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ID PMID Title PublicationDate abstract
17911454 Rapid and deep control of inflammation in rheumatoid arthritis with infliximab and its cor 2007 Sep Rheumatoid arthritis (RA) is a chronic inflammatory disease with predominant joint involvement and possible systemic compromise, which leads to a handicapped status and poor quality of life. An optimal approach to treat RA requires early and intensive intervention with close monitoring of treatment response. Tumor necrosis factor (TNF) blockers are recommended in cases of active RA after the unsuccessful use of effective disease-modifying antirheumatic drugs (DMARDs); even adding them to treatment or replacing these drugs. Anti-TNF therapies have been demonstrated to reduce significant joint damage and to relieve symptoms during a prolonged time (see Scott and Kingsley, 2006). The efficacy of infliximab in an open-label trial is summarized with respect to speed of onset of action, durability of response, and its correlation between clinical and laboratory parameters. Safety for long-term treatment is also summarized. We studied 105 RA patients with more than 3 years' history of disease during 24 months on i.v. infliximab (75 completed study). We evaluated ACR responses at base line, and at 1, 6, 12, 16, 52, 77, and 104 weeks. Morning stiffness, swollen and tender joints, HAQ, SF-36% (PCS/MCS), polymerase chain reaction (PCR), erythrosedimentation rate (ESR), transaminases, rheumatoid factor (RF) levels, hemogram, and adverse events profile were all assessed. The treatment offered rapid and sustained clinical improvements as revealed by ACR responses and marked changes in the parameters previously described. Important changes were made in functional status and acute-phase reactants. Finally, infliximab was considered well tolerated and did not affect the safety profile of this trial.
17549500 [Intracellular signaling pathways of synovial fibroblasts in rheumatoid arthritis]. 2007 Jul Rheumatoid arthritis (RA) is a chronic autoimmune disease of still unknown etiology that results in characteristic destructive changes of the joints. Research of the past years has demonstrated that synovial fibroblasts play a central role in the initiation and perpetuation of these destructive changes. Stimulation of the synovial fibroblasts through complex and interacting intracellular signaling pathways results in a stable activation that is maintain even without continuous stimulation by inflammatory cells and their mediators. The pathological attachment to articular cartilage, increased secretion of matrix degrading enzymes and alterations in programmed cell death are main characteristics of synovial fibroblasts from patients with RA and result in the progressive destruction of articular structures. The permanent activation of a number of intracellular signaling pathways constitutes the underlying responsible mechanism for the activation of synovial fibroblasts in RA. These signaling pathways do not only show a high degree of complexity, but are also interconnected in multiple ways. This article summarizes recent findings on the activation of intracellular signaling pathways in fibroblasts and points to potential targets for novel therapeutic strategies.
19074912 Adaptation and cross-cultural validation of the rheumatoid arthritis work instability scal 2009 Nov BACKGROUND: Despite recent advances, work disability in rheumatoid arthritis (RA) remains common. Work disability is frequently preceded by a period of work instability characterised by a mismatch between an individual's functional abilities and job demands. This could raise the risk of work disability if not resolved. A work instability scale for RA (RA-WIS) has previously been developed to screen for this risk. The objective of this study was the adaptation of this scale into French, Dutch and German. METHOD: Different language versions of the RA-WIS were produced through a process of forward and back translations. The new scales were tested for face validity. English data from the original developmental study was pooled with data generated through postal surveys in each country. The internal construct and cross-cultural validity of the new scales were assessed using Rasch analysis, including differential item functioning (DIF) by culture. RESULTS: The pooled data showed good fit to the Rasch model and demonstrated strict unidimensionality. DIF was found to be present for six items, but these appeared both to cancel out at the test level and have only a marginal effect on the test score itself. CONCLUSIONS: The RA-WIS was shown to be robust to adaptation into different languages. Data fitted Rasch model expectations and strict tests of unidimensionality. This project and the continuing work on further cross-cultural adaptations have the potential to help ensure clinicians across Europe are able to support RA patients to achieve their potential in work through early identification of those most at risk.
17985113 [Shoulder arthroplasty in rheumatoid arthritis]. 2007 Nov The long-term survival rate of shoulder arthroplasties is comparable to that of hip arthroplasties, at about 85% after 15 years. The diagnosis of rheumatoid arthritis is the most important predictive factor for the end-result, with a stronger influence than the condition of the rotator cuff or whether a hemiarthroplasty or a total arthroplasty is performed. Unlike the situation in rheumatoid arthritis, in osteoarthritis wear and tear on the glenoid is caused mainly by medial erosion with cranial migration. The functional results are slightly better with total shoulder replacements than with hemiarthroplasties. Arthroplasty in rheumatoid patients is adversely influenced by the poor quality of the rotator cuff, which is either primarily defective or develops secondary insufficiency as a result of the underlying illness. Secondary cranial migration, i.e. secondary rotator cuff failure, occurs in up to half these patients in the long term. It is frequently followed by glenoid loosening after total shoulder arthroplasty. Nevertheless, glenoid loosening is frequently not progressive over long periods and is well tolerated by the majority of patients. Thus, the rate of glenoid revision operations in rheumatoid patients seldom exceeds 5% in mid- and long-term studies. Owing to poor bone quality, glenoid erosion after hemiarthroplasty is more frequent than in patients with osteoarthritis. In contrast to glenoid loosening, glenoid erosion is almost always painful and leads to poor results requiring surgical revision. In shoulder joints that are centred in the coronal plane and in which the rotator cuff is still intact or only moderately worn, with no more than one defective tendon, total arthroplasty should be given preference. The results achieved with humeral head surface replacement are as good as those yielded by conventional hemiarthroplasty; combination with the implantation of a glenoid is technically demanding but leads to even better results. Reverse arthroplasties should be reserved for patients over 70 years of age with complete or almost complete rotator cuff destruction. In younger patients bipolar implants should be used in preference; the functional results attained with these are admittedly limited, but unlike the reverse implants they do not involve the risk of loosening of the metaglenoid.
18927189 Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthr 2009 Jan RA is characterized by a systemic inflammatory state, in which immune cells and soluble mediators play a crucial role. These inflammatory processes resemble those in other chronic inflammatory diseases, such as atherosclerosis. The chronic systemic inflammation in RA can be considered as an independent risk factor for the development of atherosclerosis, and represents an important field to investigate the reasons of the increase of acute cardiovascular events in RA. In the present review, we focused on several mediators of autoimmunity, inflammation and endothelial dysfunction, which can be considered the most promising targets to prevent atherogenesis in RA. Among several mediators, the pro-inflammatory cytokine TNF-alpha has been shown as a crucial factor to induce atherosclerosis in RA patients.
16280267 Lessons for inflammatory bowel disease from rheumatology. 2006 Mar There are several areas of overlap between gastroenterology and rheumatology, some related to the side effects of drugs but others related to the similarities in probable pathogenic mechanisms and treatments. This is best illustrated by comparison between inflammatory bowel disease and rheumatoid arthritis-conditions of uncertain aetiology that are due to a combination of genetic and environmental factors and are associated with chronic inflammation in the absence of any clearly recognisable pathogen. Medical research is increasingly specialised but careful comparison of the relevant gastroenterological and rheumatological literatures suggests several common areas that are worthy of greater attention than they are currently receiving. These could include studies to address the following questions: (1) What are the functional and antigen-binding differences of the HLA class II alleles that are differently associated with rheumatoid arthritis and ulcerative colitis? (2) Why are both Crohn's disease and rheumatoid arthritis associated with smoking, yet, with one condition (Crohn's disease) increasing recently in incidence and the other (rheumatoid arthritis) becoming less common? (3) Which genetic and/or environmental factors distinguish the Turkish patients with HLA-B51-associated Behcet's disease who tend not to develop colitis and the Japanese patients with HLA-B51-associated Behcet's disease who develop colitis? (4) Is pANCA directly involved in the pathogenesis of ulcerative colitis-given evidence of its direct involvement in the pathogenesis of vasculitis? (5) Given the arguably greater similarity between rheumatoid arthritis and ulcerative colitis than with Crohn's disease, is etanercept effective in ulcerative colitis? (6) Do the very different risks of cancer in chronically inflamed colon and inflamed joints imply that cancer development requires both NFkappaB activation, to inhibit apoptosis, and the presence of agents, such as bacteria, to initiate DNA damage?
16878716 [Valve replacement for aortic regurgitation associated with rheumatoid arthritis: a series 2006 Jun Between 30 and 50% of patients with rheumatoid arthritis (RA) have cardiac involvement but only 2 to 10% have clinical manifestations. The authors report the results of a retrospective study of 5 cases of aortic regurgitation (AR) requiring valve replacement. There were 4 women and 1 man with an average age of 48.4 years. The average duration of the RA was 19.6 years. All patients had cardiac failure. Aortic valve replacement was performed in all cases, with bioprostheses in 4 out of 5 patients. The histopathological examination of the valves showed a rheumatoid nodule in 3 cases and non-specific lesions in one case. In the fifth patient, rheumatoid serology was positive in the pericardial effusion. The average interval between the onset of symptoms and cardiac surgery was 3.6 months (range 1 to 6 months) There were 3 deaths at 3 days, 20 months and 10 years, two patients survive after 12 and 14 years. The characteristic rapid progression of this form of AR, which may be life-threatening, should be emphasised.
18388522 Antibodies to citrullinated proteins in arthritis: pathology and promise. 2008 May PURPOSE OF REVIEW: The purpose of this review is to describe how the current knowledge of antibodies to citrullinated protein antigens in rheumatoid arthritis and related conditions emerged; to discuss the diagnostic and prognostic value associated with antibodies to citrullinated protein antigens as a biomarker; and most importantly for this review, to discuss the potential pathogenetic significance of these antibodies. RECENT FINDINGS: Antibodies to citrullinated protein antigens have evolved from being mainly a diagnostic marker, to being recognized as something that can help us understand fundamental etiologic and pathogenetic features of rheumatoid arthritis. Fundamental in this context is the finding that rheumatoid arthritis can be divided into two distinct subsets by means of presence or absence of antibodies to citrullinated protein antigens. Thus, several genetic as well as environmental risk factors differ between these two variants of rheumatoid arthritis. From analysis of these genetic and environmental risk factors, new testable hypotheses have been produced concerning triggering of antibodies to citrullinated protein antigens, and potential pathogenicity of antibodies to citrullinated protein antigens and accompanying immune reactions. SUMMARY: The implications of the findings are that antibodies to citrullinated protein antigens can be used for early and precise diagnosis of a subset of rheumatoid arthritis with worse prognosis than other polyarthritides, and that a new basis is formed for etiologic and pathogenetic studies of antibodies to citrullinated protein antigens-positive rheumatoid arthritis.
16934722 Atraumatic odontoid fractures in patients with rheumatoid arthritis. 2006 Sep BACKGROUND CONTEXT: Instability of the cervical spine is a common problem in patients with rheumatoid arthritis. The natural course of rheumatoid arthritis in the cervical spine is well documented. However, the true prevalence of occult fractures of the odontoid process in patients with rheumatoid arthritis is not known. PURPOSE: To draw attention to the possibility of occult, atraumatic fractures of the odontoid process in patients with rheumatoid arthritis. STUDY DESIGN: We report on two cases with previously unrecognized fractures of the odontoid process. METHODS: In this case series, we review the individual radiographic findings and clinical observations in two rheumatoid patients in whom a fracture of the odontoid process was diagnosed. RESULTS: Each one of these two rheumatoid patients had an unrecognized fracture of the odontoid process without any prior history of trauma. Their fracture was identified serendipitously during workup for neck pain. CONCLUSIONS: Occult, atraumatic fractures of the odontoid process may be found in patients with long-standing rheumatoid arthritis. This injury should be suspected if previously asymptomatic patients complain about new onset of neck pain without significant trauma.
17499710 Rheumatoid arthritis and reproduction. 2007 May Additional research is needed to establish the safety of biologic agents in pregnancy and lactation. The practitioner should convey information regarding the natural history of rheumatoid arthritis during pregnancy and safety issues related to pharmacotherapies to every woman of childbearing age with RA, well before conception and pregnancy, to ensure optimal outcomes.
17530670 Using Rasch analysis to compare the psychometric properties of the Short Form 36 physical 2007 Jun 15 OBJECTIVE: Item-response theory is increasingly used in the development of robust measurement tools. The extent to which the Health Assessment Questionnaire (HAQ) disability index (DI) and Short Form 36 (SF-36) physical functioning subscale (PF) fit a Rasch model in psoriatic arthritis (PsA) is uncertain. Our objective was to compare the psychometric properties of the HAQ DI and SF-36 PF in PsA and rheumatoid arthritis (RA) using Rasch analysis. METHODS: Patients with RA (n = 142) and PsA (n = 134) were identified from a disease register based at a regional rheumatology service that serves a population of approximately 400,000 individuals. Responses to the HAQ DI and SF-36 PF were analyzed for item fit, differential item functioning (DIF), scale length (item separation), floor effects, and item difficulty by fitting the data to a Rasch model. The extent to which each instrument measured the same concept (disability) was also assessed in the PsA cohort using the Rasch model. RESULTS: Item separation was much better for the SF-36 PF than the HAQ DI in PsA (9.12 logits versus 2.06 logits). There was evidence of marked DIF for the HAQ DI items activities, grip, and rising and relatively minor DIF for 4 items of the SF-36 PF. The distribution of SF-36 PF was better than HAQ DI in PsA, with floor effects of 3.1% versus 30.4%. Common person equating demonstrated that the 2 instruments measure the same construct in PsA. CONCLUSION: The SF-36 PF has significant psychometric advantages over the HAQ DI in PsA.
16518665 Combined use of propagation velocity and intraventricular dispersion of E wave velocity fo 2006 Jun PURPOSE: The aim of this study was to evaluate diastolic functions in patients with rheumatoid arthritis (RA) by propagation velocity and intraventricular dispersion of E wave velocity. METHODS: Thirty-four patients fulfilling American Rheumatism Association (ARA) criteria for the diagnosis of RA without evidence of cardiac disease and left ventricular systolic dysfunction were enrolled in this study. Echocardiographic examinations were performed for the evaluation of diastolic dysfunction in all patients. RESULTS: Propagation velocity in RA patients was significantly lower than the control group (42+/-16 cm/s, 54+/-15 cm/s, p=0.002). There was significant intraventricular dispersion of E wave velocity towards the cardiac apex in RA patients (p<0.001) when compared with the controls (p=0.79). There was a significant correlation between intraventricular dispersion of E wave velocity and diastolic dysfunction in the patients in which the duration of illness was longer than 10 years (p<0.001). CONCLUSION: Structural myocardial abnormalities may cause impaired left ventricular relaxation in RA patients and these changes are correlated with the duration of the disease. Our findings demonstrate that combined use of propagation velocity and intraventricular dispersion of E wave velocity can help the early determination of diastolic functions in the patients with RA.
18998141 Patients with active rheumatoid arthritis but only few tender and swollen joints: a subgro 2009 Apr The disease activity score of 28 joints (DAS28) is now commonly used for the guidance of treatment decisions in rheumatoid arthritis (RA). The goal of this work was to determine whether patients with DAS28 > 3.2 but less than 2 swollen and 2 tender joints respond differently to treatment than patients with a higher number of active joints. One hundred and ninety two patients with active RA treated in a rheumatology hospital as in-patients were studied prospectively. At admission (T1), release (T2) and 3 months after release (T3) disease activity (DAS28-CRP at T1 + 2, RADAI at T1 + 3), pain (numeric scale at T1 - 3) and function (FFbH at T1 + 3) were measured. A total of 148 patients had two or more (group 1) and 44 less than 2 swollen and tender joints at admission (group 2) but both groups had similar over all DAS28-scores. The groups significantly differed in their outcome after 3 months: group 1 had a significant better reduction of disease activity, pain and functional deficit (p < 0.001 for the fulfilment of defined response criteria and p < 0.05 for comparison of the mean values for pain and function) in comparison to group 2. Although the numbers were small sub-analysis suggested that the differences might be due to a better response to newly administered DMARD and TNF-alpha-inhibitor therapy in group 1. Active RA patients with less than 2 swollen and 2 tender joints represent a subgroup with lower response to treatment with DMARD or TNF-alpha-inhibitors. This has to be taken into account in the management of these patients.
18930987 Infliximab improves vascular stiffness in patients with rheumatoid arthritis. 2009 Aug OBJECTIVES: Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. Tumour necrosis factor alpha (TNFalpha)-blocking therapy has been shown to reduce RA disease activity measures and joint damage progression. Some observational studies suggest that TNFalpha blockade reduces mortality and incidence of first cardiovascular events. The mechanisms contributing to these outcomes are unclear. This study assessed the effects of infliximab treatment on vascular stiffness and structure in patients with RA. METHODS: A post hoc analysis of longitudinal data from a randomised placebo controlled study evaluated the effect of infliximab on vascular assessments. 26 patients received intravenous infliximab (3 mg/kg) at weeks 0, 2, 6 and every 8 weeks thereafter to week 54. Patients were followed up to 56 weeks of infliximab therapy with assessments of RA disease activity, cardiovascular risk factors, vascular stiffness (pulse wave velocity (PWV)), carotid intima media thickness (CIMT) and carotid artery plaque (CAP). Univariate analyses of changes over time by repeated measures analysis of variance (ANOVA) were followed by multivariate time-series regression analysis (TSRA) if changes were seen. RESULTS: PWV was significantly lower (better) after 56 weeks of treatment with infliximab (ANOVA p<0.01, TSRA p<0.01). However, CIMT (ANOVA p = 0.50) and CAP (chi(2) = 4.13, p = 0.88) did not change over the study period. Multiple cardiovascular risk measures did not change with treatment and did not correlate with changes in measures of vascular structure. CONCLUSIONS: Arterial stiffness improves with infliximab treatment in RA. This change may help explain the improved cardiovascular disease survival in patients with RA receiving TNFalpha-blocking therapy.
16891919 Role of anticyclic citrullinated peptide in the diagnosis of early rheumatoid factor-negat 2006 Aug BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) is a relatively new serologic marker, which has been proposed for use in the diagnosis of rheumatoid arthritis (RA) and is said to be a highly specific. OBJECTIVE: The aim of the study was to evaluate the role of anti-CCP in a South Indian population of patients with suspected RA in the early stages when rheumatoid factor is negative and clinical presentation is atypical. METHODS: Patients with early inflammatory arthritis who were rheumatoid factor-negative were investigated for anti-CCP. The patients were reviewed by a rheumatologist and, based on American College of Rheumatology criteria, were diagnosed with RA or another disease after a follow-up period of 3 to 6 months. The rheumatologist was blinded to the results of the anti-CCP. The sensitivity and specificity of anti-CCP was estimated in comparison to follow up and final clinical diagnosis. The anti-CCP was estimated by the enzyme-linked immunosorbent assay method using a commercially available kit (Euroimmune). RESULTS: One hundred forty-three patients with a mean age of 47.1 years and a male to female ratio of 0.22:1 were recruited for the study. Thirty cases were positive for anti-CCP and 41 cases were finally diagnosed RA. Twenty-six of the 30 anti-CCP-positive patients were diagnosed with RA. Thus, the sensitivity of anti-CCP in our institution for the diagnosis of RA in the early stage in a group of rheumatoid factor-negative patients with atypical presentation was 63.4% with 36.6% false-negatives and the specificity was 96.1% with 3.9% false-positive cases. The positive predictive value of anti-CCP was 86.7% and the negative predictive value was 86.7%. Kappa statistic of agreement, chi McNemar test, indicated anti-CCP to be an efficient test in this study population. CONCLUSION: Anti-CCP is a useful and highly specific but not absolutely specific or sensitive test to detect RA and supplements rheumatoid factor in the presence of a strong clinical suspicion.
17409135 Ankle/hindfoot arthrodesis in rheumatoid arthritis improves kinematics and kinetics of the 2007 Jun OBJECTIVES: To evaluate the effects of ankle/hindfoot arthrodesis in rheumatoid arthritis (RA) patients on gait pattern of the knee and hip. METHODS: In this prospective follow-up study, 14 RA patients scheduled for ankle/hindfoot arthrodesis (talo-calcaneal, talo-navicular, calcaneo-cuboid and/or talo-crural joints) and 14 age- and sex-matched healthy controls were included. Three-dimensional gait analyses of joint angles, moments and work were performed at the index operation and after 13 months of follow-up. Each patient underwent clinical assessments of pain while walking, overall evaluation of disease activity, Health Related Quality of Life Questionnaire (EQ-5D), activity limitations, maximum walking distance, difficulty with walking surface and gait abnormality. For comparisons of pre- vs post-operative conditions, Wilcoxon's matched pairs test and Friedman ANOVA by rank test were used. RESULTS: At follow-up after ankle/hindfoot fusion surgery, RA patients demonstrated a statistically significant improvement in mean range of joint motions, moments and work in the overlying joints such as the knee and hip. Moreover, there was significantly less pain, disease activity, activity limitation, difficulty with walking surface and gait abnormality. EQ-5D and maximum walking distance were also significantly improved at follow-up. CONCLUSIONS: Our results demonstrate that ankle/hindfoot arthrodesis in RA is an effective intervention to reduce pain and to improve Health Related Quality of Life and functional ability. Moreover, the overlying leg joints experience an improvement in joint motion, muscle-generated joint moments and work during walking. Three-dimensional gait analysis may assist future investigations of the effects of orthopaedic surgery on functional mobility in RA to prevent irreversible disablement.
17605425 [Glottis morphology in rheumatoid arthritis]. 2007 Rheumatoid arthritis (RA) is an inflammatory disease of the connective tissue, which can affect larynx and cricoarytenoid (CA) joints, as well. The AIM of this study was assessment of 1) glottis morphology and frequency of laryngeal structures involvement in RA of peripheral joints and 2) evaluation of rheumatoid patients' complaints which can indicate the laryngeal involvement. MATERIAL: 77 patients were examined (71 women and 16 men) in the age from 19 to 77 (mean 56,69). RA duration was from 1 month to 29 years (mean 9,38). RA was active in 61% of patients. METHOD: Anamnesis, physical examination, videolaryngoscopy, computer tomography, electromyography. RESULTS: The most frequent complaints were: foreign body sensation in the throat (51%), hoarseness (47%) with accompanying weakness of voice and dysphagia. In videolaryngoscopic examination swelling and/or redness of mucosal tissue in CA area was observed in 45% of patients. In 3 women impairment of vocal folds was stated, in 1 it was limitation of right vocal fold mobility and in 2 bilateral vocal folds immobility and tracheotomy was necessary. In patients with active RA and with foreign body sensation in the throat significantly more often inflammatory changes in larynx were visible. CONCLUSIONS: 1. Rheumatoid inflammation in the larynx is demonstrated by swelling and/or redness of mucosal tissue in CA area and in some individuals by its immobilization. 2. In the periods of RA intensification complains of foreign body sensation in the throat and hoarseness may indicate on laryngeal involvement. Our study results justify a suggestion of continuation of the morphological and functional changes estimation in patients with peripheral RA.
17634141 Erosive arthritis. 2007 Inflammation and degradation of bone are two closely linked processes. Chronic inflammatory arthritis not only leads to inflammatory bone loss but it also involves local erosion of articular bone. This osteo-destructive feature of chronic inflammatory arthritis is a major cause of disability in patients with rheumatoid arthritis. Osteoclasts are essential for the resorption of mineralized cartilage and subchondral bone in chronic arthritis. The observed up-regulation of osteoclast differentiation factors (receptor activator of nuclear factor-kappaB ligand [RANKL]) in the synovial membrane of chronically inflamed joints indicates that osteoclasts are abundant in this setting, leading to rapid degradation of mineralized tissue. Blockade of osteoclast formation is thus a key strategy in preventing structural damage in arthritis. Denosumab, a humanized antibody that neutralizes RANKL, is an attractive candidate agent to inhibit inflammatory bone loss.
16571962 Preoperative evaluation of extension capacity of the occipitoatlantoaxial complex in patie 2006 Apr BACKGROUND: The authors devised a new method, the hyomental distance ratio (HMDR), for preoperatively identifying patients with a reduced occipitoatlantoaxial extension capacity, which was defined as the ratio of the hyomental distance in head extension position to that in the neutral position. They compared the accuracy of the HMDR with that of the Bellhouse test in 40 patients with rheumatoid arthritis. METHODS: Each patient wearing goggles on which a goniometer was mounted sat upright with the head in the neutral position and then extended the head maximally. The angle of the goggles and the hyomental distance were measured in the two head positions, and a lateral cervical radiograph was taken simultaneously. The Bellhouse angle was defined as a difference in the angles of the goggles between these positions. RESULTS: Median values of the radiologic occipitoatlantoaxial extension angle and the Bellhouse angle were 11.2 degrees and 24.9 degrees , respectively. In 21 of 40 patients, the radiologic occipitoatlantoaxial extension angle was less than 12 degrees (reduced occipitoatlantoaxial extension capacity). In these patients, extension of the median angle of 16.4 degrees occurred at the subaxial regions and was greater than that of 8.5 degrees in patients with a radiologic occipitoatlantoaxial extension angle of 12 degrees or more (P < 0.01). As a result, a strong relation between the Bellhouse angle and radiologic occipitoatlantoaxial extension angle was not established (P < 0.01, r = 0.48). In contrast, the HMDR correlated well with the radiologic occipitoatlantoaxial extension angle (P < 0.0001, r = 0.88). The areas under the receiver operating characteristic curve of the Bellhouse test and the HMDR were 0.72 and 0.95, respectively. CONCLUSIONS: The HMDR was a good predictor of a reduced occipitoatlantoaxial extension capacity in patients with rheumatoid arthritis, but the Bellhouse test was not a clinically reliable method.
17203006 Drug Insight: resistance to methotrexate and other disease-modifying antirheumatic drugs-- 2007 Jan The chronic nature of rheumatoid arthritis (RA) means that patients require drug therapy for many years. Many RA patients, however, have to discontinue treatment because of drug-related toxic effects, loss of efficacy, or both. The underlying molecular cause for loss of efficacy of antirheumatic drugs is not fully understood, but it might be mediated, at least in part, by mechanisms shared with resistance to anticancer drugs. This Review outlines molecular mechanisms that could be involved in the onset of resistance to, or the loss of efficacy of, disease-modifying antirheumatic drugs in RA patients, including methotrexate, sulfasalazine, chloroquine, hydroxychloroquine, azathioprine, and leflunomide. The mechanisms suggested are based on findings from experimental laboratory studies of specific drug-uptake and drug-efflux transporters belonging to the superfamily of multidrug-resistance transporters, alterations in intracellular drug metabolism, and genetic polymorphisms of drug transporters and metabolic enzymes. We also discuss strategies to overcome resistance and the current clinical studies aiming to predict response and risk of toxic effects. More in-depth knowledge of the mechanisms behind these features could help facilitate a more efficient use of disease-modifying antirheumatic drugs.