Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3204617 | Pharmacoepidemiology: the industry's perspective. | 1988 Oct | The pharmaceutical industry has a vital interest in, and plays a central role regarding, the issues of safety of the medicines it produces. Not only does industry have the basic and broadest expertise and "ownership" in drugs, it also is in an ideal position to receive and evaluate important information. At the center of spontaneous voluntary reporting (particularly in the US) it is a partner in generating signals of potential safety problems. And, as a scientific leader, it is a vital partner with academia and government in developing and using the evolving capacity for pharmacoepidemiology for proper examination of these signals using structured epidemiology study. Particularly, the importance of the large automated database in this regard is emphasized. Where the public's health is concerned there is no "different" industry perspective. | |
| 2784309 | Serological profiles in the connective tissue diseases in Zimbabwean patients. | 1989 Jan | The serological profiles of 104 Zimbabwean patients with clinically diagnosed connective tissue diseases were determined. The prevalence of rheumatoid factor was less than would have been expected in other geographical groups, but the prevalence of antinuclear antibodies was similar. Despite considerable racial, socioeconomic, and genetic differences in our patient group compared with other previously published studies the specificity and sensitivity of antinuclear antibodies, notably to DNA and Sm, correlated well with clinical diagnoses. This study validates the use of these serological tests in the investigation of this group of patients. | |
| 3611156 | The long-term results of the Howse total hip arthroplasty. With particular reference to th | 1987 Aug | We present the results of 506 consecutive Howse hip arthroplasties with a minimum follow-up of 10 years. The mortality within one month of surgery was 0.79%. The early dislocation rate was 1.38%, two hips requiring revision. Nine hips developed deep sepsis (1.78%), eight of which required revision. At 10 years 42 hips (8.3%) had required revision, including 14 with aseptic acetabular loosening and 11 with femoral stem fractures. We feel that as judged by the dislocation rate and the need for subsequent revision, the Howse arthroplasty is an acceptable form of total hip replacement, particularly in the older patient and in those requiring total replacement for femoral neck fractures. | |
| 3151240 | Histidine analogues as potential novel antirheumatic agents. | 1986 Nov | The relative avidity of novel analogues of histidine for copper chelation, and the ability of such chelates to catalyse the dismutation of the superoxide radical have been assessed using a new in vitro test. The test, designed to detect potential novel antirheumatic agents, was based on a putative mode of action for D-penicillamine. Within the series of histidine analogues, relationships between structure and activity were determined, isohistidine (alpha-amino-2-imidazolepropionic acid) and some of its simple derivatives being particularly active. | |
| 3654712 | Total wrist replacement using the modified Volz prosthesis. | 1987 Sep | Eighteen total wrist arthroplasties in sixteen patients were done using the modified Volz prosthesis. The length of follow-up ranged from twenty-four to sixty-six months, with a mean of forty months. A 100-point scoring system was used to evaluate the outcome. Muscle imbalance developed in five wrists, the carpal component became loose in three wrists, and two prostheses dislocated. In five patients six arthroplasties (33 per cent) were considered to have failed because one reoperation or more was required for loosening of the components in two wrists, dislocation in two wrists, and muscle imbalance in two wrists. Of the remaining twelve arthroplasties (eleven patients) eight (45 per cent) had an excellent result; two (11 per cent), a good; and two (11 per cent), a poor result. The over-all rate of complications was 44 per cent. Patients who had significant preoperative deformity did poorly postoperatively. The surgeon should be prepared to perform other types of arthroplasty or an arthrodesis if the extensor tendons are structurally inadequate, as this may lead to progressive flexion deformity postoperatively. | |
| 2524590 | Autocytotoxic cells in rheumatoid synovial fluids. | 1989 Mar | The possibility that patients with rheumatoid arthritis (RA) might have autocytotoxic activity in the joints was investigated using a 51Cr release assay. Peripheral blood lymphocytes (PBL) and synovial fluid (SF) lymphocytes from 9 patients with active RA were tested for cytotoxic activity against autologous PBL stimulated with pokeweed mitogen (PWM). In 5 of 9 patients, lymphocytes isolated from the SF showed cytotoxic activity against autologous PWM-blasts, whereas none of PBL showed autocytotoxic activity. Unstimulated PBL were resistant to lysis by SF cytotoxic cells. The autocytotoxic cells in RA SF may have relevance to immunoregulatory activity in the diseased area. | |
| 3612141 | A 15-year follow-up study of 512 consecutive Charnley-Muller total hip replacements. | 1987 | This article presents a prospective study of 512 consecutive total hip replacements done with the Charnley-Muller prosthesis. The operations were performed between 1967 and 1972. The follow-up period ranges from 13 1/2 to 18 years (average, 15 years). From the initial 512 replaced hips, only 148 were available for study at the end of 1985. The failure rate due to loosening of the prosthetic components, after a mean follow-up period of 15 years, was approximately 40%. The rate of loosening of the femoral component increased during the first 10 years after surgery and then tended to decrease, whereas the incidence of loosening of the acetabular component increased with time. There was a positive correlation between the decrease of excellent results and the incidence of previous surgery. | |
| 3767463 | Significance of connective tissue proliferation in the breakdown of cartilage: a novel in | 1986 Sep | The implantation of homologous femoral head cartilage in subcutaneous tissues of random bred Wistar rats results in both subchondral and articular surfaces becoming overlaid by an adherent granulation tissue comprising predominantly fibroblast-like cells. The response of the tissue to cartilage encapsulated with cotton fibres was also similar but erosions, mainly subchondral, were more evident and proteoglycan loss markedly greater. The connective tissue response to cotton was the progressive formation of a foreign body granuloma comprising mononuclear cells, multinucleated giant cells, and fibroblasts with very few polymorphonuclear leucocytes. | |
| 2660934 | Modification of disease by preventing free radical formation: a new concept in pharmacolog | 1989 Apr | There is considerable clinical and both in vivo and in vitro experimental evidence that toxic oxygen radicals contribute to the development of tissue injury associated with the inflammatory response. There is also strong evidence that cell injury caused by activation of phagocytic cells is iron dependent. Several of the clinical studies and in vivo and in vitro experimental models supporting these conclusions and suggesting mechanisms through which iron may participate in inflammation are discussed. | |
| 3371211 | [Treatment of chronic polyarthritis with low-dose methotrexate]. | 1988 May 27 | Methotrexate, 7.5-25.0 mg, was taken in a single weekly dose by 101 patients with chronic rheumatoid arthritis. In the course of treatment there was significant improvement in pain and mobility, as well as in the number of inflamed joints, strength of hand-grip (both hands), and use of steroids. There was a significant fall in erythrocyte sedimentation rate, and haemoglobin content rose significantly. Improvement occurred in 85% of patients; within this group 30% had a remission during treatment. There were 7% non-responders. Side effects were frequent: gastrointestinal symptoms in about 50%, loss of hair and stomatitis in 10-20%. In nine patients methotrexate had to be discontinued because of side effects, but in six of them the drug was taken again later on. Transaminases increased in 50% of patients. No clear-cut histological changes were found in the liver. It is concluded that low-dose methotrexate is effective in the long-term treatment of chronic rheumatoid arthritis. | |
| 3317973 | [Importance of the determination of antibodies to n-DNA in systemic lupus erythematosus an | 1987 | Altogether 95 patients with systemic lupus erythematosus, 36 patients with rheumatoid arthritis, 10 with sclerodermia systematic, 10 with Bekhterev's disease, 9 with rheumatic fever, and 20 healthy persons were examined. An analysis of the results made it possible to establish that in SLE, sclerodermia systematic and Bekhterev's disease the frequency of detection of higher levels of antibodies to n-DNA using enzyme immunoassay and radionuclide methods was approximately the same. SLE patients were characterized by a 2-fold increase in the level of antibodies to n-DNA as compared to patients with sclerodermia systematic, Bekhterev's disease and rheumatic fever suggesting usefulness for differentiation of these diseases. In rheumatic fever and rheumatoid arthritis antibodies to n-DNA in minimal elevated levels were revealed more frequently under enzyme immunoassay than in radionuclide ones. In SLE high levels of antibodies to n-DNA under the method of radionuclide binding showed significant correlation with a decrease in complement hemolytic activity, high levels of circulating immune complexes, with a higher frequency of detection of the antinuclear factor, and reflected lupus nephritis severity. Enzyme immunoassay used for the detection of antibodies to n-DNA showed correlation of high levels of these antibodies with signs of developing cerebrovasculitis and pulmonary lesion. | |
| 2938250 | SA 96 (N-(2-mercapto-2-methylpropanoyl)-L-cysteine) in rheumatoid arthritis. | 1986 | SA 96 (N-(2-mercapto-2-methylpropanoyl)-L-cysteine) is a new sulfhydryl compound having a relatively similar chemical structure to Tiopronin and D-penicillamine. An open trial of SA 96 treatment (300 mg/day after meals for 16 weeks) was carried out in 11 patients with definite or classical rheumatoid arthritis and with therapeutic failure of previous gold salts and/or D-penicillamine therapy. Two cases were withdrawn from the trial, because of a side effect (hepatitis) in one patient and an unrelated illness in another. The results in the 9 patients completing the trial demonstrated statistically significant improvement in the clinical and laboratory measurements. A marked abatement of disease activity was noted in 5 of 9 patients who did not benefit from, or suffered a relapse during previous chrysotherapy and in 1 of 5 patients without benefit, or with relapse following previous D-penicillamine treatment. Among 4 patients who had discontinued D-penicillamine because of its intolerable cutaneous side effects, 3 patients completed the trial, with favourable results. The results of this trial seem to indicate that SA 96 is possibly of value as a slow-acting antirheumatic drug in some patients with therapeutic failure of gold salts or D-penicillamine. | |
| 2788052 | Expression of TLiSA1 on T cells from patients with rheumatoid arthritis and systemic lupus | 1989 Sep | The expression of a new activation antigen, T cell lineage specific activation antigen (TLiSA1) on peripheral blood T cells from 16 rheumatoid arthritis (RA) and 8 systemic lupus erythematosus (SLE) patients and synovial fluid T cells from RA patients was determined in the context of T cell activation. The percentages of TLiSA1 positive T cells from inactive (4.6 +/- 5.2, mean +/- SE) or active RA (19.3 +/- 8.6) or inactive (1.7 +/- 2.1) or active SLE (8.7 +/- 2.7) were significantly increased compared with that of normal controls (0.7 +/- 0.4) (P less than 0.01). All patients with vasculitis showed relatively high positive percentages. The mean fluorocytometric intensity of TLiSA1 positive T cells from RA and SLE patients was significantly higher than that from normals. Percentages of TLiSA1 positive T cells from synovial fluids (21.8 +/- 4.9%) were significantly increased compared with those from peripheral blood of the same patients, indicating the local activation of T cells in patients with RA. An increase in the expression of TLiSA1 with no increase in the expression of the very late activating antigen 1 (VLA-1) was found in peripheral blood from RA, suggesting a difference in the stage of T cell activation in RA. In RA, there was a clinical correlation with levels of TLiSA1 expression on peripheral T cells. After stimulation with PHA, TLiSA1 positive percentages were increased on Day 2 and continued to increase through 5 days of culture. The maximum expression was obtained on Day 5. An increased number of TLiSA1 positive T cells belonged to OKT8. These results suggest that there is the systemic and the local activation of T cells in RA, following antigen stimulation, or a generalized nonspecific activation of immune system that could provide a means to monitor the abnormal immunologic activity in RA. | |
| 2805498 | Total knee arthroplasty in the presence of large bony defects of the tibia and marked knee | 1989 Nov | Twenty-six patients with severe tibial bone loss and secondary varus-valgus instability of greater than 20 degrees were treated by total knee arthroplasty using autogeneic bone as a graft in the defect. With proper filling of the resultant flexion and extension spaces, instability was corrected in 22 of the knees. Hospital for Special Surgery rating scores at one, two, and three years postsurgery were not statistically different from a matched group of total knee arthroplasty patients without bone grafts. There was no statistical difference in eventual motion or rating scores between those patients with a posterior cruciate-retaining and a posterior stabilized prosthesis. Four bone grafts demonstrated fragmentation and dissolution within the first year with implant subsidence. Needle biopsy performed one year postoperatively in nine knees in which the graft had not fragmented revealed osteocytes in the lacunae in only four grafts. In each of four further knees, there was a complete radiolucency between the graft and the tibial host bone. The overall success rate at five years was only 67%. This high failure rate has led the authors to reevaluate the use of prosthetic shims or wedges in large fragment defects but to continue to use bone grafting for smaller, circumscribed defects. | |
| 3500826 | Natural course and prognosis of HLA-B27-positive oligoarthritis. | 1987 Sep | A long-term follow-up of 119 patients with the descriptive diagnosis of B27-positive oligoarthritis showed that after a time between months to several years about half of the patients with this condition develop a definite disease of the seronegative spondarthritis group, especially ankylosing spondylitis. Another great part of the patients go into a complete and presumably persistent remission of their arthritis. After a follow-up time of 8 to 12 years, about 10% present a recurrent B27-associated oligoarthritis with some special clinical features. It is to be discussed whether this condition is a separate disease entity or still an abortive form of a well-known disease of the seronegative spondarthritis group. | |
| 2789457 | [The effect of HLA-DRB4 on the clinical picture of chronic polyarthritis]. | 1989 May | 61 patients suffering from classic erosive rheumatoid arthritis (RA) with a condition persisting for more than 5 years, were examined together with 69 healthy control subjects with regard to associations to "supertypic" HLA-D specificities. We found a significant increase of HLA-DRw53 in patients with seropositive RA (SPRA) (31/42 patients = 73.8%, Chi 2 = 18.4, p less than 0.01, RR = 7.3). Our results confirm the hypothesis, that the HLA-DRB4 gene is closer related to the disease susceptibility genes of SPRA than of DR4 (DRB1). | |
| 2833431 | Superoxide dependent iron release from ferritin in inflammatory diseases. | 1988 | Convincing evidence is presented that oxygen free radicals are involved in the pathogenesis of rheumatoid arthritis (RA). Superoxide is produced by polymorphonuclear leucocytes (PMN) in synovial fluid and by macrophages in the synovial membrane. Tissue damage typical for free radical attack is detected in RA. No absolute deficiency of protective factors is found in RA compared to controls, but the available protection is insufficient to cope with all radicals formed. The toxicity of superoxide is increased by iron. It is doubtful whether a low molecular weight iron pool is present. Superoxide is able to release iron from ferritin, providing a suitable source of iron, for the formation of hydroxyl radicals. This new pathogenetic mechanism stimulates to the application of iron chelators in the treatment of RA. Preliminary results with desferrioxamine were disappointing because of serious side-effects. Hopefully in the future intra-articular injection of iron chelators with better pharmacodynamics will be possible. The interaction of free radicals and ferritin is probably also involved in the pathogenesis of other inflammatory diseases such as systemic lupus erythematosus, hepatitis, and haemochromatosus. | |
| 2012625 | Serum keratan sulfate. Quantitative and qualitative comparisons in inflammatory versus non | 1991 Apr | The concentration of keratan sulfate (KS) epitope was measured in the serum of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) by enzyme-linked immunosorbent assay and compared with that in the serum of patients with primary fibromyalgia syndrome (PFS) and of controls who had no joint disease. By Student's tau-test, the mean serum KS concentrations in OA and RA patients measured with monoclonal antibodies (MAb) 5-D-4 and 2-D-3 were significantly increased over those in the PFS and normal groups; similar findings were observed using a nonparametric test, except that levels in RA patients showed no difference from those in PFS patients and normal subjects. There was no significant correlation between joint scores or disease duration and KS levels in OA or RA patients. Gel filtration of sera revealed mainly large, polydisperse KS-bearing fragments which eluted in a broad profile. KS purified from sera by immunoaffinity chromatography consisted mainly of high-density proteoglycans. Electrophoresis of pooled high-density KS fractions in polyacrylamide-agarose gels followed by Western blotting with MAb 5-D-4 showed diffuse bands with relative mobilities corresponding to large proteoglycans. These findings are consistent with attachment of KS to protein core fragments of various sizes; KS in patient sera is comparable in size with that in normal sera. Elevations of serum KS levels occur in the presence of cartilage degradation, but do not quantitatively define the extent or duration of articular involvement. | |
| 3013992 | Lack of reactivity of rheumatoid arthritis synovial membrane DNA with cloned Epstein Barr | 1986 Jul 15 | Rheumatoid arthritis (RA) synovial membranes contain a 62,000 dalton (62 Kd) molecule that shares an antigenic epitope with the EBNA-1 antigen of Epstein Barr virus (EBV). This cross-reactive epitope(s) is defined by a monoclonal anti-EBNA-1 antibody (MoAb P135) and by a rabbit antibody directed against a (glycine-alanine)-containing synthetic peptide from the internal repeat region-3 (IR-3) of EBNA-1. To determine whether this 62 Kd protein may result from EBV infection of RA synovial membranes, we used cloned DNA probes from the Bam M, Bam V, and Eco D regions of EBV. These probes did not show detectable reactivity with RA synovial membrane DNA in Southern blotting or slot blotting experiments. Reconstruction experiments performed with purified EBV DNA demonstrated the ability to detect 0.03 pg of viral DNA per 20 micrograms of normal genomic DNA, or approximately 1 EBV copy per 100 cells. In contrast, we found a low but significant level of reactivity of RA synovial membrane DNA with the EBV-encoded Bam K probe that encodes the EBNA-1 antigen. However, this probe also was reactive with normal genomic DNA to a similar extent. These results suggest that the 62 Kd antigen in RA synovial lining cells is probably encoded by cellular genes similar to the IR-3 region of EBV and does not result from EBV infection of the RA synovial membrane. | |
| 3437417 | Low dose cyclosporine in rheumatoid arthritis: a pilot study. | 1987 Dec | A 6 month open trial of cyclosporine (CyA) was conducted in 20 patients with active rheumatoid arthritis unresponsive to second line therapy. The dosage was monitored to achieve a serum blood level of 75-150 ng/ml. A 25% reduction in ARA joint count (baseline mean 38.2; 6 month or time of CyA withdrawal mean 28.7; p less than 0.001) was observed for all patients. Fifteen completed the 6 month CyA regimen and 5 developed toxicity requiring CyA to be permanently withdrawn. For the 15 patients completing 6 months of CyA, improvement was 36% (baseline 34.7; 6 month mean 22.2; p less than 0.001). Corresponding improvements were also observed on the other main study outcomes of pain and functional ability. Improvement occurred between 12-20 weeks, somewhat later than in other studies. Toxicity included mild hypertension (4 patients) and gastrointestinal intolerance (2). Three patients were withdrawn from CyA due to nephrotoxicity. There was a clinically significant reduction in calculated creatinine clearance but this returned to baseline within 6 months after CyA was withdrawn for all except 2 patients who took 12 months to return to baseline. |