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ID PMID Title PublicationDate abstract
7801199 [Detection of autoantibodies in sera from patients with rheumatoid arthritis]. 1994 Oct Although Rheumatoid Arthritis (RA) is categorized in the systemic autoimmune diseases, specific autoantibodies in RA have been reported to be rare. We have investigated autoantibodies found in sera from patients with RA and examined their clinical significance. Immunoprecipitation techniques using 32P-labeled or 35S-labeled HeLa cell extracts and immunoblotting were utilized to detect autoantibodies in sera from 42 patients with RA and 58 patients with other connective tissue diseases as controls. Certain autoantibodies were detected in 33 of 42 patients (79%) with RA by any of the assay systems mentioned above. Anti-SSA/Ro, anti-SSB/La, anti-7-2RNP, and anti-Sm antibodies were found in 13 (29%), 3 (7%), 4 (10%), and 1 (2%) patients with RA, respectively. All 3 patients with anti-SSB/La and 9 with anti-SSA/Ro revealed Sjögren's syndrome besides RA. However, all 4 patients with anti-7-2RNP and one patient with anti-Sm showed no evidence of scleroderma nor SLE. Besides of these known autoantibodies, we have also detected 4 new antibodies which reacted with a 60kD protein in 15 (36%), 45kD in 10 (24%), 75kD in 8 (19%), 180kD in 4 patients (10%) with RA. These autoantibodies were not found in other connective tissue diseases except one of SLE for anti-60kD and one of dermatomyositis for anti-75kD, and therefore appeared to be specific for RA patients. Anti-45kD antibodies were associated with low prevalence of anti-nuclear antibodies, and anti-180kD antibodies were associated with lymphadenopathy and Sjögren's syndrome. Thus, it was demonstrated that patients with RA develop a variety of autoantibodies as well as those with other connective tissue diseases.
1405002 [Relationship between autoimmune diseases and pneumoconiosis]. 1992 Sep In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future.
8646430 Difference in expression of the plasminogen activation system in synovial tissue of patien 1996 May Proteolytic joint destruction in inflammatory and non-inflammatory arthropathy is believed to be mediated, at least in part, by the plasminogen activation (PA) system. To further investigate possible involvement of the PA system, we quantified immunoreactive urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), both plasminogen activator inhibitors (PAI-1 and PAI-2) and u-PA-receptor (u-PAR) in synovial tissue extracts of 14 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). u-PA, PAI-1, PAI-2 and u-PAR concentrations were significantly higher in RA than in OA patients. t-PA antigen levels were significantly lower in RA than in OA synovial tissue extracts. Immunohistochemistry was performed to compare the distribution and staining intensity of these components in samples of RA and OA synovial tissue. Intense immunostaining of u-PA, u-PAR, PAI-1 and, to a lesser degree, PAI-2 was observed predominantly in the synovial lining of RA patients. In OA patients, u-PA, PAI-1, PAI-2 and u-PAR were barely detectable. t-PA immunostaining was restricted to the endothelial side of vascular walls in both groups. We conclude that the observed increase of u-PA, u-PAR and PAI expression, distributed mainly in the synovial lining area of proliferative and invasively growing synovial tissue in RA patients, supports a pathogenic role for the PA system in destructive arthritis. Depressed t-PA-mediated plasminogen activation might contribute to delayed intra-articular fibrin removal.
8574610 Pancytopenia and severe cytopenia induced by low-dose methotrexate. Eight case-reports and 1995 Jul Severe adverse effects of low-dose methotrexate (less than 20 mg per week) are believed to be rare. We report eight cases of severe tricytopenia or pancytopenia seen in two medical departments of the same hospital in patients receiving low-dose methotrexate. Three patients had been under methotrexate for less than one month. Of the six patients with joint disease, five had rheumatoid arthritis and one psoriatic arthritis. A review of the literature found 92 previously reported cases of severe tricytopenia or pancytopenia induced by low-dose methotrexate. Of the total of 100 cases, 24 were fatal and 25 occurred within one month of treatment initiation. Potential risk factors were identifiable retrospectively in at least 50% of cases but were not all predictable or present at treatment initiation. In 30% of cases, no explanation for the hematologic complication was found, and in an additional 20% missing data precluded definite conclusions. The role of the risk factors incriminated in the literature is discussed. Although infrequent, cytopenia is a severe complication of methotrexate therapy that warrants a number of precautions, including periodic creatinine clearance and serum albumin determinations. Furthermore, the weekly dosing schedule should be printed on methotrexate boxes.
8768289 [Free oxygen radicals and rheumatic diseases]. 1996 May The authors assessed in blood some indicators of the reaction of the organism to the formation and action of free radicals in patients with rheumatoid arthritis, with other inflammatory articular diseases selected at random and with degenerative diseases of the joints and spine. From the results ensues that subjects with inflammations of the synovial membrane respond relatively frequently by a rise of indicators of the antioxidant system such as the activity of superoxide dismutase, glutathione peroxidase or the antioxidant capacity of plasma. Obviously a defence reaction of the organism is involved to the increased formation and action of free oxygen radicals in the inflamed articular lining. The authors conclude that the mentioned laboratory indicators of the action of free radicals could be used when checking the progress of treatment in rheumatic diseases.
8032050 Invasive pulmonary aspergillosis associated with low dose methotrexate therapy for rheumat 1994 Apr Opportunistic infections complicating low dose methotrexate therapy are rare, consisting predominantly of Pneumocystis carinii pneumonia. We report a case of invasive pulmonary aspergillosis which developed in a patient being treated for seropositive rheumatoid arthritis with low dose methotrexate (5-7.5 mg weekly) for 8 years. The patient was successfully treated with itraconazole 200 mg daily for 6 months. This case adds to the growing evidence implicating low dose methotrexate with opportunistic infections and should heighten clinical awareness in patients on this treatment.
7799341 Intermittent treatment with D-penicillamine is effective in lower doses and with fewer adv 1994 Sep OBJECTIVE: To determine whether intermittent rather than daily administration of D-penicillamine (D-Pen) would effectively reduce the incidence of adverse effects without significantly diminishing the clinical benefits. METHODS: We conducted an open prospective trial comparing daily and intermittent schedules. Among 76 Japanese patients with rheumatoid arthritis (RA), 37 underwent daily treatment with D-Pen while 39 were given D-Pen intermittently (every Monday, Wednesday, and Friday). RESULTS: The mean D-Pen dose was 166.8 and 99.4 mg/day for daily and intermittent groups, respectively, the difference being highly significant (p < 0.0001, Mann-Whitney's U test). The incidence of adverse effects was significantly lower in the intermittent group. Both schedules significantly reduced the activity of RA, as evaluated by clinical and laboratory variables. No significant differences were observed in the degree of improvement between the 2 schedules. CONCLUSION: Intermittent therapy with D-Pen is an effective treatment for patients with RA and its higher degree of flexibility can lead to maximum efficacy for management of patients with RA.
8498896 [Role of opioid peptide in rheumatoid arthritis--detection of methionine-enkephalin and le 1993 Mar A relationship between rheumatoid arthritis (RA) and endocrinological abnormality has been suspected for many years. In the present study, we immunohistologically identified the presence of methionine-enkephalin (Met-enk) and leucine-enkephalin (Leu-enk), in synovial tissues collected from RA patients and determined the amount of these peptides and interleukin 1 beta (IL-1 beta) in the culture supernatant of tissue explants by RI and ELISA. Synovial membrane samples obtained by biopsy during artificial joint replacement and plasma samples simultaneously collected from 11 RA patients (11 joint) diagnosed as having classic or definite RA according to the diagnostic criteria of the American Rheumatism Association were used. All 11 patients were females and aged between 36 and 64 years (mean: 45.8 years). As a result of immunohistological standing (ABC method), Met-enk was detected in vascular endothelial cells and Leu-enk in superficial cells, vascular endothelial cells and interstitial cells. Leu-enk concentrations (42.3 +/- 15.8 pg/ml) were higher in the culture supernatant of the synovial membrane than in the plasma (20.7 +/- 13.3 pg/ml). Furthermore, in the culture supernatant the concentration of Leu-enk was positively correlated with that of IL-1 beta (r = 0.789). These findings suggest that Met-enk and Leu-enk are locally produced by synovial tissues and may exert an immunological and/or inflammatory role in RA synovitis.
1355956 [Salazosulfapyridine in rheumatoid arthritis. A study of 49 patients]. 1992 The results of an open retrospective study of 49 patients treated with salazosulfapyridine (SASP) (sulphasalazine) for rheumatoid arthritis (RA) are reported. The patients, 7 men and 42 women, had a mean age of 53 years, and their mean duration of evolution of RA was 13.3 years. Sixty percent of them had undergone more than 3 previous disease-modifying drugs. The mean length of SASP treatment was 15.3 months. The initial response was favorable in 34 patients (69%). Treatment was ineffective and stopped in 12 cases (24.5%); the inefficacy was primary in 6 and tachyphylactic in the other 6. Twenty patients (41%) experienced at least one side effect. SASP was stopped in 11 patients (20.4%) due to undesirable side effects; 9 of the 11 times were during the first 2 months of treatment. Digestive system intolerance was the most common but led to drug withdrawal in less than half the patients. In all cases, mucocutaneous, neurosensory, hematological and hepatic side effects regressed during the month following SASP withdrawal. The therapeutic maintenance level was 67% at 1 year, 60% at 18 months, 52% at 2 years and 45% at 3 years. SASP has a role in the treatment of relatively slightly evolved forms of RA, before prescribing methotrexate. The possibility of delayed intolerance reactions, notably hematological and hepatic, justify prolonged biological monitoring of these patients.
7481581 Cytokine autoantibodies in rheumatoid arthritis. 1995 Sera from 42 patients with rheumatoid arthritis (RA) and 40 healthy controls (HC) were examined for cytokine autoantibodies (CK-aAb) by accurate and sensitive radioimmunoassays. The prevalences of detectable CK-aAb in RA (HC) were: aAb-IL-1 alpha = 36% (38%); aAb-IL-6 = 29% (13%), p = 0.06; aAb-IL-8 = 0% (0%); aAb-IFN alpha = 12% (3%), p = 0.11. The levels of the individual CK-aAb did not correlate, and there were no correlations between CK-aAb levels and clinical or laboratory variables. CK-aAb levels remained constant in 8 RA patients tested over a period of 6 months. With regard to alterations in aAb-IL-1 alpha levels, 4/11 HC were consistently positive over 18-36 months; 2/11 converted and became highly positive. The levels of aAb-IFN alpha and aAb-IL-6, but not aAb-IL-1 alpha, tended to be increased in RA patients; aAb-IL-8 were undetectable in both RA and HC.
7801054 Occupation, occupational exposure to chemicals and rheumatological disease. A register bas 1994 The cumulative incidence of rheumatoid arthritis (RA) was compared between different occupations, and between different exposure groups based on a job-exposure matrix (JEM). The study population comprised those subjects who in 1980 lived in one of 13 Swedish counties, were born between 1905 and 1945, and who had stated the same occupation in the censuses of 1960 and 1970, a total of 375,035 men and 140,139 women. The study population was followed concerning hospital care for rheumatoid arthritis in 1981-1983 by lineage to the Swedish Hospital Discharge Register. In general there were rather small differences in the relative risk of RA in different exposure groups and different occupations. Most of the occupations associated with an increased risk of RA were occupations in which it was possible to work when the disease was present, i.e. cost accountants, estimating clerks and working proprietors in the retail trade. However, an increased relative risk of RA was also observed in some occupations where selection of RA patients out of heavy work should have biased genuinely increased relative risks towards unity. Such occupations were farmers, upholsterers, lacquerers, concrete workers, and hair-dressers. Substantial handling of organic solvents, according to the JEM, was associated with an increased relative risk.
8257029 [Familial form of rheumatoid nodulosis]. 1993 We report a familial form of rheumatoid nodulosis where the early lesions appeared in the first years of life in a young man and his son. The numerous papular and nodular skin lesions disclosed an ulcerative evolution leaving atrophic scars mainly near the limbs' joints. In both patients the evolution was characterized by the late onset of polyarthralgias and of a non-destructive seronegative polyarthritis; intra-osseous lesions were present in the metatarsal bones in the father. Rheumatoid nodulosis is a rare disease, sometimes considered as a benign variant of rheumatoid arthritis without destructive joint involvement. A serum rheumatoid factor is inconstantly present and the intra-osseous geodes have been shown to be rheumatoid nodules exhibiting the same histological structures of palisading granulomas as the subcutaneous nodules. The main symptom of the disease is the occurrence of multiple nodules followed by the delayed onset of a polyarthritis with a benign course without systemic involvement.
7569504 Comparing the bivariate effects of toxicity and efficacy of treatments. 1995 May 15 Medical studies often involve comparing the toxicity and efficacy of drugs. Separately evaluating toxicity and efficacy, the usual practice, does not correspond to how doctors manage patients and does not use the information provided in their bivariate relationship. This paper presents methods for analysing the bivariate data. One method is based on assessing the benefit for patient values to lie in different regions of the toxicity-efficacy plane. A second method includes patient thresholds for tolerating drugs. We propose dividing the toxicity-efficacy plane into regions where patients are likely to tolerate the drug. Several statistics are defined on these regions for measuring the toxic-therapeutic relationship, and the bootstrap is proposed for estimating their variances. We illustrate with treatment information available on rheumatoid arthritis patients.
7965126 Fracture of a sublaminar stainless steel cable in the upper cervical spine with neurologic 1994 Dec Sublaminar cables have been used to stabilize bone grafts for arthrodesis in the cervical spine in recent years. Previous accounts of their use have indicated no instances of breakage or neurological injury. This report is of a delayed cable fracture that resulted in penetration of the dura with neurological injury in a patient who had undergone atlantoaxial fusion for rheumatoid subluxation. The cable fracture occurred in the epidural space beneath the attempted arthrodesis and resulted in uncoiling of the cable, which penetrated spinal canal and caused a one-sided sensory deficit.
7482065 [A case of rheumatoid arthritis with malignant lymphoma taking methotrexate]. 1995 Aug We describe one case with rheumatoid arthritis who developed non-Hodgkin's lymphoma during treatment with low dose weekly methotrexate. A 73 year-old man had seropositive RA since 1974. He had been treated with several medications, including nonsteroidal antiinflammatory drugs, gold sodium thiomalate (from January, 1987), and bucillamine (from January, 1988). He presented to this hospital in April 1988, at a time when his rheumatoid arthritis worsened. Methotrexate was administered at a weekly dose of 7.5 mg orally, together with a daily dose of 5 mg of prednisone. He had had no joint-related pain and no side effects until December 1991 (total dose 1290 mg) when severe abdominal pain was started abruptly. The chest X-ray showed an abdominal free air and a diagnosis of acute panperitonitis was made. An emergency operation was carried out. There was a soft-tissue mass in the terminal of ileum which was ruptured with massive ascites. Histologic examination of the mass revealed a diffuse large cell lymphoma. The oncogenic potential of MTX and rheumatoid arthritis is reviewed.
8012254 The treatment of intracapsular hip fractures with total hip arthroplasty in rheumatoid art 1993 Summer Total hip arthroplasty was performed on 41 patients with rheumatoid arthritis for 43 intracapsular hip fractures from 1971 to 1989. Followup, observation of clinical signs, and radiographs were conducted between one to ten years. Of the 41 patients, 25 had died by the end of the study. Total hip arthroplasty was found to be effective in relieving joint pain, and the walking ability of patients generally recovered to pre-injury status following the operation. Some patients experienced deterioration of the knee and ankle joints due to rheumatoid arthritis, and in such cases there was progressive loss of walking ability. Nevertheless, the function of the hip joint was well preserved, and most patients reported that pain had disappeared and the joint range of motion had returned to normal. In only one case was revision surgery necessary. There was little overall loosening of prostheses, and there were no problems concerning the durability of the artificial joint. The presence, therefore, of femoral neck fractures in patients with rheumatoid arthritis, who are to be encouraged to get out of bed and begin walking as soon as possible, is a strong indication for total hip arthroplasty.
8934479 Clinical results of the Mayo total ankle arthroplasty. 1996 Nov Two hundred and four primary Mayo total ankle arthroplasties were performed in 179 patients at the Mayo Clinic from 1974 through 1988. We evaluated the clinical result after 160 arthroplasties in 143 patients who had been followed for two years or more (mean, nine years; range, two to seventeen years). The result was good for thirty-one ankles (19 per cent), fair for fifty-five (34 per cent), and poor for seventeen (11 per cent); fifty-seven arthroplasties (36 per cent) were considered to be a failure (defined as removal of the implant). Adequate preoperative and follow-up radiographs were available for 101 ankles (eighty-nine patients). There was radiographic evidence of loosening of eight tibial components (8 per cent) and fifty-eight talar components (57 per cent), but we found no association between the clinical and radiographic results. Complications occurred after nineteen (12 per cent) of the 160 arthroplasties, and ninety-four additional reoperations were necessary after sixty-six (41 per cent). On the basis of these findings, we do not recommend ankle arthroplasty with a constrained Mayo implant for rheumatoid arthritis or osteoarthrosis of the ankle.
1618601 Strategies for the development of new antiarthritic agents. 1992 Apr Therapeutic advances in rheumatoid arthritis (RA) have largely focused on the development of non-steroidal antiinflammatory drugs (NSAIDs) with improved characteristics compared with aspirin [Brooks & Day, New Engl. J. Med., 324, 1716-1725 (1991)]. For example, greater potency, safety, improved tolerance in the elderly and reduced frequency of dosing have been achieved. However, these agents are generally considered to be palliative treating of the symptoms of the disease. The development of disease modifying drugs (DMD), also known as second line drugs, for RA has not been very successful. Most of the agents that are currently used in this category were originally used to treat other diseases such as malignancy (cyclophosphamide, methotrexate), Wilson's disease (d-penicillamine) and tuberculosis (gold salts) [Pullar, Br. J. clin. Pharmac., 30, 501-510 (1990)]. Unfortunately, none of the agents is ideal and each has potentially serious side-effects. There have been several attempts to develop agents with new mechanisms of action that hopefully will greatly improve these current therapies.
1371728 In situ hybridization of interleukin-1 in CD14-positive cells in rheumatoid arthritis. 1992 Mar Interleukin 1 (IL-1) has been implicated as an inflammatory mediator in rheumatoid arthritis (RA). Many cell types, including macrophages, lymphocytes, fibroblasts, and endothelial cells, can produce IL-1 and it is known that IL-1 production is under transcriptional control. It has, however, been difficult to define in vivo the predominant cellular source of this mediator in RA. Here, we have used the combination of in situ hybridization of mRNA and cellular immunophenotyping with monoclonal antibodies to show that the IL-1 beta gene is expressed predominantly by CD14-positive macrophages in synovial tissue from patients with RA. Synovial macrophages were also associated with the immunoreactive IL-1 peptide. These cells appear to be the major source of IL-1 beta within the rheumatoid synovium in vivo and must be regarded as playing a central role in the chronic inflammation and joint destruction of RA.
1518750 Resurgence of rheumatic fever in the United States. The changing picture of a preventable 1992 Sep 1 The recent resurgence of rheumatic fever reported in eight locations in the United States after years of decline has several noteworthy characteristics. Most patients were children of families in high- to middle-income brackets with ready access to medical care. In four of the outbreaks, the majority of patients were adults, who were more likely than children to have arthritis and less likely to have Sydenham's chorea. Many patients had no clinical history of streptococcal pharyngitis. Rheumatic fever developed in some patients despite antibiotic treatment for streptococcal pharyngitis. Analysis of the outbreaks supports the following conclusions: No population is exempt from rheumatic fever. Physicians should be diligent in performing throat cultures in cases of suspected streptococcal pharyngitis. The efficacy of orally administered penicillin in preventing rheumatic fever should be reexamined, and oral antibiotics that are potentially more effective should be sought.