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ID PMID Title PublicationDate abstract
1994909 Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. 1991 Feb The effect of treatment with a monoclonal antibody against the CD4 antigen present on T helper cells was studied in 10 patients with severe intractable rheumatoid arthritis. In an open trial, monoclonal antibody 16H5 was infused at a dosage of 0.3 mg/kg of body weight on 7 consecutive days. Studies of the kinetics demonstrated a drastic depletion of CD4+ cells, to as low as 25 cells/microliters, 1 hour after the first infusion. The subsequent recovery of the CD4+ cell numbers 24 hours after infusion did not reach initial levels, and after the full 7-day treatment cycle there was a significant reduction of the number of CD4+ cells (mean +/- SD 51 +/- 28%; P less than 0.02). There was a reduced or even inverse CD4:CD8 ratio, which generally persisted 3-4 weeks. Lymphocyte transformation assays demonstrated significantly reduced reactivity in 5 of the 9 patients who completed the 7-day course, whereas 4 individuals exhibited an unexpected elevation in the T cell response to mitogens and common antigens. Parallel laboratory studies showed a significant decrease in the erythrocyte sedimentation rate (P less than 0.05), rheumatoid factor titer (P less than 0.04), and total immunoglobulin values (P less than 0.01), as well as a reduction in C-reactive protein levels, in 7 of the 9 patients. Clinically, there was a significant reduction in the Ritchie articular index (P less than 0.05) and in the number of swollen joints (P less than 0.04). Adverse effects were urticaria in 2 patients, which led to withdrawal of therapy in 1 of them, and chills with fever, suggestive of a lymphokine release syndrome, in another 2 patients. Only low levels of human anti-mouse immunoglobulin antibodies developed (not exceeding 1.7 mg/liter). It was therefore possible to repeat the treatment cycle, achieving still better efficacy, in 4 of the patients (reductions in the Ritchie index and the number of swollen joints P less than 0.02). Our findings indicate that treatment with monoclonal antibodies against the CD4 antigen leads to immunomodulation which results in clinical benefits, at least during initial observation periods (up to 6 months postinfusion). However, it remains to be determined whether long-term remission can be induced with this therapeutic approach. The use of immunosuppressive therapies or repeated antibody treatments will have to be considered.
2569874 Increased expression of p150,95 and CR3 leukocyte adhesion molecules by mononuclear phagoc 1989 Aug The expression of leukocyte adhesion molecules CR3 (CD11b) and p150,95 (CD11c) in synovial tissue was evaluated immunohistochemically. Although a significant proportion of synoviocytes in normal and osteoarthritic synovial membranes expressed the leukocyte common antigen and CR3, very few expressed the p150,95 molecule. In contrast, p150,95 was more evident in rheumatoid synovial membranes. Expression of this molecule was strongest in synovial membranes with a prominent macrophage infiltrate and accumulation of mononuclear phagocytes at the joint surface; p150,95 was also present on interdigitating cells in lymphoid collections. The patterns of expression suggest that these leukocyte adhesion molecules may be important in the diapedesis of mononuclear phagocytes into and through inflamed synovial membranes, as well as in cellular interactions within rheumatoid synovial membranes.
3478938 Skin surface temperature over the temporomandibular and metacarpophalangeal joints in indi 1987 Oct Temperature measurements were made on the skin surface over the temporomandibular joint (TMJ) and metacarpophalangeal (MCP) joint in 71 individuals with rheumatoid arthritis (RA) and 52 individuals without general joint disease or symptoms. The recordings were performed with thermistors in contact with the skin. Symptoms in the stomatognathic system and general joint symptoms were investigated by a questionnaire. A clinical examination was performed of the stomatognathic system. In addition, a medical examination including clinical articular indices and laboratory tests was made. The skin surface temperature over the TMJ was generally lower for the individuals with RA than for the individuals without joint disease, whereas the opposite was found for the MCP joint. The most important determinants of skin surface temperature over the TMJ in RA were duration of TMJ symptoms, room temperature, tenderness to palpation of the masseter muscle, and rheumatoid factor. The results of this study indicate that there is a correlation between both symptoms and signs of disorder in the stomatognathic system and temperature of the skin surface overlying the TMJ and MCP joint in individuals with RA.
3667304 Treatment of rheumatoid arthritis using radiopharmaceuticals. 1987 One hundred and twenty one knees in 97 patients with seropositive rheumatoid arthritis and persistent knee synovitis were treated with the intra-articular injection of 270 mCi (30 GBq) of dysprosium-165 (165Dy) bound to ferric hydroxide macroaggregates. Of 81 knees evaluated at one year, 61% had good results, 23% had fair results and 16% had poor results. Of 44 knees evaluated at two years, 64% had good results, 16% had fair results and 20% had poor results. Knees with Stage I radiographic changes showed 72 and 81% good results at one and two years, respectively. Knees and Stage II radiographic changes showed 53 and 48% good results at one and two years, respectively. Leakage of radioactivity from the injected joint was minimal. Mean leakage to the venous blood was 0.15% of the injected dose. Mean leakage to the liver 24 h after injection was 0.64% of the injected dose. Mean leakage to the draining inguinal lymph nodes was 0.17% of the injected dose. These results indicate that 165Dy-ferric hydroxide macroaggregate is an effective agent for radiation synovectomy, particularly in knees with Stage I radiographic changes. The minimal leakage rates observed offer a definite advantage over previously used agents.
1792154 [The assessment of cortical and spongy bone mineral content with quantitative computed tom 1991 Dec 25 The CT numbers of cortex at the level of 20 cm (CT20) and spongiosa in the lateral condyle at the level of 2 cm (CT20) proximal from the distal end of the femur, and the bone mineral density of spongiosa in the L3 body (BMD), were obtained by QCT. The study included 43 female patients with rheumatoid arthritis (RA), 71 female patients with primary osteoporosis (OP), 20 female nondialyzed patients with chronic renal failure (CRF:nonHD), 37 hemodialyzed patients (CRF:HD), including 13 parathyroidectomized patients (CRF:HD, PTX), and 10 healthy volunteers. CT20 correlated closely with age in RA. CT02 and BMD correlated closely with age in RA and OP. CT20 and CT02 correlated closely with the duration of hemodialysis in CRF:HD, but not with the duration of disease in RA. The values of CT20 and CT02 in the CRF:HD. PTX group were significantly lower than those in the other CRF groups. BMD in the RA groups was not different from that of healthy volunteers. The CT20 values of the one-third of RA patients older than 60 years were extremely low compared with those of the other two-thirds. The results indicated that BMD was useful in assessing bone mineral content in OP, but not in RA. CT02 and CT20 were useful in assessing bone mineral content in these three diseases, CT20 was especially useful for patients in the CRF:HD group and those with RA older than 60 years, but it was not useful in the CRF:nonHD group.
2068540 C3 activation products, C3 containing immune complexes, the terminal complement complex an 1991 Complement activation products, C9 and C3-containing circulating immune complexes (CIC), were evaluated in plasma and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis. C3 activation products and the fluid phase terminal complement complex were considerably elevated in SF from RA patients reaching levels five- to eighttimes that in plasma, consistant with a local activation of the whole cascade in the joints. The results emphazise the importance of detecting C3 activation by neoepitope expression instead of single fragment determinations. The concentration of native C9 was lower in synovial fluid compared with plasma, consistant with the excessive local complement activation. Increased CIC levels which correlated with the degree of complement activation were also found in the SF from the RA patients.
2772658 Prospective analysis of liver biopsies before and after methotrexate therapy in rheumatoid 1989 Aug The significance of hepatic changes in methotrexate-treated RA patients is unclear at this time. In our group of RA patients, there was a slight increase in the incidence of triaditis and fat during methotrexate therapy. Disease duration greater than or equal to 10 years was associated with increased hepatic triaditis before treatment. Age greater than 50 years was associated with increased hepatic fat before and after treatment. It appears that patients' ages and duration of underlying RA account for some changes, independent of methotrexate therapy. Several of our patients changed from higher to lower histologic grade or had an apparent decrease in fibrosis, fat, or triaditis on the pathologists' reports and the blind readings of the repeat biopsies. This may be explained by sampling error. More importantly, some of these changes may not be of clinical significance. One report of methotrexate-induced cirrhosis in patients with psoriasis demonstrated that in all but one of 14 patients who continued receiving methotrexate the cirrhosis decrease or did not progress. This may also be true of the hepatic fibrosis seen in RA after methotrexate treatment. In this study, there did not appear to be changes seen on pretreatment liver biopsy that were predictive of subsequent fibrosis or cirrhosis. Our data indicate that pretreatment biopsy is unwarranted in a population similar to ours. However, our practice has been to try to avoid methotrexate in patients with diabetes, prior liver disease, alcoholism, or obesity because of previous reports suggesting that these patients are at increased risk for the development of cirrhosis. Only the above-mentioned patient, eventually diagnosed as having cirrhosis, might have been handled differently. Including the study, none of the approximately 700 RA patients in the literature having liver biopsies after methotrexate therapy have developed cirrhosis consequent to its use. Most of these had received a total dose of approximately 1,500 mg in small weekly doses, and alcohol was prohibited. Below this cumulative dose the risk of clinically significant liver damage in carefully selected patients is very low. In view of this experience, the recommendation that RA patients have liver biopsies after 1,500 mg of methotrexate (a holdover from the psoriasis literature) may be too conservative in low-risk RA patients, provided methotrexate is administered weekly and alcohol is prohibited. Recognizing that the absolute need for biopsy is unproven, a more realistic milestone for those choosing biopsy might be after each 2,000 to 2,500 mg.(ABSTRACT TRUNCATED AT 400 WORDS)
2787183 Immunohistological features in the synovium obtained from clinically uninvolved knee joint 1989 Aug The spectrum of immunohistological change in the affected joints of patients with rheumatoid arthritis has been well described. In this study, the immunohistological features in synovial membrane obtained from apparently uninvolved knee joints of 16 patients with active untreated rheumatoid arthritis were examined and compared to tissue from control subjects. Synovial tissue was obtained by needle biopsy. Hyperplasia of the synovial lining layer, present in 69%, was the most frequently observed abnormality in synovium obtained from uninvolved joints. Perivascular mononuclear cell infiltration was present in 31% and consisted predominantly of helper T-cells. Increased vascularity and fibrin deposition were not notable features. Clinically overt synovitis emerged in only two patients during a follow-up period of up to 36 months. In conclusion, a considerable degree of histological change was observed in the apparently uninvolved knee joints of patients with active rheumatoid arthritis. The presence of subclinical synovitis challenges current concepts of disease activity and clinical remission. Further study is required to determine whether the features described may be associated with progressive joint erosion.
2925127 [Initial results following implantation of silastic wrist joint prostheses in patients wit 1989 Jan Implantation of titanium grommets should protect the flexible implant from the sharp bone edges and avoid fracture of the implant. In case of bone cysts and thin corticalis they should provide further support against countersinking. Swanson et al. (1982) reported bone remodeling phenomena around the grommets and the implant. Eight patients suffering rheumatoid arthritis have been reviewed at an average of 18 months (12 to 24 months) following operation with the flexible implant and additional grommets. The following results were observed: 1. No fractured implants were noted in any patient. 2. In two cases resorption was noted around the proximal grommet. 3. In no case was new bone formation noted. 4. In one case the flexible implant and the grommets became countersunk into bone.
3704509 [Sulfhydryl maintenance treatment in rheumatoid polyarthritis. A series of 120 cases follo 1986 Jan The authors present a series of 120 cases of sero-positive rheumatoid arthritis followed for ten years and treated with D-penicillamine, gold salts and pyrithioxine used either alone or sequentially after stopping one of these treatments because of failure, intolerance or escape. This series can be broken down as follows: 13% of patients are under treatment after ten years, 27% had a favourable result with one of the three treatments for five to ten years, 59% had a poor result (less than 5 years) or no effect. However, it appeared that a failure or an escape from one of these products did not signify a failure with another product and side effects did not necessarily recur with a change of treatment.
3723500 The antigen induced arthritis model: the relevance of the method of induction to its use a 1986 Apr The much favoured ovalbumin antigen induced model of arthritis in rabbits is widely used in rheumatoid arthritis (RA) research. When examined histologically, it was found to have important deficiencies as parallels to the human disease. After sensitization to ovalbumin, 2 intraarticular challenge doses of a magnitude at each end of the spectrum used by investigators were used in 152 rabbits. The effects of the high and low dose challenges were examined histologically with particular attention to the articular cartilage. With high doses, the gross and histological changes in the knee joint were remarkably akin to acute cartilage necrosis rather than RA1. In the low dose, a milder smoldering arthritis was produced. These observations suggest that, depending on the challenge dose used, there is a tremendous variability in the kind of arthritis produced by the antigen induced arthritis model. Furthermore, it is suggested that previous conclusions about the pathophysiology and immunology of RA drawn from the models that produce a rapid and severe arthritis should be reexamined.
2186625 Pyarthrosis in patients with rheumatoid arthritis: a report of 13 cases and a review of th 1990 May PURPOSE: The purpose of this study is to report 13 cases and review the literature for pyarthrosis occurring in the setting of rheumatoid arthritis (RA). Special emphasis is placed on evaluating both the changing, as well as the constant, features of this complication and on assessing diagnostic and therapeutic aspects that have a bearing upon outcome. PATIENTS AND METHODS: A retrospective review of records from our institution revealed 13 cases of pyarthrosis in patients with RA over the past 14 years. Information obtained included patient demographics, RA history, concomitant illnesses and medications, length of symptoms prior to the diagnosis of pyarthrosis, peri-articular manifestations, probable source of infection, joint(s) involved, relevant laboratory data, and information on treatment and outcome based on initial surgical therapy versus closed needle drainage. In addition, 213 cases from 45 citations were reviewed for similar information. RESULTS: Our series was notable for a high percentage of associated serious medical illnesses and peri-articular manifestations of the pyarthrosis (i.e., sinus tract formation, concomitant septic bursitis, or infected synovial cyst). The erythrocyte sedimentation rate was a useful monitor of adequate therapy and was often a signal of recurrent infection. In all patients, the skin was the major source of infection. The mortality from pyarthrosis has declined over the past 40 years but is still unacceptably high, especially in patients with polyarticular involvement. Preliminary observations suggest that an initial surgical approach to joint drainage may be preferable to closed needle drainage in order to improve joint outcome in patients with RA and pyarthrosis. CONCLUSION: Pyarthrosis occurring in patients with RA continues to produce unacceptable morbidity and mortality despite 40 years' experience. Earlier recognition (which may include peri-articular features) and perhaps an aggressive surgical approach to drainage may improve the prognosis.
3165585 Skin surface temperature over the masseter muscle in individuals with rheumatoid arthritis 1988 Jun Temperature measurements were made on the skin surface over the masseter muscle in 71 individuals with rheumatoid arthritis (RA group) and in 52 individuals without general joint disease or symptoms (C group). The temperature recordings were performed with thermistors in contact with the skin. Symptoms in the stomatognathic system and general joint symptoms were investigated by means of a questionnaire. A clinical examination was made of the stomatognathic system. In addition, a medical examination including clinical articular indices and laboratory tests was made. The skin surface temperature over the masseter muscle was generally decreased for the individuals with RA compared with the C group but increased with duration of temporomandibular joint (TMJ) symptoms, approaching normal values. Duration was also the most important variable among those investigated in determining the skin surface temperature over the masseter muscle. Hypothermia in the RA group was correlated with craniomandibular disorders such as lateral deviation of the mandible on mouth opening and TMJ clicking, whereas individuals with a history of swelling in the TMJ region had a higher temperature than average in this group. The results of this study show that there is a correlation between craniomandibular disorders and decreased skin surface temperature over the masseter muscle in individuals with RA.
1667989 Neutrophil chemiluminescence and superoxide production in patients with rheumatoid arthrit 1991 Aug Previous study demonstrated that platelet activating factor (PAF) was a potent inducer of polymorphonuclear leukocyte (PMN) activation. This study used a luminometer to measure the chemiluminescence (CL) of peripheral blood (PB) PMNs in 15 patients with rheumatoid arthritis (RA). Superoxide production from PB and synovial fluid (SF) PMNs was also determined by inhibiting reduction of ferricytochrome C with superoxide dismutase. Neutrophils obtained from 12 age- and sex-matched healthy subjects (HS) were used as controls. The results showed that PAF at both 1 microM and 10 microM significantly increased neutrophil CL in both RA (1.40 +/- 0.90 mv, 1.87 +/- 1.18 vs control 0.66 +/- 0.18) and HS (1.70 +/- 0.72, 2.22 +/- 1.25 vs control 0.67 +/- 0.13), with no significant difference between the two groups. Both PMA and zymosan also significantly enhanced PMN CL in both RA (41.51 +/- 17.42, 40.0 +/- 26.51) and HS (43.42 +/- 17.28, 39.91 +/- 27.24), and those values were much higher than those of controls or via PAF stimulation, but, again, there was no difference between RA and HS groups. Lipopolysaccharide (LPS)-stimulated mononuclear cell supernatant can induce neutrophil activity, too. Like CL, PAF had a weak effect on the generation of superoxide from PMNs. Neutrophils from seven RA SF stimulated with PMA or PAF showed a significant increase in superoxide production (76.05 +/- 2.14, 2.83 +/- 0.18) and these were higher than in PB of either RA patients (54.35 +/- 12.46, 1.03 +/- 0.74) and HS (55.70 +/- 17.9; 1.08 +/- 1.12) (p less than 0.05). These findings demonstrated the PMNs were more activated in SF than those in PB of RA patients and HS, suggesting some unidentified factors in SF provoked PMNs activation.
3704514 [Role of phagocytic cells in rheumatoid polyarthritis]. 1986 Jan Three groups of subjects were selected for this study. Patients suffering from rheumatoid arthritis (RA) diagnosed according to the criteria of the ARA (mean: 6 criteria) and treated with gold salts. Control subjects treated with one type of non-steroidal anti-inflammatory agent (diclofenac). Healthy subjects receiving no treatment. The granulocytes and monocytes in the peripheral blood were tested separately for the ingestion of 3 types of particles and for the stimulation of the production of the superoxide anion. In the patients with rheumatoid arthritis, all of the phagocytic cells had a normal phagocytic response and a normal superoxide anion production. The serum of the patients did not inhibit the activity of these cells. Diclofenac did not act on phagocytosis or on the oxidative activity of the control cells. It is therefore logical to consider that the phagocytic cells are involved in RA via other mechanisms of action.
2533769 [Quantitative detection of keratan sulfate specific epitopes in synovial fluid in inflamma 1989 Nov The release of keratan sulphate (KS) bearing proteoglycan fragments from the extracellular matrix of cartilage into the synovial fluid is believed to be an early event in most joint pathologies. Quantitative analysis of KS in body fluids is therefore regarded as having a certain potential in monitoring articular cartilage catabolism. We describe the application of a non-competitive enzyme linked immunosorbent assay (ELISA) for the quantitation of KS-epitope in synovial fluids, using a monoclonal anti-KS antibody. Synovial fluids from 75 patients were analyzed, comprising the following disease groups: i) rheumatoid arthritis (n = 42), ii) osteoarthritis (n = 20), iii) gouty arthritis (n = 5), and iv) reactive arthritis (Reiter's disease, n = 8). Highest concentrations of synovial KS-epitope were found in reactive arthritis (median = 1410 ng/ml), and in gouty arthritis (median = 2105 ng/ml). However, significantly lower concentrations of KS-epitope (p less than 0.01) were observed in synovial fluids from patients with rheumatoid arthritis (median = 197 ng/ml) and osteoarthritis (median = 337 ng/ml). Although considerable variation of individual values was observed in all groups, a weak and inverse correlation between synovial levels of KS-epitope and inflammatory disease activity was seen only in patients with rheumatoid arthritis. However, KS-epitope levels did not correlate with either the synovial IL-1 activity, nor the number of synovial leucocytes.
1783455 Improved on-line thoracic duct drainage for lymphocytapheresis. 1991 Dec Lymphocytapheresis using thoracic duct drainage (TDD) is a recognized technique of extracorporeal immunomodulation for various autoimmune diseases such as rheumatoid arthritis (RA), and its clinical benefit has been reported and generally accepted. Lymphocytapheresis using TDD is very selective for removing lymphocytes (especially helper T-cells) but raises some problems such as hypoproteinemia due to the massive removal of lymph, and difficulties in repeated treatment. Along with the development of a new polyester fiber filter, we have developed a simple and effective method of lymphocytapheresis for wide adoption for these techniques. We performed lymphocytapheresis using TDD in patients with RA and previously reported its clinical efficacy indicated by the significantly lower number of peripheral lymphocytes and T4/T8 ratio. We present here our newly-developed on-line system designed to prevent hypoproteinemia. Furthermore we report on the advantages with a new subcutaneous vascular access device set up to manage the problems of repeated treatments. A small reservoir for keeping the thoracic duct open and returning lymph to the patient permitted sufficient lymph drainage and removal of lymphocytes and the clinical application of TDD is discussed.
3516496 Tiopronin-nephropathy: clinical, pathological, immunological and immunogenetic characteris 1986 Jan Nine patients who developed proteinuria while on Tiopronin (a D-Penicillamine-like drug) have been studied. Nephrotic syndrome was observed in six cases. Immunologic analysis revealed a high frequency of ANA positivity and RF seronegativity by the time nephropathy appeared. Six patients were biopsied. Immunofluorescence, electron and light microscopy studies showed: glomerulonephritis with segmental deposits in the mesangium and along the capillary walls in one patient, mesangioprolipherative glomerulonephritis in one case and stage 1 membranous glomerulonephritis in four cases. Immunogenetic typing disclosed a strong association with B35-Cw4 class I antigens.
3494398 HLA-DR4 and pulmonary dysfunction in rheumatoid arthritis. 1987 Apr Rheumatoid arthritis is associated with an increased frequency of the B cell alloantigen HLA-DR4, and preliminary work has suggested an association between HLA-DR4 and obstructive lung disease in subjects with rheumatoid arthritis. To prospectively evaluate the influence of HLA-DR4 on pulmonary involvement in patients with rheumatoid arthritis, pulmonary function was measured in four groups of subjects with rheumatoid arthritis in whom HLA-DR4 and smoking status was known: 16 DR4-positive smokers (six current and 10 exsmokers), 16 DR4-negative smokers (six current and 10 exsmokers), eight DR4-positive nonsmokers, and eight DR4-negative nonsmokers. Significant reductions in one-second forced expiratory volume and forced vital capacity were observed in DR4-positive subjects compared with DR4-negative subjects irrespective of cigarette smoking status. In addition, patients with keratoconjunctivitis sicca (secondary Sjögren's syndrome) demonstrated significant reductions in one-second forced expiratory volume, forced vital capacity, and ratio of one-second forced expiratory volume to forced vital capacity compared with those patients without evidence of secondary Sjögren's syndrome. It is concluded that the presence of the HLA-DR4 antigen and secondary Sjögren's syndrome are associated with abnormal pulmonary function in patients with rheumatoid arthritis.
2422209 Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that sha 1986 May A monoclonal antibody, selected for reactivity with the Epstein-Barr virus (EBV)-encoded antigen EBNA-1, exhibited strong reactivity with the synovial lining cells in joint biopsies from 10 of 12 patients with rheumatoid arthritis (RA) and adherent cells eluted from these tissues. No staining of RA synovial membrane frozen tissue sections or eluted synovial-lining cells was obtained with monoclonal antibodies directed against other EBV-encoded antigens (anti-p160, anti-gp200/350) or with monoclonal antibodies directed against antigens encoded by cytomegalovirus, herpes simplex viruses, or human T cell leukemia virus type I. Among 12 osteoarthritis and normal synovial biopsies only rare reactive cells were noted. Characterization of the antigen(s) in RA synovium by the Western immunoblotting technique revealed a 62,000-molecular-weight (mol-wt) protein, in contrast to the 70,000-85,000-mol-wt EBNA-1 antigen found in EBV-transformed cells. The structural basis for the cross-reactivity of the RA synovial membrane 62,000-mol-wt protein and the EBNA-1 antigen appears to reside in the glycine-alanine rich region of these molecules. A rabbit antibody directed against a synthetic peptide (IR3-VI-2) derived from the glycine-alanine-rich region of EBNA-1 reacted with the 70,000-85,000-mol-wt EBNA-1 antigen in EBV-infected cells and with the 62,000-mol-wt molecule in RA synovial membrane extracts. Since strong antibody responses to EBNA-1 are known to exist in RA patients, these results suggest that immune responses to a cross-reactive antigen may play a role in the pathogenesis of RA.
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