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ID PMID Title PublicationDate abstract
8377390 [Ocular manifestations of rheumatic diseases. Cooperation between internist/ophthalmologis 1993 May A red or painful eye may be the clue to a systemic condition, many of which are of a rheumatological or immunological nature. Conjunctivitis may occur in Sjögren's Syndrome, Reiter's Syndrome (and other sero negative spondyloarthropathies) and with infections such as chlamydia and viruses. 70% of cases of episcleritis are idiopathic, the other 30% being associated with rheumatoid arthritis or other connective tissue diseases or herpes zoster infection. Scleritis may be seen with connective tissue diseases or auto immune conditions (rheumatoid arthritis, Wegener granulomatosis, polyarteritis nodosa, relapsing polychondritis, SLE), infections (herpes, tuberculosis, syphilis, aspergillosis) or metabolic (gout, porphyria, cystinosis). Retinal vasculitis is seen in SLE, Behçet's Disease, sarcoidosis, polyarteritis nodosa, Whipple's disease and Crohn's disease among others. However, uveitis presents perhaps the greatest diagnostic challenge and interface between ophthalmology and rheumatology. Some syndromes are purely ophthalmological (eg: Fuch's heterochromic cyclitis) but others may lead to the diagnosis of a rheumatic disorder (eg: recurrent unilateral acute anterior uveitis and ankylosing spondylitis). Systemic syndromes most likely to be associated with uveitis are Reiter's disease, ankylosing spondylitis, sarcoidosis, juvenile arthritis, interstitial nephritis, inflammatory bowel disease, syphilis. The patterns are different, eg: acute painful unilateral anterior uveitis with ankylosing spondylitis and chronic asymptomatic bilateral uveitis in juvenile arthritis (ANA positive, pauci-articular) or bilateral symptomatic uveitis in sarcoidosis. An illustrative case will be presented and an algorithm for the evaluation of uveitis discussed.
7896431 Reduction of EDA(+) fibronectin and its clinical importance on cryofiltration. 1994 Oct Cryofiltration (CRYO) removes cryogel, which is a combination of fibrinogen (Fbg) and fibronectin (FN), containing pathological substances. The purpose of this study was to measure cryogel EDA(+) FN and study the relationship between EDA(+) FN and clinical symptoms in patients with rheumatoid arthritis, SLE and polymyositis. Cryogel contains 51 times more EDA(+) FN than plasma. The patients with rheumatoid arthritis showed a high level of EDA(+) FN in their plasma, and the EDA(+) FN level in plasma corresponded with changes in joint pain. We calculated the clearance level at several points in cryofiltration, and the reduction enabled us to evaluate the CRYO device. The EDA(+) FN clearance was 23.3 +/- 6.4 ml/min, the pFN clearance 16.5 +/- 4.1 ml/min, and the Fbg clearance 22.9 +/- 5.7 ml/min. As the plasma flow in cryofiltration was 30 ml/min, a clearance of EDA(+) FN and Fbg, approximately 23 ml/min, was obviously high. The study of the plasma level change of EDA(+) FN during cryofiltration revealed a temporary elevation. These results suggest that the EDA(+) FN was most efficiently reduced by cryofiltration, would become a good indicator on plasmapheresis, and might move from other tissues into the blood during cryofiltration.
8982362 A simple nested RT-PCR method for quantitation of the relative amounts of multiple cytokin 1996 Dec 15 It is difficult to quantitate cytokine mRNA profiles in small human tissue specimens obtained by a needle biopsy, even using standard RT-PCR methods, because the amount of mRNA in the specimens is very small. To address this problem, we developed highly sensitive, quantitative, nested RT-PCR techniques to evaluate the expression of multiple cytokine mRNAs in synovial specimens obtained by needle biopsy. To reduce effects of variation of initial RNA concentrations, cDNA from each target RNA sample was normalized, using a simplified competitive PCR method, to the levels of beta-actin cDNA. The first and the second (nested) PCR were performed in the same tube to prevent contamination. The number of PCR-product bands, evident on polyacrylamide gel electrophoresis, was used to quantitate the relative amounts of target cDNA. Using our methods, it was possible to evaluate, in a single synovial tissue specimen obtained by needle biopsy, the relative amounts of mRNAs for 10 cytokines (TNF-alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12 p40, IL-13, IL-15, IFN-gamma) and CD3 delta chain. Our methods are particularly valuable if there are multiple target mRNAs, numerous samples, or if the amounts of mRNAs are limited. The methods are applicable to a wide variety of tissues and target mRNAs.
8651964 Acute febrile toxic reaction in patients with refractory rheumatoid arthritis who are rece 1996 Jun OBJECTIVE: To assess the frequency and clinical features of an acute febrile toxic reaction (AFTR) in patients with refractory rheumatoid arthritis (RA) receiving combined therapy with methotrexate (MTX) and azathioprine (AZA). METHODS: A cohort of 43 RA patients being treated with MTX/AZA combination therapy were studied. In all of them, RA had been refractory to single-therapy disease-modifying antirheumatic drugs. We analyzed the frequency and clinical features of AFTR, which consisted mainly of the development of fever, leukocytosis, and cutaneous leukocytoclastic vasculitis when AZA was added to the MTX regimen. RESULTS: Four of the 43 patients (9.3%) who had been receiving long-term, well-tolerated treatment with MTX (mean +/- SD 375.5 +/- 159.5 days, range 227-561 days) developed AFTR shortly (mean +/- SD 25.7 +/- 13.6 days, range 17-46 days) after the addition of AZA to the regimen. The AFTR resolved rapidly (3 +/- 1.4 days) after discontinuation of AZA and MTX. In 2 cases, rechallenge with AZA and MTX was linked to a new flare of AFTR. CONCLUSION: The knowledge of this side effect is particularly important because it mimics a severe infectious complication related to immunosuppressive therapy, and because rechallenge can produce severe toxicity. Most of the new combined therapies for RA do not seem to be more toxic than single-drug treatment. Nevertheless, clinicians should be aware of a possible increase in side effects due to drug interactions or some other unidentified mechanism.
7523012 A case of germinal center formation by CD45RO T and CD20 B lymphocytes in rheumatoid arthr 1994 Oct In rheumatoid arthritis (RA) disease activity occurring as joint destruction of cartilage and bone is thought to be driven by inflammatory reactions which are initiated by exogenous microbial mechanisms and perpetuated by endogenous autoimmune mechanisms. According to the synovial model of RA, these reactions originate in the adjacent synovial tissues. The following set of observations is presented herein to suggest an alternate model involving subchondral bone. Lymphocytic infiltrates accompanied by immunoglobulin deposits were identified in rheumatoid subchondral bone near areas of cartilage undergoing destruction by local subchondral inflammation. CD45RO T lymphocytes also were identified with these infiltrates as well as with CD20 B lymphocytes in an area of subchondral bone containing a well-organized germinal center. Analysis of extracts of rheumatoid subchondral bone revealed a high incidence of autoantibodies directed against type II collagen, the major protein constituent of cartilaginous tissue. Analysis of IgG subclass and cyanogen bromide peptide specificity revealed a pathogenic subset of these autoantibodies. A passive transfer study utilizing similar antibodies from collagen arthritic animals confirmed that such autoantibodies would have the potential of contributing directly to disease activity observed in rheumatoid subchondral bone. These studies suggest that (i) subchondral bone may be playing an active role in RA as a local site of immune-mediated disease activity and (ii) basic and therapeutic studies aimed at understanding and eventually controlling RA should be diversified to include the study of not only synovial tissue, but also subchondral bone as a local source of the antigenic, cellular, and humoral immune components of joint destruction.
8820754 Perimenopausal and postmenopausal hormone replacement therapy. Part 1. An update of the li 1996 Jan As life expectancy increases and members of the postwar generation settle into their fifth decade of life, hormone replacement therapy--estrogen or an estrogen-progestin combination--has become a major research interest. An extensive, but often confusing and even contradictory, literature exists on the uses of hormone replacement for the treatment and prevention of a multitude of difficulties that may be associated with the perimenopausal and postmenopausal periods. These include hot flushes, vaginal changes, urinary tract changes, changes in sexuality, affective or emotional symptoms, changes in the oral mucosa and skin, loss of memory and Alzheimer's disease, bone loss and osteoporosis, and cardiovascular disease. This article reviews the literature in each of these areas. It also reviews studies relating to possible side effects of hormone therapy, including endometrial cancer, gall bladder disease, and breast cancer. The article outlines principles for practitioners to follow in assisting women to make informed and individualized decisions about this therapy. Part II of this article, which will appear in the May/June 1996 issue of the Journal of Nurse-Midwifery, will cover specific therapeutic regimens and their management, as well as alternative therapies and preventive measures.
7561400 Early active mobilization after tendon transfers using mesh reinforced suture techniques. 1995 Jun 23 tendon transfers in the hand and forearm were performed using a polyester mesh sleeve to reinforce conventional suture techniques. All transfers were mobilized with active flexion and extension within 3 days of operation. Excluding one rupture (due to extreme unintentional loading) and depending on the type of transfer used, a mean of between 69% and 78% of the final active range of motion was obtained 1 month post-operatively. With the exception of transfers for wrist extension, the mean final active range of motion amounted to between 91% and 100% of the available passive range of motion and between 75% and 100% of the corresponding "normal" active range of motion in the opposite hand. The mean final active range of motion after reconstructions for wrist extension amounted to 85% of the passive range of motion and to at least 80% of the maximum range of motion potentially available with the transfers used. The results indicate that early active mobilization after tendon transfers may offer significant advantages in terms of quicker and simpler rehabilitation as well as improved results.
7981929 The efficacy and relative bioavailability of diclofenac resinate in rheumatoid arthritis p 1994 Aug The pharmacodynamics and pharmacokinetics of 75 mg resin-bound diclofenac (resinate) were compared with enteric-coated tablets containing 75 mg of diclofenac in a double-blind randomized crossover trial in 16 patients suffering from rheumatoid arthritis. Diclofenac was significantly faster absorbed from the resinate than from the enteric coated formulation (tlag = 0.454 h vs. 0.998 h, tmax = 1.41 h vs. 2.56 h) and reached lower peak concentrations (Cmax = 1.64 micrograms/ml vs. 2.59 micrograms/ml). No significant differences were found concerning the area under the plasma level-time curves and the mean residence times. Smaller variances were found for the tmax and the mean residence times in the group treated with diclofenac resinate. Onset and duration of analgesia, as assessed by visual analogue scales were similar in both treatment groups, but did not correlate with the plasma concentrations. Four patients experienced adverse effects including gastric pain, transaminase increases, proteinuria and plasma creatinin increase. No uncommon adverse effects were observed with the new preparation.
7979579 Frequency and clinical associations of anti-chromo antibodies in connective tissue disease 1994 Oct OBJECTIVES: To assess the frequency and clinical associations of anti-chromo antibodies in connective tissue disease and to study their relationship to anti-centromere autoreactivity. METHODS: Anti-chromo and anti-centromere antibodies (ACA) were measured by immunoblotting in 50 patients with systemic sclerosis (SSc) and 58 connective tissue disease controls. Common epitopes on centromere and chromo antigens were sought using affinity-purified antibodies from immunoblots. RESULTS: Anti-chromo antibodies were detected in three of 32 sera with ACA and no controls. The three patients with anti-chromo antibodies had limited cutaneous SSc, and two had erosive arthritis. No cross-reactivity between chromo or centromere-related proteins was demonstrated. CONCLUSIONS: Anti-chromo antibodies form a rare autoantibody specificity that may identify an overlap group of patients with SSc and arthritis. Chromo and centromere antigens are associated but immunologically distinct autoimmune targets. Whether they localise to the same chromosomal site remains unknown.
8434868 Immunoaffinity purification of prostaglandin E2 and leukotriene C4 prior to radioimmunoass 1993 Jan When human synovial fluid as such was subjected to radioimmunoassays of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), there was no linear increase in PGE2 and LTC4 as the amount of synovial fluid was raised. For removal of substances thus disturbing the assay we developed a method of immunoaffinity purification of PGE2 and LTC4. A monoclonal antibody against PGE2 or LTC4 was coupled to BrCN-activated Sepharose 4B. When synovial fluid mixed with radiolabelled PGE2 or LTC4 was applied to the column of immobilized antibody, the ligand was adsorbed to the column and eluted with a mixture of methanol/water in a recovery of about 80%. The purified material showed a linearity between the amount of the sample and the value of radioimmunoassay. The one-step method was applied to synovial fluid from patients with rheumatoid arthritis, osteoarthritis and other joint diseases.
8346982 Absence of an association between HLA-DRB1*04 and rheumatoid arthritis in newly diagnosed 1993 Jul OBJECTIVES: To determine HLA-DR4 and DR1 allele frequencies in a series of patients with newly diagnosed early inflammatory arthritis. METHODS: HLA-DR1 and DR4 frequencies were determined by oligonucleotide typing of 208 patients classified as having either rheumatoid arthritis (RA) or undifferentiated inflammatory polyarthritis. RESULTS: The frequency of occurrence of DR4 in these patients with RA did not differ significantly from that in controls in the United Kingdom (42 v 37%). HLA-DR1 was increased in the group with inflammatory polyarthritis (25 v 18%). CONCLUSIONS: The frequency of DR4 is not increased in newly diagnosed community based patients with RA. This supports the hypothesis that DR4 is less important as a marker for susceptibility to RA than it is for disease persistence or severity.
9013084 Molecular analysis of the T-cell receptor beta-chain repertoire in early rheumatoid arthri 1996 Dec To gain insight into the nature of the immune response with respect to accumulation and composition of the T-cell receptor (TCR) repertoire in synovial tissue in rheumatoid arthritis (RA), we have determined the nucleotide sequence of TCRBV regions transcribed by T lymphocytes derived from synovial tissue. Synovial tissue was obtained by needle biopsies from three different sites of the same joint in two early RA patients. We found that the TCRBV region repertoire among synovial tissue-infiltrating mononuclear cells was heterogeneous when the different biopsies taken from each patient were compared. However, DNA sequence analysis of TCRBV rearrangements of synovial T lymphocytes showed conserved amino acid usage profiles in the CDR3 domains of different TCRBV regions, which exhibited an individual specific character. These CDR3 motifs were not present in paired samples of peripheral blood. The existence of homologous CDR3 amino acid profiles within the TCRBV regions derived from synovial tissue is indicative of an antigen-driven immune response.
1618240 The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in 1992 We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.
9010384 Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis. 1996 Dec OBJECTIVE: To evaluate the impact of chronic inflammation on lipoprotein lipase (LPL) levels and tri-glyceride metabolism in patients wit rheumatoid arthritis (RA). DESIGN: Plasma levels of LPL activity and mass before and after heparin were determined in post-menopausal women with active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with triglyceride levels were also measured before and 6 h after an oral fat load. SETTING: The study was performed on in- and outpatients at a University Rheumatology clinic. The controls came from the same reference area. SUBJECTS: Altogether 17 consecutive postmenopausal female patients with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the fat load. Of these, one patient and one control were excluded. MAIN OUTCOME MEASURES: LPL determination: basal levels and post-heparin levels of LPL activity and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides), lipoprotein levels (high density lipoprotein, HDL: low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor alpha. TNF-alpha: interleukin 1 beta, IL-1 beta: and interleukin-6. IL-6). Fat tolerance test: LPL activity. mass and triglyceride levels before and 6 h after a per oral fat load. RESULTS: Pre-heparin LPL mass (P < 0.01) and activity (P < 0.01) were significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters: it was significant for orosomucoid (rs = -0.63, P < 0.05) and C-reactive protein (CRP) (rs = -0.54, P < 0.05) and close to significant for haptoglobin (rs = -0.48, P = 0.087) and IL-6 (rs = -0.52, P = 0.061). Six hours after.a lipid load the LPL activity and mass were significantly lower in RA (P < 0.05 and P < 0.01, respectively) but the triglyceride level was not significantly different compared to controls. CONCLUSION: An inverse relationship exists between inflammatory status and pre-heparin LPL mass. Preheparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor-related protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of the level of monomeric LPL in plasma may thus be beneficial for remnant catabolism. The same mechanism may on the other hand increase macrophage uptake of lipids. This may not affect global lipid metabolism but may be important in driving the atherosclerotic process in the vessel wall.
8240430 Differential in vivo expression of collagenase messenger RNA in synovium and cartilage. Qu 1993 Nov OBJECTIVE: To compare quantitatively the in vivo expression of collagenase messenger RNA (mRNA) and stromelysin mRNA in the joint tissues of human osteoarthritis (OA) and rheumatoid arthritis (RA) patients and in two animal models of acute inflammatory arthritis. METHODS: In vivo levels of metalloproteinase mRNA and protein were determined by quantitative Northern hybridization and by enzyme-linked immunosorbent assay, respectively. RESULTS: In synovium, mean levels of collagenase mRNA were similar to those of stromelysin mRNA; however, in cartilage, mean levels of collagenase mRNA were significantly lower. The ratios of collagenase mRNA to stromelysin mRNA levels in RA and OA cartilage reflected similar ratios of collagenase protein to stromelysin protein levels in synovial fluid. CONCLUSION: The regulation of collagenase mRNA expression in cartilage is distinct from that of stromelysin, suggesting distinct roles for these two metallo-proteinases in normal and abnormal physiologic functioning of cartilage.
8666695 Ulcerating rheumatoid nodule of the vulva. 1996 Jan A case of an ulcerating rheumatoid nodule of the vulva in a 76 year old woman with rheumatoid arthritis complicated by Felty's syndrome is reported. The patient presented with a mass in the vulval region. On clinical examination, she had an ulcerated mass associated with inguinal lymphadenopathy. These findings resulted in a clinical diagnosis of invasive carcinoma of the vulva and an excision biopsy was carried out. On microscopic examination, the lesion showed the characteristic features of a rheumatoid nodule with ulceration of overlying epidermis. Adjacent vessels showed inflammation and fibrinoid necrosis of their walls suggestive of a vasculitis. Awareness of the possibility of ulceration in rheumatoid nodules may facilitate diagnosis and avert unduly aggressive treatment.
7546351 Transoral surgery: some lessons learned. 1995 The experience gained over the last decade has provided some further understanding of the rare, but potentially fatal problems associated with pathology at the craniovertebral junction. Some original concepts of the disease in the area have been challenged; new evidence has been provided to explain our alternative theories. The transoral procedure as a surgical tool is now well established. It is, however, technically demanding, and requires careful anatomical study and 'hands-on' workshop training before the novice will be competent.
8872162 Allelic variants of human TCR BV17S1 defined by restriction fragment length polymorphism, 1996 Sep 1 Several human TCR BV gene subfamilies, including BV3, BV14, and BV17S1, are single member genes but are overutilized among activated CD4+ synovial T cells in the rheumatoid arthritis (RA). To define the role of these TCR BV genes in the pathogenesis of disease, it is critical to characterize the genomic organization and the allelic variations of these genes. In this study we describe allelic variations of BV17S1 defined by restriction fragment length polymorphism (RFLP), single strand conformation polymorphism (SSCP), and amplification refractory mutation system (ARMS) analyses. A single nucleotide replacement (C/T) results in an amino acid substitution (F/L) in the leader and distinguishes BV17S1*1 from BV17S1*2. This nucleotide substitution was found to create a BsmAI restriction enzyme recognition site in BV17S1*2. Therefore genotypic analyses can be performed either by the SSCP or RFLP method. The analyses of 75 unrelated individuals show that the frequency for allele BV17S1*1 is 52.7% and for allele BV17S1*2 is 47.3%. Both alleles are functionally expressed and are distributed within CD4+/CD8+ T cell subsets. Another point mutation in the CDR2 region of BV17S1, which results in the amino acid replacement of Gln by His, originally identified form a cDNA clone, has now been confirmed as an allele by ARMS analysis using genomic DNA preparations and designated to as BV17S1*3. Screening of this CDR2 related variant among normal populations indicates that this is a rare allele (1 of 75). Although this variant may be of functional significance, the genotypic analysis and functional studies are difficult due to the low frequency of BV17S1*3. In an attempt to define a correlation between BV17S1 allelic usage and susceptibility to RA, the germline distribution of BV17S1 alleles *1 and *2 has been examined in a small number of RA patients and no skewed usage has been identified.
8734077 [Joint and systemic manifestations related to type 2 anti-mitochondrial antibodies]. 1995 The aim of the study was to assess the significance of type 2 anti-mitochondrial antibodies in patients with systemic and inflammatory rheumatic disease. Articular and systemic manifestations of 8 patients associated with type 2 anti-mitochondrial antibodies are described. All the patients had hepatic abnormalities, and 5 of them disclosed a primary biliary cirrhosis. Articular and systemic manifestations were similar to those observed in primary biliary cirrhosis. Therefore, the finding of anti-mitochondrial antibodies in patients with systemic or inflammatory rheumatic disease implies research for other systemic manifestations such as primary biliary cirrhosis.
7631137 Monozygotic rheumatoid arthritis twin pairs express similar levels of conserved immunoglob 1995 Jul The degree of polyclonal RF heterogeneity was assessed in diseased and non-diseased twins with rheumatoid arthritis (RA). The distribution of variable region determinants encoded by a set of immunoglobulin germline, or minimally mutated germline, genes within IgM RF, IgG RF and IgA RF isotypes was determined by ELISA using specific mouse monoclonal antibodies (MoAb) in fractionated plasma from 12 members of six monozygotic twin pairs with RA. The results reveal that at least 40% (range approximately 18-87%) of IgM RF are encoded by a small set of approximately 10 genes from the VH1, 3 and 4 families. Furthermore, a significant proportion of IgG RF and IgA RF (approximately 30%) are also encoded by these same genes. Comparison with RF-negative fractions of immunoglobulins showed that the examined variable region determinants were overrepresented in the RF fractions. The level of expression of the variable region determinants in RF were generally similar within twins but different between unrelated twin pairs irrespective of disease status. The variability of VH gene usage between unrelated individuals suggests that the level of expression and regulation of the variable region determinants may be genetically regulated or influenced by common environmental factors.