352 Genetic variations in ZFP36 and their possible relationship to autoimmune diseases. 2006 May The ZFP36 gene codes for TTP, a regulator of TNF alpha. In mice, TTP deficiency results in a systemic autoimmune inflammatory syndrome with severe arthritis. We hypothesized that genetic variations in ZFP36 are associated with autoimmune disease in humans. The primary objective of this study was to identify human ZFP36 genetic variants in autoimmune disease cases and controls, determine their frequencies in a general clinic population, and construct haplotypes. We resequenced ZFP36 in 316 individuals with autoimmune diseases and identified 28 polymorphisms and determined the frequency of all the known ZFP36 polymorphisms in 484 participants of the Environmental Polymorphism Registry, a regional registry being conducted by the NIEHS. Based on the sequence-verified ZFP36 genotypes, 34 haplotypes were constructed. As a secondary objective, we examined autoimmune disease cases and controls for potential ZFP36 genetic associations. One novel polymorphism, ZFP36*8, a C to T transition in the protein coding domain, was significantly associated with rheumatoid arthritis (RA) in African-Americans (RR=1.23, 95% CI: 1.11-1.36). The data presented here suggest a tentative association between ZFP36 and RA. This finding, as well as the ZFP36 polymorphisms and haplotypes identified here, should form the basis for future association studies in autoimmune diseases.
17148556 Association of PTPN22 haplotypes with Graves' disease. 2007 Feb CONTEXT: A recent study reported associations of a series of single nucleotide polymorphisms (SNPs) within PTPN22, including rs2476601, with rheumatoid arthritis. OBJECTIVE: Having previously reported significant association of the T allele of rs2476601 in a Graves' disease (GD) cohort, we sought to determine whether novel rheumatoid arthritis-associated SNPs were also contributing to susceptibility to GD. DESIGN: Case control and family-based studies of five PTPN22 tag SNPs were performed. SETTING: An United Kingdom academic department of medicine was the setting for the study. PATIENTS OR OTHER PARTICIPANTS: A total of 768 GD patients, 768 control subjects, and 313 families with autoimmune thyroid disease participated. MAIN OUTCOME MEASURE: Tests for association with disease were the main outcome measure. RESULTS: No association with disease of any of the individual SNPs and no correlation between genotype and clinical phenotype were seen. However, haplotype analysis of the SNP markers with addition of rs2476601 did reveal a strong association of a haplotype containing the T allele, in both the case control (chi2 = 29.13; P = 6.77 x 10(-8)) and family data sets (chi2 = 5.24; P = 0.02). Furthermore, a novel protective effect of a haplotype containing all six SNPs was observed (chi2 = 17.02; P = 3.7 x 10(-5)). CONCLUSIONS: These data suggest that the association of SNPs within the PTPN22 region differs between autoimmune diseases, occurring individually and/or as part of a haplotype, indicating that the mechanisms by which PTPN22 confers susceptibility to GD may, in part, be disease specific.
15692471 Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumato 2005 Feb BACKGROUND: Methotrexate (MTX) is a folate analogue used in the treatment of moderate to severe psoriasis and rheumatoid arthritis (RA). It oppositely affects inflammation and hyperhomocysteinemia-two independent risk factors for vascular disease. To date, there are no published reports evaluating the impact of these potentially paradoxical action of MTX. OBJECTIVE: The purpose of this study was to evaluate the effect of MTX therapy on the incidence of vascular disease in patients with psoriasis and RA. METHODS: We conducted a retrospective cohort study in which we analyzed computerized records of 7,615 outpatients diagnosed with psoriasis and 6,707 with RA at the Veterans Integrated Service Network 8. RESULTS: Patients prescribed MTX therapy had a significantly reduced risk of vascular disease compared to those who were not prescribed MTX (psoriasis: RR = 0.73, 95% CI = 0.55-0.98; RA: 0.83, 0.71-0.96). This reduction was most evident for patients prescribed a low cumulative dose of MTX (psoriasis: RR = 0.50, 95% CI = 0.31-0.79; RA = 0.65, 0.52-0.80). Concomitant use of folic acid (FA) with MTX also reduced the incidence of vascular disease in patients prescribed MTX (psoriasis: RR = 0.56, 95% CI = 0.39-0.80; RA: 0.77, 0.38-1.56). CONCLUSIONS: MTX therapy reduced the incidence of vascular disease in veterans with psoriasis or RA. Low to moderate cumulative dose appears more beneficial than the higher dose. We hypothesize that this effect is caused by its anti-inflammatory properties. In addition, a combination of MTX and FA led to a further reduction in the incidence of vascular disease.
16705477 Right ventricular diastolic abnormalities in rheumatoid arthritis and its relationship wit 2006 Dec OBJECTIVES: To investigate right ventricular diastolic function in rheumatoid arthritis (RA) and its relationship with left ventricular and pulmonary involvement. METHODS: Thirty-five RA patients and 30 healthy subjects were submitted to conventional Doppler (CE) and tissue Doppler echocardiography (TDE) to assess left and right systolic and diastolic function and to estimate maximal arterial systolic pulmonary pressure (PAP). To detect pulmonary involvement, pulmonary function tests and high-resolution computed tomography (HRCT) scans were performed in all RA patients. RESULTS: An abnormal RV filling, as expressed byan inverted tricuspid (Tr.) E/A ratio, was detected in 12 (34%) of the 35 RA patients and in 2 (7%) of the 30 controls (P<0.004). If compared to CE findings, prevalence of RV diastolic abnormalities were found higher in patients with RA by TDE (RV annulus Em/Am ratio <1 (in 31 (89%) of 35 patients) (P = 0.002). Twenty-two (63%) of 35 patients had abnormal HRCT findings. Pulmonary involvement with pulmonary hypertension (PHT) (36+/-5 mmHg) was detected in 10 (29%) of 35 RA. In this group, increase of RV annulus and basal Am wave, decrease of Tr. E/A ratio and RV annulus Em/Am ratio were statistically significant compared to RA (12 (34%) of 35) patients with pulmonary involvement who had normal PAP (19+/-5 mmHg), (P = 0.014, P = 0.006, P = 0.015, P = 0.049, respectively). CONCLUSIONS: This study points out an impaired RV filling in a significant part of RA patients without overt heart failure. Impairment of RV diastolic function may be a predictor of subclinic myocardial and pulmonary involvement in patients with RA.
16107132 Peptide hormones and histamine in plasma and synovial fluid of patients with rheumatoid ar 2005 Jan OBJECTIVES: Hormones other than adrenal and gonadal steroids may play also a significant role in the pathogenesis of rheumatoid arthritis. The aim of this study was to investigate the levels of selected peptide hormones and histamine in synovial fluid of knee joints and in plasma of patients with rheumatoid arthritis and with osteoarthrosis. METHODS: The concentrations of insulin, C-peptide, prolactin, growth hormone, free triiodothyronine (FT3), thyrotropin (TSH), and histamine were determined in synovial fluid and plasma of 27 patients with rheumatoid arthritis (RA) and in 12 patients with osteoarthrosis (OA). RESULTS: The presence of peptide hormones in synovial fluid was demonstrated. The levels of TSH and growth hormone were lower in synovial fluid than in plasma in both groups, while those of prolactin were comparable in synovial fluid and in plasma. The levels of C-peptide (p < 0.05), insulin and FT3 were higher in synovial fluid than in plasma of OA patients, but lower in synovial fluid of RA patients as compared to their levels in plasma. Significant positive correlations between the levels in plasma and synovial fluid were observed in prolactin (p < 0.001, r = 0.741) and TSH (p < 0.05, r = 0.88) only. After age adjustment, no significant differences in synovial fluid and in plasma levels of all hormones were found between OA and RA patients. The levels of histamine in plasma were similar in RA and OA patients, in synovial fluid of both groups histamine was found in almost undetectable amounts. CONCLUSIONS: The selected peptide hormones, e.g. insulin, C-peptide, prolactin, growth hormone, FT3 and TSH, are present in synovial fluid of RA and OA patients, some of them in the concentrations comparable to these in plasma. The role of the locally present hormones in pathogenesis of RA has to be investigated in further studies and analyses.
16766365 The activity of exoglycosidases in the synovial membrane and knee fluid of patients with r 2006 May OBJECTIVE: To determine the activities of the five exoglycosidases that catabolize glycoconjugates (proteoglycans, glycoproteins, and glycolipids) in the synovial membrane and knee joint fluid of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). METHODS: The following exoglycosidases were analysed with the p-nitrophenyl derivatives of appropriate sugars as substrates: hexosaminidase (HEX) and its isoenzymes A and B, beta-glucuronidase, beta-galactosidase, alpha-mannosidase, and alpha-fucosidase. RESULTS: Our results show that the activity of all exoglycosidases tested in the synovial membrane of patients with RA and JIA was significantly higher than in synovial fluid. We demonstrated that only the enzymatic activity of HEX was significantly higher in the tissue of patients with inflammatory diseases in comparison to the activity in the control group. CONCLUSION: These data support the concept that the synovial cells of patients with RA and JIA are the main source of exoglycosidases, which catabolize glycoconjugates of cartilage.
16287919 Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumoco 2006 Jan OBJECTIVE: To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both. METHODS: Patients with RA (n = 149) and healthy controls (n = 47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination. RESULTS: Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P = 0.037 for 23F and P = 0.004 for 6B) or MTX alone (P<0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses. CONCLUSIONS: Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.
16723942 Diagnosis of early arthritis: outcomes of a nurse-led clinic. 2006 Apr 13 Recent data suggest that early treatment of inflammatory arthritis can improve patient outcomes. While rheumatologists recognized this need for early evaluation and treatment, the current load on the rheumatology service nationwide may limit the capacity for timely evaluation. The authors developed a protocol to be applied through a specialized early arthritis clinic that is able to discriminate between different categories of early arthritis, to shortening the time taken to reach the correct diagnosis and provide the appropriate management. A total of 108 patients have been reviewed in the early arthritis clinic over 12 months. It took 3 weeks for the patients to be fully assessed in the rheumatology clinic instead of 16 weeks. Completing the clinic proforma helped the assessor to cover all causes of arthritis/arthralgia. Disease-modifying antirheumatic drug (DMARD) therapy was initiated within a few weeks (2 to 5 weeks) once diagnosis was confirmed, instead of 8 to 10 months previously. This early arthritis clinic model helped to shorten the referral lag time (duration between symptoms onset and first rheumatologist assessment) as well as lag time to DMARD therapy (duration between symptom onset and the institution of DMARD therapy).
15773413 [Epitope mimicry and its role in the development of autoimmune reactions]. 2005 Jan The role of molecular mimicry in the development of some autoimmune diseases, such as rheumatism, rheumatoid arthritis, the Julian-Barré syndrome, the antiphospholipid syndrome, multiple sclerosis, is reviewed. The data on the presence in bacteria and viruses antigenic determinants similar to those in human tissues are presented. The phenomenon of epitope mimicry is considered in the light of the latest research in the field of IgE autoreactivity, which may take part in the pathogenesis of allergic diseases.
15715001 [Bucillamine-induced dermatomyositis-like clinical features in a patient with rheumatoid a 2005 Jan A 78 year-old woman was admitted to our hospital because of subacutely progressive dysarthria, dysphagia, proximally dominant muscle weakness and erythema in the neck and back. She was diagnosed as having rheumatoid arthritis (RA) at the age of 60 and treated with bucillamine (BUC) for 8 years. Laboratory tests included a rheumatoid factor of 1,472U/ml. Serum creatine kinase level was slightly elevated. The activated T cells in the peripheral blood were markedly increased. Needle EMG demonstrated myogenic changes. The magnetic resonance image of the left upper arm showed diffuse muscle atrophy and inflammatory changes in the triceps muscle. The muscle biopsy revealed perivascular inflammatory cell infiltraton and type II fiber atrophy. A biopsy from the skin showed mild perivascular inflammatory cell infiltraton. According to the results of these findings, she was thought to have dermatomyositis due to BUC. After withdrawal of BUC followed by the administration of prednisolone 1mg/kg, her symptoms improved and activated T cells in the peripheral blood were decreased. In Japan, BUC is widely accepted as an effective drug in the treatment of RA, even though it is known to induce some autoimmune diseases. However, the mechanism of the development of autoimmune disease is unclear. We considered that the long-term use of bucillamine could trigger an autoimmune response such as an increase in activated T cells and the development of dermatomyositis-like clinical features in our patient. In conclusion, when RA patients treated with BUC show a clinical picture compatible with dermatomyositis, its causative relationship has to be considered.
16470008 Evidence for genetic variation as a factor in maintaining health. 2006 Feb For many chronic diseases, the influence of genetics is subtle and complex and does not conform to simple Mendelian patterns of inheritance as is seen with single-gene disorders. Genetic variation can influence the propensity for the initiating event, the progression to a clinical disease state, and the trajectory of disease. One example of how genetic variations may affect complex diseases is provided by the interleukin 1 family of cytokines. This cytokine family plays a key role in mediating inflammation, which is a central component of many chronic diseases, including coronary artery disease and rheumatoid arthritis. Recent research has identified many sequence variations in the regulatory DNA of the genes coding for important members of the interleukin 1 family, and these variations are associated with differential effects on the inflammatory response. These in turn alter the risk of some diseases in which inflammation plays a role and also affect physiologic responses, such as the inflammatory response to exercise. As this new genetic knowledge is developed and extended, it may be possible to make health care interventions at an earlier stage, before clinical disease is established, rather than after tissues have been permanently damaged.
16078324 Clinical and serological heterogeneity in patients with anticentromere antibodies. 2005 Aug OBJECTIVE: To evaluate the clinical and serological heterogeneity in patients with anticentromere antibodies (ACA). METHODS: One hundred twenty patients with ACA were analyzed retrospectively. ACA were detected initially on the basis of indirect immunofluorescence on HEp-2 cells, and then antibodies to CENP-B were measured by ELISA. Antibodies to other nuclear antigens were also detected by double immunodiffusion and/or ELISA. RESULTS: Eighty-four patients (70.0%) had systemic sclerosis (SSc; scleroderma) and 36 patients (30.0%) had other rheumatic diseases or miscellaneous disorders. Among patients with SSc, 35 patients (41.7%) had SSc in overlap mostly with Sjögren's syndrome (SS), in part with rheumatoid arthritis and/or primary biliary cirrhosis (PBC). Five of 36 patients (13.9%) without SSc also had overlap syndrome of more than 2 rheumatic diseases or PBC. All CREST features (calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, telangiectasias) were found significantly more in SSc than in other diseases. A combination of RST was the most frequently seen, followed by CREST and CRST in the SSc group. In contrast, 22 of 36 patients (61.1%) without SSc had no CREST features, and the rest had only Raynaud's phenomenon and/or telangiectasia. Twenty-five of 75 patients (33.3%) with SSc and 6 of 25 patients (24.0%) with other diseases had a slight elevation of creatine phosphokinase concentration with no apparent myositis signs and/or skin lesions, suggesting a new additional sign of patients with ACA. Seventy-two patients (60.0%) had ACA alone and 48 patients (40%) had ACA mixed with other disease marker antinuclear antibodies (ANA). ACA alone occurred more frequently in patients with SSc and in the non-overlap group, whereas patients with ACA mixed with other ANA were more frequently found in the other disease and the overlap syndrome groups. Anti-CENP-B ELISA levels of the SSc group were significantly higher than those of other disease groups in all patients, in patients with ACA alone, and in patients having ACA together with other ANA. The most frequently concurrent ANA were anti-SSA/Ro antibodies; and the other ANA, including anti-SSB/La, RNP, topoisomerase-I, Jo-1, Ku, and dsDNA antibodies, were also positive alone or combined with more than 2 ANA in patients with ACA. Five patients with CREST syndrome having ACA and anti-RNP antibodies had clinical manifestations compatible with mixed connective tissue disease. SS was found in 37.0% of patients who had higher anti-CENP-B ELISA levels and higher coincidence of anti-SSA/Ro antibodies than the patients without SS. CONCLUSION: ACA were positive mostly in patients with SSc with CREST features and partly in other rheumatic disorders. The high levels of ACA may be necessary for the development of CREST features, and frequent concurrence of other disease marker ANA may contribute to the development of heterogeneous clinical characteristics, including overlap syndrome, in patients with ACA.
16690410 Analysis of a functional BTNL2 polymorphism in type 1 diabetes, rheumatoid arthritis, and 2005 Dec The aim of this study was to test whether the functional variant rs2076530 of the BTNL2 gene confers susceptibility to the autoimmune diseases type 1 diabetes (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Our study populations consisted of 326 patients with T1D and 351 healthy subjects, 808 patients with RA and 1137 healthy controls, and 372 patients with SLE and 280 healthy controls. Genotyping of the BTNL2 gene rs2076530 polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. We observed statistically significant differences in the distribution of BTNL2rs2076530 alleles between patients with T1D, RA, and SLE and healthy controls (p=0.0035, 0.000003, and 0.00002, respectively), but in two divergent ways: the G allele was associated with T1D and RA, and the A allele was associated with SLE. However, the polymorphism exhibited strong linkage disequilibrium with HLA DQB1-DRB1 haplotypes previously identified as predisposing to the diseases. When the BTNL2 polymorphism was tested conditional on HLA DQB1-DRB1haplotypes, the BTNL2 effect was no longer significant in all three study populations. The BTNL2 rs2076530 polymorphism is associated with T1D, RA, and SLE because of its strong linkage disequalibrium with predisposing HLA DQB1-DRB1 haplotypes in Caucasian populations.
16255036 A novel mechanism of neutrophil recruitment in a coculture model of the rheumatoid synoviu 2005 Nov OBJECTIVE: Rheumatoid arthritis (RA) is classically thought of as a Th1, T lymphocyte-driven disease of the adaptive immune system. However, cells of the innate immune system, including neutrophils, are prevalent within the diseased joint, and accumulate in large numbers. This study was undertaken to determine whether cells of the rheumatoid stromal microenvironment could establish an inflammatory environment in which endothelial cells are conditioned in a disease-specific manner to support neutrophil recruitment. METHODS: Human umbilical vein endothelial cells (ECs) and fibroblasts isolated from the synovium or skin of RA patients were established in coculture on opposite sides of porous transwell filters. After 24 hours of EC conditioning, the membranes were incorporated into a parallel-plate, flow-based adhesion assay and levels of neutrophil adhesion to ECs were measured. RESULTS: ECs cocultured with synovial, but not skin, fibroblasts could recruit neutrophils in a manner that was dependent on the number of fibroblasts. Antibody blockade of P-selectin or E-selectin reduced neutrophil adhesion, and an antibody against CD18 (the beta2 integrin) abolished adhesion. Blockade of CXCR2, but not CXCR1, also greatly inhibited neutrophil recruitment. Interleukin-6 (IL-6) was detectable in coculture supernatants, and both IL-6 and neutrophil adhesion were reduced in a dose-dependent manner by hydrocortisone added to cocultures. Antibody blockade of IL-6 also effectively abolished neutrophil adhesion. CONCLUSION: Synovial fibroblasts from the rheumatoid joint play an important role in regulating the recruitment of inflammatory leukocytes during active disease. This process may depend on a previously unsuspected route of IL-6-mediated crosstalk between fibroblasts and endothelial cells.
15754027 Heat shock protein 90 is required for increased DNA binding activity of activator protein- 2005 Apr We have studied the DNA binding profiles of activator protein-1 (AP-1) involved in synovial overgrowth and osteoporosis in rheumatoid arthritis (RA) in relation to the molecular chaperon heat shock protein 90 (HSP90). The AP-1 binding activity of the nuclear extracts of rheumatoid synovial cells was basically increased as compared with osteoarthritic synovial cells. Upon stimulation with inflammatory cytokines IL-1beta or TNFalpha, the AP-1 binding activity was further increased in rheumatoid synovial cells, and increased AP-1 protein was composed as heterodimers of Fos and JunD which was not known before as a major component of AP-1 in rheumatoid synovial cells. The increase of AP-1 binding activity as induced by inflammatory cytokines was specifically inhibited by geldanamycin, radicicol or herbimycin A, specific inhibitors of HSP90, while AP-1 protein was not decreased by geldanamycin. Further, HSP90 protein was not decreased by the inhibitors. The findings indicate that HSP90 is required for increased AP-1 binding activity of rheumatoid synovial cells under inflammatory stimuli and that AP-1 binding activity is inhibited by functionally inactivating HSP90 with the inhibitors.
16953150 Improving outcomes in tumour necrosis factor a treatment: comparison of the efficacy of th 2006 Jun AIM: The aim of this study was to evaluate the differences between infliximab and etanercept, in terms of clinical efficacy and rapidity of action. METHODS: We selected 32 patients with rheumatoid arthritis (RA) with an incomplete response to disease modifying anti-rheumatic drugs (DMARDs), and randomly assigned them to etanercept or infliximab. We evaluated the efficacy after 14, 22, 54 weeks of treatment, using the American College of Rheumatology (ACR) 20, 50 and 70 criteria, and the improvement of quality of life using the Health Assessment Question-naire (HAQ). RESULTS: After 14 weeks, the 54.4% of patients was considered ACR-responders in the etanercept group, whereas, in the infliximab group, the percentage of responders was 74.4%: infliximab gave better results for the tender joint count and for physician's global assessment. After 22 weeks, no significant difference was present. After 54 weeks, etanercept resulted more effective than infliximab for tender joint count (TJC) value, for visual analogic scale (VAS) for pain score, for global disease assessment value, with 74.4% of patients considered ACR-responders in the group treated with etanercept and 60% in the group treated with infliximab. As regards HAQ, patients in the infliximab group presented higher scores at week 14, but in weeks 22 and 54, patients in the etanercept group showed better results. Therefore, both infliximab and etanercept are efficacious in RA, but infliximab is more efficacious than etanercept in week 14. Vice versa, in week 54 etanercept is the most efficacious drug. CONCLUSIONS: Physicians have 2 weapons in their armamentarium, with the same target but distinct clinical, pharmacokinetic and pharmacodynamic properties.
16195160 Work ability of Dutch employees with rheumatoid arthritis. 2005 Jul OBJECTIVES: To (i) examine the association between fatigue, psychosocial work characteristics (job control, support, participation in decision making, psychological job demands), and physical work requirements on the one hand and work ability of employees with rheumatoid arthritis (RA) on the other, and (ii) determine the advice that health care professionals give to employees with RA on how to maintain their work ability. METHODS: Data were gathered from 78 employees with early RA (response = 99%) by telephone interviews and self-report questionnaires. RESULTS: Fatigue, lack of autonomy, low coworker/supervisor support, low participation in decision making, and high physical work requirements (i.e. using manual force) predicted low work ability. High psychological job demands, however, did not predict low work ability. The rheumatologist, occupational physician, occupational therapist, physiotherapist, and psychologist gave advice on how to cope with RA at work to 36, 30, 27, 26, and 17% of the employees, respectively. Advice was directed mainly at factors intrinsic to the employee. Employees expressed a positive attitude towards this advice. CONCLUSIONS: Fatigue, lack of support, lack of autonomy, lack of participation in decision making, and using manual force at work (e.g. pushing and pulling) threaten the work ability of employees with RA. According to the employees with RA, involvement of health care professionals from different disciplines and the implementation of organizational and technical interventions would help them to tackle these threats.
16343832 Iatrogenically-related, fatal methotrexate intoxication: a series of four cases. 2006 Jan 27 Since the early eighties, the folic antagonist methotrexate (MTX) has been used in long-term treatment of rheumatoid arthritis. Because of the high toxic potential clinical and laboratory controls at regular intervals and patient education in order to avoid misadventure is of overriding importance. We present four cases of fatal MTX intoxication due to medical malpractice from the Tübingen Institute of Forensic Medicine autopsy material, which show the severe consequences of MTX overdose. It becomes evident that among non-rheumatologists there still is need for information about toxicity and dose limitation in MTX low-dose treatment.
16464988 Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in 2006 Nov OBJECTIVE: To evaluate the efficacy and safety of etanercept (ETN) monotherapy compared with combination ETN and methotrexate (MTX) treatment in patients with rheumatoid arthritis who had an inadequate response to MTX monotherapy. (The response was defined by the presence of Disease Activity Score-28 joint count (DAS28) >or=3.2 or a combination of >or=5 swollen joints, >or=5 painful joints and erythrocyte sedimentation rate >or=10 mm/h.) METHODS: Patients with active rheumatoid arthritis taking MTX >or=12.5 mg/week for >or=3 months were included in this 16 week, randomised, open-label study. Patients were randomly assigned to either ETN (25 mg subcutaneous injection twice weekly) added to the baseline dose of MTX or ETN monotherapy. RESULTS: 315 patients were randomised to ETN (n = 160) or ETN plus MTX (n = 155). The primary end point, DAS28 (4) improvement of >1.2 units, was achieved by 72.8% and 75.2% of patients treated with ETN and those treated with ETN plus MTX, respectively, with no significant difference (p = 0.658) between the two groups. The European League Against Rheumatism response criteria of good or moderate response was attained by 80.0% of patients in the ETN group and by 82.4% of patients in the ETN plus MTX group. American College of Rheumatology 20%, 50% and 70% response rates achieved by both groups were also similar: 71.0% v 67.1%, 41.9% v 40.1% and 17.4% v 18.4%, respectively. The rates of adverse and serious adverse events were similar between the treatment groups. CONCLUSION: Both the addition of ETN to MTX and the substitution of ETN for MTX in patients with rheumatoid arthritis who had an inadequate response to MTX resulted in substantial improvements in clinical signs and symptoms and were generally well-tolerated treatment strategies for improving clinical signs and symptoms of rheumatoid arthritis.
16081018 The medial approach to triple arthrodesis. Indications and technique for management of rig 2005 Sep Between 1995 and 2002 the authors treated 17 patients who had a rigid hindfoot valgus deformity, and for whom a triple arthrodesis was planned, using a single medial incision. The indication for surgery was pain that was refractory to shoe wear, orthotic, and brace modifications. The severity of the hindfoot deformity itself was not a sufficient indication for this procedure. All 17 patients were examined a mean of 3.5 years following surgery (1-8 years). Subtalar and talonavicular arthrodesis was achieved in all patients and calcaneocuboid arthrodesis was achieved in 15 of 17 patients (2 asymptomatic pseudoarthrosis). The medial approach to triple arthrodesis is a reliable procedure, and can be used with a predictable outcome in patients who are at risk for wound healing complications for correction of hindfoot valgus deformity.