Biomedical subjects
Publications and source records attributed to I A Magnus.
Fourteen patients suffering from actinic prurigo were treated with thalidomide. Eleven patients showed lasting improvement on the drug and three of these remained symptom-free after discontinuing therapy. No major side-effects were observed. Thalidomide is an effective drug in the treatment of actinic prurigo but it must be used with adequate contraception in women of child-bearing age.
The production of the sunburn cell by UV-A radiation and topical psoralens in hairless mouse epidermis has been studied. It has been shown that the appearance of this cell is dependent on the dose of both UV-A radiation and of the psoralen. The time-course with 8-methoxypsoralen has peak sunburn cell numbers at 28 hr postirradiation. A comparison of 2 bifunctional (8-methoxypsoralen and 5-methoxypsoralen) and 2 monofunctional (angelicin and 3-carbethoxypsoralen) psoralens showed the former are more potent. This suggests that DNA crosslink lesions may play a rle in sunburn cell production.
A series of controlled trials of treatments for polymorphic light eruption (PLE) with oral beta-carotene, ketoprofen and chloroquine, and topical benzimidazole sunscreen cream is described. Clinical features were recorded using diary cards filled out by the patients, and exposure to UVR was measured individually in all patients with film badges. Symptoms were found to be dependent on exposure. None of the treatments proved very effective, but beta-carotene seemed to give significant slight protection against irritation and erythema, though this was not confirmed in a repeat study using a higher dose. Chloroquine seemed to protect slightly against irritation. As the degree of improvement with chloroquine and beta carotene is quite small, equivalent to a protection factor of 2, it is arguable whether these treatments as used here are worthwhile and in the case of chloroquine, with its risk of adverse side effects, whether it is justifiable. Other treatment and dose regimes are possible and further trials seem worthwhile. Our studies have helped to define the special difficulties in collecting objective data in PLE and should improve the methods for assessing treatment in the photodermatoses.
The UVR radiometry of a long-term mouse photocarcinogenesis project is described. The methods used were (a) a phototherapy (UV-A) radiometer, (b) an electronic integrating dosimeter, (c) indirect spectroradiometry and (d) polysulphone and phenothiazine film badges for UV-B and UV-A respectively. The merits of the various methods are discussed. All but the phenothiazine film were considered to be satisfactory. The importance of reliable UVR radiometry is emphasized.
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The histological change known as individual cell shrinkage necrosis (so-called "sunburn cell' in mammalian epidermis) would seem to be suitable for quantitative morphological studies on the effect of psoralen treatment and near UV irradiation. The number of sunburn cells per unit length of epidermis versus varying doses of narrow waveband UVR, 305-375 nm, has been studied and an action spectrum constructed which has maximal activity at 320-335 nm. The implications of these findings are discussed.
The weal and flare produced by monochromatic irradiation in solar urticaria may be treated as a classical dose-response. This has been used to investigate therapy with H1 and H2 antihistamines. The conventional H1 drug proved superior. But from the practical viewpoint, solar urticaria is difficult to suppress even with a relatively efficient H1 Antihistamine, chlorpheniramine; the mean protective factor in 5 patients was only 2, insufficient for satisfactory clinical management.
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We report clinical, genetic and biochemical findings in 13 families with the photosensitive genodermatosis, xeroderma pigmentosum. All patients had a defect in repair of DNA damage provoked by ultraviolet radiation. Eleven patients and their three affected sibs were defective in the excision repair of UVR induced DNA lesions while the other two were defective in post-replication repair. One in the former group was diagnosed prior to the development of permanent skin abnormalities and preventive measures succeeded for almost five years in maintaining a normal appearing skin. In addition, two cases were diagnosed prenatally and aborted therapeutically. Some patients' parents showed slightly reduced repair of UVR induced DNA damage. In xeroderma pigmentosum (XP), the defect in the excision of DNA lesions appears to be due to homozygosity for one of at least seven different mutations and, accordingly, XP patients can be assigned to seven so-called complementation groups, A to G. Of these, groups A, C and D are the most common. Somatic cell fusion allowed three of the families reported here to be assigned to group A, four to group C and four to group D. Fibroblasts of patients from these three groups were shown to differ not only in the degree and kinetics of their residual DNA repair but also in the kinetics with which their defect is complemented by fusion with normal or XP cells of other groups. This confirms that mutations of different genes play a role in XP and provides a basis for understanding how such genes interact to secure repair of DNA lesions in normal cells. We discuss the phenotype of XP from different complementation groups in relation to the severe neurological abnormalities which may develop and must be considered in genetic counselling. We also discuss the biochemical anomalies of XP and the cellular effects of physical and chemical agents which damage DNA. In the practical management of XP, the importance of early differential diagnosis and prompt initiation of treatment is emphasized. Lastly we review the relationship between DNA repair and skin cancer in XP.
It has been shown that light may stimulate hepatic porphyria in the rat. This is evidently due to a neuro-endocrine pathway involving retina, nerve pathways in the brain and including the sympathetic chain, the pineal gland and the gonads. This light effect in porphyria appears to be via a circadian rhythm in the liver.
A novel method for separating porphyrin polycarboxylic acids is described and illustrated by its application to the direct analysis of biological (deep-sea medusae), clinical (urine) and chemical ('haematoporphyrin derivative') samples.
The analysis of skin porphyrins in biopsies in patients with porphyria cutanea tarda has been achieved by high pressure liquid chromatography. Porphyrins were determined as their methyl ester copper-chelates and 2-,4-,5-,6-,7- and 8-carboxylic porphyrins distinguished and quantified.
A lapel badge dosimeter sensitive to short wave UVR has been used in a preliminary trial to survey photosensitivity in psychiatric patients on phenothiazine therapy. The badge was found easy to use and the results suggest that chlorpromazine is more photosensitizing than other phenothiazines.
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Preliminary work on a dosimeter suitable for measuring UVR exposure on individual persons is described. It is based on the use of polysulfone film which, on exposure, shows a change in absorbance that is determined spectrophotometrically. The results of studies of groups of persons with vastly different degrees of solar exposure, e.g., outdoor and indoor workers and geriatric patients, and psychiatric patients with photosensitivity from phenothiazine drugs are presented. We consider the dosimeter may also be suitable for epidemiologic studies in sunlight-induced skin cancer.
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