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Biomedical subjects

M W Greaves

Publications and source records attributed to M W Greaves.

At least 109 records · Page 6Linked to original sources
PubMed1990

Pharmacologic and clinical effects of lonapalene (RS 43179), a 5-lipoxygenase inhibitor, in psoriasis.

The pharmacologic and clinical effects of the 5-lipoxygenase inhibitor, lonapalene, have been determined in a double-blind, placebo-controlled, topical study in ten volunteers with psoriasis. A statistically significant clinical improvement was seen in lesions treated with 2% lonapalene ointment as compared with vehicle-treated sites. Although there was a statistically significant reduction in the levels of material similar or identical to the chemoattractant arachidonate 5-lipoxygenase product, leukotriene B4, in skin chamber fluid samples from lonapalene versus vehicle treated lesions, no significant reduction in arachidonic acid or 12-hydroxy-5,8,10,14-eicosatetraenoic acid was seen. The reduction in leukotriene B4 equivalents occurred before significant clinical improvement in lesions was seen. This and the selectivity of the pharmacologic response suggest that the therapeutic effect of topical lonapalene in psoriasis might be related to inhibition of leukotriene B4 synthesis. These results support the view that 5-lipoxygenase inhibitors may be useful in the treatment of psoriasis, and that leukotriene B4 is a relevant mediator of the pathology of this disease.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

The presence of autoantibody to recombinant lipocortin-I in patients with psoriasis and psoriatic arthritis.

Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kDa protein, lipocortin-I. Anti-lipocortin-I antibodies (ALA) were measured by enzyme-linked immunosorbent assay (ELISA) in 23 patients with plaque-type psoriasis alone (NAP), in 21 patients with psoriasis and arthritis (PA), and in 67 healthy controls. Only two of 23 NAP patients had elevated ALA, whereas six of 21 PA patients had raised levels of ALA (P = 0.2). Sero-negative polyarthritis was the most common pattern of joint disease in those PA patients with elevated ALA (4/6). ALA levels did not correlate with the extent or severity of cutaneous involvement, and are unlikely to be involved in the pathogenesis of cutaneous psoriasis.

Adult↗
PubMed1990

Skin exudate levels of interleukin 6, interleukin 1 and other cytokines in mycosis fungoides.

The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material. Interleukin 2 and tumour necrosis factor activity, and gamma interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides.

Adult↗
PubMed1990

Aquagenic pruritus associated with the idiopathic hypereosinophilic syndrome.

Patients with the idiopathic hypereosinophilic syndrome (HES) may develop associated skin disorders. We describe a patient who had xerosis since birth, but who first developed symptoms of aquagenic pruritus soon after he presented with HES. Photochemotherapy with psoralen and UVA treatment reduced his peripheral blood eosinophil count. The good response to treatment suggests that there was a close relationship between the dermatosis and the blood disorder.

Eosinophilia↗
PubMed1990

[The development of recent strategies in the treatment of urticaria as a result of clinically oriented research].

New therapeutic approaches in urticaria are presented with special respect to chronic and physical types including symptomatic dermographism, cholinergic urticaria, pressure and solar urticaria as well as vibratory angioedema. Clinical efficacies of several antihistamines (clemastine, astemizole, terfenadine, acrivastine, hydroxyzine, cimetidine), of ketotifen as a H1 receptor antagonist and mast cell stabilizer, of tricyclic antidepressant doxepin with H1 and H2 antagonist properties, of the calcium channel antagonist nifedipine, of topical corticosteroids and of the attenuated androgen danazol are presented. The data are specified by a detailed description of the design and particular conditions of the underlying study protocols.

Angioedema↗
PubMed1990

The new dermatology. Implications for the dermatologist and for dermatological training.

The advent of new drugs including 'over the counter' (OTC) drugs, the increasingly aged population with its special requirements for skin care, and environmental and occupational factors will affect the nature of future dermatological practice in developed countries. The role of sub-specialists is likely to increase, and the case for expansion of the dermatological consultant grade is debatable. Consultant training should place more emphasis on highly specialised training in specific areas, including occupational dermatoses, environmental dermatology, dermatopharmacology, dermatological surgery and dermato-oncology. A strategy for dermatological research in Europe needs to be established which is based upon fewer, larger groups of a multi-disciplinary character. Corporate support could well help achieve this aim.

Aged↗
PubMed1989

Effect of dithranol treatment on arachidonic acid and its lipoxygenase products in psoriasis.

The concentrations of arachidonic acid and its lipoxygenase metabolites were measured in exudates from lesional psoriatic skin during treatment with 0.25% dithranol (anthralin) applied topically for 10 days. Dithranol caused a reduction in the concentration of arachidonic acid at 10 days (167 +/- 42 and 358 +/- 55 ng ml-1 treated and control sites respectively, p less than 0.05) concurrent with clinical improvement of the lesions. Neither 12-hydroxyeicosatetraenoic acid nor leukotriene B4 concentrations were significantly affected. These results do not support the view that lipoxygenase products are of major importance in the pathogenesis of psoriasis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

A comparison of the proinflammatory effects of 12(R)- and 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid in human skin.

Topical application of racemic 12-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R,S)-HETE] produces erythema and leucocyte accumulation in human skin. Since 12(R)-HETE is more potent than its epimer 12(S)-HETE as a neutrophil chemoattractant in vitro, their proinflammatory effects have now been compared in vivo. 12(R)- and 12(S)-HETE (0.5 - 20 ug/site) were applied topically to the forearm skin of 5 healthy volunteers and the sites occluded for 6 h. Five ug each of the two enantiomers were also applied to the opposite forearm. At 6 and 24 h blood flow and the areas of erythematous responses were measured. The 5 ug application sites were biopsied at 24 h. Both enantiomers caused dose related erythema and increased blood flow at 6 and 24 h, which were not significantly different at either of the time points tested. In contrast, pronounced neutrophil infiltrates were seen in the epidermis (25.2 +/- 13 cells/hpf) and dermis (13.2 +/- 5.1 cells/hpf) 24 h after application of 12(R)-, but not 12(S)-HETE (0.02 +/- 0.02 and 1.02 +/- 0.7 cells/hpf in epidermis and dermis respectively). However, the numbers of dermal mononuclear cells accumulating in response to the two enantiomers were similar. 12(R)-HETE thus appears to be a more potent neutrophil chemoattractant than 12(S)-HETE in human skin in vivo and may be of potential importance as a mediator of inflammation in man.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) does not stimulate proliferation of human neonatal keratinocytes.

We have developed an assay to study the effect of drugs on the proliferation of neonatal human skin-derived keratinocytes in vitro. Expanding populations of neonatal keratinocytes were cultured in low concentrations (0.5%) of fetal calf serum for up to 12 d. Growth of the cultures was determined by measurement of DNA using a sensitive fluorimetric assay. Addition of 10(-9)-10(-6) M 12(RS)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(RS)-HETE) neither stimulated keratinocyte proliferation nor enhanced the incorporation of [3H]thymidine. The ability of neonatal keratinocytes in low serum medium to respond to exogenous factors was demonstrated by increased growth in response to a mixture of cholera toxin, hydrocortisone, and epidermal growth factor. Confluent keratinocyte cultures in 10% human AB serum exposed to 12(S)-HETE for 72 h also showed no changes in DNA, [3H]thymidine incorporation, or labeling index. Metabolism of 12(S)-[3H]HETE was greater in cultures containing low concentrations of serum but there was no evidence for the formation of 12,20-dihydroxyeicosatetraenoic acid.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

Delayed pressure urticaria, objective evaluation of a variable disease using a dermographometer and assessment of treatment using colchicine.

A randomized double-blind placebo controlled trial of colchicine in the treatment of 13 patients with delayed pressure urticaria enabled us to assess some of the variables in this disorder. We have modified a previously described method of pressure testing using a calibrated dermographometer and shown a pressure induced papular dose response curve. Assessment of disease activity was based on the number of pressure weals which occurred, the size of delayed pressure induced papules using a dermographometer calibrated at 9.75 x 10(5) pascals for five separate time periods on the back and estimations of erythrocyte sedimentation rate and the acute phase protein levels. We have been unable to show a therapeutic effect using colchicine 0.5 mg bd for I week.

Adult↗
PubMed1989

Vibratory angioedema: lesion induction, clinical features, laboratory and ultrastructural findings and response to therapy.

We report the investigation and treatment of a 28-year-old woman with the rare condition of non-familial vibratory angiodema. Lesions were reproduced using a vibrator set at pre-determined frequencies and amplitudes, applied for a fixed time period. There was no indication of the production of tolerance in the patient with repeated vibration, but terfenadine produced a good therapeutic response. There was no evidence of mast cell degranulation at the ultrastructural level. The patient also had mild delayed pressure urticaria and dermographism, thus demonstrating the clustering frequently found in the physical urticarias.

Adult↗
PubMed1989

Symptomatic dermographism: wealing, mast cells and histamine are decreased in the skin following long-term application of a potent topical corticosteroid.

Clobetasol propionate 0.05% ointment and an otherwise identical steroid-free base were applied topically to a 10 cm2 area on the anterior thighs of six patients with symptomatic dermographism for 6 weeks. Four patients showed a significantly decreased wealing response to stroking of steroid pretreated skin compared to that of control sites. There was a parallel decrease in mast cell numbers and histamine levels in skin biopsies taken from the steroid treated areas. At 6 weeks two patients demonstrated a decrease in flare areas following the intradermal injection of compound 48/80 in steroid pretreated skin compared to base treated sites. Flare areas following intradermal injection of histamine in these two patients were equivalent in base and steroid treated skin.

Administration, Cutaneous↗
PubMed1989

Most women with acne have polycystic ovaries.

Out of 98 female referrals with acne vulgaris it was possible to define ovarian morphology by high resolution ultrasound imaging of the pelvis in 82 (84%). Sixty-eight (83%) were shown to have polycystic ovaries, compared with 19% in a control group without acne. The presence of polycystic ovaries in the acne patients did not correlate with acne severity, infertility, menstrual disturbance, hirsutes, or biochemical endocrinological abnormalities.

Acne Vulgaris↗