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

ID PMID Title PublicationDate abstract
1564339 Identification of IgG rheumatoid factors by a novel method utilizing immunoblotting. 1992 Apr 8 Monoclonal IgG rheumatoid factors (RFs) are identified using a novel immunoblot assay which detects RFs that bind to SDS-denatured Fc on nitrocellulose. Recognition of these self-associating antibodies is by the use of F(ab')2 fragments of light chain-specific antisera. In this way, IgG RFs can be easily identified and the precise binding characteristics to different isotypes of IgG, or other antigens, further specified. The assay can also be used to detect other classes of RFs such as IgM RFs. Although less sensitive than the standard ELISA, the use of this immunoblot RF assay (IRFA) will identify IgG RFs and their target antigen with precision.
8388601 Nailfold capillaroscopy in connective tissue disorders and in Raynaud's phenomenon. 1993 This article focuses on the value and the limitations of nailfold capillaroscopy in the differential diagnosis of certain connective tissue diseases and in the early recognition of secondary Raynaud's phenomenon. The finding of a "scleroderma-pattern" (apical enlargement and drop-out of capillaries) points almost certainly to an underlying progressive systemic sclerosis, mixed connective tissue disease or dermatomyositis.
1523314 Rheumatic and nonrheumatic disease in the temporomandibular joint: gadolinium-enhanced MR 1992 Oct Magnetic resonance (MR) imaging of 36 temporomandibular joints (TMJs) in 27 patients and six healthy volunteers was performed before and after injection of gadopentetate dimeglumine. Twelve asymptomatic joints were used as controls, 12 TMJs had symptomatic internal derangement, and 12 TMJs had rheumatic inflammatory disease. A small or moderate joint effusion was seen in one asymptomatic joint, four joints with internal derangement, and one joint with rheumatic involvement; in all of these, contrast enhancement of the effusion was observed. A large effusion in one rheumatic joint was enhanced only after delayed imaging. In healthy controls and patients with internal derangement, no or only minimal enhancement of intraarticular tissues was seen. Eleven of the 12 rheumatic TMJs showed moderate or intense soft-tissue enhancement along the disk and articular surfaces (ie, in areas normally devoid of synovial membrane). The one rheumatic joint without enhancement had bony ankylosis and no remaining soft tissue within the joint space. Gadolinium-enhanced MR imaging of the TMJ may effectively depict the proliferating synovium of rheumatic inflammatory joint disease.
1535101 Meta-analysis of second-line antirheumatic drugs: sample size bias and uncertain benefit. 1992 Jun Placebo controlled trials of methotrexate, auranofin, penicillamine, azathioprine, sulphasalazine, gold sodium thiomalate and chloroquines were subjected to meta-analysis. The difference between drugs and placebo in the erythrocyte sedimentation rate was 8.8 mm/hr [95% confidence interval (CI), 6.4-11.3]. In multiple linear regression analyses, with the physician's global evaluation and relative change in joint tenderness count as outcome variables, a substantial sample size bias was demonstrated. The effect decreased with increasing sample size. The risk of dropping out from any cause was larger on drug than on placebo (odds ratio, 1.17; CI, 0.99-1.38). No evidence of a worthwhile effect on radiological changes was found. Of the 3439 patients, 4 went into complete remission on drug. We conclude that the benefit of second-line drugs is uncertain.
8242001 99mTc-citrate versus 67Ga-citrate for the scintigraphic visualization of inflammatory lesi 1993 Oct Citric acid was labeled with 99mTc with an efficiency of > 99%. The biodistribution of 99mTc-citrate was studied in mice with turpentine-induced abscesses in comparison to 67Ga-citrate. The max. abscess/muscle concentration ratios were 4.61 +/- 1.92 (3 h) for 99mTc-citrate and 4.76 +/- 2.04 (4 h) for 67Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of 99mTc-citrate showed increased activity involving the synovium. The max. arthritic/contralateral knee ratio was 3.19 +/- 1.29 (3 h) and 6.47 +/- 3.71 (24 h) for 99mTc- and 67Ga-citrate, respectively. The blood clearance curve of 99mTc-citrate in rabbits was biexponential with a fast (T1/2 = 36 min) and a slow (T1/2 = 18 h) component, compared to mono-exponential clearance of 67Ga-citrate (T1/2 = 23 h). In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 +/- 0.81 and 4.95 +/- 2.56 for 99mTc-citrate and 99mTc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that 99mTc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to 67Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion.
8354886 Two-site ELISA for quantification of the terminal C5b-9 complement complex in plasma. Use 1993 Aug 9 A quantitative ELISA procedure using monoclonal and polyclonal antibodies against neoantigens of the terminal C5b-9 complement complex has been developed. The ELISA was demonstrated to be both sensitive and reproducible. The normal range for C5b-9 determinations, defined as 2.5-97.5% interval of the values obtained in 76 healthy blood donors, was 3.12-10.3 AU/ml. The presence of rheumatoid factor did not affect the determination of C5b-9 as demonstrated by immunoabsorption studies.
7722459 Peptide binding specificity of HLA-DR4 molecules: correlation with rheumatoid arthritis as 1995 May 1 We have investigated whether sequence 67 to 74 shared by beta chains of rheumatoid arthritis (RA)-associated HLA-DR molecules imparts a specific pattern of peptide binding. The peptide binding specificity of the RA-associated molecules, DRB1*0401, DRB1*0404, and the closely related, RA nonassociated DRB1*0402 was, therefore, determined using designer peptide libraries. The effect of single key residues was tested with site-directed mutants of DRB1*0401. The results have demonstrated striking differences between RA-linked and unlinked DR allotypes in selecting the portion of peptides that interacts with the 67-74 area. Most differences were associated with a single amino acid exchange at position 71 of the DR beta chain, and affected the charge of residues potentially contacting position 71. The observed binding patterns permitted an accurate prediction of natural protein derived peptide sequences that bind selectively to RA-associated DR molecules. Thus, the 67-74 region, in particular position 71, induces changes of binding specificity that correlate with the genetic linkage of RA susceptibility. These findings should facilitate the identification of autoantigenic peptides involved in the pathogenesis of RA.
8431211 Divergent T cell receptor gamma repertoires in rheumatoid arthritis monozygotic twins. 1993 Feb OBJECTIVE: To determine if the expressed T cell receptor (TCR) gamma repertoire is altered in rheumatoid arthritis (RA). METHODS: Peripheral blood lymphocytes were collected from monozygotic twins who were either concordant or discordant for RA, or from a normal twin pair. TCR gamma-specific complementary DNA libraries were constructed using the anchored polymerase chain reaction. Gene usage was analyzed by plaque hybridization and sequencing. RESULTS: The expressed TCR V gamma repertoires both in RA patients and normal subjects were extremely diverse. Monozygotic twins who were concordant for RA expressed very different frequencies of TCR V gamma genes. CONCLUSION: RA does not lead to a specific clonal expansion or deletion of TCR V gamma genes in peripheral blood.
1616360 Intranasal calcitonin for the prevention of bone erosion and bone loss in rheumatoid arthr 1992 Jun The effect of intranasal salmon calcitonin on pain, erosion progression, and bone loss in 40 women with rheumatoid arthritis was investigated. The study design was double blind, placebo controlled for the first four months and open for the next 36 months, allowing for cross over to active drug treatment or to the control group. Morning stiffness was reduced in the group treated with salmon calcitonin after two and four months. After an average follow up of 28 months no significant effect on erosion progression was observed using the Larsen score. The mean (SD) monthly progressions in the Larsen score in the calcitonin and control groups were 0.21 (0.22) and 0.23 (0.28) respectively. The bone mineral density was evaluated in the forearm and spine. During the 12 months of follow up the control group lost bone at a rate of 2%/year at the spine and 4.8%/year at the radius distal third. In contrast, the group receiving nasal calcitonin gained 1% in bone mineral density at the lumbar spine and no loss at the radius distal third. The increase in bone density at the spine in the calcitonin group was not sustained and a loss of 1.8%/year was observed in the second year. The difference with the placebo group remained significant.
8205405 Consistency of morning stiffness: an analysis of diary data. 1994 Jun This study aimed to determine the within-individual daily variation in morning stiffness (MS) of RA patients, and to validate the routine clinically derived duration of MS against that recorded prospectively by patients. Forty-nine RA patients, who during a detailed clinical interview reported experiencing MS that week were studied. They were asked to prospectively record, using a diary, daily information on the duration of their MS. The times both of waking and of getting up were noted, as well as the times to first improvement, maximum improvement and complete disappearance of MS, providing six possible estimates of MS duration, three of which, using waking as starting points, could be compared with the interview. The daily variation of MS was assessed by the within-patient range. The median duration of the diary scores was then compared with the MS estimates recorded at the interview. There was a large intra-individual variation in duration of MS, whichever of the six definitions were used. Half of the patients recorded ranges of MS scores of 3 h or more within the same week. There was also marked variation between the median diary derived duration and that ascertained by interview. This variation was at its smallest when the duration of MS was calculated as time until maximum improvement. The routine recording of the 'typical' duration of MS seems to have little clinical value in the face of the large within-patient variation. Of the possible choices for estimating duration, the time from waking to maximum improvement appeared to be the best indicator of the average duration of MS in RA patients.
8948303 Adding low-dose cyclosporin A to parenteral gold therapy in rheumatoid arthritis: a double 1996 Nov A double-blind, randomized comparison between parenteral gold therapy (PGT) and cyclosporin A (CyA) vs PGT and placebo during 6 months was performed in 40 RA patients experiencing a decreasing effect of ongoing PGT. Patients' overall assessment of health was the only efficacy variable significantly better in the CyA- and PGT-treated vs the placebo- and PGT-treated group. Higher blood pressure and more signs of renal impairment were found during the 6 months treatment in the former compared with the latter group. Six months after the end of the combination therapy, a higher potassium value in the CyA-treated group was the only difference. In conclusion, no effects additional to those expected with single-drug therapy or additional risks of side-effects of either drug were found when combining low-dose CyA with ongoing PGT in RA patients with long disease duration.
1468212 HLA-DR alleles and sterile ulcerative keratitis. 1992 Nov Human leukocyte antigen-DR typing was performed on 18 unrelated white patients with sterile ulcerative keratitis (SUK) to determine whether these patients share common immunogenetic susceptibility genes. There was no statistically significant increase in any DR allele among the entire group of SUK patients. There was a trend in the frequency of DR1 in the rheumatoid arthritis (RA) patients (5 of 8, 63%) versus the non-RA patients (1 of 10, 10%), which was not statistically significant, possibly due to the small number of patients in the study. Screening patients with RA without known SUK from our RA register revealed one DR1-positive patient with an inactive peripheral marginal melt. These findings suggest a possible relationship between DR1 and RA sterile corneal melting, which will need to be confirmed with a larger study.
8517074 [Ultrasonic diagnosis of inflammatory rheumatic diseases]. 1993 Mar During the last two decades, sonography has become more and more important in the diagnosis of rheumatic diseases. With the development of high-frequency realtime transducers, detailed images of the musculoskeletal system can be provided. Furthermore, sonography or echocardiography is able to detect systemic manifestations of connective tissue diseases. Compared to plain films, which mainly evaluate bony lesions of inflammatory joint diseases, sonography is used to assess non-bony abnormalities (synovial membrane, cartilage, menisci, tendons) and synovial space. Pannus and effusion as indicators of inflammatory rheumatic disease can easily be examined by sonography. However, sonographic findings in rheumatic diseases are mostly nonspecific and can rarely be used to distinguish between different diagnoses, which is sometimes possible using plain x-rays (i.e., pencil-in-cup). Sonography has proven to be a meaningful diagnostic tool in evaluating tumors in subcutaneous tissue or muscles. The diagnostic results of musculoskeletal sonography are today compared to those obtained by computed tomography (CT) and magnetic resonance imaging (MRI). Although musculoskeletal MRI can visualize bony and non-bony structures at the same time, sonography is still of particular interest in the diagnosis of rheumatic diseases, because it is a noninvasive, widely available, relatively inexpensive imaging modality which can be rapidly performed and repeated.
1445446 Quantitation of chondroitin 4-sulfate and chondroitin 6-sulfate in pathologic joint fluid. 1992 Nov OBJECTIVE: To investigate the correlation between joint disease and the composition of chondroitin sulfate in the joint fluid, unsaturated disaccharide isomers of chondroitin 4-sulfate (delta di-4S) and chondroitin 6-sulfate (delta di-6S) were measured in joint fluids obtained from patients with osteoarthritis (OA), rheumatoid arthritis (RA), or traumatic arthritis (TA). METHODS: These pathologic joint fluids were digested with chondroitinase ABC, and the delta di-4S and delta di-6S produced were determined by high performance liquid chromatography combined with fluorometry. RESULTS: Total content of delta di-4S plus delta di-6S was 71.8 +/- 30.0 nmoles/ml (mean +/- SD) in OA, 55.4 +/- 29.3 nmoles/ml in RA, and 211 +/- 149 nmoles/ml in TA joint fluids. The ratio of delta di-6S to delta di-4S was 3.81 +/- 0.992 in OA, 1.13 +/- 0.527 in RA, and 5.75 +/- 2.46 in TA joint fluids. Differences between groups were statistically significant. CONCLUSION: These results strongly suggest that the levels of chondroitin sulfate isomers and the delta di-6S: delta di-4S ratio in joint fluid reflect the proteoglycan metabolism of joint tissues, particularly of articular cartilage; hence, they could be used to diagnose joint diseases and to predict articular cartilage destruction from such joint diseases.
8832979 Distinct alterations in lineage committed progenitor cells exist in the peripheral blood o 1996 Mar OBJECTIVE: Due to the elevated levels of hematopoietically active cytokines such as tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GMCSF) in rheumatoid arthritis (RA) serum and synovium, the increased bone marrow activity in RA, and the effectiveness of GMCSF in mobilizing progenitor cell release from the bone marrow into the periphery, we hypothesized that hematopoietic progenitors are altered in the peripheral blood (PB) of patients with RA. METHODS: Flow cytometry assisted cell surface analysis was employed to compare the distribution of myeloid (CD34+CD33+), B lymphoid (CD34+CD10+), and erythroid (CD34+CD71+) committed progenitor cell subsets in the PB of healthy controls and patients with RA. Since RA and Sjogren's syndrome (SS) are related autoimmune disorders, primary SS PB was also investigated. RESULTS: Only those patients with RA exhibiting clinically active disease (RA-A) demonstrated increases in myeloid and B lymphoid progenitor cell subsets. Growth of RA-A progenitors in cytokines promoting myelopoiesis (GMCSF, TNF, stem cell factor) produced increased monocyte and dendritic cell progeny, in support of the flow cytometry data. Lineage committed (CD34+CD38+) progenitors were increased in SS PB (p <0.03). However, these did not correlate with either the myeloid, erythroid, or B lymphoid lineages. CONCLUSION: Distinct alterations in the distribution of PB progenitors are present in RA and primary SS. Since progenitor cells retain a proliferative capacity, their infiltration into the synovial/glandular environment may contribute to the accumulation of inflammatory cells within these sites. We propose that PB progenitors enter the diseased microenvironment through similar mechanisms as mature hematopoietic elements.
1487463 Intraarticular osteoid osteoma of the elbow. 1992 Oct The case of a man who developed osteoid osteoma of the elbow is presented. Intraarticular osteoid osteoma of the elbow is a rare lesion presenting both diagnostic and therapeutic problems. The radiologic features of intraarticular osteoid osteoma include osteosclerosis (usually a dominant feature at initial imaging and typically enveloping the nidus), joint effusion and periosteal reaction that can involve the bone in which the osteoid osteoma arises and the adjacent bones. Awareness of these features facilitates correct diagnosis, thereby enabling timely and appropriate treatment.
8660109 Low dose desensitisation does not reduce the toxicity of sulphasalazine in rheumatoid arth 1996 May OBJECTIVE: To examine the proposal that pretreatment low dose desensitisation may reduce the incidence of toxicity of sulphasalazine in the treatment of rheumatoid arthritis (RA). METHODS: A double blind, placebo controlled trial was performed with 422 patients satisfying the American College of Rheumatology criteria for RA who required sulphasalazine treatment because of increased disease activity. Patients received either sulphasalazine desensitisation, or placebo, for three weeks before commencement of sulphasalazine treatment. The frequency and nature of adverse effects and changes in clinical and laboratory parameters of disease activity were measured after three and six months. RESULTS: Improvement in the efficacy of sulphalasazine (measured by clinical and laboratory parameters) was significant and similar in magnitude in both groups. There was no significant difference between actively and placebo desensitised patients as regards the incidence or profile of adverse effects (toxicity). CONCLUSION: Pretreatment low dose desensitisation is unhelpful in reducing the toxicity associated with sulphasalazine treatment of RA.
8523001 Hybrid fixation modular tibial prosthesis. Early clinical and radiographic results and ret 1995 Aug A prosthetic tibial component has been designed with features for fixation to bone using a combination of acrylic cement and ingrowth interfaces. This hybrid concept affords the component the immediate stability of cement fixation and the potential long-term stability of biologic fixation. The ingrowth interfaces (coupled with the central stem) are intended to shield the cement interface beneath the tibial tray from the tensile liftoff forces that result from eccentric loading, while avoiding the fretting and osteolysis associated with screw fixation. A disassembly capability allows the tray to be removed from the stemmed anchorage assembly, facilitating component extraction and limiting bone loss. A clinical and radiographic review of 50 consecutive primary total knee arthroplasties with a mean follow-up period of 35 months revealed stable interfaces with no progressive radiolucencies and minimal remodeling changes. The mean Knee Society knee score was 92.2. At final follow-up evaluation, 88.6% of patients noted no or mild (occasional) pain. Retrieval of three prosthetic knees with chronic sepsis showed extensive ingrowth into the porous interfaces and an osteointegrated bony sleave around the smooth central stem.
7732491 [Analysis of cases showing adverse reactions toward many kinds of DMARDs]. 1995 Feb There are only six DMARDs (disease modifying anti-rheumatic drugs) available in the clinical practice, such as gold sodium thiomalate, D-penicillamine, bucillamine, auranofin, salazosulphapyridine, and lobenzarit disodium. It is important to select an appropriate DMARD for the patient. However, 57 of the 171 patients showed an adverse reaction toward one DMARD and 26 (46%) of these 57 patients showed undesirable reactions to other DMARDs. In this paper we emphasized (1) that this rate 46% of adverse reaction against multiple DMARDs was elevated and (2) that the rate of frequency of adverse reactions against two drugs was elevated. The ranking orders of the frequency of the adverse reactions of the switching of one DMARD to another are as follows; 1. gold sodium thiomalate to D-penicillamine, 2. gold sodium thiomalate to bucillamine, 3. D-penicillamine to bucillamine. Therefore, a special attention for switching DMARDs should be paid to the patient who has already shown an adverse reaction to one DMARD, and we should lower the dose of DMARDs administered to the patient. In addition, steroid was found not to decrease the rates of the adverse reaction against DMARDs.
1353712 Effect of anti-CD4 antibody treatment on inflammatory arthritis in MRL-lpr/lpr mice. 1992 Aug MRL-lpr/lpr mice develop an inflammatory arthritis in association with other manifestations of autoimmunity. Although a variety of immune cell disturbances have been described in these mice, the relationship of these abnormalities to the pathogenesis of arthritis has not yet been determined; the role of T cells is especially unclear since synovial hypertrophy and joint erosions have been noted in some studies in the absence of a significant T cell infiltrate. Therefore, to determine if T cells are required for arthritis in MRL-lpr/lpr mice, we evaluated the effects of prolonged treatment with a monoclonal anti-CD4 antibody. Knee joints from treated mice had markedly reduced arthritis compared to saline-treated control animals as measured by the degree of synovial hypertrophy and inflammation. Nephritis in these mice was concomitantly reduced. In contrast, rheumatoid factor levels were not affected by CD4+ cell depletion, despite significant effects on anti-DNA. These results indicate that in MRL-lpr/lpr mice anti-CD4 therapy can inhibit arthritis, suggesting an important role of T cells in the pathogenesis of this lesion.