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Biomedical subjects

J Highton

Publications and source records attributed to J Highton.

At least 37 records · Page 2Linked to original sources

Video image analysis of hands: development of an 'anatomic index' as a potential outcome measure in rheumatoid arthritis.

In this study, we used video image analysis for the measurement of hand dimensions to reflect destructive changes in rheumatoid arthritis. Thirteen dimensions were measured from anteroposterior and lateral views of the hands, open and closed. Comparison of measurements in 19 patients and 19 control subjects showed significant differences for nine of the 13 measurements. Five were reproducible on retesting in a subset of patients and normals. Two were eliminated because they were similar to other measurements. The three remaining measurements selected for differentiation of patients and normals, and reproducibility, were combined in an arbitrary 'anatomic index'. This enhanced separation of normals and patients with rheumatoid arthritis. The results demonstrate that measurement of certain hand dimensions and their combination in an 'anatomic index' could provide a measure reflecting the progressive anatomical abnormality caused by rheumatoid arthritis. Validation of this concept could provide a further outcome measure in patients with rheumatoid arthritis.

Aged↗

Changes in the phenotype of monocytes/macrophages and expression of cytokine mRNA in peripheral blood and synovial fluid of patients with rheumatoid arthritis.

Data from a previous study suggested that peripheral blood monocytes in patients with rheumatoid arthritis (RA) may be activated. Therefore, in this study we sought further evidence of 'presynovial' activation of monocytes. Our results show that phenotypic changes are demonstrable in peripheral blood monocytes in patients with RA, including increased expression of CR3 (CD11b/CD18) and FcRI (CD64). However, changes are most extensive in synovial monocytes/macrophages and especially for HLA-DR and intercellular adhesion molecule-1 (ICAM-1) (CD54). We conclude that monocyte/macrophage activation is most evident within the joint, and that 'presynovial' changes occur but are of limited extent.

Adult↗

Differential relationships between stress and disease activity for immunologically distinct subgroups of people with rheumatoid arthritis.

Immunologically distinct subgroups of patients with rheumatoid arthritis (RA)--those with the autoantibody rheumatoid factor (seropositive RA) and those without (seronegative RA)--were compared on a variety of clinical and self-report measures in a consecutive series of women with disease of 7 years' or less duration. The groups were comparable on clinical, pain, functional, and psychosocial variables. However, the seronegative RA group reported elevated levels of preonset negative life event stress. Postonset life event stress and disease activity were significantly correlated for the seronegative RA group, but not for the seropositive RA group. Results suggest that stress factors may be more important in the etiology and maintenance of seronegative RA and that the seronegative RA group may possibly derive particular benefit from psychological techniques to enhance stress management skills.

Adult↗

A self-report articular index: relationship to variations in mood and disease activity measures.

Self-report can provide an inexpensive method for monitoring disease activity or treatment response in RA, but may be affected by confounding variables such as the patient's mood. The relationship of a self-report articular index (AI) to other relevant parameters was assessed from data gathered at approximately monthly intervals from 16 women with RA. Statistical analysis showed that the AI covaried most strongly with other measures of disease activity and functional disability, while mood variables and ESR covaried separately. These results indicated that responses on the self-report AI paralleled disease activity, and were not merely an artifact of variations in the patient's mood.

Adult↗

A search for Chlamydia trachomatis in synovial fluids from patients with reactive arthritis using the polymerase chain reaction and antigen detection methods.

A polymerase chain reaction (PCR) technique to detect Chlamydia trachomatis DNA was used to examine synovial specimens from patients with reactive arthritis. We were able to detect C. trachomatis DNA in synovial specimens which had been seeded with intact elementary bodies or chlamydial DNA. However, we were unable to detect chlamydial DNA in unseeded synovial specimens from 10 patients with sexually acquired reactive arthritis, 17 patients with reactive arthritis and 11 control patients with other arthropathies. In addition, using a monoclonal antibody technique, we were unable to detect chlamydial antigen in any of the synovial cell deposits examined. We conclude that C. trachomatis DNA was not present in the joints of these patients at the time of synovial fluid collection, and suggest that either DNA degradation occurred rapidly after viable chlamydiae had entered the joint or that chlamydial DNA was not present at any stage of the reactive response.

Antigens, Bacterial↗

Immunohistochemical analysis of synovial membranes from inflammatory and non-inflammatory arthritides: scarcity of CD5 positive B cells and IL2 receptor bearing T cells.

Rheumatoid Arthritis (RA) synovial membranes were examined by single and dual immunohistological techniques with a number of monoclonal antibodies against lymphocyte and macrophage related antigens. CD4 positive T lymphocytes frequently expressed MHC Class II antigens and were found in sublining collections in close association with activated macrophages as well as B lymphocytes. CD8 positive T cells surrounded these collections as well as being scattered throughout the membrane and also frequently expressed MHC Class II antigens. IL2 receptor (IL2r) expression on T cells and CD5 expression on B cells were rarely seen in these synovial membranes. Similar immunohistological architecture was found in synovial membranes from patients with psoriatic arthritis (PA) and Reiter's Syndrome (RS). Normal synovium contained few T cells, with few cells expressing MHC Class II antigens. Synovium from osteoarthritis (OA) patients also demonstrated similar immunohistological changes to those found in inflammatory arthritides, suggesting that there are only quantitative rather than qualitative differences between the synovial membrane immunohistological architecture from patients with inflammatory and noninflammatory arthritides.

Adult↗

Phenotypic markers of lymphocyte and mononuclear phagocyte activation within rheumatoid nodules.

We investigated rheumatoid subcutaneous nodules using monoclonal antibodies recognizing functional determinants on mononuclear phagocytes (Mph) and lymphocytes. Mph at the center of rheumatoid nodules showed strong expression of the leukocyte intergrins CR3 and p150,95 which would be consistent with the presence of a central chemotactic stimulus. Mph expression of FcR1, a gamma interferon regulated molecule, was decreased in 5/13 cases despite strong expression of MHC class II. There was a variable unstructured infiltrate of T lymphocytes, a majority of which were CD8 positive. Lymphocytes showed increased MHC class II expression but interleukin 2 receptor expression was low. We discerned no relationship between the number, distribution or phenotype of the T cell infiltrate and the phenotype of the predominant Mph population.

Adult↗

Increased expression of p150,95 and CR3 leukocyte adhesion molecules by mononuclear phagocytes in rheumatoid synovial membranes. Comparison with osteoarthritic and normal synovial membranes.

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.

Adolescent↗

Development of the gout tophus. An hypothesis.

Sequential stages have been demonstrated in the development of individual focal deposits of crystalline urate and associated cell infiltrates within subcutaneous gout tophi. The findings suggest that acini of macrophages are formed and that active cellular transport of urate from the interstitial fluid into the central zones of these structures accounts for the focal nature of crystallization within the tophus. This process seems to account for the formation of focal urate deposits up to some 1.5-2 mm in diameter. The corona then commonly disappears and adjacent deposits may fuse. These events may lessen the consequences of hyperuricemia.

Aged↗

Cells of the monocyte-macrophage series in peripheral blood and synovial fluid in inflammatory arthritis. A preliminary study of cellular phenotype.

The phenotype of peripheral blood and synovial fluid cells of the monocyte-macrophage series was studied by FACS to extend previous immunohistological observations made in synovial membranes. The results of this preliminary study suggest that changes can be found in peripheral blood monocytes which might influence diapedesis and interaction with immune complexes. The phenotype of synovial fluid macrophages does not provide evidence of advanced maturation and is most consistent with rapid recruitment of the cells into the joint. Synovial fluid macrophages showed increased expression of the leukocyte integrin p150.95 which functions as an adhesion molecule and complement receptor. This is consistent with our previous observation of upregulation of this molecule on Mph in inflamed synovial membranes. This preliminary study has indicated areas for more detailed analysis with the aim of defining sequential changes in macrophage expression of functional surface molecules in inflammatory arthritis.

Adult↗

Quantification of macrophage cell surface molecules in rheumatoid arthritis.

The response of macrophages to stimulation by interferon-gamma (IFN-gamma) in vitro is characterized by an increase in the cell surface expression of MHC class II HLA-DR antigen (HLA-DR) and the high-affinity Fc-receptor for immunoglobulin G (FcRI) while the expression of the C3b-receptor (CR1) is reduced. Based on these observations, we have examined further the possibility that IFN-gamma may modulate the activation of mononuclear phagocytes (Mph) in patients with rheumatoid arthritis (RA). As reported by others, we found low levels of IFN-gamma in the synovial fluid of these patients (less than 0.3 IU/ml using radioimmunoassay). As an alternative means of establishing whether Mph are influenced by levels of IFN-gamma too low to measure directly, we have quantified the expression of membrane associated HLA-DR, FcRI and CR1 on cell populations isolated from synovial fluid and peripheral blood. The expression of these molecules by Mph is known to be influenced by IFN-gamma. We found that Mph isolated from the synovial fluid of patients with RA showed a significantly increased HLA-DR expression. Significantly less CR1 was associated with the synovial fluid Mph than with peripheral blood monocytes. However the expression of the FcRI by the synovial fluid Mph and peripheral blood monocyte populations was similar. The quantitative changes in HLA-DR and CR1 expression by synovial fluid Mph (but not those of FcRI) were consistent with those seen following IFN-gamma activation of monocytes in vitro. While these results indicate that IFN-gamma may have a role in activating the Mph present in synovial fluid, the apparent independent regulation of FcRI observed suggests other mediators may also be involved.

Antigens, Differentiation↗

A double blind comparison of tiaprofenic acid with placebo.

The results of a double blind crossover comparative trial of the nonsteroidal antiinflammatory drug tiaprofenic acid with placebo in the treatment of rheumatoid arthritis are reported. Tiaprofenic acid was confirmed as being an effective drug of this class and no untoward side effects were encountered. Individual response was varied and not related to disease activity.

Activities of Daily Living↗

Sequential nailfold capillary microscopy in scleroderma and related disorders.

Sequential nailfold capillary microscopy was carried out monthly for seven months in seven patients (four with scleroderma, one with dermatomyositis, one with mixed connective tissue disease, and one with limited connective tissue disease). Progressive enlargement of some capillary loops was observed, with a number becoming obliterated, leaving avascular areas. Extravasation from capillaries usually preceded capillary loss. These observations have shown the progressive nature of the nailfold capillary abnormalities associated with these disorders and suggest that capillary enlargement is the result of injury, rather than compensation for capillary loss.

Adult↗

Lipid peroxidation and malondialdehyde in the synovial fluid and plasma of patients with rheumatoid arthritis.

The concentration of lipid peroxides in the plasma and synovial fluid of 65 arthritic patients was determined using a new ion-pairing reverse phase HPLC technique. Patients with rheumatoid arthritis receiving only non-steroidal anti-inflammatory drugs, had a significantly higher mean concentration of lipid peroxides in synovial fluid samples (162 +/- 22.0 micrograms/l) than osteoarthritic patients (40.0 +/- 8.0 micrograms/l, p less than 0.0001). Mean concentrations in both groups correlated strongly with the level of beta-glucuronidase activity as a measure of lysosomal enzyme release (r = 0.71, p less than 0.0001). Contrary to previous reports by investigators using less specific methods, we were unable to demonstrate any increase in plasma levels of lipid peroxides in the rheumatoid patient. Treatment of rheumatoid arthritis with D-penicillamine was associated with a significant reduction of lipid peroxide levels (83.2 +/- 11.5 micrograms/ml, p less than 0.002), suggesting that this drug may function as an oxygen radical scavenger in the joint cavity. These results give further support to the concept of oxygen-free radicals playing an important role in the pathogenesis of chronic inflammatory disorders.

Anti-Inflammatory Agents, Non-Steroidal↗