Richard B. Stoughton

Essential fatty acid deficient hairless mouse: a model of chronic epidermal hyperproliferation

Epidermal DNA synthesis has been shown to be increased approximately three‐fold in hairless mice that were fed a diet deficient in essential fatty acids (EFA deficient) for 65 days, compared with animals fed a standard diet. Autoradiographic labelling indices showed a 330% increase in the EFA deficient mice over controls. The animals developed evidence of a diffuse thickening, scaling and loss of elasticity of the skin after 40 days on the EFA deficient diet. Histologically, the epidermis of the EFA deficient animals showed acanthosis, hypergranulosis, hyperkeratosis and increased intracellular epidermal spaces. Increased mitotic indices were found with Feulgen staining.

An animal model for screening drugs for antipsoriatic properties using hydroxyapatite to isolate DNA rapidly from the epidermis.

A new, rapid, simple and accurate procedure for extracting DNA from the epidermis is described involving hydroxyapatite. This compound has an unique property of high affinity for double stranded native DNA, but none for RNA and protein. The technique has been applied to a hairless mouse model for screening systemic and topical agents for cell inhibitory properties in proliferating epidermis for potential use in the therapy of psoriasis.

Acute tolerance to effects of topical glucocorticosteroids

Tachyphylaxis (acute tolerance) to two important actions of topical glucocorticosteroids is demonstrated. In humans, topically active glucocorticoids applied to the skin cause vasoconstriction initially but this response fades with successive applications. In hairless mouse epidermis, inhibition of DNA synthesis and mitosis is caused by one application of a glucocorticoid but with repeated administration of the drug this effect is lost. The degree of inhibition of cell division appears to be similar 30 and 54 h after one application of steroid to that following three or five applications during such a time period. These findings suggest that an optimum therapeutic approach to the use of these agents exists.

Penetration of drugs through the skin.

Various methods for measuring percutaneous absorption are discussed with particular reference to glucocorticosteroids. Increasing concentrations of steroids in a given formulation will yield a decreasing percent of amount penetrating and a corresponding propertionate decrease in biologic activity. The formulation can shift the relationships of concentration to penetration and to biologic activity. The use of bioassay methods to detect penetration of antibiotics has been applied to find an active topical antibiotic for treatment of acne vulgaris.

Anti-inflammatory properties of a prostaglandin antagonist, a corticosteroid and indomethacin in experimental contact dermatitis

The topical effects of N0164 (a phenyl phosphonate derivative which is a partially selective antagonist of prostaglandin E2), indomethacin and triamcinolone acetonide have been shown to reduce the erythema and ear weight gain from inflammation induced by experimental contact allergic eczema. Oxazolone sensitized Swiss Webster mice were used, ear erythema and ear weights being used as a measure of the anti‐inflammatory response to the drugs. N0164 was also shown to have systemic anti‐inflammatory activity after intraperitoneal injection.

An animal model for screening topical and systemic drugs for potential use in the treatment of psoriasis using a new, rapid and simple technique of extracting DNA from epidermis involving hydroxyapatite column chromatography

A new hairless mouse model using ultraviolet light to stimulate increased epidermal cell turnover and hyperplasia and thus simulate psoriasis has been designed so that drugs may be tested both topically and systemically for possible therapeutic value in this disease. Two methods of determining drug antimitotic activity have been used, the mitotic index and the extraction of epidermal DNA and the determination of the radioactivity of the sample. Results show that 2% 5-fluorouracil in propylene glycol and 2% nitrogen mustard in water topically and cyclophosphamide systemically, which are drugs known to be effective in psoriasis, significantly reduce the mitotic index. DNA synthesis is similarly decreased by the latter two drugs. The effect of the topical agents is shown to be local and not systemic. Cyclophosphamide, which is ineffective topically in psoriasis, is ineffective in the model.

Status of topical therapy

Topical therapy is an ancient and honorable rite performed for eons by kings and quacks of the art of medicine not to mention the myriads of lesser informed members of human society. Considering the enormous variety and quantity of molecules the ancients and moderns have applied to skin in the ever hopeful management of skin disease, it is quite remarkable that almost all such diseases have remained steadfast and full‐blown in the face of incredibly imaginative potions and poultices.

The Effect of Alclometasone Dipropionate Cream 0·05% on the Hypothalamic-Pituitary-Adrenal Axis of Normal Volunteers

In an open study of ten evaluable normal volunteers, 30 g of alclometasone dipropionate cream 0·05% was applied to 80% of body surface each morning and evening for 21 days. A plastic body suit effectively occluded the treated area for 12 hours/day. As demonstrated by continued normal levels of 8 a.m. plasma cortisol and 24-hour urinary 17-hydroxysteroid and free cortisol, no suppression of the hypothalamic-pituitary-adrenal axis occurred. Local adverse reactions were mild and transient.

A benign "malignant" ulcer.

Summary.— A case is presented which is not amenable to exact diagnosis. In the presence of active auto‐immune thyroiditis, this lady developed a florid phagedaenic ulcer without obvious aetiology. No pathogen could be isolated and the lesion does not fit into any neoplastic or pseudo‐neoplastic category. Her excellent response to conservative treatment favours a non‐malignant background, but even long term follow‐up will not resolve all doubts, as she has received a course of radiotherapy.

CLEVELAND DERMATOLOGIC SOCIETY

Panel Members:Dr. Richard B. Stoughton(moderator),Dr. Gerard DeOreo, Dr. Leon Goldman, Dr. John Haserick, Dr. A. E. Walker. Dermatomyositis; Diabetes Mellitus. Presented byDr. C. F. H. Vickers, MRCP (service of Dr. Richard B. Stoughton). History .—This 52-year-old white male was admitted to University Hospitals in October, 1962. He had first noticed itching and erythema on the left shoulder three weeks before admission. Three days later, early morning muscle stiffness associated with aching appeared. Two days prior to his admission he developed itching of the eyelids, forehead, and upper chest at the same time that he noticed that his fingers became white on exposure to cold, a phenomenon he had never observed before. Physical Examination .—On admission his temperature was 38.8 C (101.8 F) and his blood pressure was 145/82. He was an obese man in no obvious distress. There was a violaceous erythema of the forehead, upper