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ID PMID Title PublicationDate abstract
11361222 Inflammatory arthropathy in MRL hematopoietic chimeras undergoing Fas mediated graft-versu 2001 May OBJECTIVE: To determine whether overexpression of the Fas ligand (FasL) on activated lpr T lymphocytes could induce arthritic lesions when grafted into syngeneic wild-type MRL mice expressing normal Fas receptor levels. METHODS: Lethally irradiated MRL+/+ mice were reconstituted with congenic MRL/lpr bone marrow cells and splenocytes overexpressing FasL. Fas-mediated cytotoxic properties of repopulating lpr splenic lymphocytes were evaluated in vitro. Simultaneously, the hind paw ankles of the hematopoietic chimeras were histologically examined. RESULTS: The lpr lymphocytes repopulating the spleen overexpressed FasL and had in vitro Fas-mediated cytotoxic activity. Simultaneously, in vivo, articular (synovitis, pannus) and periarticular (periostitis) inflammation with bone resorption were observed. CONCLUSION: Arthritic lesions may be induced in Fas-expressing recipients by persistent engrafted syngeneic lymphocytes overexpressing FasL.
9234629 [Bronchiolitis obliterans and no radiographic abnormalities in a patient with rheumatoid a 1997 May A 53-year-old woman was given a diagnosis of rheumatoid arthritis in 1988, and begun treatment with D-penicillamine in September 1992. She noticed dry coughing and exertional dyspnea that began in April 1993. Chest X-ray and CT films revealed no abnormal opacities. However, bronchiolitis obliterans was suspected because of a low FEV1% (23%). Examination of specimens obtained by thoracoscopic lung biopsy revealed constrictive obliteration by granulation tissue in proximal bronchioles and follicular bronchiolitis. Alveoli and respiratory bronchioles were intact. After corticosteroid and cyclophosphamide pulse therapy, FEV1% increased to 35%. At the time of this writing she was alive 2.5 years after hospitalization.
10626050 Antimalarial drugs for rheumatoid disease during pregnancy. 1999 Dec QUESTION: One of my patients, who has rheumatoid arthritis, has just found out she is pregnant. She is being treated with hydroxychloroquine. I could not find anything about the safety of this drug during pregnancy. ANSWER: Most of the literature on this drug relates to prophylaxis for malaria. Much lower doses than those used for rheumatic diseases are given with no adverse fetal effects. Several studies on use of the drug for rheumatic diseases during pregnancy also failed to show adverse fetal effects, although, in most cases, only first-trimester exposure was reported.
10914846 Patterns of drug use in rheumatoid arthritis. 2000 Jul OBJECTIVE: Treatment strategies for rheumatoid arthritis (RA) are rapidly evolving, but few data exist on current prescribing patterns in distinct populations of patients and physicians. We described patterns of drug use for RA in a large population including use of nonsteroidal antiinflammatory drugs (NSAID), disease modifying antirheumatic drugs (DMARD), and corticosteroids. METHODS: We identified a cohort of 10,262 New Jersey Medicaid/Medicare/PAAD (Pharmacy Assistance for the Aged and the Disabled) beneficiaries with at least one episode of care for RA between January 1, 1992, and January 1, 1995, and at least one episode of care after December 31, 1995. All patients were present for the entire study period and thus constituted a closed cohort. All filled prescriptions, hospitalizations, nursing home care, and physician visits during 1995 were analyzed. RESULTS: The cohort was 67 years old on average, 82% female, and 63% white; 63% were enrolled in Medicaid and 9% were in a nursing home at the beginning of followup. During the study year, 68% of patients filled at least one prescription for any of the drug groups studied. The most frequently prescribed medication was an NSAID (57%), followed by corticosteroids (23%) and DMARD (13%). Thirty-nine percent of patients used only NSAID, 2% only DMARD, and 6% only corticosteroid. Patients taking NSAID used them on average for 3 months during the study year, corticosteroids for 4 months, and DMARD for over 7 months. During the study year, one-third of DMARD users stopped all DMARD therapy. One-third of prednisone users were taking doses higher than 10 mg/day. CONCLUSION: While our RA cohort was older than would be expected, they represent a typical Medicare and Medicaid or PAAD population. In this cohort of patients with a diagnosis of RA cared for by either general practitioners or rheumatologists, NSAID were the most commonly prescribed medication, with substantially lower rates of use for DMARD and corticosteroids. Drug discontinuation and medication switching were common.
10852284 Musculoskeletal examination teaching in rheumatoid arthritis education: trained patient ed 2000 Jun OBJECTIVE: To assess whether students taught by trained patients acquire the same levels of competence in musculoskeletal examination skills as students taught by nonspecialist doctors. METHODS: Year 1 Graduate Medical Program (GMP) students (N = 25) at Hospital A were randomized to 8 tutorial groups, each comprising 3-4 students. Groups were taught hand and wrist examination skills by patient educators trained by the Searle Patient Partners in Arthritis program (patient partners). Students at Hospitals B and C (N = 12) remained in their normal tutorial groups, each comprising 3-4 students. Groups at Hospitals B and C were taught hand and wrist examination skills by doctors who had no specialized training in musculoskeletal medicine or orthopedics, with an untrained patient present. RESULTS: Students' mean self-ratings of examination skills before and students' patient partners, and consultants' mean ratings of students' examination skills after the tutorial were summed. Before the tutorial there were no significant differences in level of skill between students at Hospitals A, B, and C as measured by students' self-ratings. After the tutorial all students showed clear gains in levels of skill. Students taught by patient partners had higher levels of skill than those taught by doctors for 3 (p<0.01) and 4 (p<0.05) out of 14 examination skills and all 4 communication skills (p<0.05), as measured by both patient partners' and consultants' ratings. Students taught by doctors showed higher levels of skill for 2 observation skills, but these differences were not significant. CONCLUSION: Patient partners are either equal or superior to doctors not specifically trained in musculoskeletal medicine or orthopedics, in the teaching of musculoskeletal examination techniques and basic communication skills.
10211892 Fertility and pregnancy outcome in women with systemic sclerosis. 1999 Apr OBJECTIVE: To determine fertility and pregnancy outcome in women with systemic sclerosis (SSc; scleroderma) who had disease onset before age 45 years. METHODS: All living women with scleroderma who had first been evaluated at the University of Pittsburgh Scleroderma Clinic after January 1, 1972 were sent a detailed self-administered questionnaire in 1986 specifically concerning pregnancy outcomes and infertility. This group was compared with 2 race- and age-matched control groups, one comprising women with rheumatoid arthritis (RA) and one comprising healthy neighborhood women identified by random-digit dialing. We determined the number, history, treatment, and outcome of women who either had never been pregnant or had attempted to become pregnant unsuccessfully for more than 1 year. We also obtained data regarding pregnancy outcomes, including the frequency of miscarriage, premature births, small full-term infants, perinatal deaths, and births of live healthy infants. RESULTS: The study group comprised 214 women with SSc, 167 with RA, and 105 neighborhood controls. There were no significant differences in the overall rates of miscarriage, premature births, small full-term births, or neonatal deaths between the 3 groups. Women with SSc were more likely than those without SSc to have adverse outcomes of pregnancy after the onset of their rheumatic disease, particularly premature births (also seen in RA women after disease onset) and small full-term infants. Although a significantly greater number of women with SSc had never been pregnant, there were no significant differences in the frequency of never having been pregnant or of infertility in the 3 groups after adjustment for contributing factors. CONCLUSION: This study indicates that women with SSc have acceptable pregnancy outcomes compared with those of women with other rheumatic disease and healthy neighborhood controls. Infertility was not a frequent problem. We believe that there are no excessive pregnancy risks to women with SSc or their infants. However, a well-timed pregnancy with careful obstetric monitoring will maximize the likelihood of a successful outcome.
9671989 HLA haplotype sharing in rheumatoid arthritis sibships: risk estimates subdivided by proba 1998 There is a well-known association between rheumatoid arthritis (RA) and HLA-DR4. Recent research has indicated that both DR4 haplotypes are important in disease predisposition (favoring a recessive mode of inheritance). Others have suggested that certain combinations of genotypes, in particular Dw4/Dw14 heterozygotes, may be more important than others. We examined the mode of inheritance of RA using data from the Arthritis and Rheumatism Council's national repository of family material [Worthington et al. (1994) Br J Rheumatol 33:970-976]. There were 85 affected sibships consisting of 77 sib pairs, 6 trios, 1 quintuplet, and 1 sextuplet. The affected sibs shared two, one, and zero parental HLA haplotypes in a ratio of 0.42:0.43:0.15, which was significantly different from random expectations (P = 0.00009). Risk estimates for RA to sibs were calculated based on an overall sibling recurrence risk of 3.9%. Risks for those sharing two, one, and zero parental HLA haplotypes were 6.5% [95% confidence interval (CI) = 5.1-7.9%], 3.3% (95% CI = 2.6-4.0%), and 2.5% (95% CI = 1.5-3.5%), respectively. We also examined the risk of RA based on the DRbeta1 genotype status of sib and proband. After excluding genotypic combinations with small numbers, the highest genotype-specific risks were seen for sibs sharing two haplotypes with either a DRbeta1*0401/DRbeta1*0404 (12.5%, 95% CI = 6.9-15.2%) or a DRbeta1*0401/DRbeta1*0408 (11.1%, 95% CI = 4.5-15.1%) proband. An independent assessment based on the AGFAP methodology confirmed the increase in risk for these genotypes, in particular for DRbeta1*0401/DRbeta1*0408. The excess being due to *0401/*0408 rather than to *0401/*0404 may explain why the Dw4/Dw14 effect is not always observed.
9002048 Influence of the QKRAA/QRRAA/RRRAA motifs of the third hypervariable region of HLA-DRB1 in 1997 Jan Most patients with rheumatoid arthritis (RA) express HLA-DR4, HLA-DR1, or HLA-DR10. The DRB1 chains of these alleles have highly homologous 3rd hypervariable regions, with the motifs QKRAA, QRRAA, or RRRAA. The role played by the QKRAA, QRRAA, and RRRAA motifs in the development of RA is unknown. It may involve interaction with a T cell, an antigenic peptide, or an unknown ligand. We investigated the role played by the QKRAA motif and observed that it was expressed on numerous proteins from bacteria and viruses. However, we detected no anti-QKRAA autoimmunization in patients with RA. We found that QKRAA is a binding motif for bacterial and human 70 kDa heat shock proteins, and suggest that this may explain both its being expressed on so many proteins and its role in the development of RA.
9559235 Rheumatoid nodules: MRI characteristics. 1998 May Rheumatoid nodules are not uncommon in patients with rheumatoid arthritis. Two patients with rheumatoid arthritis and rheumatoid nodules are described. The MRI characteristics and enhancement patterns of five nodules are examined.
11757457 [Naproxen-induced pseudoporphyria]. 2001 Nov A 12 year old boy developed scars at light-exposed areas following long-term therapy with naproxen for rheumatoid arthritis. Erythrocyte and urine porphyrin levels were not increased, and there was no evidence of increased photosensitivity. Pseudoporphyria is reported in 10-20% of those treated with naproxen for > 4 weeks. As compared to other nonsteroidal anti-inflammatory agents, the specific risk for naproxen is increased about 6fold. While the underlying abnormality has not been elucidated, formation of phototoxic metabolites in a subgroup of genetically predisposed individuals has been suggested as the most likely mechanism. Both dermatologists and rheumatologists should be aware of the risk of naproxen-induced pseudoporphyria and discontinue therapy early in order to avoid scar formation in light-exposed areas.
11482129 HLA-DQA1 genotyping in patients with rheumatoid arthritis in Taiwan. 2001 Apr To investigate the role of HLA-DQA1 genotypes and their interaction with HLA-DRB1 in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, HLA-DQA1 was determined in 71 patients with RA and 108 healthy controls by SSP-PCR method. HLA-DRB1 and HLA-DQA1 were simultaneously detected in 55 RA patients and 101 healthy controls. PCR/SSOP method was used to determine the HLA-DRB1 genotypes, and the subtypes of HLA-DR4 were determined by cloning and sequencing. The phenotypic frequency of HLA-DQA1*0301 was significantly lower in RA than in controls, and, in contrast, the HLA-DQA1*0302 and DQA1*0303 were significantly higher in RA than in controls. The associations of DQA1*0301, *0302, and *0303 with RA were independent of DR4 and DRB1*0405. Moreover, the interactions between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303 could enhance the development of RA. We also found that the prevalence of bone erosion and seropositivity of rheumatoid factor (RF) were significantly higher in HLA-DQA1*0303 positive RA patients than in healthy controls. HLA-DQA1*0302 and DQA1*0303 are the risk factors for susceptibility to RA, while HLA-DQA1*0301 is a protective factor. A synergistic effect for the susceptibility to RA can be found between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303. We also found that the HLA-DQA1*0303 was related to bone erosion and seropositivity of RF in RA patients.
9811054 Nuclear factor kappaB/p50 activates an element in the distal matrix metalloproteinase 1 pr 1998 Nov OBJECTIVE: To determine how interleukin-1 (IL-1), through activation of collagenase 1 (matrix metalloproteinase 1 [MMP-1]) transcription in synovial fibroblasts, contributes to cartilage degradation in rheumatoid arthritis. METHODS: Primary rabbit synovial fibroblasts were transiently transfected with MMP-1 promoter/ luciferase constructs, and promoter activity in response to IL-1 was assessed. A minimal IL-1-response element was defined and used to evaluate DNA binding proteins by electrophoretic mobility shift assay and in situ ultraviolet crosslinking assay. RESULTS: Transcriptional activation of the MMP-1 gene by IL-1 in rabbit synovial fibroblasts required a dorsal-like element, which was located at nucleotide (nt) -3,029, as well as an activator protein 1 site at nt -77. Importantly, an IL-1-induced DNA binding activity that was specific for the dorsal-like element contained the p50 subunit of nuclear factor kappaB (NF-kappaB). CONCLUSION: These studies demonstrate, for the first time, a role for NF-kappaB in the induction of MMP-1, and suggest a mechanism of NF-kappaB-mediated cartilage degradation in rheumatoid arthritis.
10779770 Stat4 is expressed in activated peripheral blood monocytes, dendritic cells, and macrophag 2000 May 1 Stat4 is a key transcription factor involved in promoting cell-mediated immunity, whose expression in mature cells has been reported to be restricted to T and NK cells. We demonstrate here, however, that Stat4 expression is not restricted to lymphoid cells. In their basal state, monocytes do not express Stat4. Upon activation, however, IFN-gamma- and LPS-treated monocytes and dendritic cells express high levels of Stat4. Monocyte-expressed Stat4 in humans is phosphorylated in response to IFN-alpha, but not IL-12. In contrast, the Th2 cytokines, IL-4 and IL-10, specifically down-regulate Stat4 expression in activated monocytes, while having little effect on Stat6 expression. Moreover, macrophages in synovial tissue obtained from patients with rheumatoid arthritis express Stat4 in vivo, suggesting a potential role in a prototypical Th1-mediated human disease. IFN-alpha-induced Stat4 activation in human monocytes represents a previously unrecognized signaling pathway at sites of Th1 inflammation.
9645419 TAP2 alleles in inflammatory arthritis. 1998 Sixty patients with reactive arthritis (ReA) and 40 with rheumatoid arthritis (RA), were typed for H LA-B27 and class II antigens DR and DQ, and studied for TAP2 gene polymorphism in comparison with 60 healthy controls. TAP2 polymorphisms at positions 379, 565, 665, and 687 were analyzed using amplification refractory system-based PCR and polymorphisms at positions 386 and 651 using oligonucleotide hybridization. The frequency of the TAP2A/A genotype was 30%(12/40) in RA, in contrast to 13% (8/60) in the controls. This genotype was further associated with DRB1*04 positive RA (10/24, 42%, P=0.01), as well as the TAP2A allele (31/48, 65%, P =0.012). Thr/Thr dimorphism at TAP2 position 665 (24/40, 60%, P=0.024) and Stop/Stop dimorphism at TAP2 position 687 (24/40, 60%, P=0.024) were found to be increased in RA patients as compared to controls. When TAP2I/J polymorphism was studied, TAP2J positivity was found associated with the HLA-B27DR4-DQB1*0301-haplotype in ReA patients. 9/12 of these were positive as compared to 20/60 in random controls (P=0.010). Polymorphisms of the TAP2 gene were found to be associated with subgroups of RA and ReA patients with disease associated markers (e.g. TAP2A in DRB1*04 positive RA, or TAP2J in HLA-B27-DRB1*04-DQB1*0301 positive ReA). These may thus serve as additional markers of specific haplotypes associated with susceptibility to inflammatory arthritis.
9510410 Rheumatoid arthritis associated with renal amyloidosis and crescentic glomerulonephritis. 1998 Jan A 43-year-old woman with rheumatoid arthritis (RA), renal amyloidosis and crescentic glomerulonephritis had severe abdominal pain, melena and progressive renal failure. Autopsy findings revealed vasculitis of small and middle size of vessels and there was a deposition of amyloid in the small intestines. Although there were no findings of vasculitis in the kidney, amyloid deposition was noticed and 70-80% of glomeruli showed a crescentic formation. No immunological abnormality was found in glomeruli. Although the immunological mechanisms of crescentic glomerulonephritis were not necessarily eliminated, amyloid deposition may play a role in crescent formation.
11876141 [Leflunomide--a new disease modifying anti-rheumatic agent]. 2001 Nov 10 BACKGROUND: Leflunomide is a novel disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis. The agent has been developed for the treatment of rheumatoid arthritis, but its multiple immunomodulatory properties may in the future be of interest in the treatment of other rheumatic and immunological diseases. MATERIAL AND METHODS: Review of the literature in order to present the current relevant clinical documentation of the drug. RESULTS: The clinical documentation is mainly based on three large, prospective, randomized trials of six months "to two years" duration comparing leflunomide with placebo, sulphasalazine or methotrexate. The efficacy of leflunomide in all trials was superior to placebo and comparable to sulphasalazine and methotrexate. The frequency of adverse events was also comparable to the comparators. INTERPRETATION: Leflunomide is a safe and efficacious addition to the roster of antirheumatic drugs, but further clinical trials and experience from clinical practice are needed in the evaluation of its place as a disease-modifying agent.
10550441 [Wrist joint arthrodesis. Technique and outcome]. 1999 Oct Arthrodesis of the wrist joint is indicated in degenerative joint desease, instability and restricted and painful range of motion. Further indications are: failed reconstruction, partial arthrodesis or arthroplasty/total joint replacement. The surgical technique depends mainly on the quality of bone substance and degree of joint degeneration. Differences can be made concerning the type of bone graft and osteosynthesis being used. The aim is to create, a stable joint in a good functional position. The position of arthrodesis depends on the patients needs. In patients with rheumatoid arthritis a straight position is generally accepted, where as in patients with degenerative joint desease, a slight wrist extension and ulnar deviation is preferred. A stable osteosynthesis with plates is reliable and allows early rehabilitation. We present 28 cases of arthrodesis with intramedullary rods and 61 cases of arthrodesis with plates. The complication rate was low, the functional results were good. We saw significant reduction of pain, increase of strength and handfunction. Arthrodesis of the wrist joint has proven to be a long term reliable and safe procedure. Loss of motion is accepted to obtain sufficient pain relief.
10076964 Non-union of undisplaced radial neck fracture in a rheumatoid patient. 1999 Non-union of an undisplaced fracture of the radial neck in a rheumatoid patient is presented. Possible causes are discussed, and the literature reviewed.
9794437 Oncostatin M up-regulates tissue inhibitor of metalloproteinases-3 gene expression in arti 1998 Nov 1 Cytokines and growth factors regulate physiologic and pathologic turn-over of cartilage extracellular matrix (ECM) by altering the balance between tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs). Oncostatin M (OSM) is a cytokine of the IL-6 family whose levels are increased in the serum and synovial fluids of patients with rheumatoid arthritis. We examined responsiveness of the TIMP-3 gene to OSM in articular chondrocytes and studied the regulatory and signaling mechanisms of this response. OSM induced TIMP-3 mRNA and protein expression in a dose- and time-dependent fashion. Concomitantly, stromelysin-1 and collagenase-1 RNA and activities were also induced. A cartilage matrix growth factor, TGF-beta, induced TIMP-3, but combined OSM and TGF-beta did not further increase the extent of induction, suggesting a lack of synergy between the two. OSM induction of TIMP-3 gene expression was dependent upon de novo protein synthesis and transcription. RNA decay time-courses suggested that the OSM-mediated increase of TIMP-3 RNA was not due to enhanced message stability and, along with inhibition by actinomycin-D, suggested a transcriptional control. The antiinflammatory glucocorticoid, dexamethasone, down-regulated this augmentation. Investigation of the signaling mechanisms revealed that protein tyrosine kinase inhibitors genistein and herbimycin A, as well as the specific mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059, suppressed OSM-induced TIMP-3 message expression, suggesting the involvement of tyrosine kinases and mitogen-activated protein kinase cascades in the signaling of OSM leading to TIMP-3 RNA enhancement. Thus OSM can potentially alter the cartilage matrix metabolism by regulating genes like TIMP-3 and matrix metalloproteinases.
9133922 A distinct profile of six soluble adhesion molecules (ICAM-1, ICAM-3, VCAM-1, E-selectin, 1997 Feb Soluble forms of ICAM-1, VCAM-1, E-selectin, L-selectin, P-selectin and, more recently, ICAM-3 are known to exist in human serum and have elevated levels in numerous diseases. Previous studies have demonstrated that in rheumatoid arthritis (RA) the levels of circulating sICAM-1 and sE-selectin are elevated relative to healthy controls. We have compared the serum profiles of these six soluble adhesion molecules in patients with RA (n = 22) to those seen in healthy controls (n = 10) using sandwich ELISA. In the patients, there were significant elevations of serum sICAM-1 (P < 0.0001), sICAM-3 (P = 0.0327), sVCAM-1 (P = 0.0025), sL-selectin (P = 0.0194) and sP-selectin (P = 0.0025), but not E-selectin (P = 0.0672). However, only sP-selectin was found to correlate with disease activity in the patients (r = 0.461, P < 0.05). Thus, there is a distinct profile of soluble adhesion molecules in RA of which only sP-selectin correlates with disease activity.