Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8670584 | Antibodies to four gram-negative bacteria in rheumatoid arthritis which share sequences wi | 1996 Jun | The bacteria Proteus, Serratia, Escherichia and Pseudomonas possess sequences resembling the rheumatoid arthritis susceptibility sequence EQRRAA, but antibodies were elevated only to Proteus in 66 RA patients (P<0.001) when compared to 61 active ankylosing spondylitis patients and 60 controls. | |
| 8445047 | A potential role for costo-chondral grafting in adults with mandibular condylar destructio | 1993 Jan | Little attention has been directed towards reconstruction of the mandibular condyles in adult patients with rheumatoid arthritis, other than with allogenic implants which are now known to cause serious complications. There is a relatively high incidence of condylar erosion and breakdown in rheumatoid arthritis, often leading to anterior open bite and retrognathia. Costochondral grafting does not appear to have been considered as a logical option for reconstruction, despite its high success rate in many other situations. A case is described of rapid bilateral condylar destruction occurring in a young woman with rheumatoid arthritis, leading to anterior open bite. Reconstruction was undertaken using bilateral costochondral grafts, giving an excellent clinical result which has been maintained over the follow-up period of two-and-a-half years. Radiologically complete healing of severe glenoid fossa erosion has taken place. | |
| 7966066 | Osteocalcin in patients with rheumatoid arthritis. A one-year followup study. | 1994 Jul | OBJECTIVE: To analyze clinical, radiological, and drug (disease modifying antirheumatic drug, DMARD) dependent factors influencing bone turnover in patients with rheumatoid arthritis (RA). METHODS: We investigated in a one-year double blind randomized study comparing intramuscular (im) gold with im methotrexate (MTX), whether the variation of inflammatory activity or functional capacity, the ascending anatomic stage, or DMARD treatments have an influence on bone formation (osteocalcin) in patients with RA. RESULTS: Patients (n = 48) enrolled at the beginning of our study had significantly increased osteocalcin levels (3.45 +/- 0.93-->4.42 +/- 1.39 ng/ml p < 0.02) after one year if inflammatory activity decreased (> or = 1 SD: erythrocyte sedimentation rate (ESR) 26.4 mm/h, C-reactive protein (CRP) 3.8 mg/dl). We found a significant negative correlation of the one-year CRP- (r = -0.44, p < 0.001) or ESR differences (r = -0.45, p < 0.001) with the corresponding osteocalcin differences. This was also evident if these patients were pooled with 15 patients excluded from the double blind study as already receiving DMARD treatment (n = 63; p < 0.01). Patients with impaired functional capacity also had significantly reduced osteocalcin levels (p < 0.01). In both cases, alkaline phosphatase showed no significant differences. CONCLUSIONS: Our data suggest that osteocalcin, a useful followup variable of bone turnover, is changed significantly (p < 0.02) in patients with RA regarding inflammatory activity and functional capacity. In contrast to alkaline phosphatase, a fall in inflammatory activity stimulated and impairment of functional capacity significantly decreased osteocalcin levels in patients with RA. | |
| 8296082 | [Rheumatoid arthritis. Therapeutic efficacy of methotrexate and its hepatotoxic effects]. | 1993 Jul | The efficacy and toxicity (specially hepatic) of methotrexate in low doses (7.5 mg/week) was prospectively assessed in 21 patients with rheumatoid arthritis refractory to treatment with gold or penicillamine, during two years. Three patients were prematurely withdrawn from the protocol. A fast and significant improvement of RA was observed during the first six months, which tapered thereafter. Erythrocyte sedimentation rate decreased from 51.5 +/- 20.1 to 27.7 +/- 11.5 mm/h (p < 0.05). A rise in serum transaminases, always raising to less than twice the normal value, was observed in 75% of patients in some moment of the follow up. Hepatic scintigraphy did not show significant changes. Hepatic histological alterations were mild and no changes were observed after two years of treatment. The main secondary effects were moderate and transitory gastrointestinal and hematological disturbances. The prednisone dose was decreased from 6.8 +/- 2.6 to 4.8 +/- 1.9 mg/day at twelve months. There were no withdrawals due to drug toxicity. It is concluded that methotrexate proved to be efficacious in the treatment of rheumatoid arthritis refractory to conventional treatments. Its secondary effects, although frequent, were discrete and transitory and there were no changes in liver histology. | |
| 7580285 | Blood monocytes in rheumatoid arthritis are highly adherent to cultured endothelium. | 1995 Nov | Monocytes from 17 patients with rheumatoid arthritis (RA) were more adherent than monocytes from 17 control patients to monolayers of pig aortic endothelium irrespective of whether sera was included (median 27-34% increase; p = 0.002) or omitted (median 27% increase; p = 0.022) from the culture media. When human umbilical vein endothelial cells were used as the adherence substrate, rheumatoid monocytes from an additional 21 patients demonstrated a median 31% (p = 0.004) and 20% increase (p = 0.004) in adhesion when compared with monocytes from 21 normal healthy subjects in the absence and presence of autologous sera, respectively. Activation of control monocytes with muramyl dipeptide or treatment with RA sera increased their attachment to endothelium (mean 34 +/- 14% increase; p < 0.001). The expression of the adhesion molecules CD11b (p < 0.005), CD18 (p < 0.005), CD62L (p = 0.01) was enhanced on rheumatoid monocytes, but antibody-blocking studies suggested that CD18 and CD62L were not responsible for the augmented binding of the rheumatoid cells. A subpopulation of rheumatoid monocytes possessed a very low net negative surface charge, a property that favours binding to vessel walls. We propose that many rheumatoid monocytes are predisposed for sheer-resistant adhesion to vascular endothelium. | |
| 8484694 | Detection of Luse bodies, spiralled collagen, dysplastic collagen, and intracellular colla | 1993 Apr | BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease leading to alterations of the extracellular matrix in tendons, ligaments, and cartilage. The structural changes of the collagenous systems in rheumatoid connective tissues are largely unknown, however. METHODS: Thirty four samples of menisci, 36 cruciate ligaments, and four tendons were taken during joint surgery in patients with rheumatoid arthritis. Eighteen menisci, 35 ligaments, and 30 tendons obtained at necropsy served as a control group. The extracellular matrix in the two groups was analysed by the combined use of transmission and scanning electron microscopy, immunohistochemistry with monoclonal antibodies recognising collagen types IV and VI, and ultramorphometry. RESULTS: Normal tendons and ligaments predominantly showed a unidirectional fibril arrangement. Whereas type IV collagen showed a positive staining pattern along all basement membranes, type VI collagen formed fine, filaments aligned in parallel. In patients with rheumatoid arthritis a significant reduction of the mean diameter of the collagen fibrils was found owing to the presence of thin collagenous fibrils 20-60 nm in diameter. Most of these fibrils showed considerable changes in their arrangement with irregular courses (so-called interfibrillar dysplastic collagen). Up to 410 nm thick frayed fibrils with irregular outlines (spiralled collagen) and intracellular collagen forms were found in rheumatoid tissues. In addition, atypical thick collagenous structures with 41 nm periodicity (Luse bodies) were detected in the matrix. The upregulation of type IV collagen in rheumatoid arthritis was associated with an increase in the vascular density. The expression of type VI collagen was upregulated in fibrotic zones. CONCLUSIONS: The dramatic ultrastructural collagen changes lead to a structural and functional insufficiency of the extracellular matrix in rheumatoid connective tissues. The results suggest that collagen alterations may contribute to the development of tendon and ligament ruptures in rheumatoid arthritis. | |
| 8323402 | Rheumatoid arthritis, the contraceptive pill, and androgens. | 1993 Jun | Evidence is accumulating that low androgen concentrations are a cause of rheumatoid arthritis. This would explain a number of established features of the epidemiology of the disease. These include: (a) the variation of disease activity with pregnancy; (b) the variation of age at onset by sex; (c) the variation by sex with HLA-B15; (d) the association with bone mineral density; and (e) the differing time trends in incidence rates by sex. It is argued, moreover, that if one makes a plausible assumption--namely, that women who choose oral contraceptives have high androgen concentrations at the time they first make this choice--then an explanation becomes available for the confusion about the relation between rheumatoid arthritis and oral contraception. Grounds are adduced for that assumption. If this line of reasoning is substantially correct it also has implications for the relations between rheumatoid arthritis and smoking and consumption of alcohol. | |
| 1555338 | Uncemented total hip arthroplasty in rheumatoid arthritis diseases. A two- to six-year fol | 1992 Apr | Forty primary uncemented total hip arthroplasties (THAs) were performed in 34 patients with an average age of 41.2 years (range, 21-78 years). Four hips had one component placed with cement: three femoral, one acetabular. Diagnoses included rheumatoid arthritis (30 hips), juvenile rheumatoid arthritis (seven hips), and systemic lupus erythematosus (three hips). The follow-up period averaged 3.7 years (range, two to six years). Thirty-five percent of the patients were using corticosteroids before hip replacement and throughout the follow-up period, whereas 44% of the patients had been using steroids in the past. Additionally, 79% of the patients were taking some form of antiinflammatory medications at follow-up examination. Clinical evaluation based on a ten-point rating scale indicated significant improvements from preoperative to the most recent follow-up examination for pain (from 3.1 to 9.0), walking (4.0-7.3), function (3.5-6.0), and activity (3.0-4.9). None of the hips required revision surgery, and none are pending. There was no evidence of roentgenographic failure; however, 43% of femoral and 12.8% of acetabular components showed some minor radiolucencies with sclerotic lines. None of these involved 100% of the bone-prosthesis interface. Femoral component subsidence occurred in two hips, and acetabular component migration occurred in one hip. Complications included three (8.1%) intraoperative femoral fractures, of which two required internal fixation. One patient had postoperative, culture negative, wound drainage. No deep sepsis occurred. These findings suggest that uncemented THA may be successful in the rheumatoid patient. Pain relief, walking, function, and activity levels are similar to those seen in cemented replacements with this length of follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 9091886 | [Complicated course of rheumatoid arthritis with pulmonary involvement, myocardial fibrosi | 1996 Dec | We report on a 67 year old man in whom the chest x-ray revealed marked interstitial opacities in both lungs. The diagnosis of Rheumatoid Arthritis (RA) was established by the presence of five criteria of the American College of Rheumatology for diagnosing RA. High resolution computertomography of the chest confirmed the abnormalities seen in the conventional chest x-ray. A biopsy, taken by open lung surgery, showed the typical pattern of pulmonary involvement in RA and confirmed the association of RA and interstitial lung fibrosis. The histologic examination pointed out lymphocytic infiltration of the bronchies, thickened alveolar walls with lymphoplasmarcellular infiltration and an increase in fibrous connective tissue. A congestive heart failure with severe arrhythmias and an obstructive sleep apnea syndrome (OSAS) were diagnosed in addition. The rhythm disturbances were attributed to the participation of the myocardium in RA and/or by the OSAS. By the treatment with prednisolone, methotrexate, mexiletine and continuous positive airway pressure (CPAP) the rhythm disturbances were alleviated and the patient's condition improved. | |
| 7927579 | Restriction fragment length polymorphisms in HLA-DR4-DQ3 haplotypes associated with rheuma | 1994 May | Restriction fragment length polymorphism (RFLP) patterns were studied in serologically confirmed DR4-DQ3 positive patients with rheumatoid arthritis by Southern blot analysis using full length cDNA probes specific for DRB, DQA and DQB hybridized with genomic DNA digested with informative restriction endonucleases. The RFLP patterns correlated with serology confirming all patients to be DR4+ve. The DQB1*0302 (DQ8) allele identified by 12.0kb BamHI, 3.3kb Hind III and 1.8kb Taql fragments was present in all patients suggesting them to be DR4-DQB1*0302. Hybridization of Taq 1 and PVU II digested genomic DNA with DQA cDNA probe revealed four informative RFLP patterns. While three of them correlated with known DR4 subtypes, one was a new polymorphism observed specifically in Indian patients with rheumatoid arthritis. The study further indicated that two of the several known subtypes of DR4, viz., DRB1*0401-DW4-DQB1*0302 and DRB1*0404-DW14-DQB1*0302 may be implicated in susceptibility to rheumatoid arthritis in the Indian population. | |
| 7473466 | Technetium-99m labelled polyclonal human IgG scintigraphy before and 26 weeks after initia | 1995 Aug | OBJECTIVE: To determine effectiveness of technetium-99m labelled polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to monitor variation in arthritis activity in patients with rheumatoid arthritis (RA). METHODS: The results of semiquantitative 99mTc-IgG scintigraphy were compared with those of examination before and 26 weeks after initiation of parenteral gold treatment in 19 patients with RA. RESULTS: Clinical and laboratory variables of arthritis activity as well as the scores of 99mTc-IgG scintigraphy were significantly lower after gold treatment compared to the scores before treatment. However, the difference between the mean scores of 99mTc-IgG scintigraphy before and after treatment was statistically significant for more joints than such difference in scores for joint pain and joint swelling. CONCLUSION: 99mTc-IgG scintigraphy is able to reflect variations in arthritis activity in patients with RA. | |
| 8265831 | Neurologic complications of rheumatoid arthritis. | 1993 Nov | Neurologic complications are common extraarticular manifestations of RA, involving both the peripheral and central nervous systems. Because RA patients suffer from pain, stiffness, and weakness, the detection of neurologic impairment is often difficult. Thus, close vigilance and thoughtful use of various diagnostic methods will help in the early diagnosis of cervical spine involvement, compression neuropathies, peripheral neuropathies, myopathies, and central nervous system involvement. Prompt and timely interventions may prevent permanent neurologic sequelae. | |
| 8689286 | Membranoproliferative glomerulonephritis, p-antineutrophil cytoplasmic antibodies, and rhe | 1996 Feb | Many rheumatoid arthritis patients have renal dysfunction induced either by the drugs used to treat their joint disease or by the chronic inflammation. A case of rheumatoid arthritis with p-antineutrophil cytoplasmic antibodies and mesangial glomerulonephritis that progressed to type I membranoproliferative glomerulonephritis is reported. The glomerular abnormalities were diagnosed by two renal biopsies done at a one-year interval. Reasons for the first and second renal biopsies were renal dysfunction with hematuria and impure nephrotic syndrome, respectively. Unusual features in this case include the succession of two histologic forms of glomerular disease in a patient with rheumatoid arthritis, the correlation between p-antineutrophil cytoplasmic antibody titers and activity of the renal disease. In addition, type I membranoproliferative glomerulonephritis is exceedingly rare in rheumatoid arthritis patients. | |
| 1512766 | Determinants of synovial fluid lactate concentration. | 1992 Jul | The resting intraarticular pressure and the type of arthropathy [rheumatoid arthritis (RA) or non-RA] have been examined for their importance as determinants of synovial fluid (SF) lactate concentration in patients with knee effusions. SF lactate concentration was higher in RA than in non-RA knees. This difference was not related to the resting intraarticular pressure at the time of sampling. After drainage of SF and saline lavage of the joint, the rate of increase of lactate in a fixed volume of intraarticular saline was examined under resting conditions. The rate of increase of the lactate concentration was significantly greater in RA joints. It is most likely that SF lactate concentration under resting conditions will reflect the lactate concentration during the preceding period of activity which, in turn, is probably a composite function of the extent of synovial hypoxia due to hypoperfusion and the type of arthropathy. | |
| 1616323 | Increased incidence of urinary tract infection in patients with rheumatoid arthritis and s | 1992 May | The incidence of lower urinary tract infection in 120 women with rheumatoid arthritis and secondary Sjögren's syndrome was evaluated retrospectively. Thirty one patients (26%) had secondary Sjögren's syndrome. Recurrent urinary tract infection was significantly more common in these patients (11/31) than in patients without Sjögren's syndrome (4/89). Habitual leucocyturia was also more common in patients with secondary Sjögren's syndrome (18/31) than in patients with rheumatoid arthritis without Sjögren's syndrome (8/89). Of seven patients with vaginal sicca symptoms, six had recurrent urinary tract infection. Urinary 24 hour mucopolysaccharide excretion in 20 patients with Sjögren's syndrome was similar to the excretion in 10 patients without Sjögren's syndrome. These results show that recurrent urinary tract infection is significantly more common in women with rheumatoid arthritis and secondary Sjögren's syndrome. A local deficit in protective urinary mucosal secretion or other immune mechanisms may be responsible for this susceptibility. | |
| 7779114 | American College of Rheumatology. Preliminary definition of improvement in rheumatoid arth | 1995 Jun | OBJECTIVE: Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. METHODS: Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. RESULTS: The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. CONCLUSION: We present a definition of improvement which we hope will be used widely in RA trials. | |
| 1301961 | Impaired urinary excretion of soluble IL-2 receptors in patients with systemic lupus eryth | 1992 Feb | Several previous studies have demonstrated increased in vivo release of soluble interleukin-2 receptors (sIL-2R) in patients with disorders associated with cellular activation. In this study attempting to understand better the role of sIL-2R released in vivo, we investigated the sIL-2R levels in paired serum and urine samples from 25 patients with systemic lupus erythematosus (SLE), 41 patients with rheumatoid arthritis (RA) and 20 healthy subjects. Using an ELISA for sIL-2R, we detected significantly increased urinary sIL-2R levels in normal individuals (868 +/- 114 units/ml) compared to the corresponding serum samples (209 +/- 25, P < 0.001, mean urine/serum sIL-2R ratio: 4.5 +/- 0.6), which suggests that the clearance of sIL-2R from circulation is largely kidney-dependent. The patients with SLE and RA exhibited significantly increased serum sIL-2R levels compared to normals (682 +/- 115 and 734 +/- 101 units/ml, respectively, P < 0.001) and these levels correlated with disease activity. However, urinary excretion of sIL-2R in these patients (SLE: 620 +/- 154 units/ml; RA: 1084 +/- 148 units/ml) was found to be significantly decreased (mean urine/serum sIL-2R ratio in SLE: 0.9 +/- 0.2; in RA: 1.9 +/- 0.2; P < 0.001) compared to normals, possibly contributing to the accumulation of these soluble receptors in the serum of autoimmune patients after their release from cells. Our findings can be attributed either to the binding of the sIL-2R to serum protein(s) or to distinct structural features of serum sIL-2R in SLE and RA patients, interfering with the urinary excretion of these molecules. | |
| 7481076 | Expression of neutrophil activation markers and neutrophil adhesion to chondrocytes in rhe | 1995 Feb | Neutrophil infiltration in synovial fluid is an important step in inflammation characterizing rheumatoid arthritis (RA). In this study, the activation and functional state of neutrophils in the blood and synovial fluid of patients with rheumatoid arthritis were compared: mean density of neutrophil activation markers CD11b, CD18 and L-selectin was measured with a flow cytometer, and adhesion to chondrocytes using a fluorimetric assay. No significant differences between control and patient peripheral blood neutrophils were observed. When comparing neutrophils of patient peripheral blood with paired synovial fluid, an increase in CD11b (p = 0.008) and a decrease in L-selectin (p = 0.008) were measured. For neutrophils of control and patient peripheral blood, fMet-Leu-Phe stimulation induced upregulation of CD11b (resp p = 0.007 and p = 0.008) and CD18 (resp p = 0.005 and p = 0.01). In the synovial fluid, no significant increase in CD11b and CD18 could be induced with fMet-Leu-Phe. Percentages of adherent neutrophils were comparable between controls and patients, both in peripheral blood and synovial fluid. Adhesion to chondrocytes of peripheral blood neutrophils of patients was correlated with clinical (Ritchie) and biological (erythrocyte sedimentation rate) parameters (resp r = 0.67, r = 0.73). In conclusion, these results demonstrate that peripheral blood neutrophil adhesion to chondrocytes was correlated with active disease, and that synovial fluid neutrophils were activated in vivo. These findings provide further evidence for the contributing role of neutrophils in articular destruction in RA. | |
| 8783416 | Only weak association between disease severity and HLA-DRB 1 genes in a Swiss population o | 1996 | This study analyses the prognostic value of HLA-DRB 1 genes for Swiss patients with rheumatoid arthritis (RA). HLA-DRB 1 genotyping was performed in 83 patients using the polymerase chain reaction and subsequent oligonucleotide hybridisation. They were categorised according to the presence of one or two putatively relevant genes (DRB 1*01 and/or DRB 1*04) and retrospectively evaluated for sex, age at disease onset, seropositivity, erosive disease and extraarticular manifestations. Sixty-one patients (73%) had disease-associated alleles. Twenty-four patients showed HLA-DRB 1*04 variants on both alleles or combined an HLA-DRB 1*04 variant with HLA-DRB 1*01, while 37 patients expressed only one relevant allele. Interestingly, 22 patients did not express any relevant allele. Some 52% of patients had nodular disease, 88% were seropositive. 96% had joint erosions and 11% expressed vasculitis and/or rheumatoid organ disease. A significant difference was observed only for the number of seropositive individuals, which was slightly higher in the group of patients expressing a double dose of disease-associated alleles than in patients who had no relevant alleles. Moreover, patients expressing homozygous DRB 1 alleles had a significantly earlier onset of disease than those who were heterozygous. We conclude from these findings that HLA-DRB 1 genotyping in a Swiss population of RA patients only weakly identifies clinical subsets with distinct profiles of disease manifestations and is not of strong prognostic value to determine disease severity in individual patients. | |
| 8749347 | A technique to evaluate foot function during the stance phase of gait. | 1995 Dec | A technique to measure foot function during the stance phase of gait is described. Advantages of the method include its three-dimensional approach with anatomically based segment coordinate systems. This allows variables such as ground reaction forces and center of pressure location to be expressed in a local foot coordinate system, which gives more anatomical meaning to the interpretation of results. Application of the measurement technique to case examples of patients with rheumatoid arthritis demonstrated its ability to discriminate normal from various levels of pathological function. Future studies will utilize this technique to study the impact of pathology and treatment on foot function. |