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Biomedical subjects

A M Denman

Publications and source records attributed to A M Denman.

At least 19 recordsLinked to original sources
PubMed2001

Thrombosis in Behçet's disease: a retrospective survey from a single UK centre.

OBJECTIVE: To contribute to knowledge of vascular occlusion in Behçet's disease (BD), prevalence and relative risk for thrombosis were ascertained retrospectively in a cohort of Caucasian patients with the disease. PATIENTS: The study included 73 BD patients (36 males, 37 females, mean age 45+/-11 yr) attending the Immunology/Rheumatology Department of Northwick Park Hospital. A group of 146 patients without BD, attending the same department, served as a control group. RESULTS: Thrombosis was more frequent in BD patients than in controls (23/73, 32% vs 7/146, 5%, P<0.001). This was accounted for by a higher prevalence of venous thrombosis in BD patients (18/73, 25% vs 4/146, 3%, P<0.001). Gender-adjusted data revealed an 11-fold risk of developing any thrombosis and a 14-fold risk of developing venous thrombosis in BD. After adjusting for differences in age at first symptoms, male BD patients showed a 6-fold higher risk of vein thrombosis. Males reported more often thrombophlebitis (13/36, 36% vs 0/0, P<0.001), folliculitis (8/36, 22% vs 1/37, 3%, P<0.01) and retinal vasculitis (13/36, 36%, vs 4/37, 11%, P=0.01) than females, in whom arthralgia prevailed (23/37, 62%, vs 12/36, 33%, P=0.01). CONCLUSION: In our population, BD confers a 14-fold risk of developing venous thrombosis. The risk is sixfold higher in male BD patients, who fare worse than females with regard to thrombophlebitis, folliculitis and retinal vasculitis.

Behcet Syndrome↗
PubMed1999

Neurological complications in Behçet's syndrome.

The neurological complications of Behçet's syndrome have not been characterized with clarity. We present the clinical features, imaging characteristics and CSF findings of a series of 50 patients seen at the National Hospital for Neurology and Neurosurgery over the past 10 years. In this series, vascular complications had a low prevalence, whereas involvement of the brainstem was common; spinal cord lesions, hemisphere lesions and meningoencephalitis also occurred. Optic neuropathy, vestibulocochlear and peripheral nerve involvement occurred, but were rare. The prognosis for recovery was in general good, and the majority of those followed-up over a median of 3 years (range 1-19 years) had only single attacks. One-third of patients underwent further attacks, and four underwent progressive deterioration leading to disability. Factors suggesting a poor prognosis are repeated attacks, incomplete recovery, progressive disease course and a high level of CSF leucocytosis during acute attack. These data should be of help in the further definition of the clinical characteristics of this rare neurological disorder and in the planning of treatment trials.

Adult↗
PubMed1995

A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour necrosis factor (TNF) production.

Patients presenting with prolonged systemic illnesses with no specific clinical or serological defining features may be diagnosed as having atypical systemic vasculitides, but often turn out to have occult malignancies. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study we describe a patient presenting after 2 years of a severe systemic illness with a marked acute phase response, due to an occult mediastinal angiomatoid malignant fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the local and systemic production of cytokines induced by this tumour. Blood samples were taken pre- and post-operatively for cytokine studies. In vitro production of IL-2, IL-2R, IL-1 beta, IL-6 and TNF-alpha by cultured monocytes from the patient, as well as plasma cytokine levels, were measured by ELISA. Tumour cytokine production was also evaluated immunocytochemically, and by in situ hybridization with specific cDNA probes. Plasma IL-2R and IL-6, and IL-6 and TNF-alpha production by peripheral blood monocytes were markedly elevated before tumour resection, normalizing post-operatively. Most tumour cells and infiltrating lymphocytes stained with antibodies to IL-6, IL-6R and TNF-alpha, and expressed HLA class II. IL-6 and TNF-alpha mRNA production in the tumour was confirmed by in situ hybridization studies. We have described the first case of an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies of cytokine expression suggested that chronic TNF, IL-6, and IL-2 production by leucocytes and tumour cells in this patient was responsible for the severe systemic illness with which she presented.

Adult↗
PubMed1993

Rheumatoid arthritis in a patient with primary hypogammaglobulinaemia.

A 44-year-old woman with primary hypogammaglobulinaemia developed classical RA and inflammatory bowel disease. She represents an example of rheumatoid disease developing in the absence of endogenous antibodies and raises interesting questions regarding the pathophysiology of the disease.

Adult↗
PubMed1992

Polyclonal origin of rheumatoid synovial T-lymphocytes.

Nineteen T-cell clones from seven patients with RA were obtained by cloning infiltrating lymphocytes from needle synovial biopsies. Southern blot analysis of the T-cell receptor (TCR) beta-chain genes in these clones revealed that there were no T-cell clones with an identical rearrangement of the TCR beta gene. These results do not support the idea that the infiltrating T-lymphocytes in RA are of monoclonal or oligoclonal origin.

Arthritis, Rheumatoid↗
PubMed1992

Activation of IL-6 production by UV irradiation of blood mononuclear cells from patients with systemic lupus erythematosus.

Cultured mononuclear cells from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and normal donors were assayed for their ability to secrete IL-6 both spontaneously and after exposure to UV light. Mononuclear cells from SLE, RA and atopic control patients produced IL-6 spontaneously, while those from normal donors did not. Spontaneous production of IL-6 occurred in the non-adherent cell population. UV light-induced IL-6 production was confined exclusively to the SLE patients and was present only in the macrophage/monocyte fraction. This stimulation was induced by wavelengths in the UVA, UVB but not the UVC portion of the spectrum. These results suggest that cytokine release may be involved in the exacerbations of SLE provoked by photosensitivity.

Humans↗
PubMed1992

Chimeric CD7 monoclonal antibody therapy in rheumatoid arthritis.

Murine monoclonal antibody (Mab) therapy in patients with rheumatoid arthritis (RA) produces an antimouse immunoglobulin response by the recipient. We studied a chimeric (human/mouse) CD7 Mab, in a dose ranging tolerability study in 10 patients with RA. Modest improvements in disease activity occurred with frequent acute adverse effects of malaise, fever and nausea. After treatment, peripheral blood T lymphocyte numbers fell by 50% and CD7 expression fell by 97% for less than 7 days. Our study demonstrates chimeric Mab function in vivo and illustrates the influence of antibody isotype and patient characteristics on adverse effects.

Adult↗
PubMed1991

Infectious arthritis in primary disorders of immunoglobulin synthesis.

Disorders of immunoglobulin synthesis are of great interest to rheumatologists. At the diagnostic level, such disorders not uncommonly mimic commoner rheumatic diseases, so it is important that the diagnostic possibility of immunodeficiency be kept in mind. Infections often complicate immunodeficiency and may present in an atypical manner. From the theoretical standpoint, the interactions between infectious agents and patients with impaired immunity suggest ways in which the same or similar agents could be responsible for arthritis of unknown etiology. Furthermore, many immunodeficiency disorders predispose to autoimmunity; establishing the mechanism of this association may offer good insights into the factors that trigger autoimmune disorders in patients with seemingly normal immune competence.

Agammaglobulinemia↗
PubMed1991

Cytokine-independent progression of immunoglobulin production in vitro by B lymphocytes from patients with systemic lupus erythematosus.

B lymphocytes from patients with systemic lupus erythematosus (SLE) secreted high levels of immunoglobulin spontaneously when cultured in vitro. Addition of the cytokines interleukin-2, interleukin-4 and interleukin-6 either alone or in combination failed to augment spontaneous immunoglobulin synthesis. Percoll-separated low-density SLE B lymphocytes matured into immunoglobulin-secreting cells also independent of exogenous interleukins. During maturation these cells became enlarged and less dense, and began to express CD23. This was in contrast to normal B cells, which did not secrete immunoglobulin spontaneously but synthesized IgM after interleukin stimulation. These results indicate that in vitro immunoglobulin synthesis by SLE B cells is already initiated in these cells and progresses independently of further stimulatory manoeuvres.

Antigens, Differentiation, B-Lymphocyte↗