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ID PMID Title PublicationDate abstract
8921427 Induction of cytokines and ICAM-1 by proinflammatory cytokines in primary rheumatoid synov 1996 Oct The role of transcription factor NF-kappa B in the induction of cytokines and ICAM-1 upon stimulation with proinflammatory cytokines, IL-1 and tumor necrosis factor (TNF)-alpha was investigated in primary synovial fibroblasts obtained from patients with rheumatoid arthritis (RA). Nuclear translocation of NF-kappa B was demonstrated after 30 min of treatment with IL-1 or TNF-alpha. Thereafter, the production of several cytokines including granulocyte macrophage colony stimulating factor, IL-6 and IL-8, that are known to be abundantly produced in the synovial cavity of RA patients, was greatly augmented. Similarly, cell surface expression of ICAM-1 was induced by the IL-1 or TNF-alpha treatment. Since expression of these genes is induced in rheumatoid synovial tissue, this experimental system is considered to represent the in vivo situation of RA pathophysiology. Using this cell culture system we attempted to modulate the intracellular signaling cascade for NF-kappa B activation and examined the effects of N-acetyl-L-cysteine (NAC) and acetylsalicylic acid (aspirin), which were previously reported to inhibit NF-kappa B activation. Pretreatment of the primary synovial fibroblasts with NAC inhibited nuclear translocation of NF-kappa B. Subsequently, the induction of these cytokines and ICAM-1 was considerably suppressed. On the other hand, pretreatment with aspirin blocked these phenomena only partially. These observations indicate the pivotal role of NF-kappa B in RA pathogenesis thus highlighting the possibility of a novel therapeutic strategy.
8452577 Determinants of serious liver disease among patients receiving low-dose methotrexate for r 1993 Mar OBJECTIVE: To assess the risk of serious liver disease in patients with rheumatoid arthritis (RA) taking methotrexate (MTX). METHODS: We surveyed members of the American College of Rheumatology to determine previous use of MTX in the treatment of rheumatoid arthritis and to identify cases of cirrhosis and liver failure. Cases were confirmed by review of pathology specimens, findings from diagnostic testing, and clinical presentations. A case-control study was then conducted to ascertain prognostic factors. Case and control medical records were reviewed for information on MTX therapy as well as other possible determinants of serious liver disease. RESULTS: Twenty-four cases of cirrhosis and liver failure were identified, giving a 5-year cumulative incidence of approximately 1/1,000 treated patients. Six of the 24 patients had died: 4 died of the initial liver disease, 1 of hepatic complications of another illness, and 1 of unrelated causes. Two patients continue to have active liver disease. Late age at first use of MTX and duration of therapy with MTX were independent predictors of serious liver disease. CONCLUSION: Serious liver disease is an uncommon, age- and dose-related complication of low-dose MTX therapy for RA.
7632086 Work disability in early rheumatoid arthritis. 1995 Jun OBJECTIVE: To assess the impact of early rheumatoid arthritis (RA) on work status. METHODS: The employment status of 119 patients who had jobs before the onset of RA was examined. Patients with work disability were compared with those without, for several disease characteristics, therapeutic regimen, and educational level and age. RESULTS: Sixty two percent of the patients, particularly manual workers, reported some kind of work disability (7% worked less, 13% were on sick leave, and 42% had quit their jobs). Forty five patients (38%) stated that they were working without any restrictions; however, only 12 of this latter group (10% of the total group) had not encountered any changes at all within their jobs. The patients who reported work disability had a lower level of education and scored higher for several disease characteristics (erythrocyte sedimentation rate (ESR), joint tenderness, Health Assessment Questionnaire (HAQ), and Groningen Activity Restriction Scale) and were provided with more medication compared with patients without work disability, though only the educational level, disease duration, HAQ and ESR contributed significantly to work disability in logistic regression analysis. CONCLUSION: Even at an early stage, RA has a considerable impact on work status. This study indicates that work disability is dependent on disease characteristics and on the educational level of the patient.
8982963 Sural nerve biopsy in vasculitic neuropathies: morphometric analysis of the caliber of inv 1996 We performed histologic and morphometric analyses of the sural nerve in 13 patients with vasculitic neuropathies. The ratio of vessels with vasculitis, the caliber of involved vessels, and pathologic changes of myelinated fibers were evaluated. In patients with polyarteritis nodosa (PN), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), marked vasculitis with inflammatory cell infiltration and occlusion were observed in epineurial arteries greater than 100 microns in diameter, and mild vasculitic changes were noted in arterioles 40 to 100 microns in diameter. In vessels less than 40 microns, mild vasculitis with perivascular cuffing was noted in patients with RA and SLE, but not in PN. In a patient with microscopic PN, mild inflammatory cell infiltration was encountered around small vessels at diameters less than 40 microns as well as those greater than 100 microns. In a patient with nonsystemic vasculitic neuropathy, vasculitic changes were identified only in vessels less than 40 microns. In patients with Churg-Strauss syndrome (CSS), there were no distinct findings of vasculitis in any biopsy material. In conclusion, morphometric analyses of the caliber of involved vessels may be useful in the differential diagnosis and classification of underlying vasculitic neuropathies.
8252318 Additive effect of combined naproxen and paracetamol in rheumatoid arthritis. 1993 Dec The clinical effect and plasma naproxen levels were studied in 20 patients with RA receiving three doses of naproxen and two naproxen doses combined with paracetamol (acetaminophen) in a randomized, double-blind, comparison in five 2-wk treatment periods. A significant dose-concentration effect relationship was found for the three naproxen doses (500, 1000 and 1500 mg daily). The following variables were measured: global clinical effect, joint index, morning stiffness, activity of daily living (ADL), pain during movement and at rest. The naproxen dose-concentration effect relationship curve was moved to the left by the addition of 4 g paracetamol daily. No major side effects were observed, but complaints concerning the gastrointestinal tract were fewer on lower naproxen doses and these were not increased by concomitant paracetamol treatment. The results show that the clinical effect of naproxen in RA may be significantly increased by concomitant paracetamol administration.
8824576 Spread of clonal T-cell expansions in rheumatoid arthritis patients. 1996 Jun Despite a large number of studies identifying expanded T-cell clones among infiltrating lymphocytes, little is known about their distribution in patients suffering from rheumatoid arthritis. To evaluate the clonality of alpha/beta T-cell populations in arthritic locations and PBL, we determined the CDR3 size lengths of TCR beta-chain transcripts using BV (Vbeta), BC (Cbeta), BJ (Jbeta), and clonotype-specific primers. Transcripts from PBL of healthy donors show gaussian profiles of approximately eight CDR3 size peaks in most BV subfamilies. Dominant peaks standing out above the normal background identify expansions of one or several T-cell clones within a given BV subfamily. The analysis of six patients suffering from rheumatoid arthritis showed clonal expansions in all samples including PBL. Synovial tissue infiltrates revealed less complex repertoires with a greater number of expanded clones than PBL. Expanded clones varied from one patient to another; no recurrences were observed. Most interestingly, identical clones were identified bilaterally in arthritic knee joints and PBL from the same patient. Our data show that given T-cell clones are not only locally expanded but can also be found in the periphery, and strongly suggest that many similar clones spread throughout the bodies of patients.
7791150 Minocycline in the treatment of rheumatoid arthritis: relationship of serum concentrations 1995 Apr OBJECTIVE: To assess the relationships between serum concentrations of minocycline and clinical efficacy and toxicity during the treatment of patients with rheumatoid arthritis (RA) with minocycline. METHODS: Forty patients with active RA were administered minocycline (maximal oral dose 100 mg twice a day) for 26 weeks. At 3 time points during the treatment, serum samples were collected for measurement of minocycline activity using a microbiological assay. An analysis of variance was performed to estimate an extrapolated concentration at time = 0 (C0) for each patient separately and this value of C0 was regarded to be proportional to the average serum concentration in each patient. The relation between C0 and clinical response and between C0 and the occurrence of adverse effects was evaluated. RESULTS: Minocycline was detected in 96 serum samples from 37 patients. Eighty-two percent of the variance in serum concentrations was accounted for by a model incorporating patient, dose, and time effects. A weak correlation between C0 and clinical response, as expressed by a Ritchie articular index and number of swollen joints, was demonstrated. No correlation was seen between C0 and toxicity, including gastrointestinal or vestibular adverse effects. CONCLUSION: Results suggest a relationship between the serum concentrations of minocycline and the clinical response, including Ritchie articular index and number of swollen joints, in the treatment of patients with RA. No relationship was seen between the serum concentrations of minocycline and its toxicity.
1525627 Detection of Mycobacterium tuberculosis antigen in synovial fluid of patients with rheumat 1992 Sep By use of antimycobacterial saline extract antibodies, Mycobacterium tuberculosis (MT) antigens have been detected in synovial fluid (SF) of patients with rheumatoid arthritis (RA) by a highly specific and sensitive double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Absorbance for 15 gout, 14 osteoarthritis (OA) patients, 12 patients with spondylarthropathies (SA) and eight patients with other inflammatory disorders (OID) ranged from 0.001 to 0.025 with the mean values of 0.0086 +/- 0.0078, 0.0077 +/- 0.0051, 0.0069 +/- 0.0059 and 0.0113 +/- 0.0059, respectively. Among 65 SF of patients with RA examined, 34 were found to be negative for MT antigen with absorbance ranging from 0.002 to 0.024 and a mean value of 0.0114 +/- 0.0070. For 31 (47.7%) MT antigen-positive specimens of RA, optical density ranged from 0.052 to 2.446 with a mean value of 0.5564 +/- 0.7354. Significant statistical difference (P less than 0.05) was found when MT antigen positives were compared with MT antigen negatives, gout, OA, SA and OID groups. Our results indicate that MT may be relevant to the pathogenesis of RA.
8992004 A modified version of Larsen's scoring method to assess radiologic changes in rheumatoid a 1995 Oct We describe the development and application of a modified version of the radiologic scoring method proposed by Larsen in patients with rheumatoid arthritis (RA). We modified Larsen's method adding a semiquantitative description of the loss of joint surface area and provide standardized reference films for all stages at different anatomical sites (metacarpophalangeal joints, proximal interphalangeal joints, wrists, metatarsophalangeal joints). To evaluate the method, standard anteroposterior radiographs of hands, wrists and forefeet of 24 patients with early erosive RA taken at baseline (t0) and after 36 months (t1) were read by 2 raters in a blinded fashion. The interrater difference was compared with the interpatient (t0 to t1) difference using a hierarchical analysis of variance. Moreover, the method was applied to patients included in a 2 year clinical trial to evaluate the efficacy of intramuscular methotrexate (MTX) and gold sodium thiomalate (GSTM) with radiographs taken at baseline and after 6, 12, and 24 months. There was a good agreement between the 2 raters and the change could be well documented. The estimation of the intrapatient variance (at t0 and t1) was 8 times higher than the estimation of the interreader variance. The method was easily applicable in 57 patients treated with MTX and 53 patients under treatment with GSTM, showing a slowing of radiologic progression after Month 6 with both drugs. The modification of Larsen's scoring method is a reliable measure to assess baseline status and radiologic progression in patients with RA.
9064335 Increased expression of blood mononuclear cell nitric oxide synthase type 2 in rheumatoid 1996 Sep 1 Nitric oxide (NO) is an important inflammatory mediator in nonhuman animal models of rheumatoid arthritis (RA). The purpose of the present study was to determine whether blood mononuclear cells from patients with active RA (as compared to control subjects) have higher levels of NO synthase type 2 (NOS2) and produce more NO in vitro. Leukocytes from 25 RA patients and 20 normal subjects were examined. Arthritis activity was assessed by tender and swollen joint counts, duration of morning stiffness, patient assessment of pain, physician and patient global assessment of disease activity, the modified Stanford Health Assessment Questionnaire, and by blood levels of acute phase reactants. Blood mononuclear cell NOS enzyme activity/antigen content and nitrite/nitrate formation in vitro were measured. Blood mononuclear cells from RA patients had increased NOS activity and increased NOS2 antigen content as compared to those from normal subjects, and responded to interferon-gamma with increased NOS expression and nitrite/nitrate production in vitro. NOS activity of freshly isolated blood mononuclear cells correlated significantly with disease activity, as assessed by render and swollen joint counts. Our results demonstrate that patients with RA have systemic activation for NOS2 expression, and that the degree of activation correlates with disease activity. Increased NOS2 expression and NO generation may be important in the pathogenesis of RA.
8670078 Site-specific glycosylation of human immunoglobulin G is altered in four rheumatoid arthri 1996 Mar 1 Alterations in the glycosylation of human IgG have been shown to occur in rheumatoid arthritis (RA). However, the precise nature and location of these changes have not been fully established. Therefore we carried out a detailed analysis of the oligosaccharides chemically released from intact human serum IgG and fragments of the molecule. Serum samples were from three healthy ('normal') individuals, and from four patients with RA. Site-specific glycolsylation of the glycoprotein was shown to occur, which extended to sites even within the Fab fragment. These were differences in galactosylation, sialylation and the presence of a bisecting N-acetylglucosomide. Disease related alterations were also shown to be site-specific. In particular, an increase in the proportion of agalactosylated oligosaccharides occurred on the Fc fragment in RA (P=0.057), but, in contrast to previous reports there was an increase on the light chain in the proportion of fully galactosylated, bisected and core fucosylated oligosaccharides (from 13% of total in normal to between 18 and 35% in RA, P=0.057)). There was also an Fab-specific increase in oligosaccharides bearing a bisecting N-acetylglucosamine and a core fucose (P=0.075) The site-specific glycosylation changes described in this paper reveal the complexity of the regulatory mechanism, perhaps reflecting the many levels at which regulation can occur.
8523334 Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis. 1995 Sep OBJECTIVE: To examine the localization and role of vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, in rheumatoid arthritis (RA). METHODS: Immunohistochemical staining, reverse transcription polymerase chain reaction (RT-PCR) analysis and in situ hybridization for VEGF were performed on synovial tissues from 10 patients with RA, 5 patients with osteoarthritis (OA) and 3 autopsy cases. RESULTS: In RA, the proliferative ratio of synovial lining cells and vascular endothelial cells was significantly higher than that in OA and normal synovial tissues. Immunohistochemical staining demonstrated that VEGF polypeptide was strongly expressed in subsynovial macrophages, fibroblasts surrounding microvessels, vascular smooth muscle cells, and synovial lining cells, but not in vascular endothelial cells of patients with RA. On the other hand, in patients with OA and normal cases, VEGF polypeptide was slightly expressed in synovial lining cells and fibroblasts. RT-PCR showed a positive reaction for VEGF messenger RNA in RA, OA, and normal synovial tissues. A large number of subsynovial macrophages, fibroblasts, vascular smooth muscle cells, and synovial lining cells from patients with RA expressed VEGF mRNA using in situ hybridization. CONCLUSION: In RA, VEGF is synthesized and released by a large number of subsynovial macrophages, fibroblasts surrounding microvessels, vascular smooth muscle cells, and synovial lining cells and may stimulate endothelial proliferation in a paracrine manner via VEGF receptors.
1634581 Arthrodesis of the ankle in patients who have rheumatoid arthritis. 1992 Jul We reviewed thirty-two arthrodeses of the ankle in twenty-six patients who had rheumatoid arthritis. In seventeen patients (eighteen ankles), a compression arthrodesis was done and external fixation was used. In eight patients (twelve ankles), we used internal fixation with 6.5-millimeter cancellous-bone screws. In the remaining patient, an arthrodesis with external fixation was done in one ankle and internal fixation was used in the other ankle; data for the appropriate ankle are included in each group. The patients were followed for an average of thirty-three months. The two groups were comparable with respect to age, sex, preoperative medications, and severity of disease. The average time to fusion was nineteen weeks in the compression arthrodesis group and seventeen weeks in the internal fixation group. Of the nineteen ankles that had a compression arthrodesis, four failed to fuse; all of the failures were associated with infection. Infection developed in two additional patients, there was malposition of the fusion in three patients, and neurapraxia developed in three patients. Of the thirteen ankles that had internal fixation, three ankles failed to fuse; one of the failures was associated with infection. Infection developed in one additional ankle. In two patients, the ankle fused in excessive valgus. Comparison of the two groups revealed comparable rates of fusion: fusion occurred in fifteen of the nineteen ankles in the group that had compression arthrodesis and in ten of the thirteen ankles in the group that had internal fixation. The method of arthrodesis did not affect the time to fusion or the rate of complications.(ABSTRACT TRUNCATED AT 250 WORDS)
8711536 [Bucillamin induced lung injury in rheumatoid arthritis]. 1996 Feb Thirteen cases with rheumatoid arthritis who experienced lung injury during the treatment with bucillamine (Bc), about whom the questionnaires were answered by the physicians and whose X-ray films could be rechecked, were studied. Nine cases out of the 13 showed patchy mottled infiltrates in the bilateral center sparing the periphery, and the other 4 showed diffuse infiltrates. In these 9, serum gamma-globulin level decreased when lung injury appeared. The gamma-globulin level before the start of Bc administration, the level when lung injury appeared, the gamma-globulin decrease, and its ratio to the level before Bc were 1790 +/- 661 mg/dl, 1297 +/- 666 mg/dl, 459 +/- 320 mg/dl and 29.1 +/- 18.0%, respectively. In 5 out of the 9, gamma-globulin level reincreased when they recovered from the injury: 2 out of the 5 showed the reincrease even after steroid therapy. The data were obtained only from 2 out of the 4 with diffuse pattern in X-ray, and the decrease and the decrease ratio were 200 mg/dl (5.8%) in 1, and 49 mg/dl (3.6%) in the other. The characteristics of Bc-induced lung injury might be mottled infiltrates in the center appearing concurrently with serum immunoglobulin decrease.
8593418 Chromatographic investigation of the glycosylation pattern of alpha-1-acid glycoprotein se 1995 Sep In certain pathophysiological conditions, such as rheumatoid arthritis, there are alterations in the glycosylation pattern of the acute phase protein, alpha-1-acid glycoprotein (AGP). These changes are likely to be functionally significant, however, verification of the latter role requires a system which reflects in vivo glycosylation changes in AGP and also produces sufficient quantities of the protein for further study. The human hepatoma cell line HepG2 is documented as displaying a shift in the glycosylation pattern of glycoproteins from normal state to acute phase after stimulation with inflammatory mediators. We have isolated AGP from the culture medium of HepG2 cells both before and after stimulation with a cytokine preparation and analysed the glycosylation pattern of each preparation, after enzymatic release, by high pH anion-exchange chromatography. Before stimulation, the glycosylated population was similar to a profile of AGP isolated from normal plasma; however, cytokine stimulation resulted in a shift to a profile which was consistent with that of AGP from a rheumatoid arthritis sufferer. Thus a HepG2 cell culture system is capable of being a crude model of the changes in glycosylation of acute phase proteins although it has a tendency to produce oligosaccharide chains which are not fully sialylated.
8495258 Efficacy and safety of radiation synovectomy with Yttrium-90: a retrospective long-term an 1993 May In this long term retrospective study of radiation synovectomy with Yttrium-90 (Y90), we evaluated the results of 164 applications in 82 patients with RA, OA with synovitis, ankylosing spondylitis and psoriatic arthritis. Radiation synovectomy with Y90 has an overall success rate of approximately 50% and is therefore an effective alternative to surgical synovectomy in chronic synovitis which fails to respond to conservative treatment. Elbow and knee responded significantly better than shoulder and ankle joints. Patients with radiological stages from 0 to 2 showed a significantly better success rate than those with stage 3 changes. In responders, repeat therapy for recurrence of symptoms or treatment of a symptomatic corresponding symmetrical joint is advisable. Repeat therapy in a previous non-responder is associated with an unacceptably high failure rate. Therefore, when a joint fails to respond after 6 months, arthroscopy should be performed to evaluate further treatment procedures. A successful result was found in only 11 of 25 joints treated with arthroscopic synovectomy followed by radiation synovectomy within 2 weeks, indicating no benefit of this combination.
8618448 Analysis of the platelet-type thrombin receptor in 20 cases of large granular lymphocyte p 1996 Apr The platelet-type thrombin receptor was expressed by large granular lymphocytes (LGLs) in a variety of proliferative diseases. Twenty patients with LGL proliferative disease were examined, including five T cell clones and a variety of polyclonal proliferations, some secondary to rheumatoid arthritis and Felty's syndrome; 17/20 showed high number of CD3+, CD8+, and CD57+ lymphocytes and 9/20 also had high numbers of CD16+ or CD 56+ positive lymphocytes. The thrombin receptor was present on more than 20% of the LGLs in 13/20 patients. The clonal T cell expansions showed the highest receptor expression with greater than 75% cells positive. Regression analysis of all 20 cases showed striking and highly statistically significant positive Spearman rank correlation between the proportion of thrombin receptor and CD57-positive LGLs (r = 0.56, P = 0.009). A negative correlation with CD56 was also found (r = -0.46, P= 0.043). Dual antibody flow cytometry showed the receptor was more often co-expressed with CD57 (64%) than with CD16 (19%) or CD56 (11%). The expression of the platelet-type thrombin receptor by LGLs of this phenotype raises the possibility of a functional role for thrombin in the pathogenesis of LGL proliferative diseases.
7614736 Increased synovial expression of the adhesion molecules CD66a, CD66b, and CD31 in rheumato 1995 Aug Leukocyte-endothelial interaction mediated by adhesion molecules may play a role in the ingress of inflammatory cells into the rheumatoid (RA) synovial tissue (ST). A number of these molecules have been shown to be up-regulated in the inflamed compared to normal ST. We studied the distribution of two members of the CD66 carcinoembryonic antigen adhesion molecule family, as well as that of CD31, an antigen structurally related to CD66, on various cell types in the RA compared to osteoarthritic (OA) and normal ST. Immunoperoxidase histochemistry was carried out using monoclonal antibodies to CD66a, CD66b, and CD31. This study was performed on ST from 10 patients with RA, 10 with OA, and 4 normal individuals. CD66a, and CD66b were expressed on RA and OA ST myeloid cells but not on normal ST lining cells and interstitial macrophages, suggesting that these antigens may be specific markers of diseased compared to normal ST macrophages (P < 0.05). CD31 was present on more RA and OA than on normal ST macrophages. Also, CD31 was present on most RA, OA, and normal ST endothelial cells. Our results indicate that the expression of CD66a, CD66b, and CD31, members of the immunoglobulin superfamily of adhesion receptors, is up-regulated on cells of myeloid origin in the inflamed compared to normal ST. These results suggest that the CD66 antigens and CD31 may be involved in the adhesive events in the inflamed synovium.
8205397 Lamellar bodies in synoviocytes, mesothelium and specific epithelia as possible site of au 1994 Jun Intracytoplasmic lamellar organelles identical in ultrastructure to surfactant-containing lamellar bodies found in type II pneumocytes, have been demonstrated in other tissues, in synoviocytes and mesothelial cells, in a distribution pattern which reflects the systemic expression of rheumatoid disease. Antibodies raised against surfactant protein A (SP-A), exhibit a ranking of tissue reactivity in area, intensity and density of cells which also parallels the frequency and degree of pathological involvement characteristic of rheumatoid disease, showing in ascending order of immunopositivity, lacrymal and salivary epithelia, pulmonary parenchyma, mesothelium and synoviocytes. Maximal tissue reactivity to anti-SP-A antibodies was found in the synovium of 55 rheumatoid patients exhibiting classical histopathological appearances of RA, in a pattern of immunostaining identical to that obtained with ML30, an antibody to mycobacterial heat shock protein 65kDa which, in turn, cross-reacted with SP-A in dot blot testing.
7653157 Hyaluronidase in human somatic tissues and urine: polymorphism and the activity in disease 1995 The polymorphism of hyaluronidase (EC 3.2.1.35) (Hyase) was studied on a hyaluronan-polyacrylamide gel. Liver, placenta, ovary and breast tissue were found to have 7 active isoforms while leukocytes and platelets 5 and fibroblasts displayed no hyaluronidase activity. In serum, synovial fluid and urine soluble the most acidic forms are present. Desialylation showed that most of the hyaluronidase isoforms differ in the content of sialic acid. In patients with rheumatoid arthritis, hyaluronidase activity in the synovial fluid varied from not detectable to very high. A partial deficiency was demonstrated in sera from some patients with dysostosis multiplex without mucopolysacchariduria. In I-cell disease, hyaluronidase activity in serum was as that in controls.