Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
11469521 Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis 2001 The efficacy of weekly low-dose methotrexate treatment of rheumatoid arthritis is well documented. Efficacy and adverse effects are both dose dependent. and adverse effects rather than lack of efficacy are the main reason for discontinuing therapy. Several adverse effects are related to folate deficiencies, largely due to the antifolate properties of methotrexate. In order to reduce adverse effects without compromising drug efficacy, numerous clinical investigations have been performed using supplementation with folic or folinic acid during methotrexate therapy of patients with rheumatoid arthritis, addressing both the timing of folate supplementation and the weekly folate-to-methotrexate ratio. Based on these studies, an individually adjusted supply of folic acid rather than folinic acid is proposed. For many patients, however, a properly balanced diet is sufficient to avoid folate deficiency.
10904249 Cytokines in rheumatoid arthritis: trials and tribulations. 2000 Aug Biological agents that inhibit the activity of proinflammatory cytokines are being investigated for use in the treatment of rheumatoid arthritis. Thus far, two of these agents, both of which neutralize tumor necrosis factor alpha (TNF-alpha), have received US Food and Drug Administration approval for the treatment of the disease. Etanercept is a bioengineered fusion protein of the p75 soluble TNF receptor, and infliximab is a chimeric monoclonal antibody to TNF-alpha. Other agents that target proinflammatory cytokines are also being developed. By allowing earlier treatment and better-tolerated long-term therapy, biologics might help slow or prevent disease progression and joint destruction.
9032818 Evaluation of synovial cytokine patterns in rheumatoid arthritis and osteoarthritis by qua 1997 To compare the cytokine profile with the degree and composition of cellular infiltration in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium, synovial membranes from patients with RA (n = 14) and OA (n = 5) were examined, employing immunohistochemistry and competitive reverse-transcriptase polymerase chain reaction (RT-PCR), for interleukin (IL)-I beta, IL-2, IL-4, IL-5, IL-6, and IL-10, and tumour necrosis factor-alpha (TNF-alpha) gene expression. It was found that the strength of cytokine gene expression within the synovial membranes of patients with RA was not significantly correlated with the degree of synovial infiltration of T-cells, B-cells, or macrophages. No IL-2, IL-4, or IL-5 RNA was detected in the synovium of either RA or OA. Quantitative cytokine determination showed a similar pattern in RA and OA, although the two diseases differed in total synovial infiltration and the composition of infiltrating cellular elements. Thus the number of cell types known to produce certain cytokines does not appear to determine the strength of synovial cytokine expression measured by quantitative RT-PCR. Furthermore, the pattern of T-cell specific cytokines found in RA synovium does not accord with the concept of the TH0, TH1, and TH2.
11407084 Inhibitory effect of enzyme therapy and combination therapy with cyclosporin A on collagen 2001 May OBJECTIVE: There is increasing interest in the use of combination therapy for rheumatoid arthritis and in the possibility of combining the conventional drug approach with newer antirheumatic therapy. The present study investigates the efficacy of long-term prophylactic enzyme therapy and combination therapy with cyclosporin A in rats with collagen-induced arthritis. METHODS: Rats with collagen-induced arthritis were administered the following drugs: cyclosporin A (5 mg/kg/day and 10 mg/kg/day orally); a mixture of enzymes containing pure substances (bromelain, trypsin, rutin) in the same ratio as in Phlogenzym (PHL, 150 mg/kg, twice daily intrarectally); and a combination of 5 mg/kg/day cyclosporin A plus 300 mg/kg/day PHL for a period of 50 days from the immunization. Levels of serum albumin, serum nitrite/nitrate concentrations, changes in hind paw swelling and bone erosions were measured in the rats as variables of inflammation and destructive arthritis-associated changes. RESULTS: Treatment with 10 mg/kg cyclosporin A, as well as combination therapy with half dosages of cyclosporin A (5 mg/kg) plus PHL significantly inhibited both inflammation and destructive arthritis-associated changes. Significant differences in favor of combination therapy with 5 mg/kg CsA + 300 mg/kg PHL as compared to 5 mg/kg CsA alone were seen in hind paw swelling. Also, reduction of the radiographic scores was more significant in the combination therapy group. Five mg cyclosporin A or PHL alone reduced the disease markers studied to a lesser extent, and in the case of enzyme therapy this occurred at a later stage of arthritis development. CONCLUSION: Our results show the inhibitory effect of enzyme therapy on collagen-induced arthritis in rats, as well as the efficacy of cyclosporin A given in low doses in combination with enzyme therapy, which may be useful in the treatment of rheumatoid arthritis.
11182731 Grammont reverse total shoulder arthroplasty in patients with rheumatoid arthritis and non 2001 Jan This study was undertaken to determine whether patients with severe rheumatoid arthritis and irreparable rotator cuff rupture can be treated successfully with the Grammont shoulder arthroplasty. Seven patients with rheumatoid arthritis (8 shoulders) with nonreconstructible rotator cuff lesions and Larsen stage-V radiographic changes of the glenoid and the humeral head underwent a Grammont reverse shoulder arthroplasty. The Constant score improved from a mean of 17 points (range 4 to 25) preoperatively to a mean of 63 points (range 41 to 79) at a mean of 54 months (range 48 to 73) after shoulder arthroplasty. The mean strength at 90 degrees of abduction measured 3.6 kg (range 1 to 6). Shoulder instability was not observed. Complications included septic implant loosening (1 shoulder), aseptic glenoid loosening (2), and failed acromion osteosynthesis following the transacromial approach (3). These data of Grammont arthroplasty are encouraging with respect to restoration of stability and satisfactory function in rheumatoid, cuff-deficient shoulders. However, glenoid loosening remained a serious problem, and transacromial approaches were complicated by failure of acromial fixation.
11081013 The Short Version of the Sequential Occupational Dexterity Assessment based on individual 1999 Dec OBJECTIVE: The Sequential Occupational Dexterity Assessment (SODA) is a reliable and valid instrument to measure bimanual hand function in rheumatoid arthritis. Since administering SODA is time-consuming, the aim of this study is to construct a short SODA (SODA-S). METHODS: Dexterity was measured with the SODA twice (with an interval of one year) in 94 patients. Item analyses based on the different SODA tasks were carried out to determine which of the 12 individual tasks were most responsible for the observed changes in dexterity. RESULTS: Six of the 12 SODA tasks were identified as sensitive to change. Based on these 6 tasks, the SODA-S was computed. Internal consistency of the SODA-S is good (Cronbach's alphas at baseline and followup were 0.82 and 0.85, respectively). The correlation between the SODA and SODA-S is 0.92. This means that the information gathered from the SODA-S is almost equal to the information gathered from the full SODA. Norm scores are provided for both instruments. CONCLUSION: The SODA-S is a good alternative to the full SODA in following patient's dexterity in daily practice. However, when evaluating the effect of specific hand treatment, the full SODA may be preferred.
9402863 Mesangial glomerulonephritis as an extra-articular manifestation of rheumatoid arthritis. 1997 Nov Mesangial glomerulonephritis (MesGN) is a frequent renal biopsy finding in patients with rheumatoid arthritis (RA) presenting with haematuria and/or proteinuria. The purpose of this study was to describe the mesangial immunofluorescence (IF) findings in 37 such RA patients, and to correlate the nature of the glomerular immunodeposits with clinical data, levels of serum immunoglobulins and the concentrations of serum rheumatoid factors (RFs). The serological findings in RA patients with MesGN were correlated with those of RA patients matched for age, sex and duration of RA, but without clinically evident renal disease. The most characteristic mesangial IF finding in 37 RA patients with MesGN was IgM observed in 29 specimens (78%). IgA (n = 16) and C3 (n = 15) deposits were also frequently found, whereas C1q (n = 3) and IgG (n = 2) deposits were only occasionally seen. Two main patterns of IF findings could be classified. (1) Granular IgM deposits as a sole or main finding (IgM GN; 25 specimens). The intensity of the mesangial IgM deposits did not correlate with the duration or severity of RA nor with the levels of serum immunoglobulins. However, a significant correlation with the intensity of mesangial IgM deposits and the levels of serum IgM class RF was observed. (2) Granular IgA deposits usually together with the complement component C3, i.e. IgA glomerulonephritis (IgA GN; nine specimens). The intensity of mesangial IgA deposits correlated significantly with the duration and severity of RA, and especially with serum IgA levels. Both RA patients with IgA GN or IgM GN were associated with a more frequent occurrence and higher titres of serum RFs when compared with the RA patients without nephropathy. The clinicopathological correlations and the association with RF support the concept that MesGN is related to the basic rheumatoid disease, and it should be regarded as an extra-articular manifestation of RA.
9988288 Medication adherence in rheumatoid arthritis patients: older is wiser. 1999 Feb OBJECTIVES: To create a profile of individuals nonadherent to their medications in an age-stratified sample (ages 34-84) of community-dwelling rheumatoid arthritis patients. The relative contributions of age, cognitive function, disability, emotional state, lifestyle, and beliefs about illness to nonadherence were assessed. DESIGN: A direct observation approach was used in conjunction with structural equation modeling. All participants were administered a preliminary assessment battery. Medications were then transferred to vials with microelectronic caps that recorded medication events for all medications for the next 4 weeks. PARTICIPANTS AND SETTING: A volunteer sample of 121 community-dwelling rheumatoid arthritis (RA) patients were recruited from newspaper ads, posters, and via informal physician contact from private rheumatology practices in Atlanta and Athens, Georgia. Written verification of the RA diagnosis and a disease severity rating were obtained from personal physicians before patients were enrolled in the study. Patients were tested in a private physician's office, and their medication adherence was monitored electronically for a month in their every-day work and home settings. MEASUREMENTS AND RESULTS: Structural equation modeling techniques were used to develop a model of adherence behavior. Cognitive and psychosocial measures were used to construct latent variables to predict adherence errors. The model of medication adherence explained 39% of the variance in adherence errors. The model demonstrated that older adults made the fewest adherence errors, and middle-aged adults made the most. A busy lifestyle, age, and cognitive deficits predicted nonadherence, whereas coping with arthritis-related moods predicted adherence. Illness severity, medication load, and physical function did not predict adherence errors. Omission of medication accounted for nearly all errors. CONCLUSION: Despite strong evidence for normal, age-related cognitive decline in this sample, older adults had sufficient cognitive function to manage medications. A busy lifestyle and middle age were more determinant of who was at risk of nonadherence than beliefs about medication or illness. Thus, practicing physicians should not assume that older adults have insufficient cognitive resources to manage medications and that they will be the most likely to make adherence errors. Very busy middle-aged adults seem to be at the greatest risk of managing medications improperly.
10441166 CD44 involvement in experimental collagen-induced arthritis (CIA). 1999 Aug CD44 is a pro-inflammatory cell surface molecule that supports cell migration and cell lodgment in target organs. Therefore, CD44 targeting with specific monoclonal antibodies (mAbs) should be useful for the inhibition of collagen-induced arthritis (CIA) as well as other autoimmune diseases that are dependent on inflammatory cells. In the present paper, we confirm and expand previous reports showing the anti-arthritogenic effect of anti-CD44 mAbs directed against constant epitopes of the CD44 receptor. We demonstrate that such anti-CD44 mAbs can induce resistance to CIA after disease onset. Even accelerated disease developed after two injections of type II collagen was markedly inhibited by IM7.8.1 anti-CD44 mAb. Although KM81 anti-CD44 mAb is a less efficient anti-arthritogenic reagent than IM7.8.1, its Fab' fragments partially inhibit CIA. This finding implies that the antibody blocks CD44 function rather than modulating CD44 cell surface expression or mediating Fc-dependent activities. Histopathological analysis revealed that the anti-CD44 mAb markedly reduces the synovial inflammatory cellular response and the consequent damage to the joint. As CD44 is an alternatively spliced multistructural molecule, similar anti-arthritogenic effects may be achieved by mAbs directed against CD44 isoforms expressed on the pathological cells in question, but not on normal cells, thus leaving the physiological functions intact.
11794267 The long-term results of resection arthroplasties of the first metatarsophalangeal joint i 2001 We performed a retrospective study in 188 patients (254 feet) with rheumatoid arthritis and compared the late results of Keller's procedure with those of Hueter-Mayo's technique after 7.9 years. More than 60% of the Keller group and 30% of the Hueter-Mayo group were suffering from persistent metatarsalgia due to increased forefoot pressure as well as experiencing pain around the great toe. Plantar callosities, recurrent hallux valgus deformity, lack of plantar flexion and weakened push-off were more frequent after Keller's procedure.
10957821 The role of pain anxiety, coping, and pain self-efficacy in rheumatoid arthritis patient f 2000 Sep Anxiety about pain is increasingly recognized as one factor contributing to increased pain perception and pain behavior [McCracken, L. M., Faber S. D., & Janeck A. S. (1998) Pain-related anxiety predicts nonspecific physical complaints in persons with chronic pain. Behavior Research and Therapy, 36, 621-630; McCracken L., & Gross R. (1995). The pain anxiety symptoms scale (PASS) and the assessment of emotional responses to pain. Innovations in clinical practice: a source book, 14, 309-321]. To assess this emotional reaction to pain in chronic pain patients, McCracken, Zayfert and Gross [McCracken, L., Zayfert, C., & Gross, R. (1992). The Pain Anxiety Symptom Scale: development and validation of a scale to measure fear of pain. Pain, 50, 67-73] developed the Pain Anxiety Symptom Scale (PASS) composed of four subscales: Cognitive Anxiety, Fearful Appraisal, Escape Avoidance and Physiological Anxiety. The present study extended previous work by examining the relationship among pain anxiety dimensions, use of active and passive coping strategies and arthritis self-efficacy as predictors of functional status in 154 rheumatoid arthritis (RA) patients. Functional status was assessed using the Five-Factor Model of the Arthritis Impact Scale, 2nd ed., (AIMS2): Physical Functioning, Affective Experience, Symptoms, Social Interaction and Role Function. Hierarchical multiple regression analysis on each of the AIMS2 criterion variables showed that pain anxiety, pain and symptom self-efficacy, health status and coping strategies were able to explain between 9 and 38% of the variance in the five AIMS2 variables. The present results support the hypothesized role of pain anxiety along with previously established contributions of self-efficacy and coping strategies, in affecting physical, social, emotional and role functioning in chronic RA patients.
9632064 Comparison of the original and the modified Larsen methods and the Sharp method in scoring 1998 Jun OBJECTIVE: To compare the original Larsen method and the proposed modification of the Larsen method with omission of scoring soft tissue swelling and periarticular osteoporosis, and the Sharp method in measurement of radiographic progression in early rheumatoid arthritis (RA). METHODS: Radiographs of hands and feet were assessed by the 3 scoring methods at Months 0 and 12 in 83 patients with recent onset RA. Sensitivity to change was determined using standardized response mean (SRM). RESULTS: Highly significant radiographic progression was observed by all 3 methods. The modified Larsen method showed the largest SRM (0.88), but the differences were slight between the 3 scoring methods (SRM 0.80 for the original Larsen method, SRM 0.72 for the Sharp method). High interobserver reproducibility was observed for all methods tested. CONCLUSION: In early RA the sensitivity to change of all 3 scoring methods was high, but in this patient population the newly modified Larsen method was the most responsive method.
10391080 [A case of limb-girdle type myasthenia gravis in whom rheumatoid arthritis appeared immedi 1999 Feb We report a 48-year-old female who presented limb-girdle type myasthenia gravis with inflammatory lung lesions and rheumatoid arthritis. She demonstrated a rapidly progressive muscle weakness of extremities. Neurological examination revealed facial muscle weakness, and proximal dominant limb muscle atrophy and weakness. Ptosis, ophthalmoplegia, and bulbar palsy were not observed. The edrophonium test and serum anti-acetylcholine receptor antibody were positive. The repetitive nerve stimulation showed 55% waning in the thenar muscles. From these findings, she was diagnosed as having myasthenia gravis. Plain chest X-P and body CT showed tumor-like lesions in the lung. Lung biopsy revealed the infiltration of lymphocytes. These lesions decreased in size after thymectomy and corticosteroid administration. Immediately after thymectomy, she began to have morning stiffness with pain and swelling of the finger and knee joints. RAHA test, which was negative before thymectomy, became highly positive. These findings were consistent with rheumatoid arthritis. In this patient, thymus probably played a role to suppress the development of rheumatoid arthritis.
9951823 Atypical Takayasu arteritis: late onset and arthritic manifestations: report of two cases. 1998 Oct 1 We recently experienced two cases of Takayasu arteritis rendered atypical by late onset (over 60 years of age) of disease, involvement of distal branch arteries, and association with rheumatoid arthritis. In both cases, roentgenologic examination revealed typical appearance of the abdominal aorta and stenosis of the subclavian artery entirely compatible with Takayasu arteritis. In addition, Case 1 had occlusive lesions of the superficial femoral arteries and Case 2 manifested occlusion of the axillary artery. Laboratory findings showed increased ESR and CRP but negative HLA B52 locus. Both cases showed arthritis symptoms with swelling, pain, and tenderness in joints. Case 1 did not manifest erosive lesions and positive RA test; Case 2 showed roentgenologic erosive lesions in hand joints with positive RA test. A surgical specimen from the femoral artery of Case 1 showed lesions suggesting Takayasu arteritis. Based upon these findings, we diagnosed the two patients as having atypical Takayasu arteritis with late middle age onset and arthritic manifestations.
10976082 Predictive value of interleukin 1 gene polymorphisms for surgery. 2000 Sep OBJECTIVES: To determine the influence of interleukin 1alpha (IL1alpha), IL1beta, and IL1 receptor antagonist gene polymorphisms on disease outcome as assessed by the need for major joint surgery within 15 years of diagnosis. PATIENTS AND METHODS: 50 patients with rheumatoid arthritis (RA) who required major joint surgery (hip, knee, or shoulder arthroplasty) within a 15 year period of disease diagnosis and 50 patients with RA with disease duration greater than 15 years and no major surgery were recruited together with 66 normal west of Scotland controls. Genomic DNA and polymerase chain reaction were used to determine polymorphisms in the genes for IL1alpha, IL1beta, and IL1 receptor antagonist. For all patients with RA recruited to the study, HLA-DR beta1 gene status was recorded as was the erythrocyte sedimentation rate (ESR) at the first ever clinic visit. RESULTS: No difference in the allele frequencies or genotypes of the IL1alpha and IL1 receptor antagonist gene polymorphisms was found between the controls and patients with RA, with or without previous surgery. IL1beta allele 2 was overrepresented in patients with RA who had undergone surgery compared with patients who had not (40% v 27%, chi(2)=4, 1df, p=0.04). ESR at the first ever clinic visit was significantly higher in those carrying allele 2 (36 mm/1st h v 22 mm/1st h, p=0.04). When patients, with or without previous surgery, who did not carry two disease associated HLA-DR beta1 alleles were compared, an increase in allele 2 was observed in the surgery cohort (42% v 25%, chi(2)=4.8, 1df, p=0.03). CONCLUSIONS: Patients who require major joint surgery were found to carry the IL1beta allele 2 more often than expected. Patients with this allele also had a higher initial ESR. This may be useful in predicting early surgery in patients who do not carry two disease associated HLA-DR beta1 alleles. Although these findings are interesting, further functional and epidemiological studies to confirm these observations are required.
10811006 Inflammatory neutrophils retain susceptibility to apoptosis mediated via the Fas death rec 2000 May Apoptosis and clearance of neutrophils is essential for successful resolution of inflammation. Altered signaling via the Fas receptor could explain the observed prolongation of neutrophil lifespan and associated tissue injury at inflammatory sites. We therefore compared inflammatory neutrophils extracted from joints of rheumatoid arthritis patients, with peripheral blood neutrophils. Inflammatory neutrophils underwent constitutive apoptosis in culture more rapidly than peripheral blood neutrophils; this was not explained by changes in surface expression of Fas or by induction of Fas ligand. Inflammatory neutrophils remained sensitive to Fas-induced death, at levels comparable to those seen in peripheral blood neutrophils. Similarly, granulocyte-macrophage colony-stimulating factor reduced apoptosis but did not abolish signaling via Fas. These data provide evidence for the rate of apoptosis in inflammatory neutrophils being continually modulated by death and survival signals in the inflammatory milieu. This allows for rapid resolution of inflammation as levels of survival factors fall, and suggests new strategies for inducing resolution of inflammation.
11812024 The role of nitric oxide in tissue destruction. 2001 Dec Nitric oxide (NO) is synthesized via the oxidation of arginine by a family of nitric oxide synthases (NOS), which are either constitutive (ie. endothelial (ec)NOS and neuronal (nc)NOS) or inducible (iNOS). The production of nitric oxide plays a vital role in the regulation of physiological processes, host defence, inflammation and immunity. Pro-inflammatory effects include vasodilation, oedema, cytotoxicity and the mediation of cytokine-dependent processes that can lead to tissue destruction. Nitric oxide-dependent tissue injury has been implicated in a variety of rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis and osteoarthritis. Conversely, the production of NO by endothelial cell NOS may serve a protective, or anti-inflammatory, function by preventing the adhesion and release of oxidants by activated neutrophils in the microvasculature. In this chapter we describe the multifaceted role of nitric oxide in inflammation and address the potential therapeutic implications of NOS inhibition.
10098824 Depression, illness perception and coping in rheumatoid arthritis. 1999 Feb This study aimed to establish the relationship between depression, illness perception, coping strategies, and adverse childhood events in rheumatoid arthritis patients. Sixty-two out-patients with rheumatoid arthritis (RA) completed the Hospital Anxiety and Depression Scale, Illness Perception Questionnaire, London Coping with Rheumatoid Arthritis Questionnaire, and Childhood Development Questionnaire, and underwent a clinical assessment of their physical state. Depressed patients were more disabled than the nondepressed, had a more negative view of their illness, and used more negative coping strategies. There was no association between depression and childhood adversity. Once disability was controlled for, there continued to be a significant correlation between depression and: (i) viewing the consequences of the illness negatively (Spearman's correlation coefficient [r]=0.37, p=0.003); and (ii) the perceived ability to control the illness (r= -0.26, p=0.04). The relationship between depression and negative coping strategies became insignificant. This study indicates the close relationship between depression and a negative view of the illness.
10488748 Polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in patients wi 1999 Aug Polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-a gene were examined to study the genetic background of rheumatoid arthritis (RA). Four variant alleles, -1,031C/ -863A, -1,031C/-238A, -857T and -308A, were identified and examined in 387 RA patients and 575 healthy Japanese controls. The frequency of the -857T allele in RA patients was significantly higher than that in the controls. However, the HLA-DRB1 analysis in the same subjects showed that the DRB1*0405 allele, which is in linkage disequilibrium with the -857T, was more strongly associated with the disease susceptibility than the -857T allele. These results suggest that the susceptible gene to RA is more closely linked to the HLA-DRB1 locus than to the TNF-alpha locus.
9458257 Survivorship analysis of total knee arthroplasty with the kinematic prosthesis in patients 1997 Dec Eighty-eight primary total knee arthroplasty procedures in 61 patients with rheumatoid arthritis were performed using the Kinematic total knee prosthesis (Howmedica, Rutherford, NJ) with cement between 1980 and 1985. No patients were lost to follow-up evaluation. Thirty-one of 61 patients died during the study period. Survivorship for all patients by life-table method was estimated as 56% at 10 years. This was shorter than the expected survival rate of a sex- and age-matched control group. Fifty procedure outcomes in 34 patients (27 women, 7 men) who were followed for more than 10 years were available for clinical evaluation. Complications occurred in 11 cases; in 4 of these, revision surgery was required. With revision as the endpoint, the survival rate of the prostheses was estimated as 93% at 10 years.