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Biomedical subjects

B R Allen

Publications and source records attributed to B R Allen.

At least 19 recordsLinked to original sources

Selective activation of circulating CD4+ lymphocytes in severe adult atopic dermatitis.

An analysis of peripheral blood lymphocyte subsets and their expression of activation markers was performed using flow cytometry in 12 adult patients with severe atopic dermatitis, and compared with 14 normal individuals. Repeated measurements were made over an 8-week period during which disease activity was also assessed. Increased percentages of activated and unactivated CD4+ lymphocytes, and decreased percentages of CD8+ cells were observed in atopic dermatitis. Increasing disease activity was associated with an increase in the proportion of activated and unactivated CD4+ lymphocytes and a fall in the proportion of CD8+ cells. This study demonstrates that in adults with severe atopic dermatitis, increasing disease activity is associated with selective activation of CD4+ lymphocytes and a relative expansion of the CD4+ cell subset.

Adolescent

Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis.

A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.

Adolescent

Dermatomyositis responding to treatment of associated toxoplasmosis.

We report a 59-year-old woman with severe dermatomyositis in association with high serum toxoplasma antibody titres who was successfully treated with pyrimethamine and sulphadiazine. This case supports an aetiological role for toxoplasmosis in the pathogenesis of some cases of dermatomyositis.

Dermatomyositis

The metabolism of leukotriene B4 by peripheral blood polymorphonuclear leukocytes in psoriasis.

The formation of leukotriene B4 and its omega-oxidised metabolites has been compared in calcium ionophore-stimulated polymorphonuclear leukocytes, in the absence of exogenous substrate, from fourteen psoriatic subjects and thirteen healthy controls. Although there was no significant difference in the levels of leukotriene B4, the psoriatic cells synthesised significantly greater amounts of omega-oxidation products than control cells. This difference was confirmed in an experiment comparing the time course of formation of the omega-oxidation products of leukotriene B4, under similar conditions, in polymorphonuclear leukocytes from four psoriatic subjects and three healthy controls. The kinetic constants for the metabolism of exogenous leukotriene B4 by 20-hydroxylase were determined by a radiochromatographic enzyme assay in polymorphonuclear leukocytes from three patients with psoriasis and three healthy controls. No significant differences were found in the apparent Km and Vmax values. It is concluded that the increased formation of omega-oxidation products in psoriatic cells may be secondary to increased synthesis of leukotriene B4 by these cells, with consequent increased metabolism, rather than to an inherent abnormality of the 20-hydroxylase system. Further work is needed to determine the kinetics of the enzymes involved in leukotriene B4 synthesis in the psoriatic polymorphonuclear leukocyte, and also to assess the contribution of the leukotriene B4 and omega-oxidation products from polymorphonuclear leukocytes infiltrating the skin to the pathogenesis of the psoriatic lesion.

Adult

The effects of dietary supplementation with fish oil in patients with psoriasis.

Ten patients with psoriasis resistant to conventional topical treatment were given dietary supplements of fish oil, providing approximately 12 g of eicosapentaenoic acid daily for a period of at least 6 weeks. In eight patients there was a modest improvement in their psoriasis, the principal effects being a diminution of erythema and scaling. The dietary treatment resulted in a substantial inhibition of leukotriene B4 production by the peripheral blood polymorphonuclear leukocytes in vitro. The discrepancy between the high degree of inhibition of leukotriene B4 synthesis and the modest therapeutic effect suggests that leukotriene B4 is not the only mediator involved in the development of the psoriatic lesion. Furthermore, the in vivo cutaneous levels of leukotriene B4 might not have been inhibited to the same extent as the polymorphonuclear leukocyte levels in vitro. Further studies on the use of fish oil supplements, both on their own and in conjunction with other forms of treatment in psoriasis are warranted. It will also be important to determine whether the altered profile of 5-lipoxygenase products found in the blood is also seen in the skin.

Adult

Arachidonic acid metabolism by polymorphonuclear leukocytes in psoriasis.

The metabolism of endogenous arachidonic acid by human polymorphonuclear leukocytes (PMNL) isolated from peripheral blood has been studied in 19 patients with chronic plaque psoriasis and 19 healthy controls. Using calcium ionophore A23187 as a stimulus, the PMNL synthesized leukotriene B4 (LTB4), 6-trans-leukotriene B4, 12-epi-6-trans-LTB4, and 5-hydroxy-6,8,11,14-eicosatetraenoic acid. There was no significant difference in the amounts of the products formed between the psoriatic and control groups. The elevated levels of LTB4 that have been described in psoriatic skin may therefore be due to the PMNL infiltrate or to enhanced synthesis by another cell type. The reported increase in activity of the circulating PMNL in psoriasis does not appear to be due to increased 5-lipoxygenase activity in these cells.

Adult

Arachidonic acid metabolism by peripheral blood cells in psoriasis.

The metabolism of arachidonic acid by mixed suspensions of leukocytes and platelets prepared from peripheral blood has been studied in 20 patients with psoriasis and 21 healthy controls. A lipoxygenase-derived product, identified as 12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid was formed in increased amounts by the cell suspension from the psoriatic patients. This product results from the metabolism of platelet-derived 12-hydroxy-5,8,10,14-eicosatetraenoic acid by the polymorphonuclear leukocyte 20-hydroxylase enzyme. By contrast, synthesis of the cyclo-oxygenase products 12-hydroxy-5,8,10-heptadecatrienoic acid and thromboxane B2 was diminished. Benoxaprofen, which is known to be beneficial in psoriasis, diminished the levels of 12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid formed in vitro.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid