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Biomedical subjects

M W Greaves

Publications and source records attributed to M W Greaves.

At least 181 records · Page 10Linked to original sources

Topical steroid treatment reduces arachidonic acid and leukotriene B4 in lesional skin of psoriasis.

Topical clobetasol propionate or vehicle ointment was applied daily for 3 days to psoriatic plaques on eight patients. Skin chamber exudates from untreated, steroid and vehicle treated lesions were assayed for arachidonic acid (AA), leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) before, and at 24 h and 72 h after treatment. Significant reductions in AA and LTB4 were observed at 72 h in steroid treated lesions. The reduction in 12-HETE levels observed after steroid treatment was not statistically significant. PGE2 levels in lesional psoriatic skin were unaltered. The reduction of AA, and LTB4 was associated with clinical improvement of psoriasis.

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

Cholinergic dermographism.

We report a patient with cholinergic urticaria in whom stroking the skin produced a band of erythema studded with the small weals characteristics of cholinergic urticaria. This response was suppressed by pre-treatment with topical scopolamine. Light and electron microscopy of the weal showed mast cell degranulation and a moderate mononuclear cell infiltrate.

Acetylcholine↗

Release of prostaglandin D2 and histamine in a case of localized heat urticaria, and effect of treatments.

A case of localized heat urticaria in a 70-year-old woman is reported. Increased plasma levels of prostaglandin D2 and blood histamine after heat challenge indicate a role for mast cell degranulation in the pathophysiology of the syndrome. Treatment with astemizole increased the temperature threshold to wealing, but not to itch or erythema. The patient was partially desensitized by repeated exposure to heat and this was further improved by indomethacin. After treatment there was no increase in plasma prostaglandin D2 on challenge. No evidence was found for the activation of the alternative complement pathway.

Aged↗

Recurrent angioedema: familial and oestrogen-induced.

We report two sisters who both have had severe attacks of urticaria and angioedema only when taking the contraceptive pill and during the latter half of pregnancy. Although they exhibited many features in common with hereditary angioedema (HAO), the C1 esterase inhibitor levels and other complement components were consistently normal, including levels measured during pregnancy and at the height of the eruption after oestrogen challenge. Aetiological factors in relation to other patterns and causes of urticaria are discussed.

Adult↗

Increased cutaneous fibrinolytic activity in aquagenic pruritus.

Aquagenic pruritus is a disease in which itchy prickling skin discomfort is evoked by contact with water at any temperature without observable cutaneous lesions. Little is known about its etiology and pathogenesis. Previous reports show that increased levels of blood histamine and cutaneous mast cell degranulation are present before water exposure and that they increase still further with water challenge. This paper shows that fibrinolytic activity is markedly increased both before and after water exposure, while circulating fibrinolytic activity is normal before water exposure in three cases of aquagenic pruritus. A patient who was asymptomatic at the time of the study had no observed increase in fibrinolytic activity either before or after water challenge, suggesting that the remission of symptoms of aquagenic pruritus and normalization of cutaneous fibrinolytic activity are interdependent factors.

Adult↗

Irritation and staining by 10-butyryl dithranol (butantrone) in psoriasis.

An open clinical trial was carried out using butantrone ointment in the treatment of 10 patients with psoriasis in order to assess staining and irritation in relation to efficacy. At 0.5% and 1.0% strengths, butantrone produced significant levels of irritation and staining with minimal clinical response and poor patient compliance.

Adolescent↗

The perivascular cell populations in human skin after topical application of leukotriene B4.

Fifteen timed biopsies of human skin were performed after application of 100 nanograms of leukotriene B4 in a Finnchamber for six hours. The number of inflammatory cells were counted per high power perivascular field and compared to three control biopsies. At 24 hours a peak of neutrophiles was observed and subsequently lymphocytes predominated. Eosinophils were never prominent. This pattern of successive cell populations has been described in inflammatory and whealing skin disease.

Administration, Topical↗

Water-induced itching without cutaneous signs. Aquagenic pruritus.

Aquagenic pruritus is now a well-recognized symptom complex, usually of unknown origin. A few prove to have polycythemia rubra vera. We describe an important and distinct subset, termed aquagenic pruritus of the elderly, in which old age, dry skin, and seasonal weather conditions are major factors. Unlike other varieties, aquagenic pruritus of the elderly responds to appropriate local measures.

Adult↗

Actions of prostaglandin E2 metabolites on skin microcirculation.

The actions of prostaglandin, E2 on skin microcirculation were compared with two of its metabolites. 2-10 ng prostaglandin E2, 2-10 micrograms 15-keto prostaglandin E2 and 5-10 micrograms 13,14-dihydro-15-keto prostaglandin E2 produced the following dose-related effects: increased area and intensity of erythema in human skin, increased vascular permeability in rat skin, potentiation of the increased vascular permeability elicited by either histamine or bradykinin, potentiation of carrageenan-induced oedema in the rat paw. The prostaglandin E2 metabolites are about 1000 times less active than the parent prostaglandin and are unlikely to account for the inflammatory actions of prostaglandin E2.

Animals↗

Leukotrienes C4 and D4 in psoriatic skin lesions.

Chemoattractant arachidonate lipoxygenase products have been recovered from the skin lesions of psoriasis, and may play a role in eliciting the intra-epidermal neutrophil infiltrate that characterises this disease. In view of evidence for lipoxygenase activity in psoriasis, the characteristic vasodilation in psoriatic lesions, and the vasodilator properties of leukotriene (LT) C4 and D4 in human skin, the presence of these LTs in psoriatic lesions has been investigated. Skin chamber fluid from abraded psoriatic lesions contained significantly greater amounts of immunoreactive material than that from clinically normal skin, as determined by a double antibody radioimmunoassay (RIA) that uses antiserum cross-reacting with both LTC4 and LTD4. Purification of lesional chamber fluid and scale extracts by high performance liquid chromatography (HPLC) and RIA of fractions showed immunoreactivity which co-eluted with standard LTC4 and LTD4. These findings suggest that LTC4 and LTD4 may play a role in mediating the vasodilation and increased blood flow that characterise psoriatic skin lesions.

Adolescent↗

Aquagenic pruritus.

The clinical characteristics of aquagenic pruritus (AP) based on a series of thirty-six patients are presented. AP is characterized by the development of severe, prickling-like skin discomfort that is without observable skin lesions and that is evoked by contact with water at any temperature. Other causes of pruritus associated with water contact must be excluded. In the thirty-six patients, skin discomfort developed within minutes of water contact in approximately half. In others, discomfort began 2 to 15 minutes after water exposure had ceased. The pruritus was usually generalized, lasting from 10 to 120 minutes (average, 40.6 minutes), and in 55% was associated with symptoms of acute emotional liability. There was no increased prevalence of atopy. Thirty-three percent reported a family history of water-related itching. Of fourteen patients treated with ultraviolet B phototherapy, eight (57%) noted significant relief. Of thirty-four patients, sixteen (47%) noted partial relief with oral antihistamine therapy. Patients with polycythemia rubra vera (PRV) may present with symptoms similar to those of AP, and all patients with symptoms consistent with AP should be investigated for the presence of PRV.

Adolescent↗

The responses of normal and psoriatic skin to single and multiple topical applications of leukotriene B4.

Topical application of single doses of leukotriene B4, (5-500 ng) under occlusion to the skin of normal volunteers and to the clinically normal skin of patients with untreated stable plaque psoriasis caused an inflammatory reaction lasting several days. Histologically, intraepidermal neutrophil microabscesses were seen in both groups following 50 ng applications of leukotriene B4, but there were significantly fewer intraepidermal neutrophils in the psoriatic than in the normal subjects. Nine repeated daily applications of leukotriene B4 (50 ng) to the same site were associated with a reduction of the visible inflammatory response in both volunteer groups, although application of a single 50 ng dose of leukotriene B4 to an adjacent, previously untreated site at the end of the multiple dose experiments elicited acute erythema and edema. Histologically, there were significantly fewer intraepidermal neutrophils in biopsies from sites to which 9 applications of leukotriene B4 were made than in sites to which 1 dose had been applied at the end of the multiple-dose experiments in both psoriatic and normal volunteers. Therefore, repeated application of leukotriene B4 is associated with decreased responsiveness which is due to a local mechanism in the repeatedly treated skin. No subject developed psoriasis following single or multiple applications of leukotriene B4, suggesting that the production of leukotriene B4 in the epidermis is unlikely to be a primary pathogenic event in this disease.

Administration, Topical↗

Cutaneous responses to 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE).

The responses to 12-HETE in normal human skin have been investigated by means of intradermal and topical administration in 15 subjects. Intradermal infusion of 12-HETE produced a neutrophil polymorphonuclear and mononuclear infiltrate in the dermis. Topical administration resulted in a dose-related erythematous response to 200 ng-50 micrograms. This was accompanied by a neutrophil and mononuclear dermal infiltrate at 6 and 24 h after application. In addition, collections of neutrophils were present in the epidermis in 4 of 10 subjects biopsied at 6 h and in all patients biopsied 24 h after topical application. Intradermal and topical application of 9-hydroxyoctadecadienoic acid (9-HODD), a chemically similar but chemokinetically inactive substance, did not produce neutrophil infiltration of the epidermis, nor did the chemical irritant nonanoic acid. The results suggest that the cellular infiltrates produced in vivo in humans by 12-HETE are due to its chemoattractant properties and are not the result of a nonspecific inflammatory response.

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

Lipoxygenase products of arachidonic acid in human inflamed skin.

Monohydroxy acids (HETEs) and leukotriene B4 (LTB4) metabolites of arachidonic acid were measured in skin of healthy volunteers after ultraviolet B irradiation, and in the uninvolved skin of psoriatics after topical dithranol application. Exudate was collected from suction bullae on control and inflamed abdominal skin, and analysed for 12-HETE and PGE2 by GC-MS and LTB4 by bioassay. 12-HETE and PGE2 were raised at 24 h but not at 72 h after u.v.B irradiation: control and 24 h values were 13.7 and 41.5 ng ml-1 (P less than 0.05, n = 6) for 12-HETE respectively, and 4.5 and 30.2 ng ml-1 (P less than 0.01, n = 6) for PGE2. Dithranol application raised PGE2 levels from 23.1 ng ml-1 in control exudate to 62 ng ml-1 (P less than 0.01, n = 6) at 24 h before declining to base levels at 72 h. However, 12-HETE was raised at 72 h (200 ng ml-1, P less than 0.01, n = 5) but not at 24 h (104 ng ml-1) compared to control levels (50 ng ml-1, n = 5). The levels of the LTB4 were low (less than 100 pg ml-1), and no significant increases were observed. Arachidonic acid in inflamed skin can be metabolised by the cyclo-oxygenase and lipoxygenase pathway. It is probable that the lipoxygenase product 12-HETE is involved in these inflammatory reactions.

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