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ID PMID Title PublicationDate abstract
8000441 Some biochemical and pharmacological aspects of free radical-mediated tissue damage. 1994 May Living in aerobic conditions carries a risk of oxidative stress, in connection with free radical deleterious action on tissues and cells. Free radical mechanisms have been implicated in the pathogenesis of many diseases, as well as in host defense against various invading microorganisms. A substantial body of evidence has been reported on free radical involvement in inflammation, ischaemia/reperfusion injury, atherosclerosis and many other pathologies. The aim of this paper is to review selected literature and opinions concerning free radical-induced damage to tissues and to present xenobiotic contribution to oxidative stress.
1481580 [Characteristics of pharmacotherapy of rheumatic diseases in advanced age]. 1992 Nov Drug treatment in the polymorbid elderly should focus on the more important symptoms. Pharmacokinetic differences should be considered, e.g. a reduced volume of distribution and decreased liver and renal function. Special alterations in the pharmacodynamics with respect to the central nervous system and other organs are important. Drug therapy in the elderly has to be done very cautiously. The indication, dosage and duration of therapy has to be evaluated again and again. Antirheumatics in the elderly should improve the quality of life avoiding untowanted side effects, especially of the gastrointestinal tract, the renal function and bone marrow. Non-narcotic analgesics and opioids may be helpful, when antirheumatics were not tolerated.
8651986 Synergy between T cell receptor beta gene polymorphism and HLA-DR4 in susceptibility to rh 1996 Jun OBJECTIVE: To investigate the etiologic significance of germline polymorphisms in the T cell receptor beta variable region 6S7 (TCRBV6S7) gene segment and adjacent loci in susceptibility to rheumatoid arthritis (RA). METHODS: Ten TCRB allelic polymorphisms were analyzed from 3 groups of white women: 112 with RA, 72 with systemic lupus erythematosus, and 70 healthy controls. All participants were also HLA typed. RESULTS: HLA-DR4+ RA patients showed significantly increased frequencies of TCRBV6S7*1, 13S5P*1 (an allelic variant of BV13S5 promoter), and 12S4*2, compared with healthy controls. The combination of DR4 with either BV6S7*1, 13S5P*1, or 12S4*2 conferred greater risk for RA than HLA-DR4 alone. Pairwise analyses showed a high degree of linkage disequilibrium (P = 10(-5)-10(-8)) between these 3 TCRBV loci that span 47 kilobases (kb). CONCLUSION: Our data suggest that a TCR gene segment in or linked to this 47-kb region may be involved in genetic susceptibility to RA through an interaction with HLA-DR4.
8146789 [The choice of the method for intravascular laser therapy in rheumatoid arthritis]. 1994 A randomized placebo-controlled study was made of the clinical efficacy of four different methods of intravascular laser blood irradiation (ILBI) with helium-neon laser in 150 patients suffering from rheumatoid arthritis (RA). As to ILBI methods used, the most remarkable clinical effect was produced by daily procedures. The positive effect of ILBI was of liminal character bearing in mind the power range examined whereas the negative effect of irradiation was dose-dependent. ILBI may cause an exacerbation of the inflammatory process in RA whatever the single dose and frequency of procedures. The best clinical effect with daily ILBI was attained in women, individuals with the presence of rheumatoid factor but with low titers thereof, and in patients with initial stages of RA and minimum inflammation activity. The efficacy of ILBI may be predicted on the basis of the patient's clinical findings.
1494440 Treatment of scleromalacia perforans with dura mater grafting. 1992 Dec We describe, to our knowledge for the first time in the English literature, the successful use of cadaveric dura mater in reinforcing the sclera in a rheumatoid arthritis patient with scleromalacia perforans.
8572738 Relationship between genotype for the cytochrome P450 CYP2D6 and susceptibility to ankylos 1996 Jan OBJECTIVES: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to ankylosing spondylitis (AS) and rheumatoid arthritis (RA), or linked with any specific clinical or familial features of the two conditions. METHODS: CYP2D6 genotypes were determined in 54 patients with AS, 53 patients with RA, and 662 healthy controls. Leucocyte DNA was analysed for the presence of mutations by restriction fragment length polymorphism analysis with the restriction enzyme Xbal and by two separate polymerase chain reaction assays. RESULTS: On the basis of odds ratio (OR), individuals with two inactive CYP2D6 alleles were more susceptible to AS than controls (OR 2.71, 95% confidence interval (CI) 1.04 to 7.08), with a stronger effect for the CYP2D6B allele (OR 4.11, 95% CI 1.54 to 11.0). No significant differences in the distribution of overall genotypes and allele frequencies were observed between RA and controls. No significant relationships were found between the skeletal, extraskeletal or familial features of AS or RA (iritis, psoriasis, inflammatory enteropathy and rheumatoid nodules, kerato-conjunctivitis sicca, pleuritis, rheumatoid and antinuclear factors) and the overall genotype. CONCLUSIONS: Our findings suggest a modest association between homozygosity for inactive CYP2D6 alleles, particularly CYP2D6B alleles, and susceptibility to AS. However, our results fail to demonstrate a genetic link between CYP2D6 genotype and RA.
8099519 Optimizing the assessment of disease activity during treatment with anti-rheumatoid drugs. 1993 Jun Clinical trials in RA usually involve the use of several laboratory assessments of disease activity. Their use is not universal and the relative value of many novel assessments has not been determined in relation to existing clinical and laboratory methods. This study attempts to investigate the value of established and novel assessments of disease activity during treatment with accepted DMARDs. Over a 48-week study period, changes in cytidine deaminase (CD), beta 2-microglobulin, alpha 1-acid glycoprotein (alpha 1-AGP), serum antibodies to Clostridium perfringens alpha-toxin, pre-albumin and caeruloplasmin were compared to a group of established clinical and laboratory assessments including plasma viscosity, CRP haemoglobin and platelet count during treatment with the established second-line drugs, D-penicillamine (n = 20), sulphasalazine (n = 17), gold (n = 12) and hydroxychloroquine (n = 18). Overall, the assessments showing the greatest degree of change were plasma viscosity, articular index, summated change score, platelet count, CD, white cell count, alpha 1-AGP, CRP and pain score. The assessments showing the greatest degree of change were not homologous between the treatment groups and no single assessment was outstanding for a particular drug treatment.
8467620 Lymphoma developing in a patient with rheumatoid arthritis taking methotrexate. 1993 Mar We report one case of non-Hodgkin lymphoma in a patient, with a 30-year history of rheumatoid arthritis, taking low dose methotrexate weekly over a 10-month period. The mild immunosuppression that occurs with methotrexate therapy probably places patients with rheumatoid arthritis at added risk of developing lymphoproliferative diseases, but coincidence cannot be excluded.
1502565 Cyclosporine in rheumatoid arthritis: documented efficacy and safety. 1992 Jun The experience from eight open studies and five controlled trials of cyclosporine in rheumatoid arthritis is reviewed. A therapeutic approach characterized by low initial doses and slow upward titration appears to minimize the toxicity while retaining sufficient amounts of the efficacy seen with higher doses, although the onset of benefit is slower. In short-term studies, renal dysfunction and other side effects appear to be reversible. However, studies of combinations of cyclosporine and other slow-acting agents, long-term studies, and more renal biopsy specimens are needed to determine the appropriate use of this agent. Cyclosporine holds promise as an important addition to the therapeutic armamentarium for patients with rheumatoid arthritis.
8880834 Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification. 1996 Aug The hypervigilance model of pain perception states that chronic pain patients have a heightened sensitivity to pain (e.g. low threshold and tolerance) because of increased attention to external stimulation and a preoccupation with pain sensations. This study tested the hypothesis that individuals with fibromyalgia, a chronic pain disorder of undetermined origin, have a generalized hypervigilant pattern of responding that extends beyond the pain domain. Twenty fibromyalgia out-patients, 20 rheumatoid arthritis (RA) patients, and 20 normal controls served as subjects. The RA and normal control subjects were age and sex matched to the fibromyalgia patients. Subjects were tested for pain tolerance, pain threshold, and noise tolerance and were asked to complete a number of questionnaires that assessed hypervigilance. As predicted, the responses of the fibromyalgia patients to both the pain and auditory stimuli were consistent with the generalized hypervigilance hypothesis. These patients had significantly lower threshold and tolerance values than the RA patients, who in turn, had lower values than the normal control subjects. The results of the psychological questionnaires revealed that the fibromyalgia and RA patients preferred lower levels of external stimulation than the control subjects. The outcome of this study supports the generalized hypervigilance hypothesis, suggesting that fibromyalgia patients have a perceptual style of amplification. The implications of these findings for understanding the role of biological, cognitive, and perceptual factors in pain disorders are discussed.
8015285 Excess of metalloproteases over tissue inhibitor of metalloprotease may contribute to cart 1994 Jun BACKGROUND: In an attempt to identify the factor(s) involved in the modulation of the degradative pathway of articular cartilage, we previously reported a possible imbalance between the levels of biologically active forms of metalloproteases and tissue inhibitor of metalloprotease (TIMP) in osteoarthritis (OA) cartilage. EXPERIMENTAL DESIGN: We extended our analysis on the protein level and the synthesis of stromelysin-1, collagenase, TIMP-1, and TIMP-2 in normal, OA, and RA cartilages, and provided information on the synthesis pattern of these proteins in respect to the action of interleukin-1 (IL-1). These protein concentrations were determined by specific sandwich EIA assays. RESULTS: This study allowed us to establish that the concentration of stromelysin-1 and collagenase is elevated in both OA and rheumatoid arthritis (RA) cartilages when compared with normal, with significantly higher levels of collagenase found in OA (p < 0.0003) and RA (p < 0.0001), and of stromelysin-1 in RA (p < 0.02). In all cases, the level of stromelysin-1 significantly exceeded (a few 100-fold) the collagenase level. The cartilage TIMP-1 level was notably enhanced only in RA, whereas TIMP-2 was increased in both OA and RA cartilage. RA patients with active disease had a higher level of metalloproteases and TIMP than those patients with inactive disease. Moreover, patients taking steroids alone or in combination with methotrexate had a markedly lower metalloprotease level without any changes in the TIMP-1 level. In culture cartilage explants, the synthesis of stromelysin-1 was enhanced in RA cartilage, whereas the level of collagenase was increased both in OA and RA explants. When compared with normal patients, the TIMP-1 synthesis was essentially unchanged in arthritic explants, whereas the level of TIMP-2 was decreased in RA explants when compared to OA. IL-1 induced a statistically significant increased synthesis of metalloproteases with the highest level found in arthritic explants. IL-1 also significantly decreased the TIMP-1 synthesis in OA and RA explants, and the TIMP-2 synthesis in OA. CONCLUSIONS: This study demonstrates that stromelysin-1 is the predominant metalloprotease synthesized in human articular cartilage and that both TIMP-1 and TIMP-2 are present in this tissue. The differential regulation of metalloprotease and TIMP syntheses by IL-1 suggests that this cytokine, during inflammatory conditions, may promote cartilage degradation by creating an imbalance between the level of these enzymes and their inhibitors.
7612413 T and B cell-dependent pathways in rheumatoid arthritis. 1995 May T and B cells remain important in the development of rheumatoid arthritis. Recent data indicate that the involvement of T cells is more complex than recognizing an arthritogenic antigen in synovia. Attempts to characterize and isolate proliferating synovial T cells have not led to a better understanding of the postulated antigen-recognition events in synovia. Experimental systems in which implants of rheumatoid synovia in severely immunocompromised mice were analyzed have shown that the T cell infiltrate does not persist, emphasizing that tissue inflammation is not a functional unit but is highly dependent on the peripheral T cell repertoire. In this compartment of circulating T cells, rheumatoid arthritis (RA) patients appear to have major abnormalities. CD4+ T cells in the blood are clonally expanded, and these clonotypes penetrate into the tissue but are not enriched compared with those in the circulation. Studies of CD8+ circulating cells also demonstrate clonal expansion. CD8 clonotypes appear to be present in healthy individuals, however, less frequently than in RA patients. Taken together, the role of T cells in RA seems to not be restricted to the joint, and their pathogenetic role may extend beyond antigen recognition in the joint. Convincing evidence has been provided that rheumatoid factor (RF) immunoglobulins can be somatically mutated, suggesting antigen selection as a driving force of RF production. However, most of the immunoglobulins with RF specificity in RA patients are in germline configuration. Emerging data support the concept that RF+ B cells normally do not secrete antibodies and antigen nonspecific stimuli may contribute to the induction of RF release in RA.(ABSTRACT TRUNCATED AT 250 WORDS)
8721495 Flare-up at contact allergy sites in a gold-treated rheumatic patient. 1996 Jan Contact allergy to gold sodium thiosulfate and gold sodium thiomalate was established by skin testing in a rheumatic patient intended for gold therapy. An intramuscular test dose of gold sodium thiomalate (Myocrisin) induced a flare-up of previously positive epicutaneous and intradermal test reactions, with a histological and immunohistochemical picture compatible with an allergic contact dermatitis. Since gold allergy is frequent, the cutaneous side-effects of gold therapy ("gold dermatitis") may be explained by such an immunopathological reaction.
7641477 Squatting following total knee arthroplasty. 1995 Apr This prospective study was performed to investigate whether postoperative alternate flexion and extension splinting (daily change in position of immobilization by splinting) was useful in restoring full range of motion (ROM) after total knee arthroplasty as compared with continuous passive motion. The alternate flexion and extension splinting group and the continuous passive motion group were each composed of 34 knees. Final ROM was measured at an average of 3.5 years postoperatively. Squatting was possible in 31 knees (45.6%) of the alternate flexion and extension splinting group. The postoperative ROM of the osteoarthritic knees (131.8 degrees +/- 12.3 degrees) was significantly greater than that of the rheumatoid knees (121.9 degrees +/- 22.4 degrees) (p < 0.05). The postoperative ROM of the alternate flexion and extension splinting group (135.1 degrees +/- 11.9 degrees) also was significantly greater than that of the continuous passive motion group (120.0 degrees +/- 19.7 degrees) (p < 0.01). There was no statistically significant relationship between the posterior slope of tibial cutting and the postoperative ROM. It is suggested that alternate flexion and extension splinting is effective in restoring full ROM after total knee arthroplasty.
1386092 IL-1 receptor antagonist protein production and gene expression in rheumatoid arthritis an 1992 Aug 1 IL-1 can participate in the perpetuation of arthritis through direct stimulation of synoviocytes and augmentation of matrix degradation. Hence, local production of the IL-1R antagonist protein (IRAP) might be an important negative feedback signal that regulates synovitis. We assessed synovial IRAP production in synovia from 30 individuals, by using a specific mAb and the immunoperoxidase staining method. IRAP was detected in 11 of 12 rheumatoid arthritis (RA) synovial tissues (ST) and was located primarily in the sublining, particularly in perivascular regions enriched for macrophages. Some staining was observed in the intimal lining of the synovium, although this was significantly less than in the sublining (p less than 0.05). Nine of 12 osteoarthritis (OA) tissues were positive for IRAP. In contrast to RA, the staining was observed primarily in the synovial lining in OA, with only minimal sublining IRAP being detected. Synovia from four patients without arthritis were negative (three autopsy specimens and one post-traumatic sample). Of the other two patients with miscellaneous diagnoses, one sample was negative (tenosynovitis) and one was positive (seronegative inflammatory arthritis) (sublining). Studies of serial sections and double-immunostaining experiments indicated that macrophages are the major cells containing immunoreactive IRAP. IRAP gene expression in vivo was determined by performing in situ hybridization on ST from 17 arthritis patients. RNA sense IRAP probes did not hybridize to any tissues. Anti-sense IRAP probes bound to two of nine RA tissues, two of six OA tissues, one of one seronegative inflammatory arthropathy tissue, and none of one flexor tenosynovitis tissue. As with immunoreactive protein, IRAP mRNA was primarily localized to cells in the synovial lining in OA but was more prominent in perivascular lymphoid aggregates in RA and seronegative inflammatory arthropathy. Northern blot analysis was performed on RNA isolated from nine ST. The appropriately sized IRAP band was identified in six of nine samples (five of six RA and one of three OA). Supernatants from cultured RA and OA ST cells contained immunoreactive and biologically active IRAP. Hence, IRAP gene expression and protein production occur in RA and OA synovium, albeit in different distributions.
8849371 Neutrophil trafficking into inflamed joints in patients with rheumatoid arthritis, and the 1996 Feb OBJECTIVE: To investigate the trafficking of circulating blood neutrophils and synovial fluid neutrophils in rheumatoid arthritis (RA) patients and the influence of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP). METHODS: Neutrophils were isolated from the circulation and from the knee synovial compartments of subjects with RA. Circulating neutrophils were labeled with technetium-99 hexametazime (99mTc-HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled from indium-111 oxine and reinjected into the knee from which they were isolated. Gamma camera images were obtained at intervals up to 24 hours post MP. Each patient had a baseline study (no MP) and a study in which MP was administered either 4 hours before (2 patients), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after (6 patients) injection of the radiolabeled neutrophils. Subsequent analysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time. RESULTS: Nine patients who had not received glucocorticoids in the previous 3 months were studied. MP significantly decreased neutrophil ingress in 13 of the 16 knees studied (almost total inhibition in 5 knees), and this occurred within 1.5 hours of MP administration in all except 1 knee. At 24 hours after MP administration, there was a significant increase in visual analog scale (VAS) scores for well-being and significant decreases in scores on the modified Health Assessment Questionnaire (P<0.05), tender joints (P<0.005), VAS for pain (p<0.005), and generalized stiffness (P<0.005), as well as a decrease in the C-reactive protein level (P<0.05). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no effect on neutrophil ingress. The other patient showed no neutrophil ingress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis. CONCLUSION: Neutrophil ingress into and egress from inflamed joints can be accurately monitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress into inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.
7794975 Predictors of hand function in patients with rheumatoid arthritis. 1995 Mar OBJECTIVES: The aims of this study were to determine: (1) what factors predict patient self-estimated hand function; (2) what factors predict actual hand function; and (3) the relationship among actual hand function, patient estimates of hand function, and self-assessed activities of daily living (ADL). METHODS: Fifty-two patients with rheumatoid arthritis completed wrist and hand mobility measures, grip strength, pain, stiffness, and estimated hand function tests, along with the Sollerman Grip Function Test (actual hand function), Health Assessment Questionnaire (HAQ), and subscales of the Arthritis Impact Measurement Scales (AIMS). RESULTS: Grip strength and stiffness were the strongest predictors of self-estimated hand function. Flexion and extension deficits in digits II through V were the strongest predictors of actual hand function. Actual hand function and self-estimated hand function were significantly correlated with each other and with the HAQ and AIMS subscales. CONCLUSIONS: Measures of deficit are the most useful in predicting actual hand function, whereas measures of strength and flexibility are most useful for estimated hand function.
7798101 Patellofemoral complications following total knee arthroplasty. Correlation with implant d 1995 Apr Results of 211 total knee arthroplasty operations were retrospectively evaluated to identify patients with knees at greatest risk for the development of patellofemoral complications and to determine the incidence and type of patellofemoral complications associated with different patellar implants. Patellofemoral complications occurred in 27 knees (12.8%). Osteoarthritis and obesity were associated with an increased incidence of patellofemoral problems. Significantly higher rates of patellofemoral complications were noted with metal-backed patellar implants and with patellar components implanted without cement. The loosening rate with cementless fixation was 13.5%. The lowest rate of patellofemoral complications following total knee arthroplasty was obtained with all-polyethylene domed patellar components implanted with cement.
7732482 [Amyloidosis of the small intestine secondary to rheumatoid arthritis and juvenile rheumat 1995 Feb We herein report two cases of gastrointestinal amyloidosis, secondary to juvenile rheumatoid arthritis (JRA) in one, and rheumatoid arthritis (RA) in the other. A 21-year-old woman, who has been suffering from JRA for the past 12 years, was transferred to our hospital due to intense pain in the epigastrium and back, diarrhea, high fever, and paralytic ileus. Treatment by corticosteroid, antibiotics, protease inhibitor, and total parenteral nutrition was not effective. The laparoscopic surgery was performed because of repeated melena followed by an episode of hypovolemic shock. The resected specimen of the ileum showed histologically marked amyloid deposition in the arteriolar walls. A 83-year-old man with RA for 14 years, was admitted to our hospital with complaints of abdominal pain, nausea, and diarrhea. He underwent an emergency operation for perforation of the ileum. The resected specimen revealed amyloid deposition and non-caseating granulomas. The fragility and impaired blood supply caused by amyloid deposition in the vascular walls may have terminated in the severe intestinal lesion. Further clinicopathological studies along this line are keenly desired in order to establish therapeutic modalities for gastrointestinal amyloidosis.
8342046 Lymphatic disorders in rheumatoid arthritis. 1993 Jun Lymphedema is a rare complication of rheumatoid arthritis (RA). Diagnosis is clinical: long-standing, painful swelling of a whole limb in association with RA. Cases described in the literature are predominantly of the upper limbs, sometimes bilateral. Diagnosis can be confirmed by biopsy of lymph nodes, lymphography, or preferably lymphoscintigraphy. The etiology of the edema is unknown. Mechanical obstruction and lymphangitis have been suggested. Pharmacological and surgical treatment of the edema have been disappointing, and treatment of the underlying RA does not improve the lymphedema. Physical treatment of the affected limb, such as massage, manual drainage techniques, light compression bandaging, and exercise, has been moderately effective.