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PMID	Title	PublicationDate	abstract
2319523	Superior vena cava syndrome caused by systemic lupus erythematosus in a patient with longs	1990 Feb	Superior vena cava syndrome is mostly related to a malignant process, but many different benign causes have also been described. We report a patient with longstanding classic rheumatoid arthritis (RA), who developed a superior vena cava syndrome due to mediastinal lymphadenopathy. At that time she also fulfilled the ARA criteria for systemic lupus erythematosus (SLE). Histological examination of a lymph node biopsy revealed necrosis, hematoxylin bodies and LE cells, while a great amount of amorphous proteinaceous material was seen positive with immunofluorescence for IgG, IgM and complement (C3 and Clq). A diagnosis of superior vena cava syndrome due to mediastinal lymphadenopathy in a patient with SLE which had evolved from longstanding RA was established.
1767079	Juvenile rheumatoid arthritis: outcome and treatment for the 1990s.	1991 Nov	There has been much discontent with the hazards and the uncertain responses of patients with juvenile rheumatoid arthritis (JRA) to time-honored modalities of management. The treatment of JRA is often thought of as a pyramid with the base formed by nonsteroidal anti-inflammatory drugs, patient and family education, physical therapy, occupational therapy, and family support. Mechanisms of human disease have begun to open the gates to understanding the why and when of connective tissue diseases; they also offer the prospect of direct therapeutic intervention. In this article, the authors scrutinize the paradigms that guide our treatment strategies, review current practices, update data derived from those practices, and propose reassessment of therapy in the 1990s.
2112569	In vitro effects of two gold compounds, and D-penicillamine on the production of interfero	1990	There are contradictory reports on Interferon Gamma (IFN gamma) production by peripheral blood mononuclear cells (PBMC) in rheumatoid arthritis (RA). Since many patients previously studied were on Gold Sodium Thiomalate (GST), Auranofin (Auf), or D-Penicillamine (D-Pen) we have investigated the effects of these drugs on IFN gamma production using PBMC from normal controls (NC), and RA patients off GST, Auf, and D-Pen. Auf in low concentrations enhanced IFN gamma production by PBMC from NC but not RA; GST, and D-Pen had no effect. In other experiments PBMC were stimulated with concanavalin A (CONA A), or phytohemagglutinin (PHA). Auf, and GST inhibited IFN gamma production by CON A - stimulated NC and RA cells; D-Pen had no effect. Auf in low concentrations enhanced IFN gamma production by PHA - stimulated NC cells, but this effect was not seen with RA cells; GST inhibited both RA and NC cell production of IFN gamma, and D-Pen had no effect. Auf has a biphasic effect on IFN gamma production by NC cells with low concentrations being stimulatory or co-stimulatory, possibly by acting on T helper cells. Higher concentrations of Auf and GST, equivalent to those achieved in vivo in the course of therapy, inhibit IFN gamma production. These results suggest that gold therapy may affect IFN gamma production in RA, and could explain discrepancies noted in previous studies.
3764723	[Treatment of rheumatoid synovitis by intra-articular administration of dimethyl sulfoxide	1986	The effect of intraarticular administration of dimethylsulfoxide combined with glucocorticosteroids (GCS) in rheumatoid synovitis has been analyzed. A study of 17 patients with verified rheumatoid arthritis has shown the superiority of this method over the antiinflammatory effect of GCS used alone in its expression and duration.
2150268	Principles of managing chronic rheumatic diseases.	1990	The principles of treating chronic rheumatic diseases are to be conceived as a complex care of the patient. Medication is just one part of the treatment, be it a very important one. Its possibilities are, however, restricted. In spite of the explosive appearance of new antirheumatic drugs we are sticking to the classical forms of treatment (salicylates, gold, antimalaric drugs). Pyrazolone derivatives and corticoids are still holding their place in the therapeutic design. They should be administered, however, wisely and one must be aware of what is to be expected of their effect. A special therapeutic problem appears to be osteoarthrosis, which has recently become more actual among the other rheumatic diseases. The therapeutic effort must be completed by social care of the patient suffering from a chronic rheumatic disease, at least in cases when the patient depends on the help of another person.
3535984	Diagnosis of rheumatic disease: a plea for contemplation of the future.	1986 Nov	In clinical practice the definition of diagnosis is far from clear, since different levels of diagnosis are employed from the symptomatic to the pathological and aetiological. The recent development of computer data bases has important implications for the future, but will require a great deal of thought regarding the nature and quality of the data to be used. Evolution of diagnosis has occurred gradually during the history of medicine. As we see it, computer-assisted data handling will have a profound effect on diagnosis and classification of disease. To meet this challenge we require to define our terms regarding diagnosis of rheumatic disorders. In this paper we comment on the state of the art of diagnosis and classification of rheumatic diseases, and then propose changes to meet the needs of future developments.
2568058	Nail-changes induced by penicillamine.	1989	Peculiar nail-changes in a 70-year-old woman with rheumatoid arthritis occurring after approximately 1 year of penicillamine treatment are described. After cessation of treatment there was a gradual resolution with regain of normal nails after 7 months. Reinstitution of penicillamine treatment caused a recurrence thus proving a causal relationship between penicillamine and the described nail-changes. The fingernails were more affected than the toenails and clinically the changes consisted of absence of lunulae, longitudinal ridging, transverse or longitudinal defects of the nailplate and a tendency of onychoschizia.
2259843	HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients.	1990	This study of 110 seropositive rheumatoid arthritis (RA) patients confirms the significant association of susceptibility to RA with HLA-DR4 specificity (P less than 0.001). The DR1 frequency is elevated in the entire seropositive patient group, reaching marginal significance (P less than 0.025). The DR4-negative patients, however, have a much higher prevalence of DR1 (P less than 0.001). Surprisingly, the DRw6 specificity is significantly increased in the remaining DR4- and DR1-negative patients (P less than 0.01). These results demonstrate that RA is not associated with a single HLA-specificity, but to various degrees with DR4, DR1, and DRw6. These findings, and particularly the newly recognized association with DRw6, support the hypothesis that functionally equivalent shared epitopes or conformations on otherwise distinct MHC molecules may confer risk for developing RA.
1883690	Methotrexate: mechanism of action, pharmacokinetics, clinical indications, and toxicity.	1991 Jun	Methotrexate has become a standard therapy for the treatment of rheumatoid arthritis. This review summarizes the recent literature on low-dose methotrexate in the rheumatologic illnesses. The effect of methotrexate on in vivo rheumatoid factor production and suppression of ex vivo leukotriene B4 generation is reviewed. New information on drug interactions and pharmacokinetics is highlighted. The efficacy and toxicity of the drug in rheumatoid arthritis and other diseases are further defined. The effects of methotrexate on liver histology are also summarized.
1977296	Rheumatoid arthritis: current concepts and management, Part 2.	1990 Sep	Rheumatoid arthritis is a systemic disorder, but primarily involves chronic polyarticular inflammation. Conservative nondrug therapy and NSAIDs are indicated initially and are effective treatment for many RA patients. For those individuals with progressive unresponsive disease an SAARD should be used. All SAARDs exhibit severe and frequent adverse effects with the risk-to-benefit ratio being the determining factor in deciding which agent to use. The first to be used is usually a gold compound; antimalarials and penicillamine provide alternatives to gold therapy. Sulfasalazine may gain a role in the therapy of early progressive RA. Methotrexate has recently been given FDA approval for use in RA and can be used, if the first three agents fail. Azathioprine and cyclophosphamide are cytotoxic agents with an increased risk of producing malignancies, but their use is sometimes required to halt serious progressive RA. Chlorambucil or cyclosporin A are relatively toxic agents that may play a role in treating refractory RA. Corticosteroids should be used for short-term adjunctive therapy as intra-articular injections or oral therapy in individuals refractory to all other therapies. The use of SAARDs early in RA or in combination with one another is controversial.
2313659	Dendritic cells and high endothelial venules in the rheumatoid synovial membrane.	1990 Jan	Since dendritic cells are believed to play a crucial role in the pathogenesis of rheumatoid arthritis (RA) we studied the microenvironmental relationship of these cells with endothelial cells, lymphocytes and macrophages in the rheumatoid synovial membrane. With the monoclonal antibodies OKIa (MHC Class II determinants), RFD1 and L25 (both specific for "active" human dendritic cells) we identified large numbers of dendritic cells. With the monoclonal antibody HECA 452 [specific for a putative adhesion molecule notably present on high endothelial venules (HEV)], a subset of dendritic cells could be detected. HECA-452 positive dendritic cells were found in 2 basic patterns: (1) associated with small lymphoid cell clusters in the neighborhood of vessels with flat, HECA-452 negative endothelium, (2) at the periphery of dense organoid lymphoid infiltrates, surrounding HECA-452 positive HEV-like vessels. Our data suggest that the influx of HECA-452, L25, RFD1 and MHC Class II positive dendritic cells is an early event in the development of the inflammatory infiltrate found in the rheumatoid synovial membrane. The formation of organoid lymphoplasmacellular infiltrates with high endothelial venules would be secondary to this event.
3382150	Identification of factors limiting the accurate measurement of plasma D-penicillamine in r	1988 Mar	Free and total reduced concentrations of D-penicillamine have been measured in the plasma of rheumatoid arthritis patients by HPLC and electro-chemical detection. A reverse-phase ion-pair separation in conjunction with a dual porous graphite electrode satisfied the requirements of robustness, sensitivity, selectivity and suitable retention time. Plasma levels measured between 1.5 and 3 h after an oral dose, were less than 0.3 to 57.6 mumol/L and 0.6 to 85.0 mumol/L (n = 26) for free and total reduced drug concentrations, respectively. Sources of error in the accurate measurement of peak plasma D-penicillamine levels were identified as oxidative loss and alteration in the free to protein-bound ratio in the period following sample collection.
3819539	[Effect of synovial extract from patients with rheumatoid arthritis on the proliferation o	1986 Nov	To determine whether or not some growth factor (or factors) plays a significant role in the disease process of rheumatoid arthritis, the effects of pathological synovial extract, cultured synovial cell medium and partially purified extract and medium by fast protein liquid chromatography on cultured rabbit chondrocyte proliferation were studied. The synthesis of DNA was investigated by incorporation of 3H-thymidine into cultured cells and by flow cytometry using propidium iodide. The following results were obtained. The incorporation of 3H-thymidine into the cultured cells was increased by addition of synovial extract and the medium of cultured synovial cells. The molecular weights of active materials from the synovial extract were 13-18, 36-52, and 105-150 K daltons and those from the medium of cultured synovial cells were 13-18, 36-52 K daltons. The increase of S and G2 + M phase cells was observed flow-cytometrically 24-48 hr after addition of the synovial extract.
2012627	The effects of cyclosporin A on eicosanoid excretion in patients with rheumatoid arthritis	1991 Apr	Alterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephrotoxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24-week period, during which treatment with nonsteroidal antiinflammatory drugs was discontinued. The initial dosage of CSA was 4 mg/kg/day; at week 24, the mean dosage of CSA was 3.9 mg/kg/day. At week 24, the mean (+/- SD) serum creatinine level (1.04 +/- 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P less than 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P less than 0.03) in the 2,3-dinor thromboxane B2 level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs, and with unimpaired formation of other vasodilator eicosanoids.
1994912	Synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis	1991 Feb	We examined the histologic and immunopathologic features of the synovial membrane of 18 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) who had undergone total knee arthroplasty. Patients were classified into 5 groups according to therapeutic regimen and disease: RA treated with nonsteroidal antiinflammatory drugs (NSAIDs), RA treated with NSAIDs and prednisone, RA treated with NSAIDs and methotrexate (MTX), OA treated with analgesics, and OA treated with NSAIDs. There were no significant between-group differences in the percentages or the distribution pattern of the infiltrating T cell subsets (CD4, CD8), HLA-DR, or interleukin-2 receptor-bearing cells. However, inflammatory indices, which included the thickness of the lining cell layer and the density of the mononuclear cell infiltrate, were significantly higher in the RA patients treated with prednisone and those treated with MTX (P less than 0.05). Similarly, fibrosis was markedly reduced in these 2 groups. The RA patients treated with NSAIDs alone and the 2 groups of patients with OA demonstrated similar profiles. These data suggest that prednisone and MTX may inhibit the development of fibrosis without altering the subsets of the inflammatory cell population. This observation raises the possibility that the action of these 2 drugs may be partly mediated by the suppression of inflammatory mediators that are responsible for fibroblast activation.
1867528	Evaluation of a filtration lymphocytapheresis (LCP) device for use in the treatment of pat	1991 Jun	A practical on-line lymphocytapheresis (LCP) system using a leukapheresis filter (Cellsorba, Asahi Medical Co.) was evaluated in six patients with refractory rheumatoid arthritis. This filter consists of nonwoven fine polyester fiber wound around a porous cylinder. The blood was passed through the polyester fiber at a flow rate of 50 ml/min for 60 min. LCP was carried out once a week in the first month and biweekly in the next 2 months. An average of 98% of the leukocytes that entered the filter (1.27 x 10(10) cells) and 100% of the lymphocytes that entered the filter (3.66 x 10(9) cells) were removed in the first LCP. A total of 96.6% of the platelets and 2.7% of the erythrocytes that entered the filter were also removed. All of the patients showed clinical improvement in morning stiffness, Lansbury articular index, and functional capacity, with no adverse reaction. The number of circulating erythrocytes and platelets and the concentration of various serum components showed no significant change during the treatments. This LCP system required no fresh frozen plasma, albumin, or other blood transfusion. The number of circulating lymphocytes decreased to 65-70% of the pretreatment circulating lymphocyte count at the last procedure, with a decrease in the ratio of Leu3a positive cells to Leu2a positive cells. The proliferative response to phytohemagglutinin and concanavalin A was improved. These data suggest that LCP to remove approximately 3 x 10(9) lymphocytes once a week or biweekly has an immunomodulatory effect.
1932367	Elevation of interleukin-8 (IL-8) levels in joint fluids of patients with rheumatoid arthr	1991 Aug	Increased amounts of interleukin-8 (IL-8) were detected in synovial fluids of patients with active rheumatoid arthritis (RA) by radioimmunoassay (RIA). The concentration of IL-8 correlated directly with the number of infiltrating neutrophils in synovial fluids. To elucidate the role of IL-8 in neutrophil accumulation at the site of synovitis, the in vivo effects of intraarticular injection of recombinant IL-8 (rIL-8) on leukocytes infiltration into the joint space and synovium were examined. Following a single injection of rIL-8 into the knee joint space of rabbits, redness of the joint and limp became apparent after 4 h and were associated with the rapid infiltration of neutrophilic leukocytes into the joint space and synovial tissues. These effects were time dependent, first becoming evident at 1 h and reaching a plateau in 4 h, and also dose dependent, with a minimal effect being elicited by 100 ng per joint. Although neutrophils were present in the greatest number at 4 h, subsequently mononuclear cells accumulated and became apparent in considerable number after 8 h. Synovial lining cells became ovoid, pleomorphic, and multilayered at 24 h. IL-8 had no effect on the breakdown of proteoglycan of articular cartilage. Based on these findings, IL-8 released from monocytes and synovial cells may be an important contributor to leukocyte accumulation and inflammatory events in the joints of RA.
3111796	Patients with rheumatoid arthritis and gold-induced pneumonitis express two high-risk majo	1987 Aug	Gold salt therapy-induced pneumonitis is a rare complication in patients with rheumatoid arthritis (RA). We studied HLA-A, B, C, D/DR, and complement factor B (Bf) and C4 alleles in 17 patients with RA and gold-induced pneumonitis and found that these patients had strikingly homogeneous major histocompatibility complex (MHC) markers. Eight of them (47 percent) had the alleles HLA-A3 B35 Dwl BfF C4A3,2 (BO), which were shown by family studies of some patients to be inherited as an extended MHC-haplotype with an apparent gene duplication in the C4A locus. The other high-risk phenotype, HLA-B40 with a C4 null allele, was found in eight patients (47 percent). All but three of the 17 patients had at least one of the two high-risk markers, the frequency of these combinations being clearly higher than in the two control groups: patients with RA but with no gold-induced side effects and healthy individuals. Our study shows that use of several MHC markers together results in a strong association between the markers and the disease.
2978114	T cells expressing gamma delta chain receptors in rheumatoid arthritis.	1988 Aug	Whereas the majority of T cells use alpha and beta chains to form their T-cell receptor, a small minority of T cells, which do not express the CD4 or CD8 surface markers, use other chains termed gamma and delta to form their receptor. Flow cytometry was performed on cells isolated from the blood and synovial joints of patients with rheumatoid arthritis. Monoclonals which recognise the gamma and delta chains were used to compare the proportion of TCR gamma delta cells in these sites. Approximately half the patients had more TCR gamma delta in the joints than in their blood and one newly diagnosed patient had high numbers of TCR gamma delta cells in both blood and joints. In this preliminary study it is not possible to evaluate the role of these cells in the disease process, but it is of interest that in some RA patients there is an overabundance of both T cells that arise early in ontogeny (TCR gamma delta cells) and B cells that arise early in ontogeny, the CD5 B cell.
3015786	Proliferative responses of T-cell lines grown from joint fluids of patients with rheumatoi	1986 Jun	T-cell lines were established by culturing, in the presence of IL-2, mononuclear cells obtained from synovial fluids (SF) of most (77%) patients with rheumatoid arthritis (RA). By contrast, SF from patients with osteoarthritis and crystal synovitis rarely yielded lines. The cell lines were identified as T-cells because they express the CD3 surface antigen and either CD8 or CD4. The ability of the T-cell lines to react with putative antigens was tested using autologous Epstein-Barr virus transformed B-cells (EBV-B) as antigen presenting cells. IgG failed to stimulate proliferation of any RA patients' T-cell lines while Type II collagen stimulated T-cell lines from one RA patient and from one with osteoarthritis. Some T-cell lines (17/26) took up more tritiated thymidine after three days culture with a mixture of autologous SF and irradiated autologous EBV-B than with either alone. The effect could not be ascribed to a mitogen in the RA SF as the fluids failed to stimulate blood mononuclear cells. We consider that RA SF contain a T-cell growth factor which can only exert its effect through an antigen presenting cell (EBV-B).