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Biomedical subjects

B Bresnihan

Publications and source records attributed to B Bresnihan.

At least 91 records · Page 5Linked to original sources
PubMed1993

Doppler echocardiographic evidence of left ventricular diastolic dysfunction in ankylosing spondylitis.

Although cardiac involvement in the form of conduction abnormalities or aortic regurgitation occurs in 5 to 10% of patients with ankylosing spondylitis, few studies have assessed left ventricular (LV) function. This study assesses the prevalence of both systolic and diastolic LV dysfunction and other cardiac abnormalities in patients with ankylosing spondylitis who have no clinical cardiac manifestations. Fifty-nine patients (49 men and 10 women, mean age 42 +/- 10 years) underwent full clinical examination, electrocardiography, 24-hour Holter monitoring and 2-dimensional, M-mode and Doppler echocardiography. Mean disease duration was 17 +/- 9 years (range 1 to 42). Seventeen patients had evidence of noncardiac extraarticular manifestations. Precordial examination was normal in all. An age- and sex-matched control group of 44 healthy subjects was also studied. On echocardiography, abnormal LV diastolic function was detected in 12 patients (20%). Prolonged isovolumic relaxation time, prolonged deceleration time, reduced rate of descent of flow velocity in early diastole (EF slope) and reversal of the early and late peak transmitral diastolic flow velocities (E/A ratio) were noted in 9 patients. In 3 patients there was an increased E/A ratio, reduced deceleration time and increased EF slope. Mild aortic regurgitation and mitral regurgitation was seen in 1 and 3 patients, respectively. No abnormalities of left atrial size, LV systolic or diastolic dimensions or wall thicknesses were noted. There was no correlation between the presence of LV diastolic dysfunction and age, disease severity, disease duration, or the presence of extraarticular manifestations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis.

OBJECTIVE: To define the immunohistologic features of the synovial membrane (SM) of patients with psoriatic arthritis (PA) and to compare them with those of an age- and disease-duration-matched population of patients with rheumatoid arthritis (RA). METHODS: Synovial membrane needle biopsy was performed on 15 PA patients with knee involvement (8 had asymmetric oligoarthritis and 7 had symmetric polyarthritis) and on 15 RA controls. Specimens were stained with monoclonal antibodies against T cells (CD3, CD8, CD4, CD45RO), B cells (CD20), macrophages (Mac387, CD14), and cells bearing class II antigens (DAKO-DR). Vascular endothelium was examined using a polyclonal antibody to Factor VIII-related antigen, and adhesion molecule expression was examined using antibodies 1.3B6, 6.5B5, and 1.4C3, which identify endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), respectively. RESULTS: There was significantly less lining layer hyperplasia, fewer macrophages, and a greater number of blood vessels in PA SM than in RA SM: ELAM-1 expression was less intense in PA than in RA SM, while there was no difference in expression of ICAM-1 and VCAM-1. Numbers of B cells, T cells, and T cell subsets (predominantly CD4, CD45RO T cells) were similar in both groups of patients. CONCLUSION: Our findings demonstrate important differences in the immunohistologic features of PA and RA SM: The PA SM is more vascular, ELAM-1 expression is less intense, and fewer macrophages invade the stroma and migrate to the lining layer than in RA SM: However, the lymphocytic infiltrate in the SM of both groups is similar.

Adult↗
PubMed1993

Assessment of cognitive function in patients with systemic lupus erythematosus.

The spectrum of central nervous system manifestations of systemic lupus erythematosus (SLE) is very broad and has been found to include subtle subclinical cognitive dysfunction which may be detected only by the lengthy process of detailed neuropsychological evaluation. This study reports the value of estimating premorbid intelligence as a simple yet effective means of screening for subclinical cognitive dysfunction. Twenty one female patients with clinically quiescent SLE underwent neuropsychological examination at entry to the study. In all patients, this examination included measurement of full-scale intelligence quotient (IQ), verbal and performance IQ as well as verbal and visual memories. In addition, premorbid intelligence was estimated using the Schonell graded word reading test. Nine patients (43%) gave a history of neuropsychiatric (NP) disease. No difference was identified between the results of the neuropsychological evaluation in these 9 patients and in either the other SLE patients or in age and sex matched control patients. Sixteen patients were re-evaluated 1 year later. A comparison of measured full-scale IQ with the estimated premorbid intelligence identified a subgroup of 3 patients who demonstrated a significant reduction in intelligence. Unlike the other 13 patients, these 3 patients had multiple (3 or more) other features of cognitive impairment.

Cognition Disorders↗
PubMed1993

Lymphedema of the upper limb in patients with psoriatic arthritis.

Upper limb lymphedema occurs rarely in rheumatoid arthritis (RA) but has been reported only once in psoriatic arthritis (PsA). The pathogenesis is unknown. This study describes four patients (three women) with upper limb lymphedema, chronic symmetrical polyarthritis, and psoriasis. Three were seronegative, diagnosed PsA; one was seropositive. Age ranged from 39 to 64 years, duration of psoriasis was 6 to 42 years, and duration of arthritis was 6 to 12 years. Onset of lymphedema was unrelated to the extent or severity of arthritis, and no other cause for this condition was identified. Radiological appearances ranged from mildly abnormal to advanced joint destruction, but carpal disease was prominent in all patients. Lymphoscintigraphy was abnormal in three subjects. Lymphedema became bilateral in two and was associated with radiological progression of arthritis. Disease-modifying therapy produced improvement of lymphedema in two patients and correction of the lymphoscintigraphic abnormality in one. This study describes upper limb lymphedema in patients with PsA and suggests that local synovitis may play a role in its pathogenesis.

Adult↗
PubMed1993

Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is the most common of the connective tissue disorders and can involve virtually any organ in the body. It is associated with pleuropulmonary manifestations in well over 50% of cases. Pleuritis with or without pleural effusion is the most common manifestation and can be particularly troublesome to manage but is rarely life-threatening. More serious manifestations in the lung include acute lupus pneumonitis with or without alveolar haemorrhage, chronic lupus pneumonitis and pulmonary hypertension. These all contribute significantly to overall mortality in SLE. The association between SLE and the antiphospholipid syndrome, leading to venous thrombosis and pulmonary embolism, is well recognized. Up to 20% of all cases of SLE present in childhood and many of these have pulmonary features at presentation or during the course of their illness. Sepsis is one of the main causes of death in SLE and pulmonary sepsis in these often immunocompromised patients contributes a significant proportion. Several drugs can produce a clinical syndrome that has many of the clinical and immunological features of SLE. Pleuritis may be seen in up to half of these cases of drug induced SLE. The development of SLE and conditions such as sarcoidosis or asbestosis in the same patient may represent a simple coincidence but there is some evidence for a closer association between these disorders.

Humans↗
PubMed1993

Irreversible blindness in systemic lupus erythematosis.

We describe a patient with systemic lupus erythematosis and renal involvement and who developed visual impairment in the absence of hypertension and anti-cardiolipin antibodies. This was attributed to occlusive vascular disease and choroidal infarction in the context of active lupus. Complete and irreversible blindness developed rapidly despite treatment and the patient died of cerebral haemorrhage 2 months after discharge.

Adult↗
PubMed1993

Spontaneous in vitro production of rheumatoid factor during infectious exacerbations of cystic fibrosis: correlation with circulating immune complex levels.

Rheumatoid factor (RF) production has been demonstrated during infections, including infectious exacerbations of cystic fibrosis (CF). The aim of this study was to evaluate the relationship of RF production to infection, and examine the mechanisms involved. Serial peripheral blood mononuclear cell (PBMC) cultures with measurement of spontaneous production of IgM RF, IgA RF, total IgM and IgA, and measurement of serum levels of immune complexes were carried out during exacerbations of CF. The percentage of B cells expressing CD5 was examined in a second cohort of acutely infected CF patients, and related to IgM RF production. IgM RF production was significantly elevated during acute infection compared with convalescence (P < 0.05), stable CF subjects (P < 0.005) and normal controls (P < 0.05). IgM RF production did not correlate with total IgM production in the majority of patients, but was closely related to circulating immune complex levels in 8/10 subjects. IgA RF production did not increase significantly during infection, and did not correlate with total IgA or IgM RF production, or with circulating immune complex levels. CD5+ B cells were not increased in the CF group, and the percentage of CD5+ B cells did not correlate with IgM RF synthesis. These observations suggest that RF production during infection is specifically induced, possibly by immune complex autoimmunization, and is not simply the result of polyclonal B cell activation. Different patterns of IgM RF and IgA RF synthesis suggest different mechanisms of induction.

Acute Disease↗
PubMed1993

IL-2 enhances polyclonal IgM but not IgM-rheumatoid factor synthesis by activated human peripheral blood B cells.

IgM-rheumatoid factor (RF) is thought to be involved in the pathogenesis of rheumatoid arthritis (RA). Several cytokines are known to regulate immunoglobulin synthesis. In this study the effects of IL-2 on polyclonal IgM and IgM RF synthesis were compared. Cytokines were added to peripheral blood B cells from normal subjects and patients with RA after activation by Staphylococcus aureus Cowan 1 (SAC). The addition of IL-2, but not IL-4 or IL-6, resulted in significant enhancement of IgM synthesis in cultures from both healthy subjects and patients with RA. Similar degrees of enhancement were seen in both peripheral blood mononuclear cell and highly purified B cell cultures. IgM-RF was synthesized after activation in cultures from healthy subjects and spontaneously in cultures from RA patients. In contrast to polyclonal IgM synthesis, IL-2 failed to augment IgM-RF synthesis in cell cultures from either healthy subjects or RA patients. This study demonstrates different effects of IL-2 on IgM and IgM-RF synthesis.

Adult↗
PubMed1993

Contrasting levels of in vitro cytokine production by rheumatoid synovial tissues demonstrating different patterns of mononuclear cell infiltration.

Synovial membrane samples obtained at knee arthroplasty from 22 patients with rheumatoid arthritis (RA) were characterized histologically. Two groups were identified. Tissue samples from 15 patients demonstrated multiple focal lymphoid aggregates of mononuclear cells (group A). Samples from the remaining seven patients demonstrated diffuse mononuclear cell infiltration (group B). Samples of each synovial membrane (0.25 g) were cultured for cytokine production. The highest levels of IL-1 beta and IL-6 were produced by group A tissues: 19.1 +/- 19.6 ng/ml IL-1 beta (mean +/- s.d.) and 264.4 +/- 301.9 ng/ml IL-6, versus 3.8 +/- 6.6 ng/ml and 54.7 +/- 42.6 ng/ml respectively. Small quantities of IL-2 and IL-4 were measured in both groups: the levels of IL-2 in group A cultures were highest (P = 0.04). Moreover, using MoAbs, the most intense cytokine staining in the tissues was detected in group A. Similar total numbers of each cell subpopulation and similar quantities of immunoglobulin and rheumatoid factor synthesis were measured in both groups. It is suggested that the presence of multiple focal lymphoid aggregates associated with higher levels of cytokine production observed in group A represent a greater degree of immunological activation, and may represent a subgroup of patients with a greater potential for articular destruction.

Adult↗
PubMed1993

A comparison of child and parent ratings of disability and pain in juvenile chronic arthritis.

OBJECTIVE: To assess parent-child agreement of child disability and pain. METHODS: Twenty children with juvenile chronic arthritis aged between 8 and 16 years and their mothers were assessed using a recently developed measure of child disability and pain. RESULTS: Results demonstrated a high level of agreement between children and their mothers with respect to disability. However, there was no correlation between the children's and their mothers' assessment of pain. CONCLUSION: This suggests that parents of children with chronic arthritis give accurate information regarding disability, but not regarding pain.

Adolescent↗
PubMed1993

Morphometric analysis of synovial membrane blood vessels in rheumatoid arthritis: associations with the immunohistologic features, synovial fluid cytokine levels and the clinical course.

The morphologic characteristics of the endothelial cells lining postcapillary venules are cytokine dependent and critical in facilitating the infiltration of mononuclear cells into synovial membrane in rheumatoid arthritis (RA). We determined the relationships between endothelial cell (EC) tallness, mononuclear cell infiltration and synovial fluid levels of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) at different stages of RA. EC tallness was greatest in synovial tissues obtained by needle biopsy of the knee joints from 18 patients with active RA who had never received disease modifying drugs (Group 1) (p = 0.000001 versus controls). EC tallness in tissues obtained from 18 patients with advanced disease undergoing knee arthroplasty (Group 2) was greater than controls (p = 0.001) only when vessels located in focal lymphoid aggregates were considered. Vascular proliferation was noted in both groups. Synovial fluid IL-6 levels were greatest in Group 1. IL-1 beta levels were greatest in Group 2. The total numbers of infiltrating mononuclear cells and the clinical measures of disease activity were similar in both groups. The differences in EC characteristics at different stages of RA suggest changing pathogenic mechanisms as disease progresses. Disease modifying antirheumatic drugs may contribute to the findings observed.

Anti-Inflammatory Agents↗
PubMed1992

Analysis of cell populations in rheumatoid arthritis synovial tissues.

Knee synovium, taken from patients with rheumatoid arthritis at the time of arthroplasty, was studied immunohistologically. Focal perivascular lymphoid infiltrates of different sizes were examined in detail to evaluate changes in cell populations as the infiltrate size increased. T cells formed the largest component of mononuclear cells of all aggregates. The large grade 3 aggregates contained substantial numbers of B cells arranged around a central venule and cells bearing the CD45RA+ phenotype. In contrast, the small grade 1 aggregates contained few B cells and the T-cell population contained relatively greater numbers of CD8+ cells. Cells bearing the CD45RO+ phenotype exceeded CD45RA+ cells in grade 1 aggregates. Detailed analysis of mononuclear cell aggregates of different sizes in the rheumatoid synovium suggests that the composition of each aggregate depends on the total number of mononuclear cells it contains.

Antigens, CD↗
PubMed1992

Prevalence of anti-Fab antibodies in patients with autoimmune and infectious diseases.

Sensitive ELISA were devised to examine the specificity of circulating IgM and IgA autoantibodies for whole human IgG, Fc and Fab fragments of human IgG. Sera from patients with autoimmune and infectious conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), tuberculosis (TB), infectious mononucleosis (IM) and cystic fibrosis (CF) were studied. Results of the ELISA assays using whole human IgG as antigen revealed that a proportion of patients in each of the groups studied had circulating IgM and IgA rheumatoid factors (RF). Fifteen normal individuals studied were negative. In the latex positive RA group, IgM RF and IgA RF had primarily anti-Fc reactivity (100% and 93% respectively), although 3/15 patients also showed IgM anti-Fab reactivity and one patient had high IgA anti-Fab activity. Patients with SLE and TB who had detectable RF levels also revealed predominantly anti-Fc specificity. In contrast, examination of 25 patients with IM showed positivity for IgM RF activity in 8% of patients using whole IgG as antigen, 24% positivity using purified Fc fragments as antigen and 45% positivity when plates were coated with Fab fragments. Similarly, a large number of CF patients (54%) also showed predominantly IgM anti-Fab activity. Of interest, 69% of the CF patients who were all studied at the time of bacterial infection had detectable IgA RF levels, with 46% of these patients showing both IgA anti-Fc and anti-Fab activity. These findings suggest that autoantibody specificities in autoimmune and infectious diseases are different.

Adolescent↗