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

ID PMID Title PublicationDate abstract
3964057 Dynamic splinting: a systematic approach to the selection of elastic traction. 1986 Apr Elastic traction is an important but occasionally misapplied component of upper-extremity dynamic splints. Information regarding a systematic approach for selection of elastic traction has been limited. A biomechanical analysis of dynamic splinting methods was done to identify factors that might help educate therapists in the proper application of elastic traction. Material properties of elastic traction were measured with a mechanical testing system capable of accurately identifying physical properties of various substances. Results of this analysis indicated that specific spring constant values for clinically used bands ranged from 134 to 531 g, original length values ranged from 0.7 to 3.2 in., the consistency of bands labeled as identical by the manufacturer was generally very good, and each band's ability to maintain its material properties with repeated elongation was similar from band to band and showed gradual diminution after several hundred repetitions. These data were combined with theoretical constructs of splint fabrication to devise a simple and logical method for analysis and determination of elastic traction requirements for various diagnostic applications. A goniometer, ruler, and spring scale are the only tools necessary to perform the analysis. Simple charts depicting forces and moments provide identification of the appropriate rubber band for application.
2147618 [Treatment of acute rheumatic-articular diseases with nabumetone]. 1990 Aug 15 Twenty patients, 10 males and 10 females, age range 32-76, mean age 57.80 years, with diagnoses of acute multiple joint disorders (9 cases), flare-ups of rheumatoid arthritis (4 cases), low back pain due to lumbosacral disc pathology (4 cases), osteoarthritis of large joints (3 cases), all with severe pain and corresponding functional limitation of the joints involved, were treated with a nabumetone preparation (1 g capsules; one capsule at night before going to bed) for 8-12 days. During treatment, symptoms subsided gradually with adequate recovery of joint function. Parameters concerning general tolerability did not reveal clinically relevant changes compared to baseline. Local tolerability was mostly satisfactory. Two patients complained of mild side effects (gastric pain and skin phenomena). Treatment was considered effective in 15 cases, scarsely effective in 4, and ineffective in one.
3698397 The patellofemoral joint in total condylar knee arthroplasty. Pros and cons based on five- 1986 Apr In this report, 100 knees in 77 patients, with an average age of 65, were followed for a period between five and 10 years. Rheumatoid arthritis was the diagnosis in 43 patients and osteoarthritis in 34 patients. The majority had varus, valgus, and biplane deformities. Twenty-one patients underwent bilateral procedures; all but one had patellar replacement. Over 90% of the knees were rated good to excellent according to The Hospital for Special Surgery Knee Disability Score Sheet. Of the 34 osteoarthritic patients (40 knees), 24 or 71% could walk ten blocks and beyond. Ten patients, or 29%, could walk between one and ten blocks. Further ambulation was restricted only by overall poor health and age (most were 74 years of age or older). Twenty-four patients, or 71%, could ascend and descend stairs without support, while six (18%) relied on bannister support when descending stairs. Four patients (11%) required bannister support for both ascending and descending stairs. Among the complications seen in this series were one loose patella and another with osteonecrosis of the anterior surface. No dislocations occurred, but 14 patellae showed tilt on skyline view roentgenograms, indicating a tight lateral retinaculum. In view of the good to excellent results achieved in the majority of patients, and the low morbidity associated with replacement, it is recommended that the patellofemoral joint be replaced in the course of total knee arthroplasty. When careful attention is paid to technical details, this procedure improves the quality of the arthroplasty.
1670453 Surgical treatment of subaxial cervical myelopathy in rheumatoid arthritis. 1991 May Between 1978 and 1988 a total of 27 operations were performed on 26 patients for cervical myelopathy due to rheumatoid disease in the subaxial spine. Three different causes were recognised: the first group had cord compression due to subluxation of the cervical spine itself (6 patients); the second had cord compression occurring from in front, with rheumatoid lesions of vertebral bodies or discs (6); the third had compression from behind the cord due to granulation tissue within the epidural space (14). Group I was treated by closed reduction of the subluxation followed by surgical fusion either from in front or behind. Group II was decompressed by subtotal resection of the involved vertebral bodies and discs, followed by interbody fusion. The patients in group III were decompressed by laminectomy and excision of fibrous granulation tissue from the epidural space. Good recovery of neurological function was observed after 18 of the operations, fair recovery after five, poor recovery followed three, and one was worse. Myelopathy recurred in four patients, all of whom had had anterior interbody fusion.
3019186 [Possible role of glutathione peroxidase in the regulation of collagenase activity]. 1986 Glutathione peroxidase (Se-GPx) is a selenoenzyme which catalyzes the reduction of hydroperoxides by glutathione (GSH), in most mammalian cells. Several Slow-acting drugs that are used in the treatment of rheumatoid arthritis, including D-Penicillamine, alpha-mercaptopropionylglycine and gold salts, are specific inhibitors of Se-GPx. In situation of oxidant stress, Se-GPx activity is a major source of glutathione disulfide (GSSG), an essential activator of leucocyte collagenase. Hence the possibility that the enzymatic reduction of hydroperoxides produced during chronic inflammation would play an important role in the destruction of joint tissue of arthritic patients. Inhibition of a protective system such as Se-GPx may therefore be involved in the mechanism of action of D-Penicillamine and gold salts, but it could also explain some of their undesirable or toxic effects. Confirmation of this hypothesis would open the way to new pharmacological strategies.
3384452 Purification of a plasma protein that inhibits complement-mediated prevention of immune pr 1988 May A pre-albumin glycoprotein that inhibits complement-mediated prevention of immune precipitation (PIP) has been purified from normal human serum by sequential affinity chromatography on IgG-Sepharose, protein A-Sepharose and Con A-Sepharose. A total of 4.7 mg of this protein were obtained from 50 ml of serum, representing a yield of 49% and a 253-fold degree of purification. We have named this glycoprotein gp60 as it has an apparent molecular weight of 60,000 on SDS-PAGE. The addition of gp60 to normal serum produced dose-dependent inhibition of both PIP and solubilization of immune precipitates. Maximum inhibition of PIP was achieved by a concentration of 600 micrograms/ml. A monospecific antiserum was produced by the immunization of rabbits, which enabled us to develop an enzyme-linked immunosorbent assay to measure serum concentrations of gp60. In 12 normal sera the mean concentration was 205 micrograms/ml (range 132-258 micrograms/ml), while that in 15 rheumatoid arthritis sera was 515 micrograms/ml (range 430-708 micrograms/ml). The serum concentration of this protein correlated with the level of inhibition of PIP (r = 0.91, P less than 0.01).
3258207 The stimulation of IgM rheumatoid factor from human B lymphocytes by rheumatoid arthritis 1988 Feb Immune complexes from rheumatoid arthritis (RA IC) and Hodgkin's disease (HD IC) sera were separated on an anti-C3g affinity column and their ability to stimulate the production of IgM and IgM RF by normal and RA B lymphocytes tested in a culture system in vitro. RA IC stimulated IgM production of which up to 91.3% had IgM RF activity. HD IC were incapable of stimulating the production of IgM and IgM RF. The stimulation of IgM and IgM RF production by RA IC required de novo protein synthesis. Both RA IC and HD IC were capable of significantly inhibiting (from 47.6 to 72.0%) pokeweed mitogen (PWM)-induced and goat F(ab)2 antihuman mu-induced B lymphocyte proliferation. Thus it is proposed that IC present in human pathological sera may regulate immunoglobulin production by an effect on B lymphocyte proliferation while some may, in addition, be capable of inducing IgM RF production from such cells.
3146207 [Blood cell concentration of methotrexate in long-term therapy of inflammatory rheumatic d 1988 To verify the possibility of a concomitant therapy control in 31 patients (18 psoriatic arthritis [PA], 13 rheumatoid arthritis [RA]) the blood cell concentration of Methotrexate (MTX) was continuously measured over a period of 6 months. The determinations were carried out by using a RIA of the CIS Corp. At any time MTX was determined laboratory and clinical examinations were done and the P-III-P serum-level was measured by using a RIA of the Behringwerke. The cellular MTX showed to be statistically significantly elevated compared to baseline, whereas within ranges of total cumulative dosages only insignificant fluctuations could be noticed. Like in the treatment of Psoriasis a strict correlation between the weekly administered dose and the cellular MTX could be established, the total cumulative dose, however, had no influence on the cellular MTX-level. In the treatment of RA slightly higher weekly dosages were necessary, which caused significantly higher cellular MTX concentrations in RA patients. Some correlations between clinical as well as serological parameters of disease activity could be noticed, nevertheless they do not allow distinct interpretations. In both diseases a significant relationship between the cellular MTX-level and the P-III-P serum-level could be realized. A storage of MTX in blood cells, especially in erythrocytes, seems to be evident. To reach therapeutical benefit in RA slightly higher mean dosages may be necessary. A therapy monitoring by the means of continuous determinations of cellular MTX seems to be impossible. In contrast an approach to the early detection of liver fibrosis can be given by the correlation between cellular MTX and the P-III-P serum levels.
1645686 Detection of hepatitis C virus antibody in patients with autoimmune hepatitis and other ch 1991 Apr To clarify the relationship between autoimmune hepatitis (AIH) and the hepatitis C virus (HCV), we investigated the prevalence of antibodies to HCV (anti-HCV) by an enzyme-linked immunosorbent assay in patients with AIH, primary biliary cirrhosis (PBC), rheumatoid arthritis and multiple myeloma. The antibody was detected in 9 out of 18 patients with AIH (50%), in 3 out of 23 with PBC (23%), in 2 out of 10 with rheumatoid arthritis (20%), and in 5 out of 9 with multiple myeloma (56%). However, the optical density values in these patients were lower than those observed in non-A, non-B hepatitis (NANBH). Anti-HCV became negative immediately after the initiation of glucocorticoid therapy in all four antibody-positive AIH patients tested. The extracted immunoglobulin G fraction from sera of 5 anti-HCV negative AIH patients became positive for the antibody. This phenomenon was not observed in 5 normal volunteer sera. The 9 family members of three anti-HCV positive AIH patients showed no anti-HCV positivity. These results suggest that autoantibodies in AIH patients may cross-react with the HCV-related antigen. Direct association of the HCV influencing the development of AIH is unlikely. Therefore, care should be taken in the evaluation of anti-HCV positivity in patients with autoimmune diseases and multiple myeloma.
1742504 Misoprostol prevents NSAID-induced gastroduodenal lesions in patients with osteoarthritis 1991 Mar The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant adverse effects on the integrity of the gastrointestinal (GI) mucosa. A unique, double-blind, placebo-controlled, randomized, multicentre study investigated the prophylactic co-therapy with misoprostol, a novel PGE1 analog, for the prevention of the NSAID-induced gastric and duodenal mucosal lesions. The study also investigated whether the co-therapy with misoprostol could interfere with the anti-rheumatic action of the NSAIDs using detailed rheumatological assessments. Patients with osteoarthritis or rheumatoid arthritis had to be free of symptoms and significant erosive and/or haemorrhagic lesions of the upper GI tract. The patients were randomized to co-therapy with misoprostol or its matching placebo. Follow-up endoscopy and symptoms assessment were carried out within 4 weeks and compared to pre-study findings. Misoprostol significantly reduced (p less than 0.01) the incidence of erosive and/or haemorrhagic gastric and duodenal mucosal lesions. Misoprostol also reduced the proportion of patients with epigastric pain (p less than 0.01). Misoprostol was well tolerated and did not interfere with the anti-rheumatic activity of the administered NSAID. We conclude that misoprostol is safe and effective in the protection against NSAID-induced gastric and duodenal mucosal lesions and symptoms.
2441454 [Anti-stratum corneum antibody in the rat esophagus, anti-epidermal keratin and anti-epide 1986 Nov Eight immunological parameters were explored in 257 patients with various rheumatic diseases including 107 rheumatoid arthritis (RA). IgG and IgM antibodies (AB) reactive with the Stratum Corneum (SC) of rat oesophagus or with the SC of human skin were assayed by 1/2 quantitative indirect immunofluorescence, IgG and IgM auto AB to epidermal keratins by a specific ELISA, and total serum G and M immunoglobulins by radial immunodiffusion. At the threshold we chose (99 p. cent specificity), IgG anti SC of rat oesophagus, were found in 50 of 107 (46.7 p. cent) RA patients: 52.5 p. cent in sero + and 39.6 p. cent in sero - ones. The other parameters, separately considered, had no diagnosis value. In Paget disease serum IgM and IgG and all the AB of M isotype were found to be broken down. In all the groups, the isotype AB were found strongly correlated to each other and to serum IgM. The RA sera with specific AB to the rat oesophagus SC, also labeled human skin SC but these labeling were unrelated to the anti-keratins auto AB level. On the contrary, the anti SC AB of G isotype, detectable on human skin in psoriatic rheumatism did not label rat oesophagus. These results confirm the diagnosis value of IgG AB to SC of rat oesophagus, usually called anti-keratins, who appear as a marker for RA. This work shows the relevance of associating specific immunochemical techniques to immunofluorescence, in order to unravel the antigenic complexity of tissular substrata.
3365530 Equianalgesic effects of paracetamol and indomethacin in rheumatoid arthritis. 1988 Apr The therapeutic and adverse effects of 2 weeks of treatment with high-dose indomethacin (150 mg/day) were compared with those of low-dose indomethacin (50 mg/day) combined with paracetamol (4 g/day) in a double-blind, double-dummy, cross-over study in 17 patients with active rheumatoid arthritis. Grip strength, Ritchie's index, joint circumference, joint pain, and patient's and physician's global assessments were estimated, and conventional laboratory parameters were followed. In addition, the time-concentration profiles of indomethacin and paracetamol were assessed during steady state. All patients had measurable plasma drug levels, indicating adequate compliance, and responders and nonresponders (five on each treatment) had equal drug levels, indicating that the variation in therapeutic efficacy was not secondary to pharmacokinetic differences. While there were fewer and milder side-effects during treatment with the drug combination, there was no difference in therapeutic efficacy. Hence, it appears that the main therapeutic profit of indomethacin in daily doses greater than 50 mg is enhanced analgesia. As such dosage involves pronounced side-effects, it seems more appropriate to employ the combination of 50 mg indomethacin and 4 g paracetamol, whereby similar analgesia can be obtained without an increase in side-effects.
3123369 Isoelectric focusing characterization of IgM-VKiiib immunoglobulin light chains and their 1987 Dec Previous studies have demonstrated that the IgM monoclonal anti-IgG autoantibodies (AGAs) characteristic of essential mixed cryoglobulinaemia (EMC) display preferential use of kappa light chains of the VKiiib sub-subgroup. In order to gain insights as to the possible basis for this V region selection, IgM-VKiiib immunoglobulin was affinity purified from normal human serum, analysed by dissociating two-dimensional gel electrophoresis and compared to the two-dimensional gel patterns of IgM-VKiiib anti-IgG autoantibodies (AGAs) from patients with essential mixed cryoglobulinaemia (EMC). The results suggest that only part of the available VKiiib light chain repertoire is selected by EMC AGAs. When AGAs from EMC, rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS) patients were analysed by ELISA, it was found that the association of the VKiiib light chains with anti-IgG autoantibodies differed significantly among the three diseases. In fact, in RA there appeared to be a negative selection against the use of VKiiib in AGAs. Clearly, the VKiiib determinant is not required for anti-IgG autoreactivity. The possibility emerges, therefore, that the genesis and perpetuation of AGA synthesis in these diseases may follow quite different pathways.
3290060 Geriatric rheumatology: safe use of potentially toxic antirheumatics. 1988 Jul Despite what is known about pharmacokinetics in the elderly, there is little information regarding the relationship between age and disease-modifying antirheumatic agents or immunosuppressive drugs. Musculoskeletal diseases are common in the aging population, and the therapeutic use of potentially toxic pharmacologic agents, including immunosuppressives, is prevalent. A number of factors influence the potential for toxicity in this age group, including polypharmacy and age-related physiologic change. An overview of clinical pharmacologic factors in the elderly is presented, and available information on efficacy and toxicity of disease-modifying antirheumatics and immunosuppressives is reviewed.
3293874 Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis. 1988 Aug Thirty-eight patients with active, definite, or classical rheumatoid arthritis were tested in a double-blind, 3-week-per-arm, multiple-crossover, randomized, block-design comparison of 100, 300, 600, and 800 mg/day carprofen given b.i.d. A linear dose-response relationship was demonstrated for six of nine efficacy measures (p less than 0.052). A plasma concentration to therapeutic response relationship was shown just before or 1 to 2 hours after a dose (p less than 0.05) for seven efficacy parameters for the patients with at least three serum carprofen concentrations. By nonparametric analysis, with the patients divided into three equal groups, the percent of responders rose from 38.1% to 50% to 59.1%. Sixty-nine percent of patients responded when carprofen concentrations were greater than 10 micrograms/ml, whereas only 9% responded when they were below 1.9 micrograms/ml. Although only seven patients had limiting side effects, there was a tendency toward a dose-toxicity relationship through 600 mg daily carprofen.
3963024 Safety of flurbiprofen in the treatment of ankylosing spondylitis, osteoarthritis, and rhe 1986 Mar 24 The safety of flurbiprofen (Ansaid, Upjohn) was assessed after pooling data on kidney and liver function collected from nine separate phase III clinical trials involving 1,677 patients (941 receiving flurbiprofen and 736 receiving comparison drugs) with ankylosing spondylitis, osteoarthritis, or rheumatoid arthritis. Multiple categories were created to discern the effects of treatment, disease, age (under 60 and 60 years or older), and duration of exposure to flurbiprofen. No clinically significant trends in kidney or liver function were detected in any category following the administration of flurbiprofen.
1747136 Aspirin alters methotrexate disposition in rheumatoid arthritis patients. 1991 Dec Intravenous methotrexate (MTX) (10 mg), either alone or with oral aspirin (ASA) (3,900 mg/day), was administered to 15 patients with rheumatoid arthritis. Systemic and renal clearance of MTX were lower, and the unbound fraction of MTX was higher when patients were also receiving ASA than when taking MTX alone. No acute hematologic, renal, or hepatic toxicity was observed with either treatment. The findings of this study therefore indicate that concomitant aspirin therapy acutely alters the clearance of low-dose MTX in patients with rheumatoid arthritis.
2341578 Binding of diltiazem to albumin, alpha 1-acid glycoprotein and to serum in man. 1990 Apr Binding of drugs can vary considerably. Therefore, binding of the calcium antagonist diltiazem was studied in protein solutions and in serum of healthy persons, patients with renal failure, patients with cirrhosis, patients with rheumatoid arthritis, patients with myocardial infarction, and intensive care patients. The effect of in vitro addition of some cardiovascular drugs (lidocaine, disopyramide, quinidine, and bupivacaine) on the binding of diltiazem in serum of healthy volunteers was also investigated. Diltiazem is bound as well to alpha 1-acid glycoprotein (AAG) as to albumin. In patients with renal failure, myocardial infarction, and rheumatoid arthritis and in intensive care patients, AAG concentrations are increased, and in the patients with myocardial infarction an increased binding of diltiazem is found. In patients with cirrhosis, AAG concentrations and diltiazem binding are decreased. In vitro addition of lidocaine, disopyramide, bupivacaine, or quinidine in concentrations between 5 and 100 micrograms/mL, before dialysis, decreases the binding of diltiazem; the displacing effect is most pronounced with bupivacaine.
3487336 Impaired natural killing activity in patients with rheumatoid arthritis. Clinical characte 1986 We have studied NK activity against K562 cells of peripheral blood mononuclear cells (PBMC) from 83 patients affected with RA and searched for correlations with some clinical and laboratory parameters. In 65 patients T lymphocyte subsets were investigated by laser flow cytometry using monoclonal antibodies against OKT3, OKT4 and OKT8 antigens and in 25 patients also HNK-1+ cells were enumerated. NK activity in patients with RA resulted significantly decreased compared with controls (relative cytotoxic index = 0.68 +/- 0.74 versus 1.00 +/- 0.60, p less than 0.01). Decreased NK activity was not correlated with sex, age, duration of disease, ESR, haemoglobin, serum alpha-2-globulin, serum gamma-globulin, rheumatoid factor titre. The only clinical parameter correlated with decreased NK activity was the anatomical stage of the disease. NK activity depression resulted to be significantly correlated with OKT3+ cell percentage and at a lesser extent with OKT4+ and OKT8+ cell percentages. HNK-1+ cell percentage resulted only slightly reduced in patients with RA (13.1 +/- 8.7 versus 15.0 +/- 7.0) and there was only a modest correlation (p approximately equal to 0.10) between NK activity and HNK-1+ cell percentage. In order to elucidate the mechanisms of impaired NK activity in RA, experiments in vitro were carried out on PBMC of 23 patients to investigate the effects of the depletion of cells adherent to plastic, incubation with beta-interferon (1000 IU/ml) and incubation with indomethacin (10 -6M). Our data suggest that decreased NK activity in RA is mainly due to functional immaturity of NK cells and sometimes to inhibition by monocytes in some cases probably through prostaglandin release.
1796207 [Epidemiological research in rheumatology: current status and prospects]. 1991 Rheumatic diseases are very common and their consequences on both the individuals (leading cause of activity limitation between the age of the 18 and 64 years) and on society (socio-economic costs) are considerable. However, the epidemiology of these diseases remains poorly known. In this paper, a review of the epidemiological data for the most frequent rheumatic diseases (including recent advances) is followed by an analysis of the specific obstacles to epidemiological research in the rheumatology field and by a proposal of possible developments.