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Biomedical subjects

D J Veale

Publications and source records attributed to D J Veale.

49 records · Page 3Linked to original sources

Human neutrophil Fc receptor-mediated adhesion under flow: a hollow fibre model of intravascular arrest.

Human polymorphonuclear cells (PMN) were found to adhere to a novel model of blood vessel wall-associated IgG. The internal surfaces of cellulose acetate hollow fibres, of comparable internal diameter to small blood vessels, were coated with normal serum human IgG, heat-aggregated IgG (HAIgG), laminin or fibrinogen. Under conditions of flow mimicking those in a small vessel, PMN were found to adhere markedly only to immunoglobulin-coated fibres. Arrest on HAIgG was inhibited by excess soluble IgG but not by bovine serum albumin (BSA), demonstrating that the adhesion was IgG-specific and presumably mediated by Fc gamma R on the PMN surface. Pre-adsorption of serum components onto HAIgG-coated fibres enhanced PMN arrest, due most probably to fixation of complement components by immobilized HAIgG, resulting in additional potential to entrap PMN via complement receptors such as CR3. Treatment of PMN with the regulatory neuropeptide substance P also enhanced adhesion to HAIgG-coated fibres and caused increased surface expression of Fc gamma RI, Fc gamma RII and Fc gamma RIII. A mouse cell line derived from L cells, hR4C6, stably transfected with human Fc gamma RII, was found to adhere under flow to HAIgG-coated fibres, whilst untransfected parent L cells did not. This adhesion was similarly inhibited by excess soluble IgG, confirming the capability of Fc gamma R to mediate cell arrest. The study strongly suggests that Fc gamma R may play an important role in intravascular PMN arrest and we speculate that in inflammatory diseases PMN may adhere via Fc gamma R to immobilized immunoglobulin on the vascular endothelium, with subsequent degranulation and tissue damage.

Animals↗

Increased prevalence of symptomatic macrovascular disease in systemic sclerosis.

OBJECTIVES: To determine the prevalence of symptomatic macrovascular disease, as defined by the World Health Organisation questionnaire for intermittent claudication, in patients with systemic sclerosis (SSc), and to compare the prevalence in this population with a cross sectional population study group reported in the Edinburgh Artery Study (EAS). METHODS: A group of 53 patients with a diagnosis of limited or diffuse systemic sclerosis were identified from our register. They were asked to complete the WHO questionnaire to establish the presence or absence of intermittent claudication. In addition, each patient's case notes were reviewed to establish the existence of definite peripheral vascular disease and to determine their risk factor profile. RESULTS: Forty six patients responded to the questionnaire, giving a response rate of 87%. Intermittent claudication was found in 10 SSc patients (21.7%) according to the questionnaire (two with diffuse and eight with limited SSc), compared with a prevalence rate of 4.6% for claudication in the EAS. Three SSc patients experienced clinical events attributable to occlusion of a major artery proven on angiography. Four patients had hypertension, there were three current and four ex-smokers, and two had increased total cholesterol. None of these patients had diabetes. CONCLUSIONS: This study demonstrated a greater prevalence of macrovascular disease in patients with SSc than had been found in a neighbouring population.

Adolescent↗

A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis.

Fish oil may be beneficial in the treatment of psoriasis and in RA. We examined the potential benefit of Efamol Marine, a combination of evening primrose oil and fish oil in the treatment of 38 patients with PsA. Patients with PsA were entered in a double-blind placebo controlled study and received either 12 Efamol Marine capsules or 12 placebo capsules daily for 9 months. All patients received placebo capsules for a further 3 months. At month 3 of the study patients were asked to reduce their intake of NSAIDs and maintain that decrease provided there was no worsening of their joint symptoms. Clinical assessments of skin and joint disease severity and activity were performed at 0, 1, 3, 6, 9 and 12 months. All measures of skin disease activity including severity, percentage body affected and itch were unchanged by Efamol Marine. The NSAID requirement remained the same between both treatment groups. In addition, there was no change demonstrated in the activity of arthritis as measured by duration of morning stiffness. Ritchie articular index, number of active joints, ESR and CRP. However, a rise in serum TXB2 was observed in the active group during the placebo phase; in addition a fall in leukotriene B4 production occurred during the active phase period followed by a marked rise during the placebo phase suggesting some laboratory documented anti-inflammatory effect. In conclusion, this study suggests that Efamol Marine may alter prostaglandin metabolism in patients with PsA, although it did not produce a clinical improvement and did not allow reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit.

Administration, Oral↗

Immunohistochemical markers for arthritis in psoriasis.

OBJECTIVES: To examine the immunohistological features in the involved skin of patients with psoriatic arthritis (PA) (n = 15), compared with those in involved skin from patients with psoriasis but no arthritis (n = 5), and with a group with normal skin (n = 4), to identify markers for arthritis in psoriasis. METHODS: Skin was obtained from patients by 6 mm punch biopsy and normal skin was provided by the department of plastic surgery. Samples were stained with monoclonal antibodies against T cells (CD3, CD8, CD4, CD45Ro), B cells (CD20), macrophages (mac387), vascular endothelium (FVIII-related antigen) and a Langerhan's cell marker (p155). The number of cells/vessels staining with each monoclonal antibody was calculated and serial sections of skin were examined to estimate the presence of DR+ keratinocytes. RESULTS: There were significantly more CD45Ro T-cells and blood vessels in patients with psoriatic arthritis compared with both psoriasis alone, and with normal controls (p < 0.02). While B-cells were not seen in psoriasis without arthritis or in normal skin, a small but significant number were observed in PA (p < 0.02). Furthermore, while DR+ keratinocytes were present in both psoriatic arthritis and psoriasis skin, there were significantly more DR+ cells in the psoriatic arthritis epidermis compared with psoriasis alone (p < 0.02). CONCLUSIONS: This study suggests that increased numbers of CD45Ro T-cells, greater vascularity, the presence of B-cells, and increased numbers of DR+ epidermal cells are markers for arthritis in patients with psoriasis.

Adult↗

South African traditional herbal medicines used during pregnancy and childbirth.

Many black South African women use traditional herbal remedies as antenatal medications or to induce or augment labour. Very little is known about the pharmacology and potential toxicity of the plants used in these herbal remedies. The ethnic background and traditional usage of these remedies was researched and a literature survey revealed that 57 different plants were used in herbal remedies during pregnancy and childbirth. Several of these plants are poisonous and details of their toxicity are given.

Black or African American↗

Preliminary isolated organ studies using an aqueous extract of Clivia miniata leaves.

An infusion of Clivia miniata leaves is a traditional medicine taken by Black South African women to induce or augment labour. A boiling water extract of C. miniata leaves was studied for its pharmacological effects on rat uterus and ileum. The extract caused concentration-dependent contractions in both the uterus and ileum, but at a fraction of the intrinsic activity of acetylcholine. When the organs were pretreated with the extract before the cumulative addition of either oxytocin or acetylcholine, the extract augmented the initial response of the organs to the reference drugs. The frequency of contractions in the spontaneously contracting uterus was increased by the presence of the extract. C. miniata extract, however, inhibited the maximal response of the ileum to acetylcholine in a non-competitive way. It did not affect the maximal response of the uterus to either oxytocin or acetylcholine.

Acetylcholine↗

Psoriatic arthritis--pathogenesis and epidemiology.

Psoriatic arthritis (PsA), recognised for over 100 years, is common representing the second most frequent diagnostic category after RA and occurring in up to 10% of patients with skin psoriasis. The pathogenic connection between psoriasis and arthritis is not yet clear although our understanding of the mechanisms of disease has progressed significantly in recent years. Factors including immunogenetics, infection, autoimmunity, angiogenesis, trauma and the nervous system are implicated in the pathogenesis of PsA. Organ involvement is largely restricted to the connective tissue of the skin and joints, including both the synovial tissue and sites of entheseal attachment. This restricted inflammatory response suggests that either a common antigen driving the immune response or that antigenic proteins or cells are present at these sites only having migrated the or arising de novo. The epidemiology of Psoriasis has been extensively examined since the 1960's, however there have been few large epidemiological studies of PsA. In addition, the lack of diagnostic criteria for the diagnosis of PsA until 1973, and the diffuse clinical manifestations of this condition have hindered meaningful conclusion regarding the epidemiology of this form of arthritis.

Arthritis, Psoriatic↗