Biomedical subjects
D S Wilkinson
Publications and source records attributed to D S Wilkinson.
Perioral dermatitis: a 12-year review.
A continuing study of perioral dermatitis over a period of 12 years is presented. A distinction is made between various patterns of circumoral and paranasal dermatitis and the clinical picture that we describe as "perioral dermatitis". No cases were seen before 1966 but the number of patients presenting to hospital clinics or in private practice rose dramatically until 1970-1972, after which there has been a progressive fall in numbers. In this period, 259 patients were diagnosed as having the condition and of these 203, resident in an area of some 275,000 population and seen by one or other of us on at least two occasions, form the basis of this study. There were 173 females, fifteen males and fifteen children under 12 years of age. In many cases it was possible to suggest the primary lesion for which patients sought treatment. In sixty-nine patients this consisted of a para-oral eruption on the side of the chin and, in forty-one a paranasal erythematous dermatitis. The characteristic appearance and spread of the eruption to the glabella and eyelids are described. A few patients, mostly male, showed lesions around the eyelids only, from treatment of seborrhoeic dermatitis. All but nine of the patients acknowledged the use of potent (not necessarily fluorinated) topical corticosteroids over long periods; in many cases these were self-administered. Some of the children had been treated with preparations intended for their mothers. The numerous aetiological agents that have been incriminated as causes of this eruption are examined. We believe that the prolonged use of topical potent corticosteroids is the only one tenable from our observations. The role of hormonal factors and of local irritant agetns is examined in this context. Tetracyclines are curative in the great majority of patients in 6 weeks if local corticosteroids are discarded. Relapses are rare. Perioral dermatitis is a most satisfying condition to treat but several questions remain unanswered. The current "revolt" against all forms of cortisone may enable us to answer some of these in the near future.
Discoid eczema as a consequence of contact with irritants.
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Comparison of patch test results in two adjacent areas of England-I. (Industrial allergens).
A 3-year study of patch test reactions to the Standard European Battery has been carried out in two adjacent areas of S. E. England with the same climatic and cultural background. The source of materials and method of testing were identical; both observers had worked together in the same Contact Dermatitis department and the interpretation of reactions can therefore be considered to be consistent. The main differences between the two areas lay in the pattern of employment and of local medicament prescribing. The first only is examined here. One area was dominated by the automobile industry, the other by the furniture industry, with important subsidiary rubber, foam and electronics factories. The pattern that emerges shows that patch test reactions to the Standard European Battery were more likely to be related to environmental allergens and medicament usage than to industrial hazards. Chrome dermatitis was less common than elsewhere in Europe but nickel sensitivity showed the same pattern. Rubber chemical sensitivity reflected industrial, as well as domestic usage. Colophony and formaldehyde appeared to have less industrial significance than we expected. Special additional industrial allergens are not considered here but were of particular importance in the furniture industry. Although the numbers analysed were relatively small, we believe that they reflect the pattern to be expected in areas of relatively low industrial risk in Great Britain at the present time.
Prognosis of hand eczema in hairdressing apprentices.
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Unusual presentation of epoxy resin sensitivity.
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Skin and nail lesions from gold potassium cyanide.
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[Some atypical forms of eczema in children (author's transl)].
Among 466 children under the age of 12 years who presented with eczema in a 5-year period, 68 p. 100 were atopic. 136 had various atypical signs of atopy. 44 suffered from pityriasis alba of sufficient intensity to justify referral for this reason; 10 had the typical features of seborrhoeic dermatitis of infants. 27 suffered from "forefoot" eczema ("juvenile plantar dermatosis"). The course and characteristics of this condition are discussed and compared with the series recently described in the West of Scotland. Our cases were exactly similar except for an aggravation in the summer months and the fact that our cases responded poorly to topical corticosteroids alone though improved with coal tar. Atopy and contact sensitivity to shoe materials are rare in both groups. We feel that this may be classified as "frictional" dermatitis and agree with our Scottish colleagues that the introduction of nylon socks during the last ten years may be important.
Metabolism of 5-fluorouracil in sensitive and resistant Novikoff hepatoma cells.
N1-S1/FdUrd Novikoff hepatoma cells, which lack thymidine kinase activity, are resistant to 5-fluorouracil (FUra) as well as 5-fluorodeoxyuridine (FdUrd), suggesting that the pathway, FUra leads to FdUrd leads to FdUMP, is utilized for the conversion of FUra to FdUMP. However, the inhibition of thymidylate synthetase activity, the presumed target of FdUMP, by 1 X 10(-4) M FUra in intact N1-S1 Novikoff hepatoma cells, which have significant levels of thymidine kinase activity, is completely eliminated by 5 X 10(-4) M hydroxyurea, which is a potent inhibitor of ribonucleotide reductase. These results imply that the formation of ribonucleotides and does not involve thymidine kinase. This apparent dichotomy can be explained by the fact that, in addition to the well known lack of thymidine kinase activity, [14C]FUra conversion to ribonucleotides is greatly depressed in the N1-S1/FdUrd cells. Hence, the formation of FdUMP from FUra in Novikoff hepatoma cells apparently proceeds primarily via the intermediate formation of ribonucleotides. The decreased conversion of FUra to ribonucleotides in N1-S1/FdUrd cells decreases not only the ability of the analog to inhibit DNA synthesis, but also its effect on RNA metabolism. FUra, at a concentration of 1 X 10(-5) M, inhibits rRNA maturation in N1-S1 cells, but not in N1-S1/FdUrd cells. Since N1-S1/FdUrd cells are completely resistant to 1 X 10(-5) M FUra, whereas N1-S1 cells are completely inhibited by 1 X 10(-5) M FUra, even in the presence of 1 X 10(-4) M thymidine, the effects of FUra on RNA metabolism appear to contribute significantly to the cytotoxicity of the analog at higher drug concentrations.
Increased thymidylate synthetase activity in 5-fluorodeoxyuridine-resistant Novikoff hepatoma cells.
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Evidence for role of purine nucleoside phosphorylase in sensitivity of Novikoff hepatoma cells to 5-fluorouracil.
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The role of the dermatologist in industrial medicine.
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The mechanism of 5-fluorouridine toxicity in Novikoff hepatoma cells.
The mechanism of 5-fluorouridine (FUrd) cytotoxicity in Novikoff hepatoma cells appears to vary under different experimental conditions. Continuous exposure to 1 X 10(-7) M FUrd results in a simple thymineless death that can be prevented by the addition of 1 X 10(-4) M thymidine to the culture medium. In contrast, 1 X 10(-4) M thymidine does not prevent the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd, despite the fact that it does prevent the inhibition of DNA synthesis. Although it has no effect on the inhibition of DNA synthesis, 1 X 10(-4) M uridine prevents the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd. Since 1 X 10(-4) M uridine, but not 1 X 10(-4) M thymidine, prevents the inhibition of ribosomal RNA maturation caused by a 1-hr exposure to 1 X 10(-5) M FUrd, it seems likely that the effects of the analog on RNA metabolism contribute significantly to the cytotoxic activity of the analog in this specific experimental situation.
Cinnamic aldehyde in toothpaste. 1. Clinical aspects and patch tests.
Although cinnamon is known to cause dermatitis in bakers and confectioners, it has only rarely been reported as causing trouble in food or cosmetics. A newly-formulated 'spicy' toothpaste containing cinnamon as a flavouring agent was the cause of oral symptoms in eight patients referred to clinics in Buckinghamshire and in Malmö and in a further eight patients discovered subsequently. Similar symptoms and patch test results were observed independently at both centres. Positive reactions were obtained with 1% cinnamic aldehyde in 15 out of 16 patients tested. Only one patient reacted to a standard sample of balsam of Peru (25% in petrolatum).
Sensitivity to cinnamic aldehyde in a toothpaste. 2. Further studies.
The authors carried out further studies to assess the significance of the findings of patients sensitive to cinnamic aldehyde in a toothpaste. Selected groups of patients in whom sensitivity to this might have been overlooked were patch-tested. With the exception of three patients, two with cosmetic sensitivity and one with hand eczema, the results were negative. The frequency of use of the original toothpaste was assessed among patients attending the clinic and this was followed by a circular letter to general practitioners and dentists inviting referral of patients with oral symptoms. As a result, five further cases, four of whom gave positive patch test reactions to cinnamic aldehyde, were discovered. The authors emphasize the importance of attempting to obtain accurate information as quickly as possible when 'new' or hitherto unsuspected allergens are implicated.
The inhibition of ribosomal RNA synthesis and maturation in Novikoff hepatoma cells by 5-fluorouridine.
The inhibition of ribosomal RNA (rRNA) maturation by 5-fluorouridine (FUrd) in Novikoff hepatoma cells appears to depend upon the incorporation of the analog into the 45 S rRNA precursor. Precursor synthesized in the presence of FUrd is not processed into mature rRNA, but precursor synthesized in the absence of the analog is processed normally after the addition of the drug. The effect of FUrd on rRNA maturation is concentration dependent. At a concentration of 1 X 10(-4)M, the analog completely inhibits the formation of mature 18 S and 28 S rRNA; while at a concentration of 1 X 10(-7)M, the analog has no significant effect on rRNA maturation. These results suggest that some minimum degree of analog substitution is necessary to inhibit the maturation process. In addition to its inhibition of maturation, FUrd also inhibits the transcription of 45 S rRNA precursor. However, this effect of the drug is less complete and more time dependent that the effect on maturation. The inhibition of rRNA maturation by FUrd persists after removal of the analog from the culture medium. Cells that had been exposed to FUrd for 2 hr were unable to process 45 S rRNA precursor 20 hr after removal of the drug from the medium.