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ID PMID Title PublicationDate abstract
3987300 Uses and abuses of analysis of covariance in clinical trials. 1985 Mar Measurement of improvement in clinical trials in chronic diseases commonly compares baseline data to endpoint values by performing t-tests or analysis of variance (ANOVA) on raw gains or percentage changes. This procedure can be misleading and the use of an analysis of covariance (ANCOVA) should be considered. Properly used, ANCOVA increases statistical power in a clinical trial. However, its advantage over t-tests can be nullified by small numbers of patients, violations of assumptions, and incorrect application of the techniques. An evaluation of ANCOVA in chronic disease studies is given, with examples of its strengths and weaknesses as seen in several drug trials in the rheumatic diseases. Recommendations on its use and a decision tree for the nonstatistician are provided.
312057 Intra-articular and circulating immune complexes and antiglobulins (IgG and IgM) in rheuma 1979 Feb Solid phase radioimmunometric methods have been used to assay immune complexes and IgG and IgM antiglobulins in paired samples of synovial fluid and serum from patients with rheumatoid arthritis (RA) or osteoarthrosis. Over 60% of RA patients had some increase in complexes in their sera, while nearly 90% had synovial fluid complexes. Moreover, the levels of complexes within the joint were much higher than in the serum. Both IgG and IgM antiglobulins were raised in most RA patients. The levels of IgG antiglobulins--and to a less extent IgM antiglobulins--were nearly always higher in synovial fluid than in the corresponding serum sample.A strong correlation was found between the levels of immune complex and IgG antiglobulin. A marked association was seen between the presence of subcutaneous nodules and increased IgG antiglobulins.
394277 Comparative clinical trials with diclofenac sodium (Voltarol) and naproxen in rheumatic co 1979 In an open, comparative multicentre trial, 96 patients with arthritis of the large joints were treated with 75 mg diclofenac in one single dose in the morning, 50 mg diclofenac given twice daily, or 250 mg naproxen administered twice a day. It was noted that the length of history of pain was significantly longer in this naproxen group. Duration of the study was 14 days. Clinical parameters showed that the best degree of improvement was obtained with the diclofenac 50 mg twice-daily dosage regime. Diclofenac, in this study, showed better tolerability than naproxen.
7055238 Clinicopathologic studies in tympanosclerosis. 1982 Jan Light-and electron-microscopic studies of the tissue from middle ears diagnosed as having tympanosclerosis, adhesive otitis media, postinflammatory ossicular fixation, and chronic otitis media revealed more or less similar findings of inflammatory response and healing. The histopathologic findings of "whitish sclerotic masses," especially around the ossicular chains, were due to fibrosis of submucosal connective tissue with hyalinization and calcification and/or metaplasia of mucosal epithelium. Longstanding and repeated undrained suppurative or nonsuppurative effusions would promote progressively more dense and avascular fibrous adhesions in the tympanum. The extensive fibrous changes in the tympanum would be a consequence of inadequate antibiotic therapy for middle ear inflammation and effusion. A new diagnostic term of tympanomastoidfibrosis is proposed to explain these clinical and histopathologic conditions as a replacement for the terms tympanosclerosis, adhesive otitis media, inflammatory ossicular fixation, and so on.
6352034 A six-month parallel group comparison of fenbufen and naproxen in the treatment of rheumat 1983 Thirty patients with definite or classical rheumatoid arthritis were enrolled in a six-month, prospective, double-blind study. Fifteen patients received 750 mg/day of naproxen and 15 patients received 900 mg/day of fenbufen. The fenbufen-treated group showed significant improvement in four parameters: pain at rest, pain on movement, duration of pain, and number of swollen joints. Naproxen produced significant improvement in three parameters: pain at rest, duration of morning stiffness, and number of swollen joints. There were no significant differences between treatments in any of the parameters at any assessment except for duration of morning stiffness at one observation point. Marked differences were noted in the number of patients with side effects and in the number of side effects reported. In the naproxen-treated group, 11 patients reported a total of 20 adverse reactions, while in the fenbufen-treated group, five patients reported a total of eight adverse reactions. Throughout the period of assessment, no consistent changes in laboratory values were observed. One patient in the naproxen-treated group showed an abnormal WBC at the third and fourth assessment, but this was not considered drug related. These results suggest that fenbufen is at least as effective as and better tolerated than naproxen in the treatment of patients with rheumatoid arthritis.
369925 A multicentre double-blind comparison of oxaprozin aspirin therapy on rheumatoid arthritis 1979 Preliminary clinical studies showed that oxaprozin (4,5 Diphenyl-2-oxazolepropionic acid) has anti-inflammatory and analgesic properties with a plasma half-life of about 40 hours. Consequently, a multicentre, double-blind parallel trial was conducted for 12 weeks at thirteen investigator sites, utilizing 212 patients with classic rheumatoid arthritis and comparing oxaprozin 600 mg/day, oxaprozin 1200 mg/day and aspirin 3900 mg/day. Both the oxaprozin and aspirin-treated patients had statistically significant improvement from baseline periods, in most key categories evaluated. Oxaprozin administered twice a day (b.i.d.) was as effective as aspirin administered four times a day (q.i.d.) and caused significantly less tinnitus (p less than 0.001). Fewer patients receiving high dose oxaprozin (2%) dropped out of the study because of unsatisfactory response than did those receiving aspirin (10%). There were no clinically significant laboratory abnormalities in the gastro-intestinal, renal, hepatic or haematological parameters monitored. This study suggests that oxaprozin is effective and well tolerated in the treatment of rheumatoid arthritis.
7288967 Clinical significance of low creatine phosphokinase values in patients with connective tis 1981 Oct 23 We have noted that values for serum creatine phosphokinase (CPK) are frequently low in patients with connective tissue diseases. Geometric mean values were 96.0 units/L among 121 disease-free males and 50.2 units/L among 63 disease-free females. The geometric mean values were 31.7 units/L in 11 males and 35.2 units/L in 49 females with systemic lupus erythematosus; 15.1 units/L in three males and 13.0 units/L in ten females with rheumatoid arthritis; and 41.6 units/L in 19 females with Sjögren's syndrome. Values within the normal range may occur in the face of active myositis in these illnesses. Findings of a low serum CPK values may occur in the absence of steroid treatment. Thus, a low serum CPK value is frequently found in patients with connective tissue diseases and a normal value should not dissuade one from the diagnosis of myositis.
6414080 Auranofin (SK + F 39162) induced enterocolitis in rheumatoid arthritis. A case report. 1983 A case of gold-induced enterocolitis in a 69-year-old female with rheumatoid arthritis who had received the new gold compound by oral administration (Auranofin (AF) for 4 weeks) is reported. Mild diarrhoea is a commonly described side effect accompanying AF, but in this case a severe colitis developed. The course of this case is very similar to those reported regarding Myochrysin. The pathogenesis is discussed. It might be a direct toxic effect on the mucosa of the bowel, evidenced by the relatively high excretion of oral gold with faeces.
6995605 Levamisole in rheumatoid arthritis -- a double-blind study. 1980 May Levamisole was used in a double blind trial in 24 patients with severe rheumatoid arthritis (RA). Each patient received either levamisole 150 mg daily, or placebo for a period of 6 months in addition to nonsteroidal antiinflammatory therapy. Ten patients, 8 of whom were taking levamisole, failed to complete the trial. Clinically 3 or 4 patients on levamisole who completed the study showed improvement whereas 5 were considered improved on placebo. The high incidence of side effects, (rashes, gastrointestinal upset, stomatitis and depression) in the levamisole treated group indicates that this drug, in the dose used, was too toxic for the management of severe RA. A much lower incidence of side effects is reported with recent recommendations using much lower daily or even weekly dosage.
41323 [Clinical study of benorilate. Co-ordinated multi-centre test (author's transl)]. 1979 Sep 18 During a co-ordinated test realized by four centres of rheumatology, 91 patients had been treated by benorilate,giving so the possibility to appreciate its efficiency and its tolerance as well in the articulary fits of degeneration as in the inflammatory rheumatisms. The observations had been collected during ambulatory treatments and consequently in the conditions of daily practice. The efficiency of benorilate has been estimated by the two big disadvantages of the rheumatic person: importance of pains and capacity to do principal movements of daily life. The almost totality of patients having been preliminarily treated by another anti-inflammatory and/or antalgesic, the judgement aimed at the amelioration given by the benorilate : 41% of patients affected by arthropathy of degeneration feeled better or much better after taking benorilate. The amelioration reaches 61% for cases of rheumatoid polyarthritis. About the four criterions which could have been numerically quoted, the amelioration that had been observed is statistically significant. No anomaly had been pointed out as for the biological tolerance. The suspension form is well accepted by the rheumatic persons.
39538 [Pulmonary lesions in systemic connective tissue diseases with immune disorders (collagen 1979 The data from the literature and the authors' own studies on changes in the lungs in systemic diseases of the connective tissue with immune disorders: systemic lupus erythematosus, progressive systemic sclerosis, rheumatoid arthritis, and periarteriitis nodosum are presented. Changes in the lungs in the above diseases have some common features: damage of the microcirculatory bed, increased vascular permeability, impregnation with plasma of alveolar septae and vessel walls, cellular reactions, and septo-alveolar sclerosis. Specific features of each of the diseases under study were demonstrated. The time course of morphological changes in the lungs was followed in relation to the severity, duration, and form of the disease.
301846 [The rheumatic foot and its treatment]. 1977 Jul 14 The alterations of form and function of the rheumatoid foot are derived from the pathomechanical conditions. The latter are used as a measure for the treatment. Type and frequency of inflammatory alterations are studied by x-ray examination and new aspects are stressed. The deformities of the rheumatoid foot can be explained conclusively through the interaction of functional, gravitational, inflammatory and anatomical influences. The deformities of the toes are induced to a great extent by the deformities of the proximal part of the foot. The possibilities of surgical treatment are discussed in detail and systematically. The results of partially own methods are compared with those of other authors, and conclusions regarding the indication are drawn. The conservative treatment is considered under the aspects of the enlarged surgical possibilities. The need of a close cooperation between the different specialists is emphasized.
3918543 Immunohistochemical studies of interleukin-2 and gamma-interferon in rheumatoid arthritis. 1985 Feb Synovial tissues were studied, using immunofluorescence techniques, for localization of lymphocytic infiltrates and immune reactants, including C3, C5b-9, C9, and Ia antigen. Tissue distribution of interleukin-2 (IL-2) and gamma-interferon was also determined, using mouse monoclonal antibodies. IL-2 was found in association with OKT8 and OKT4 T cells, and gamma-interferon was noted in association with T cells, B cells, and macrophages. Staining both for IL-2 and for gamma-interferon was surprisingly faint in view of the intensity of lymphocytic infiltration.
6194552 Study of enzyme inhibitors in the rheumatoid pannus-cartilage area. 1983 Immunoperoxidase studies were carried out on the pannus-cartilage junction (PCJ) of patients with rheumatoid arthritis (RA) and psoriatic arthritis to investigate the distribution of the enzyme inhibitors alpha 2 macroglobulin (alpha 2 M) and alpha 1 antitrypsin (alpha 1 AT). Comparisons were made with the equivalent synovial cartilage junctional area in osteoarthritis (OA). In all 12 patients with RA, prominent deposits of alpha 2 M and alpha 1 AT were found within the PCJ whereas in OA patients and the case of psoriatic arthritis fewer or no deposits were seen. Inhibitors were localised in pannus synovial lining cells, perivascular inflammatory cells, macrophage and fibroblast-like cells invading the cartilage as well as along the junctional cartilage matrix and in the adjacent pannus-free cartilage. Deposits of immunoglobulins were found in similar areas to enzyme inhibitors. The presence of enzyme inhibitors at the PCJ suggests that this area is not unprotected against enzymatic attack. Thus the concept that pannus is a prime area for cartilage damage because aggressive, invasive cells release destructive enzymes in an environment free from inhibitors should be reviewed.
6445717 Membrane and transformation characteristics of lymphocytes isolated from the synovial memb 1980 Feb Membrane and transformation characteristics of lymphocytes isolated from the synovial membrane and from paired peripheral blood samples, obtained from patients with classical rheumatoid arthritis, were studied. Synovial tissue lymphocytes were isolated by a new technique. Two suspensions of peripheral blood lymphocytes were studied: one isolated by Ficoll-Isopaque density gradient centrifugation, the other enriched in T cells by an additional step of 1 hour nylon wool column filtration. All suspensions were characterised by the percentages of mononuclear phagocytic cells, and T and B lymphocytes. The spontaneous (3)H-thymidine uptake of synovial tissue lymphocyte suspensions always exceeded that of the peripheral blood lymphocyte suspensions. The in-vitro responsiveness of synovial tissue lymphocytes to PHA, Con-A, and PWM, as measured by (3)H-thymidine uptake, was always consistently lower than that of paired peripheral blood lymphocytes whether or not enriched in T cells. The responsiveness to antigens, including PPD, varidase, and an antigen cocktail consisting of varidase, trychophyton, and Staphylococcus aureus antigen, showed the same effect. No dissociation was found between the response to PPD and the other antigens studied. These results suggest that the relative unresponsiveness to mitogens and antigens of synovial tissue lymphocytes in comparison with blood lymphocytes is not caused by mononuclear phagocyte contamination, but either by different subsets of T lymphocytes or by different functional states of T lymphocytes present in the synovial membrane and peripheral blood of patients with rheumatoid arthritis.
83591 [beta2-Microglobulin in ankylosing spondylitis and in Reiter's syndrome (author's transl)] 1978 Sep In patients with ankylosing spondylitis (AS) the plasma level of beta2-microglobulin (beta2m) is signficantly higher (1.95 +/- 0.48 mg/l) than in osteoarthritis (1.48 +/- 0.47 mg/l). In Reiter's syndrome the level of beta2m is also higher than in controls, but the paucity of results do not allow definite conclusions. The plasma level of beta2m in AS and in Reiter's syndrome is not related to the presence of HLA B 27 antigen, neither to other biological parameters as sedimentaton rate, blood cell counts, electrophoresis of plasma proteins. In rheumatoid arthritis the plasma level of beta2m is 2,67 +/- 0.84 mg/l, significantly higher than in osteoarthritis or in AS even without any association with Sjögren's syndrome. In synovial fluid, the beta2m level is closely related to the degree of inflammation, suggesting a local production of this substance.
7037867 Effects of indomethacin and carprofen on renal homeostasis in rheumatoid arthritis patient 1981 Nov The influence of carprofen and indomethacin on renal salt and water homeostasis was investigated. Carprofen is a new nonsteroidal antiinflammatory drug that is currently undergoing clinical trials in the United States. Both drugs were administered in usual clinical doses to steady state in six healthy individuals and in six individuals with rheumatoid arthritis. Blood pressure, weight, plasma renin activity, urine volume, creatinine clearance, fractional excretion of sodium and potassium, and free water reabsorption were determined. Both drugs were found to suppress plasma renin activity. Indomethacin suppressed plasma renin activity more than carprofen. Neither drug produced clinically significant changes in any of the other parameters. In healthy individuals and in patients with rheumatoid arthritis renal homeostatic mechanisms may compensate for the salt- and water-retaining effects of nonsteroidal antiinflammatory drugs.
6895084 [Biochemical study of human articular cartilage and meniscus on aging and joint disease (a 1981 Jan We studied biochemically the changes associated with aging and disease in the collagen of articular cartilages and menisci. Pepsin soluble and insoluble collagen were obtained by the method of Miller (1971) from the articular cartilages of seven healthy young and adult, six healthy aged subjects, and of six osteoarthritic and six rheumatoid arthritic patients. One portion of pathological cartilage was histologically examined to eliminate any possible contamination of the fibrous tissue and subchondral bone, and to classify the pathological findings. By the method of Miller, the pepsin soluble and insoluble collagen were also obtained from four adult and six aged menisci. Amino acid composition and carbohydrate contents were studied in insoluble collagen. The type of soluble collagen were analyzed with SDS disc electrophoresis. The amount of crosslinks in insoluble collagen was analyzed by the method of Masuda (1976) using automatic amino acid analyzer. The results obtained where shown as follow: 1) Solubility of collagen by pepsin decreased with aging on articular cartilages and menisci. In osteoarthritis and rheumatoid arthritis, the solubility of collagen by pepsin was different between the samples, and generally higher than that of collagen from the aged articular cartilages. 2) In respect to aldimine crosslinks of insoluble collagen, the dihydroxylysinonorleucine (DHLNL), hydroxylysinonorleucine (HLNL) and lysinonorleucine (LNL) increased with aging. DHLNL and HLNL were present in the nonreduced collagen in vitro. It was shown that the aldimine crosslinks had been already reduced in vivo. 3) The contents of carbohydrate of insoluble collagen from articular cartilage showed lower values than that of type II collagen as described previously. The hexosamine contents increased and those of uronic acid and hexose decreased with aging. In osteoarthritic and rheumatoid arthritic articular cartilages, the contents of uronic acid were lower than that of healthy aged group. The carbohydrate contents of menisci were similar to that of type I collagen. 4) concerning the type of collagen, healthy articular cartilages consisted of type II collagen. In collagen of aged cartilages and those of fibrillated and osteophytic cartilages in osteoarthritic and rheumatoid arthritic patients, the type II collagen were mixed with type I collagen ranging from 13.8% to 64.5%, although the analysis of articular cartilages in this study showed histological characteristics of hyaline cartilage. The type of soluble collagen in adult and aged menisci were composed of type I collagen in spite of aging.
6253801 Continuous production of monoclonal rheumatoid factor by EBV-transformed lymphocytes. 1980 Oct 2 Human B lymphocytes are immortalized by Epstein-Barr virus (EBV, ref. 1). The virus can be used to establish lymphoblastoid cell lines that produce and actively secrete specific antibodies. The original method, which we have used for various antigens is based on selection of the specific surface antigen receptor-positive lymphocytes from the peripheral blood lymphocytes of a donor who was previously sensitized to the corresponding antigen. Furthermore, by cloning the polyclonal anti-NNP cell line we have produced human monoclonal antibodies for the first time in vitro. About 5-20 microgram ml-1 stably produced specific antibody is obtained in the supernatant of the cell lines. This approach can be used for the in vitro production of monoclonal human autoimmune antibodies by EBV-immortalized lymphocytes from patients with autoimmune diseases. We demonstrate the continuous production in vitro of a monoclonal IgM and anti-IgG antibody (rheumatoid factor, r.f.) by a lymphoblastoid cell line established from a patient with rheumatoid arthritis.
322472 A comparative study of technics for the detection of antibodies to native deoxyribonucleic 1977 Apr Antibodies to native DNA have been assessed by three separate radioimmunoassay methods: the Millipore filter technic, the Farr ammonium sulfate precipitation test, and a commercially available kit method. Although each method was found to be reliably reproducible, the different units by which results are expressed made comparison difficult because of the technical variations inherent in each test. The correlation between tests was, however, high. To allow for interlaboratory standardization, it is suggested that the assay method used be clearly specified. Results are best expressed in terms of mg of DNA bound per deciliter of test serum. It appears that the centrally standardized radioimmunoassay kit is the most convenient method by which these antibodies can be measured in routine laboratories.