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ID PMID Title PublicationDate abstract
8886399 Contrast between effects of aminobisphosphonates and non-aminobisphosphonates on collagen- 1996 Sep 1. Bisphosphonates (BPs) are inhibitors of bone resorption, and many derivatives have been developed for the treatment of enhanced bone resorption. Aminobisphosphonates (aminoBPs) are particularly potent in this respect. We have shown previously that aminoBPs, such as 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP), induce histidine decarboxylase, the enzyme forming histamine, and increase macrophages, granulocytes and osteoclast numbers. Non-aminoBPs do not show this activity. 2. In the present study, an additional aminoBP, cycloheptyl-aminomethylene bisphosphonate (CHAMBP), was shown to have similar properties to AHBuBP suggesting that these actions are common among aminoBPs. 3. In experiments carried out to determine if aminoBPs affect immune responses, we found that CHAMBP and AHBuBP each exacerbated the arthritis induced in mice by the co-injection of type II collagen and an adjuvant, a model for rheumatoid arthritis. In contrast, dichloromethylene bisphosphonate (C12MBP), a typical non-aminoBP, did suppress the arthritis. 4. On the basis of these results, and those obtained previously, we propose that the exacerbating effects of CHAMBP and AHBuBP may be related to their ability to stimulate the synthesis of histamine and to increase macrophages and granulocytes. Conversely, we propose that the suppressive effect of C12MBP on arthritis is related to its cytotoxic action on macrophages or granulocytes.
8273568 The pharmacologic evaluation of locomotor activity versus inflammatory parameters in rat a 1993 Adjuvant-induced arthritis (AA) is an experimental model of inflammatory joint disease in the rat which mimics rheumatoid arthritis. Although paw inflammation (e.g., swelling) is commonly used to monitor the efficacy of antiarthritic drugs, a reduction in locomotor function may provide a more sensitive evaluation of "functional disability" in AA rats. The purpose of the present study was to investigate the effect of dietary therapy with prednisolone or ibuprofen on locomotor activity as well as arthritic symptoms in established AA (days 20-42). AA rats demonstrated an increase in arthritis scores, spleen weights, fibrinogen, and WBC along with a reduction in locomotor function. Prednisolone (2 mg/kg/day) exhibited a positive therapeutic effect on all these parameters. Ibuprofen (50 mg/kg/day) consistently lowered arthritis scores and fibrinogen; however, locomotor function only improved on day 35. In conclusion, the measurement of locomotor activity in concert with other experimental parameters may provide a more meaningful evaluation of disease severity or improvement in AA.
7678742 Release of cartilage macromolecules into the synovial fluid in patients with acute and pro 1993 Jan OBJECTIVE: Extensive changes in articular cartilage metabolism occur during the acute phase of reactive arthritis, as indicated by altered release of cartilage macromolecules into synovial fluid (SF) demonstrated immunochemically. Nevertheless, permanent cartilage lesions are rare in this disease. To monitor specific events during the evolution of reactive arthritis, we investigated the content of cartilage macromolecules in sequentially obtained SF samples from 22 patients. METHODS: Two groups of proteoglycan epitopes, the glycosaminoglycan-rich region of aggrecan (referred to as proteoglycan) and its hyaluronan-binding region (HABr), as well as one matrix protein, cartilage oligomeric matrix protein (COMP), were quantified by immunoassay. RESULTS: SF proteoglycan concentrations, which were initially elevated, decreased significantly with prolonged arthritis, whereas COMP levels changed less markedly and levels of HABr remained stable. There was a positive correlation between SF and serum concentrations of COMP in samples obtained during the early phase of the disease. CONCLUSION: Cartilage involvement in reactive arthritis is transient, in contrast to findings in rheumatoid arthritis. Reactive arthritis should therefore be a suitable model for studies of repair processes in cartilage, which will facilitate understanding of the pathophysiology of cartilage involvement in arthritis.
7668904 Antifibrotic action of interleukin-1 receptor antagonist in lapine monoarticular arthritis 1995 Jul OBJECTIVE: To determine if the administration of interleukin-1 receptor antagonist (IL-1ra) to animals with established antigen induced arthritis had any beneficial effects on the synovitis and cartilage destruction. METHODS: Antigen induced arthritis was induced in New Zealand White rabbits, and after two weeks IL-1ra was administered every six hours over a 72 hour period. Animals were then killed and joint tissues examined for the degree of synovitis, synovial fibrosis, and cartilage damage. RESULTS: The response of the arthritis to the treatment was minor in terms of joint swelling, leucocyte accumulation, or cartilage proteoglycan loss. However, the synovial fibrosis was not only halted by administration of IL-1ra, but reversed. The inflamed synovial linings of IL-1ra treated animals showed a significant loss of synovial collagen content and a reappearance of the synovial fat spaces which are prominent in the normal synovial lining. CONCLUSION: This study shows that IL-1ra has potent antifibrotic activity and suggests the use of this agent for the reversal of the fibroproliferative process which is so important in the pathology of rheumatoid arthritis.
1449627 [Spondyloepiphyseal dysplasia tarda with progressive arthropathy: 2 siblings affected]. 1992 Oct We described a Mexican family whose parents were consanguineous. Therefore two children were affected by a progressive arthropathy with deformity in all finger joints, restricted joint mobility and broad major joints. This condition was diagnosed like atypical juvenile rheumatoid arthritis (JRA) because the test for serum rheumatoid factors and antibodies were negative and failed to respond to anti-rheumatoid treatment. However their radiographic studies showed the spine with universal platyspondyly, enlargement epiphyses of the hands, the absence of destructive and the presence of the dysplastic bone changes. These manifestations permit us to do the diagnosis of spondyloepiphyseal dysplasia tarda with progressive arthropathy. In this report we suggest that a complete radiologic study of the patient will allowed to diagnosis this hereditary autosomal recessive entity; likewise it will let us differ of JRA and others polyarticular conditions of childhood.
8284907 [The importance of the HLA complex antigens in systemic rheumatoid diseases]. 1993 Nov The submitted paper reviews contemporary knowledge on the clinical impact of assessment of HLA-complex antigens in systemic rheumatic diseases. The authors explain the term "relative risk" and its practical importance. As to antigens of the HLA-complex class I, attention was paid in particular to the importance of HLA B 27 in ankylosing spondylitis, other spondylarthropathies and reactive arthritis; in this part the review is supplemented by results of the authors' own research. As to antigens of the HLA-complex class II, attention was paid to the sub-area DR in rheumatoid arthritis and other diffuse affections of connective tissue. The advance in knowledge of the clinical impact of investigations of selected HLA-complex antigens in systemic rheumatic diseases is that in many instances it reveals an association not only at the level of the nosological unit but frequently also sub-unit with prognostically important clinical and biochemical manifestations, a typical autoantibody profile and sometimes also with the risk of a greater organ toxicity of drugs.
8902492 The production of arthritis in beagles by an immunological reaction to bovine serum albumi 1996 Oct Arthritis was produced in beagles by the immunological reaction to bovine serum albumin (BSA). Dogs immunized with BSA showed the development of delayed type-hypersensitivity response to BSA and the significant increase in the titer of serum anti-BSA antibodies. The development of arthritis and the increase in a number of nucleated cells in synovial fluid were observed by the injection with BSA into the knee joints of immunized dogs. The synovial membrane of BSA-injected joints revealed a remarkable villous hyperplasia of membrane, and an infiltration of lymphocytes and plasma cells around vessels, resulting in a lymphoid nodule-like formation. The depositions of IgG and C3 on the surface of the synovial membrane were also observed in BSA-injected joints. Histopathological and immunopathological findings indicated that the immune response to BSA in the knee joints could induce a rheumatoid arthritis like chronic synovitis in dogs.
8060275 Free radicals, antioxidants and preventive geriatrics. 1994 Jul Despite a realisation that antioxidants will not delay ageing in healthy older people, there is increasing scientific interest in the role of free radical oxidants in a number of diseases associated with older age. For most of these diseases there is suggestive theoretical and laboratory evidence but not confirmatory clinical evidence. Free radical damage seems likely to be significant in the pathophysiology of atherosclerosis, ischaemia-reperfusion injury, Parkinson's disease, cataract, some cancers and rheumatoid arthritis. Evidence to suggest a protective effect from antioxidant vitamins exists for ischaemic heart disease, cataract and some cancers. Attempts to influence the outcome of other diseases such as ischaemia-reperfusion injury, Parkinson's disease and rheumatoid arthritis have so far failed to achieve positive results. Research interest in the field is increasing although hampered by methodological difficulties and the limited financial return for drug companies. In the meantime there seems no reason to discourage older people who wish to ingest extra vitamin E and vitamin C. A diet with adequate vegetables and fruits should provide sufficient beta carotene.
7516431 Anticytoskeletal autoantibody development in adjuvant arthritis. 1994 Mar OBJECTIVE: Because the presence of autoantibodies against cell components is a common feature of most autoimmune diseases and some of these autoantibodies have been detected in sera of patients with rheumatic diseases such as rheumatoid arthritis (RA), we studied the presence of autoantibodies to cell components in an experimental model of chronic inflammation in rats, adjuvant arthritis (AA), to determine possible similarities between AA and human RA. METHODS: Sera from arthritic rats were initially tested by indirect immunofluorescence using rat liver sections as a substrate. Afterwards, arthritis sera were further studied in cultures of human skin fibroblasts and the HEp-2 cell line, with or without colchicine treatment. RESULTS: Results using liver as substrate showed that 31% of the arthritic rats showed a cytoskeleton staining pattern throughout the cytoplasm, with higher intensity of staining along the surface membranes, particularly in pericanalicular regions. This staining was suggestive of intermediate filament autoantibodies. When sera were analyzed on cultured cells, the results showed that the pattern is identical to the arrangement described for intermediate filaments and different from those seen with antiactin antibodies. Colchicine pretreatments ruled out antitubulin activity. Further analysis by immunoblotting revealed that autoantibodies did not recognize intermediate filament proteins when these were denatured in the electrophoretic process. CONCLUSION: The development of autoantibodies to intermediate filament proteins, both cytokeratin and vimentin, has been demonstrated in sera from rats with AA, in a similar manner to that described in human RA.
8844906 Chronic neck pain. 1996 Aug The disorders most commonly seen in rheumatologic practice are acute to chronic cervical disc-related strains, radiculopathies, and degenerative spondylosis. Inflammatory disorders including ankylosing spondylitis and rheumatoid arthritis, although generally rare, are not uncommonly seen in a rheumatologic practice. The pertinent anatomic and pathologic features of cervical disorders are examined in the context of their implications for the hierarchy of specific therapeutic interventions. The basis for the usually favorable prognosis for these conditions, particularly in response to a rational, structured, and phased conservative regimen, is delineated.
7883198 Hand and wrist disorders: how to manage pain and improve function. 1995 Mar Pain, swelling, or impaired function of the hand or wrist may be the result of one of several chronic or acute conditions, including tendinitis, arthritis, infection, or trauma. The first step in diagnosing a hand or wrist disorder is a detailed history. Include a review of the medical history, as many systemic disorders (eg, psoriasis, diabetes mellitus, rheumatoid arthritis, and scleroderma) may affect the hand and wrist. In the physical exam, assess motions of the cervical spine and those of all joints in the symptomatic extremity. A simple neurologic evaluation is required to assess function of the major nerves in the upper extremity. X-rays are indicated in any patient with hand or wrist pain.
8977288 Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient m 1996 Dec Collagen-induced arthritis (CIA) is an animal model for rheumatoid arthritis. The disease is elicited by immunization of genetically susceptible DBA/1 mice with type II collagen, resulting in a debilitating arthritis characterized by inflammation and involvement of multiple joints. We investigated the role of endogenous interleukin (IL)-12 in the pathogenesis of this disease by undertaking an analysis of IL-12-deficient mice on the DBA/1 genetic background after immunization with type II collagen. Both the incidence and severity of disease were significantly reduced in mice unable to produce biologically active IL-12. Concomitant decreases were observed in serum levels of pathogenic, collagen-specific IgG2a antibodies and collagen-induced secretion of interferon-gamma by immune splenocytes in vitro, consistent with an impaired T helper-1 response. There were, however, a few animals which developed severe disease in a single paw in spite of this highly diminished Th1 response. Taken together, these results demonstrate an important role for IL-12 in the pathogenesis of CIA, although it is not absolutely required for disease development.
8843861 Patterns of expression of tumor necrosis factor alpha, tumor necrosis factor beta, and the 1996 Oct OBJECTIVE: To assess the expression of tumor necrosis factor alpha (TNF alpha), TNF beta, and their receptors in synovia of patients with juvenile rheumatoid arthritis (JRA) and juvenile spondylarthropathy (JSpA), and to determine similarities with and differences from adult RA. METHODS: Twenty-eight synovial tissue samples from patients with JRA, 6 from patients with JSpA, and 6 from patients with RA, selected for the presence of inflammatory infiltrates, were analyzed for the expression of TNF alpha, TNF beta, and their receptors (p55 and p75 TNFR), utilizing the dual approach of reverse transcriptase-polymerase chain reaction and immunohistochemistry analysis. RESULTS: The presence of both TNF alpha and TNF beta expression was demonstrated in most JRA and JSpA tissues, although samples from patients with pauciarticular JRA had somewhat lesser amounts of these cytokines. TNF beta expression correlated significantly with the occurrence of lymphocytic aggregates in tissues. Staining with monoclonal antibodies specific for the p55 and p75 receptors revealed that a diverse range of cell types expressed the receptors, with the most intense p55 staining on vascular endothelial cells. In the vast majority of synovial tissues, far greater numbers of cells expressed the p55 form of the receptor than the p75 form. CONCLUSION: JRA and JSpA synovia are characterized by the presence of TNF alpha, TNF beta, and cells expressing TNFR. These findings provide further evidence that TNF, through autocrine/paracrine mechanisms, may amplify local inflammation, leading to joint destruction. The prominence of TNF beta in the synovium in particular subgroups of JRA patients and in JSpA patients may be a distinguishing feature of these diseases.
7741497 Methotrexate in the treatment of psoriasis at the National Skin Centre, Singapore. 1994 Nov In the last 30 years, methotrexate has been used for treating psoriasis, rheumatoid arthritis and other inflammatory disorders. Much has been learned about its beneficial and adverse effects. Long-term use produces different effects from short-term use. This study was undertaken to study the long-term use of methotrexate in our local population. It is a retrospective study where the case reports of 72 psoriatic patients on methotrexate were analysed for its use, side effects, the monitoring of side effects and its efficacy. Our study showed that methotrexate was effective in 61 (86.0%) patients, had some side effects in 10 (14.2%) patients and was relatively safe. It also helped psoriatic arthropathy. However, adequate and close monitoring is required to prevent liver fibrosis and cirrhosis.
8061112 Essential involvement of interleukin-8 in neutrophil recruitment in rabbits with acute exp 1994 Apr Rheumatoid arthritis and related inflammatory joint diseases are characterized by massive infiltration of polymorphonuclear cells (PMN) into inflamed joints. Interleukin-8 (IL-8) has recently been identified as a leukocyte chemotactic and activating factor produced by activated tissue cells as well as monocytes/macrophages. Examination was made of the involvement of IL-8 in acute arthritis induced by injecting lipopolysaccharide (LPS) or interleukin-1 alpha (IL-1 alpha) into the joints of rabbits. The neutralizing antibody to rabbit IL-8 blocked almost completely the infiltration of PMN into the joints and provided protection from damage to tissue in the early phase of inflammation induced by LPS or IL-1 alpha. Mononuclear cell infiltration observed later was not inhibited by this antibody. This is the first paper to clearly demonstrate that IL-8 is an essential and major mediator determining whether PMN infiltration will occur in the early phase of experimental acute arthritis.
8877924 Incidence of osteoperiostitis of the great toe in psoriatic arthritis. 1996 Sep OBJECTIVE: To assess the incidence of osteoperiostitis of the distal phalanx of the great toe in psoriatic arthritis (PsA). METHODS: One thousand great toes (202 of PsA, 44 of cutaneous psoriasis, 274 of low back pain patients, 296 of rheumatoid arthritis, 136 of spondyloarthropathy, and 48 of connective tissue diseases) were studied for osteoperiostitis of the distal phalanx of the great toe (slight, moderate, or severe), destructive joint lesions of the feet, nail dystrophy, fungal infection, and HLA-B type (patients with PsA). RESULTS: Osteoperiostitis was observed in 92 great toes. Moderate and severe osteoperiostitis were observed only in PsA. Osteoperiostitis was statistically more frequent in PsA (53/202, 26.2%, especially in those with onychosis: 20/41, 48.8%) than in other groups (39/798, 4.9%) (p < 0.01). In PsA, osteoperiostitis was more frequent in patients with nail dystrophy (20/41, 48.8%) than in patients without (33/161, 20.5%) (p < 0.05). Fungal infection of the nail and HLA haplotype were not associated with osteoperiostitis. In patients with PsA, osteoperiostitis was associated with destructive joint lesions of the feet. CONCLUSION: Osteoperiostitis of the distal phalanx of the great toe is an enthesopathy evocative of PsA.
8056966 Familial positive ulnar variance with secondary radioulnar joint arthritis and extensor te 1994 May A familial pattern of extensor tendon ruptures due to distal radioulnar osteoarthritis with underlying positive ulnar variance is described. Spontaneous ruptures occurred in four members of the family (one woman and three men) in middle age. Laboratory data did not indicate any sign of rheumatoid arthritis. All cases revealed significant positive ulnar variance and distal radioulnar osteoarthritis. Younger members of the family demonstrated positive ulnar variance although without osteoarthritic changes. The tendon ruptures presumably resulted from a hereditary disorder in conjunction with degenerative changes brought about by age.
7848311 Serum cytokines in juvenile rheumatoid arthritis. Correlation with conventional inflammati 1995 Feb OBJECTIVE: To examine the usefulness of determining extended serum cytokine profiles in patients with juvenile rheumatoid arthritis (JRA), for the purpose of improving differential diagnosis and monitoring disease activity. METHODS: In a 2-year prospective study, serum levels of interleukin-1 beta (IL-1 beta), soluble IL-2 receptor (sIL-2R), IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and the p55 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme-linked immunosorbent assay in 40 patients with JRA, 13 patients with postinfectious arthropathies, and 30 healthy controls. The data were compared with conventional parameters of inflammation, such as C-reactive protein (CRP), iron and hemoglobin levels, erythrocyte sedimentation rate (ESR), white blood cell (WBC) counts, and platelet counts. WBC subsets were analyzed by flow cytofluorometry. RESULTS: At the first visit and at the peak of inflammatory activity according to CRP levels and/or ESR, serum levels of sIL-2R, IL-6, and sTNFR in JRA patients correlated significantly with conventional inflammation indicators, whereas IL-1 beta, IL-8, and TNF alpha did not. No changes in leukocyte subset distribution were noted. Among the different clinical subtypes of JRA, sIL-2R, IL-6, and sTNFR values at the time of the initial visit showed a pattern similar to CRP, whereby patients with systemic disease exhibited by far the highest values. TNF alpha and IL-1 beta were variably elevated in certain JRA subtypes. Patients with postinfectious arthropathies showed elevated levels of CRP, sIL-2R, TNF alpha, and sTNFR, which did not differ significantly from levels in the various JRA subtypes with the exception of systemic disease. Detailed analysis of types I and II pauciarticular JRA revealed that levels of CRP, IL-1 beta, and TNF alpha were elevated in patients with type I disease. While these parameters were invariably normal in patients with type II disease, sTNFR and sIL-2R were still found to be significantly elevated. Followup studies suggested that persistently high sTNFR values are a better indicator of JRA activity than are measurements of other cytokines or CRP. CONCLUSION: JRA is associated with significant and consistent changes in serum levels of inflammatory cytokines and soluble receptors. For the clinical monitoring of JRA, determination of levels of sTNFR, and to some extent sIL-2R, may be particularly useful, since these determinations yield information about subtype and/or activity of disease that is not available from conventional parameters of inflammation.
8799028 A case of adult onset Still's disease presenting with fever and a rash. 1996 Mar Adult onset Still's disease is a rare condition presenting with high spiking fever, transient maculopapular rash, myalgias, polyarthralgias or arthritis, lymphadenopathy, hepatosplenomegaly and a sore throat, associated with leucocytosis and neutrophilia. Early diagnosis is difficult because clinical features are non-specific. We report a 33-year-old Chinese female with this condition who presented with recurrent high spiking fever and rash over a 4-month period. We highlight the sequence of events leading to this diagnosis with emphasis on the cutaneous changes.
8761792 [Pulmonary manifestations of primary Gougerot-Sjögren syndrome. Apropos of 8 cases in a s 1996 Clinical, roentgenologic, functional and broncho-alveolar lavage features of lung involvement in primary Sjögren's syndrome were assessed in a retrospective study of 35 cases. Diffuse interstitial patterns on chest radiography were present in six patients and alveolar patterns were suggestive of lymphoid interstitial pneumonitis or pseudolymphoma in two. Acute and febrile onset mimicked infectious pneumonitis in three patients when dyspnea was the most common clinical feature in others. Patients with primary Sjögren's syndrome and pulmonary disease were older (65 vs 56 years) (P = 0.025), have more frequently extra-glandular manifestations (P = 0.03), keratoconjunctivis sicca (P = 0.018) and biological perturbations (hypergammaglobulinemia (P = 0.03), antinuclear antibodies (P = 0.01) than those without lung involvement. Low diffusion capacity was present in seven patients associated twice to small airways obstruction. Bronchoalveolar lavage revealed in all cases an increased total cells count (mean: 6.96 10(5)/mm3) and a lymphocytic alveolitis (range: 11 to 66%; mean: 38%) associated with an elevated percentage of alveolar neutrophils in four patients. A low CD4/CD8 ratio was related to a pejorative issue. Treatment consisted in corticotherapy combined with oral cyclophosphamide in case of pseudolymphoma.