Browse

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

ID PMID Title PublicationDate abstract
8619099 Investigational agents for rheumatoid arthritis. 1995 Aug Agents ranging from simple analgesics to antiinflammatory drugs to powerful immunomodulators have been used for the treatment of rheumatoid arthritis with varying success. Despite the availability of agents that are believed to be "second line" or "disease modifying," many patients either do not respond adequately to available agents or must discontinue their use because of intolerable or dangerous adverse reactions. For this reason, researchers continue to search for more efficacious and less toxic agents for patients with rheumatoid arthritis. This article describes pharmaceutical agents currently under investigation for use in rheumatoid arthritis, including the antiinflammatory agents, zileuton and tenidap, and the immunosuppressive agents, leflunomide, mycophenolic acid (RS-61443), tacrolimus (FK-506), sirolimus (rapamycin), amiprilose (therafectin), cladribine (2- chlorodeoxyadenosine), and azaribine.
8612021 Elevated levels of corticotrophin-releasing factor binding protein in the blood of patient 1996 Feb In view of the reported inflammatory effects of corticotrophin-releasing factor (CRF) and the associated regulatory elements in the gene of its binding protein (BP), we postulate that both BP as well as novel BP-ligands other than CRF may be involved in inflammatory disease. We have investigated BP in the blood of patients with arthritis and septicaemia and have attempted to identify CRF and other BP-ligands in synovial fluid. The BP was found to be significantly elevated in the blood of patients with rheumatoid arthritis and septicaemia. There was less BP-ligand and CRF in synovial fluid from patients with rheumatoid arthritis that from those with osteo- or psoriatic arthritis. There was at least 10-fold more BP-ligand than CRF in the fluid of all three groups of patients. A small amount of immunoreactive human (h)CRF, eluting in the expected position of CRF-41, was detected after high-pressure liquid chromatography of arthritic synovial fluid; however, the bulk of material with BP-ligand binding activity eluted earlier, suggesting that synovial fluid contained novel peptides that interacted with the BP. These results would suggest that the BP and its ligands could play an endocrine immunomodulatory role in inflammatory disease.
8535648 Long-term usage and side-effect profile of sulphasalazine in rheumatoid arthritis. 1995 Nov In a cohort of patients with early rheumatoid arthritis, sulphasalazine (SASP) was mainly given as a first-choice second-line agent. SASP resulted in a significantly better survival rate compared with hydroxychloroquine, which is also given as a first-choice agent. When the survival rate of SASP was compared with that of aurothioglucose, both given as second-choice agents, again, a statistically significant better survival rate was found for SASP. In 9% of the patients, SASP could be withdrawn as a complete remission was obtained. Adverse reactions occurred mainly during the first 3 months of treatment, and in 20% of patients these were severe enough to stop treatment. Gastrointestinal adverse reactions were most frequently observed, and all adverse reactions were completely reversible after treatment withdrawal. Treatment was started with a standard dose of 2000 mg/day. However, in approximately 30% of the patients, this dose was increased up to 3000 mg/day and, in another 30%, the dose was decreased to 1,500 or 1,000 mg/day.
7544977 Could HLA-DRB1 be the protective locus in rheumatoid arthritis? 1995 Jun Extensive studies in different ethnic groups have associated the susceptibility to development of rheumatoid arthritis (RA) with the third hypervariable region of the major histocompatibility complex (MHC) HLA-DR beta 1 molecule. On the basis of recent findings in the experimental mouse model of collagen-induced arthritis, Eric Zanelli, Miguel Gonzalez-Gay and Chella David propose that the HLA-DRB1 locus is associated with protection to RA and that the actual arthritogenic peptide-presenting molecule is HLA-DQ. Thus, the development of RA would depend upon the expression of the susceptible DQ allele and the nonprotective DRB1 alleles, along with environmental factors that trigger the autoimmune process.
8055196 HLA class 2 genes in Singaporean Chinese rheumatoid arthritis. 1994 Aug This study analysed HLA class 1 and 2 allele associations in Singaporean Chinese patients with RA. Seventy patients (ARA definite or classical) and 80 controls were typed for HLA class 1 alleles by serology and class 2 alleles by serology and the PCR/SSO method. RA patients had higher frequencies of DRB1*0405 (40 vs 12.5%; corrected probability value (PC) < 0.02, relative risk (RR) = 4.7, 95% confidence limit (CL) 2.1-10.6), DRB1*1001 (14.3 vs 1.3%; PC = 0.06, RR = 13.2, 95% CL 1.6-105.7), DQB1*0401 (38.6 vs 12.5%; P = 0.006, RR = 4.4, 95% CL 1.9-10.0) and DQB1*0501 (20 vs 5%; PC = 0.048, RR = 4.8, 95% CL 1.5-15.2). It is concluded that Chinese RA is associated primarily with HLA DRB1*0405 and DRB1*1001 which share common amino acid sequences in the third hypervariable region of the DR beta chains shown to be associated with RA in other ethnic groups. Patients without DRB1*0405 and *1001 had a higher frequency of DRB1*0901, which is in linkage disequilibrium with HLA B46 in the Chinese.
8949606 [Pancytopenia in rheumatoid arthritis treated with methotrexate]. 1996 Sep 7 OBJECTIVES: Six cases of pancytopenia were analyzed retrospectively among 350 patients with rheumatoid arthritis treated with methotrexate. Pancytopenia is an uncommon but severe secondary effect of methotrexate. CASE REPORTS: Five patients were hospitalized for infectious complications or hemorrhage with favorable outcome. One patient died due to septic shock. There were risk factors in all 6 patients: 5 were over 65 years of age, creatinine clearance was under 50 ml/min in 4, hypoalbuminemia was found in 4 and methotrexate was combined with an antiinflammatory drug in 4 and with ranitidine in 2. The pharmacological imputability of methotrexate was probable in 4 of the 6 patients. DISCUSSION: Acute pancytopenia in patients treated with methotrexate can be prevented by recognizing risk factors, regular laboratory tests and supplementation of all patients with folic acid according to protocols to be established.
8461928 Antibodies to type II collagen in early rheumatoid arthritis. 1993 Apr Antibodies to native and denatured type II collagen were investigated in a group of 79 patients with rheumatoid arthritis (RA) of disease duration less than 12 months (median 8 months; range 3-12 months). Using a solid-phase ELISA to measure these antibodies, the incidence of patients with levels above the upper limit of normal (mean of normal plus 3 SD) was low as compared to previous findings in patients with established disease. The majority of positive sera contained small amounts of IgM antibodies to denatured type II collagen whilst a few had IgG antibodies to native and denatured type II collagen. These findings suggest that the production of high levels of serum anti-type II collagen antibodies in patients with RA is a secondary phenomenon, which may exacerbate the disease rather than be a primary cause of disease.
8522746 Long-term results following digital flexor tenosynovectomy in rheumatoid arthritis. 1995 Sep A retrospective review of flexor tenosynovectomy for rheumatoid flexor tenosynovitis in the palm and digit was performed. Fifteen patients (61 fingers) were reviewed for at least 1 year (average, 4 years) after surgery. An average of 2.2 cm improvement in active flexion (pulp to distal palmar crease) was observed. A significant difference in preoperative and postoperative results was found. Sixty-seven percent of digits were classified as having excellent or good results, 21% fair results, and 12% poor results. The clinical recurrence rate was 31% and the reoperation rate was 15%. Only minimal complications from the extended surgical approach were observed. Debulking the fibro-osseous canal by excising a slip of flexor digitorum superficialis was associated with a reduction in the recurrence and reoperation rates.
7598422 Use of split-skin grafting in the treatment of chronic leg ulcers. 1995 May Chronic leg ulcers are a common problem for which many different forms of treatment have been used. In this study we reviewed the results of split-skin grafting of ulcers of different aetiologies; 26 patients were reviewed. The mean duration of ulceration was 27.5 months. Of the 28 ulcers, ten were due to venous disease, three arterial disease, six rheumatoid arthritis, seven traumatic, and two diabetic. Healing rates of 85% for traumatic and 67% for rheumatoid ulcers were achieved, whereas rates of only 20% and 33% were achieved for venous and arterial ulcers (P < 0.02 Fisher's exact test). We conclude that in the presence of vascular disease, split-skin grafting is not an effective treatment for chronic leg ulceration. Vascular assessment and treatment should be carried out before attempting skin grafting.
1540788 Antinuclear and antineutrophil cytoplasmic antibodies (ANCA) in the sera of patients with 1992 Mar The prevalence of antinuclear (ANA) and antineutrophil cytoplasmic antibodies (ANCA) has been studied in the sera of 62 patients with rheumatoid arthritis and 32 patients with Felty's syndrome. The presence of ANA was less in RA than Felty's syndrome (37% versus 69%). Specific autoantibody identification, where possible, was usually of SS-A or SS-B although two sera from patients with Felty's syndrome had low levels of DNA antibody. ANCA was detected in the sera of 33% of patients with Felty's syndrome and was absent in RA sera. The pattern of ANCA staining was either of a diffuse homogenous cytoplasmic or peripheral (pANCA) nature. Classical cytoplasmic granular staining (cANCA) was not identified.
1525846 Management of early inflammatory arthritis. Intervention with immunomodulatory agents: mon 1992 Jun Over the last three years there has been a dramatic rise in the number of trials using monoclonal antibodies in the treatment of rheumatoid arthritis. So far, the numbers of patients treated in the individual studies have been small, and the study designs not comparable. All these trials have been conducted in a non-blinded, uncontrolled fashion. The patient populations tended to represent the severe end of the disease spectrum, being usually individuals for whom all other conventional and sometimes even unconventional experimental therapeutic approaches have failed. Clearly, therefore, larger controlled double blind studies in patients with less advanced stages of rheumatoid arthritis are needed. In the trials thus far, long-standing diseases afflicting the joints, usually with severe destruction, have frequently made clinical evaluation very difficult. Moreover, apparently with the exception of one or two reagents (16H5 and possibly B-F5) routine laboratory parameters which are helpful in determining disease activity such as CRP or the rheumatoid factor usually remain unaltered with anti-T cell therapy. In addition, in some individuals there was no clinical improvement despite sometimes severe CD4 cell depletion. The notion that the mere depletion of CD4+ cells is not sufficient to permanently suppress disease activity in autoimmune disease is further supported by studies carried out by Conolly and Wofsy in 1990. In a mouse lupus model, these investigators demonstrated that a small subpopulation of CD4+ T cells may be refractory to depletion by anti-CD4 and may be able to promote the full expression of the disease. Similar mechanisms could apply to certain individuals with human autoimmune disorders. Many additional questions remain open. The most important of these is which markers identify clinical responders to therapy. Attempts to correlate clinical response to the level of T cell depletion, modulation of the target antigens or in vitro functional assays so far have not yielded significant results. Other questions relate to the frequency of antibody administration and the amounts needed to permanently suppress disease activity. The initial hope based on animal experiments of inducing a permanent tolerance to certain antigens by anti-CD4 treatment has been clearly shown not to apply to rheumatoid arthritis. Even though there are individual variations, the efficacy of anti-T cell treatment tends to wear off after 3 or even 1 month, necessitating retreatment. Protocols will have to be designed for either longer treatment periods, repeated courses or more frequent single administrations.(ABSTRACT TRUNCATED AT 400 WORDS)
8517929 Conserved motifs in rheumatoid arthritis synovial tissue T-cell receptor beta chains. 1993 Jun Rheumatoid arthritis is genetically linked to major histocompatibility complex (MHC) molecules (HLA-DR4 and related molecules) and characterized pathologically by high levels of HLA-DR expression and infiltration of proliferative of synovial tissue with CD4+ T lymphocytes. T-lymphocyte activation is driven by specific signaling through polymorphic alpha/beta T-cell receptors (TCRs) that are reactive with antigen-MHC complexes present at the sites of inflammation. We are interested in characterizing rheumatoid TCRs molecularly to ascertain potential binding surfaces for antigen+MHC in synovial tissue. Accordingly, we have recently investigated the TCR alpha and beta chain heterogeneity in a series of 10 rheumatoid synovia obtained at the time of joint surgery. The most frequently detected V beta families were V beta 12, 14, and 17, each of which was found in 80% of specimens. We report here the molecular cloning and sequence analysis of 20 cloned V beta segments amplified with a V beta 14 family-specific TCR primer, and six cloned V beta segments amplified with a V beta 17 family-specific TCR primer from four rheumatoid synovia. Comparison with the data base revealed that these sequences belonged to the closely related V beta 3, V beta 14, and V beta 17 families. Dominant clones were apparent in two of the individuals by the presence of identical V-D-J regions, suggesting an antigen-driven process. Amino acid sequence analysis revealed a conserved motif in the putative fourth hypervariable region or CDR4. Molecular modeling of this epitope suggests that charged side chains are available for binding to ligand structures (e.g., antigen, MHC, or superantigen). We suggest this epitope may play a role in the molecular pathogenesis of rheumatoid arthritis.
7575694 Tenidap in rheumatoid arthritis. A 24-week double-blind comparison with hydroxychloroquine 1995 Oct OBJECTIVE: To compare the clinical efficacy, effect on serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma interleukin-6 (IL-6) levels, and safety of tenidap with a combination of hydroxychloroquine-plus-piroxicam, and piroxicam alone, in the treatment of rheumatoid arthritis (RA) patients. METHODS: A double-blind, randomized, multicenter study in which patients with active RA were treated with tenidap 120 mg/day, hydroxychloroquine 400 mg/day and piroxicam 20 mg/day, or piroxicam alone 20 mg/day, for 24 weeks. RESULTS: At weeks 12 and 24, tenidap produced greater improvements than piroxicam based on 5 primary efficacy parameters; this improvement showed statistical significance in 4 of the 5 measures at week 12, and in 3 of the 5 measures at week 24. Clinical improvements in the hydroxychloroquine-plus-piroxicam-treated with tenidap. Compared with piroxicam, tenidap was associated with significantly greater reductions in serum CRP concentrations at 4, 12, and 24 weeks, and significantly greater reductions in SAA concentrations at weeks 12 and 24. The decrease in SAA concentrations was also significantly greater at weeks 4 and 24 in the tenidap-treated group than in the hydroxychloroquine-plus-piroxicam-treated group. Significant reductions in plasma IL-6 levels were observed at weeks 4, 12, and 24 within the tenidap group, and at week 24 within the hydroxychloroquine-plus-piroxicam-treated group. The overall occurrence of side effects, including gastrointestinal side effects, was similar in all 3 treatment groups. A small proportion of tenidap-treated patients (6.4%) manifested mild, nonprogressive, reversible proteinuria of presumed renal proximal tubular origin, and 3-4% of patients had elevated transaminase levels. CONCLUSION: In the treatment of patients with RA, tenidap is as effective as the combination of hydroxychloroquine-plus-piroxicam, and is more effective than piroxicam alone; moreover, tenidap's safety profile is comparable to that observed with piroxicam alone, and with hydroxychloroquine-plus-piroxicam. The clinical response observed in this study, as well as the prompt decreases in acute-phase protein levels of CRP and SAA, and in plasma IL-6 levels, suggest that tenidap represents a new type of antiarthritic medication, with properties similar to, but not identical to, a therapeutic combination of a nonsteroidal antiinflammatory drug with disease-modifying antirheumatic drugs.
1289197 [Cimetidine hepatitis]. 1992 Dec 15 A 41-year-old man with rheumatoid arthritis developed severe acute hepatitis 3 days after starting cimetidine for duodenal ulcer. Other causes were ruled out and he recovered after cimetidine was discontinued. Mild transient elevations of hepatic enzymes have been reported in 3.6% of patients taking cimetidine. However, only 12 cases of severe acute hepatitis associated with cimetidine, mostly secondary to idiosyncrasy, have been reported in the English literature. This rare but serious complication of cimetidine should be kept in mind.
7793105 Systemic lupus erythematosus, rheumatoid arthritis and HLA phenotypes in Jamaicans. 1995 Mar The HLA phenotypes were investigated in 30 Jamaican patients with Systemic Lupus Erythematosus (SLE), 30 with Rheumatoid Arthritis (RA) and 40 healthy controls. HLA phenotypes were determined by the microcytoxicity technique, using commercially prepared typing trays. In this study, the HLA phenotypic associations with SLE (HLA-B14, RR 4.3: HLA-A28, RR 4.3) were not statistically significant. However, a statistically significant lack of HLA-A9 (p < 0.01; CP < 0.1) was observed in SLE patients compared to healthy controls. In RA patients, a statistically significant association was noted with HLA-A2 (RR 5.1; CP < 0.01). No HLA class II associations were noted with SLE. Class II associations with RA did not achieve statistical significance but included those previously established in other populations. The preliminary data obtained from this study indicate differences in the patterns of HLA phenotypes in Jamaican patients with SLE and RA compared to those observed in such patients elsewhere. Further studies involving larger groups of patients and typing at the serological, cellular and molecular levels are clearly warranted.
8052932 [A case of rheumatoid arthritis associated with agranulocytosis during bucillamine treatme 1994 Jun Bucillamine has been reported to have beneficial effects in rheumatoid arthritis. This report concerns a case of RA in which agranulocytosis developed while on a course of bucillamine. A 52-year-old female with RA developed a rapid fall in white blood cell count after 4 weeks of bucillamine treatment at daily dose of 50 mg. Agranulocytosis was diagnosed (WBC 1300/mm3, granulocytes 5%). The administration of bucillamine was halted and she was treated with only prophylactic antibiotic regime. The peripheral granulocyte count result rapidly reversed within 3 days after discontinuation of the bucilamine treatment. Anti-leukocyte antibody was detected by the leukocyte lysis phenomenon method during the period of agranulocytosis. And high intrinsic G-CSF activities were detected in the patient serum before the recovery period of agranulocytosis. Agranulocytosis is a rare side effect of bucillamine but it is potentially more harmful than other side effects. In treatment with bucillamine, therefore, the drug should be carefully administered and regular blood examinations carried out to prevent the occurrence of this side effect.
8040507 Word completion in chronic pain: evidence for schematic representation of pain? 1994 May Schematic representation of pain information was investigated in chronic pain patients, health professionals, and nonpatient controls. Under the guise of an English-language experiment, Ss were presented with 12 word stems to be completed with the first 2 English words that came to mind. Four of the stems could be completed with sensory pain words, 4 with effective, and 4 with words associated with pain or illness. All could be completed with at least 3 other nonpain words of equal or greater frequency. Results indicate that chronic pain Ss produced significantly more pain-related completions than control Ss and that in all 3 groups the types of pain words produced were related to the extent of personal experience of pain. The theoretical implications of these findings are discussed in relation to the organization of schema, implicit memory, and the activation of mental representations of pain (schema).
7728883 Tropical rheumatology. Epidemiology and community studies: Africa. 1995 Feb There is still far too little information available on the rheumatic diseases in Africa. Epidemiological studies are required in order to determine the burden of illness from rheumatic diseases on the African continent as well as to identify local risk factors for certain diseases. Such studies will also serve to enable the development of preventative and rehabilitation strategies. Functional disability has to be assessed in relation to the prevailing sociocultural lifestyle on the continent. Measures of disability that reflect this await development whilst regional diagnostic criteria also need to be worked out. The validity of tests and the stability of test reagents in a tropical climate require analysis. Continuing assessment of rheumatological services is essential to ensure their effectiveness and efficiency in the community and in particular to determine health care priorities and the best forms of therapeutic intervention. This will enable judicious use of limited resources. Community surveys in Africa are fraught with constraints and are difficult to undertake owing to a shortage of manpower and financial resources. For this reason, most studies hitherto have been hospital based. Hospital studies though useful lack applicability to the population as a whole and consequently more emphasis on cross-sectional and longitudinal community studies are required. It is hoped that despite the restraints, these studies will be performed.
8310707 Pharmacokinetics of single oral doses of feprazone in patients with rheumatoid arthritis o 1993 Nov 1. The pharmacokinetics of feprazone have been studied in 10 patients with rheumatoid arthritis (RA), and in a further six patients with renal impairment (RI) who were not suffering from rheumatoid disease. 2. For RA patients, the mean elimination half-life (t1/2) of feprazone after a single oral dose was 21 +/- 5 h (SD), the mean apparent clearance (Cl) was 0.012 +/- 0.009 l/h per kg, and the mean apparent volume of distribution (Vd) was 0.33 +/- 0.17 l/kg. Corresponding values for RI patients were 25 +/- 13 h, 0.016 +/- 0.011 l/h per kg, and 0.46 +/- 0.24 l/kg, respectively. 3. These results show no impairment of the elimination of feprazone in RA or RI patients; Vd and Cl are greater than in healthy young volunteers or elderly subjects, the AUC values are lower, but t1/2 values are similar in all groups. 4. It is suggested that the greater Cl and Vd, and lower AUC, in RA and RI patients may be due to renal insufficiency and decreased plasma protein binding of feprazone and its metabolite, or to induction of glucuronyl transferase activity by the prior medication, thus enhancing the formation of the major metabolite, the C(4)-glucuronide, and increasing drug elimination.
8124920 Concurrent acute megaloblastic anaemia and pneumonitis: a severe side-effect of low-dose m 1993 Dec In a patient suffering from rheumatoid arthritis, we report the first simultaneous occurrence of two side effects of low-dose methotrexate: an acute megaloblastic anaemia and a pneumonitis. A combination of methotrexate suspension, folinic acid and corticosteroids led to recovery. The correlation between the haematologic and pneumologic toxicity is discussed.