Search PubMed⌕ Search

Biomedical subjects

B Bresnihan

Publications and source records attributed to B Bresnihan.

At least 109 records · Page 6Linked to original sources
PubMed1992

Production of angiotensin converting enzyme by rheumatoid synovial membrane.

Vascular proliferation and mononuclear cell infiltration are prominent changes observed in synovium from actively inflamed joints of patients with rheumatoid arthritis. Angiotensin converting enzyme (ACE) is a halide activated peptidase produced mainly by endothelial cells and by activated monocytes. It has been proposed that levels of ACE activity in synovial fluid might reflect changes in membrane vascularity, the degree of monocyte infiltration, or the thickness of the lining layer. In this study, ACE activity in serum and synovial fluid samples from 18 patients with inflammatory arthritis was measured and compared with levels in 12 control subjects with non-inflammatory arthritis. Although serum levels were similar in the two groups, ACE activity in synovial fluid was significantly increased in the group with inflammatory arthritis compared with controls (mean (SE) 37 (5) v 19 (3)). Staining of synovial membranes from patients with rheumatoid arthritis with a monoclonal antibody to ACE localised ACE to the endothelium and to mononuclear cells of macrophage origin. ACE activity was then measured in supernatants of synovial membrane from patients with rheumatoid arthritis after one and seven days of culture. A significant increase in ACE activity was observed after seven days of culture (mean (SE) day 1, 17 (5) v day 7, 25 (3)). Levels of ACE activity, however, did not correlate with the lining layer thickness, with the number of macrophages per square millimetre, nor with the number of blood vessels per square millimetre of synovial tissue. No correlation was observed either between levels of ACE in the supernatant of synovial membrane and levels of interleukin 1 or interleukin 6. In conclusion, ACE is produced by the synovial membrane of patients with rheumatoid arthritis and is localised to monocytes and endothelial cells. Levels of activity do not directly reflect membrane vascularity, monocyte or macrophage number, or the thickness of the lining layer.

Adolescent↗
PubMed1992

Echocardiographic abnormalities in ankylosing spondylitis.

Twenty four patients with ankylosing spondylitis of 10 or more years' duration were assessed for evidence of cardiac disease. Seven patients (29%) had evidence of cardiac disease, including one patient with a pericardial effusion, three with conduction abnormalities, and two with aortic incompetence. Aortic incompetence in one patient was clinically silent and was detected only with Doppler echocardiography. This patient had, in addition, thickening of the posterior aortic wall, an echocardiographic feature not previously described in ankylosing spondylitis. There was no evidence of aortic valve disease in a control group matched for age and sex. Patients with ankylosing spondylitis and cardiac abnormalities were older, had a longer disease duration, and more peripheral joint disease than those without cardiac abnormalities. Doppler echocardiography is a useful technique in the assessment of cardiac disease in ankylosing spondylitis and may detect aortic valve disease at an early preclinical stage.

Adult↗
PubMed1991

Effect of gold therapy on CD5+ B-cells and TCR gamma delta+ T-cells in patients with rheumatoid arthritis.

Circulating CD5+ B-cell levels in 15 patients with rheumatoid arthritis (RA) not receiving remittive therapy was significantly increased when compared to 17 normal controls (mean +/- SE: RA, 19.7 +/- 2.85%; controls, 11.6 +/- 1.67%; P less than 0.02). In contrast, 24 patients with RA receiving gold sodium thiomalate therapy (GST) had similar CD5+ B-cell levels (11.88 +/- 1.65) when compared to controls and significantly reduced levels when compared to the RA group not receiving remittive agents (P less than 0.01). Furthermore, TCR gamma delta+ T-cell levels were also assessed in these patients groups. These values were not significantly different between any of the groups (controls, 4.46 +/- 1.36%; GST, 6.88 +/- 1.73%; RA, 2.73 +/- 0.55%), although 42% of the GST treated group had gamma delta+ T-cell levels higher than the entire untreated RA group. No correlation was observed between the levels of TCR gamma delta + T-cells and CD5+ B-cells in any of these groups. These results suggested that therapy does influence the level of CD5+ B-cells and gamma delta+ T-cells in these patients.

Antigens, CD↗
PubMed1991

Induction of IgM and IgM-rheumatoid factor synthesis in vitro by indomethacin.

Indomethacin, which is thought to exert its therapeutic effect by inhibiting the synthesis of PGE2, is a commonly used first-line agent in the treatment of rheumatoid arthritis (RA). However, the effect of this drug on the humoral immune response in RA remains unclear. In this study, modulation of the in vitro synthesis of IgM and IgM-rheumatoid factor (RF) by indomethacin and prostaglandin E2 was examined in 11 patients with active RA and 10 normal controls. Indomethacin at a final concentration of 1 microgram/ml significantly enhanced IgM production (P less than 0.01) and RF production (P less than 0.02) in Staphylococcus aureus Cowan I (SAC) stimulated RA cultures when compared to controls in whom no net enhancement effect was observed. In the patients, this increase in IgM production was more pronounced than the corresponding increase in RF synthesis (P = 0.078), suggesting that IgM and IgM-RF-secreting RA plasma cells have different susceptibilities to PGE2 mediated suppression. Nonetheless, addition of PGE2 (10(-8) M final concentration) to the cultures inhibited IgM and RF production to a similar degree in the patient and control cultures. These findings demonstrate that PGE2 causes suppression of IgM and IgM auto-antibody production in vitro and that inhibition of endogenous PGE2 synthesis in RA patients treated with indomethacin results in a marked increase in the production of these antibodies.

Arthritis, Rheumatoid↗
PubMed1991

Experience with a juvenile rheumatology clinic.

A dedicated monthly clinic for children with rheumatic diseases was established in order to cater for the increasing number of referrals to a rheumatology department for assessment and management. The clinic was staffed by a consultant rheumatologist, registrar, nurse, physiotherapist and occupational therapist. Seventy-four children, 44 girls and 30 boys, were assessed during the first 32 months. The mean age at referral was 10 years (range 2-15). Thirty-three had juvenile chronic arthritis. Other disease categories included dermatomyositis, systemic lupus erythematosus and reactive arthritis. Twenty-eight children were referred by general practitioners and 26 by paediatricians. Hospital admission was required by 24. These observations suggest the need in Ireland for a coordinated service for children with rheumatic diseases.

Adolescent↗
PubMed1991

Immunohistological analysis of the synovial membrane: search for predictors of the clinical course in rheumatoid arthritis.

Immunohistological features which might predict the clinical course and outcome of rheumatoid arthritis were sought by examining multiple synovial membrane samples obtained by needle biopsy from the knee joints of 57 patients who had not received disease modifying antirheumatic drugs. Clinical measurements, but not biopsies, were repeated one year and three years after starting treatment. A correlation between both the intensity of synovial lining layer thickening and mononuclear cell infiltration and the clinical status at the time of biopsy was seen. After three years of treatment the correlations were maintained in patients who had presented and persisted with milder disease but not in patients who had presented with more active disease.

Adolescent↗
PubMed1991

Morphometric analysis of blood vessels in synovial membranes obtained from clinically affected and unaffected knee joints of patients with rheumatoid arthritis.

Synovial tissues from inflamed and noninflamed knee joints of 13 patients with untreated rheumatoid arthritis were examined for vascular proliferation and morphological alteration of endothelial cells. Perivascular mononuclear cell infiltration and increased thickness of the synovial lining layer were noted in tissues from inflamed and noninflamed joints of patients with rheumatoid arthritis; vascular proliferation and morphological alteration of endothelial cells to resemble high endothelial venules were seen only in tissues from inflamed joints of patients with rheumatoid arthritis. These observations suggest that the migration of mononuclear cells from the peripheral blood to the perivascular areas and lining layer occurs before vascular proliferation and morphological alteration of endothelial cells.

Arthritis, Rheumatoid↗
PubMed1991

Acute cerebrovascular episodes in systemic lupus erythematosus.

Twelve patients with systemic lupus erythematosus (SLE) who developed major acute cerebrovascular episodes are described. All patients were female, with a mean age of 43.3 years and they had suffered from SLE for between 1 month and 22 years (mean 9.3 years) at the time of stroke. All patients had multiple clinical and laboratory features of systemically active SLE. Stroke was the initial neurological feature in nine patients. Cerebral infarction was confirmed in eight patients and cerebral haemorrhage in two; the two remaining patients had convincing clinical evidence of thromboembolic neurological complications. Characteristic clinical and serological features of antiphospholipid antibodies were observed in six patients (50 per cent). Five patients died as a direct result of stroke and two other patients died within one year.

Acute Disease↗
PubMed1990

Lymphocyte infiltration and the synthesis of IgM and IgA rheumatoid factors by rheumatoid synovial membrane.

IgM and IgA rheumatoid factor (RF) synthesis by synovial membrane mononuclear cells was measured in 14 patients with rheumatoid arthritis (RA). The results were compared with blood mononuclear cell cultures and correlated with the intensity of lymphocyte infiltration of the synovium. IgM RF was produced by all synovial cultures compared with 56% of blood cultures; IgA RF was produced by 86% of synovial cultures and by 21% of blood cultures. A correlation was observed between synovial IgM RF synthesis, but not IgA RF synthesis, and the intensity of T cell and B cell infiltration of the synovial membrane.

Adult↗
PubMed1990

Bronchoalveolar lavage in patients with mild and severe rheumatoid lung disease.

The reported prevalence of interstitial lung disease in patients with rheumatoid arthritis has varied from 10% to 50%, yet less than 5% of patients with arthritis develop severe fibrosing interstitial lung disease. This suggests that subclinical disease may not always presage progressive disease. Bronchoalveolar lavage fluid from patients with rheumatoid arthritis and either clinically evident interstitial lung disease or subclinical disease was examined for the presence of factors with a putative role in the development of interstitial fibrosis. Patients with subclinical disease were identified by prospective radiographic and lung function screening of 93 patients with rheumatoid arthritis. Fourteen patients were identified in this manner and an association between subclinical disease and smoking history was noted. Eleven patients with established interstitial lung disease had increased neutrophils (p less than 0.05), collagenase, and type III procollagen N terminal peptide levels (p less than 0.01) in the bronchoalveolar lavage fluid. Preliminary characterisation of the bronchoalveolar lavage collagenase suggested that it originated from neutrophils. Ten patients with subclinical interstitial lung disease underwent bronchoalveolar lavage. Of these, one had increased neutrophils and two had increased collagenase concentrations--abnormalities associated with advanced interstitial lung disease and a poor prognosis. These results suggest that in arthritis patients with evidence of subclinical pulmonary interstitial disease bronchoalveolar lavage might be useful in identifying those who may require careful monitoring in the hope that early treatment will prevent severe fibrosis.

Adult↗
PubMed1989

Changes in lymphocyte infiltration of the synovial membrane and the clinical course of rheumatoid arthritis.

Multiple samples of synovial membrane were obtained by needle biopsy from 24 patients with rheumatoid arthritis (RA) before, and 1 year after, standard antirheumatic drug therapy was given. Changes in the immunohistologic features of the synovial membrane (read blindly) were compared with the clinical course of RA in each patient. A composite clinical index of disease activity (IDA) and spontaneous in vitro synthesis of IgM rheumatoid factor (IgM-RF) by blood mononuclear cells were also measured before and after treatment. In 16 patients (group A), the IDA indicated 26-69% improvement, and the values for spontaneous IgM-RF decreased substantially. In 8 patients (group B), the IDA indicated deterioration or no improvement, and the values for spontaneous IgM-RF were unchanged. In group A patients, the intensity of the T cell infiltrate decreased from a mean score of 1.3 to a mean score of 0.8 (P = 0.025). The ratio of T helper cells to T suppressor/cytotoxic cells was greater than or equal to 2:1 in 90% of group A patients before treatment, compared with 20% of these patients after treatment (P = 0.016), and the number of biopsy samples that contained identifiable B cells decreased from 36% before treatment to 7% after treatment. In group B patients, there were no changes in the intensity of T cell infiltration, the ratio of T helper cells to T suppressor/cytotoxic cells, or the number of biopsy samples with identifiable B cells.

Antibodies, Monoclonal↗
PubMed1989

Lymphoid irradiation in intractable rheumatoid arthritis. Long-term followup of patients treated with 750 rads or 2,000 rads.

Twenty patients with intractable rheumatoid arthritis were randomized to receive 750 or 2,000 rads of lymphoid irradiation (LI) in a double-blind comparative study, and were followed for a maximum of 48 months (mean 40 months) after treatment. During followup, sustained immunomodulation (including lymphopenia, particularly of the T helper cell subset; reduced ratio of helper cells to suppressor cells; and impaired in vitro lymphocyte proliferation in response to phytohemagglutinin and pokeweed mitogen) was observed. Significant improvements in early morning stiffness, Ritchie articular index, pain score, grip strength, and 15-meter walk time were observed in both treatment groups, but these were not sustained through the followup period. Progressive joint damage was observed radiologically in both groups during followup. Thus, LI induced sustained immunosuppression, but resulted in only short-lived clinical improvement and was associated with progressive joint erosion in these patients.

Arthritis, Rheumatoid↗
PubMed1989

Expression and regulation of the HLA-DR antigen on circulating monocytes isolated from patients with rheumatoid arthritis.

Using a modified radioimmunoassay, surface labeling of HLA-DR antigens on monocytes revealed reduced densities in patients with active rheumatoid arthritis (RA) (P less than 0.001) and in gold-treated patients (P less than 0.01) versus normal controls. Significant enhancement of DR antigen expression (P = 0.01), with values similar to those of normal monocytes, occurred in patient monocytes preincubated at 37 degrees C overnight, but not in monocytes preincubated at 4 degrees C. This suggested that a temperature-dependent metabolic process is required to enhance antigen expression. The addition of cycloheximide totally inhibited the enhancement of DR antigen density. Incubation of monocytes with exogenous prostaglandin E2 (10(-5)M final concentration) caused a reduction of DR densities on control and on RA monocytes, although this decrease was more marked in the controls. Addition of indomethacin did not affect DR antigen levels on control monocytes, but greatly enhanced the expression of DR antigens on RA monocytes. When HLA-DR antigen levels were estimated in detergent-solubilized membrane preparations, monocytes from patients with active RA demonstrated normal-to-increased densities compared with control monocytes. Thus, although RA monocytes possess a normal ability to synthesize DR molecules, surface expression of these molecules is inhibited; this inhibition may be mediated by prostaglandin E2 acting as a negative suppressive signal.

Arthritis, Rheumatoid↗