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Biomedical subjects

R Marks

Publications and source records attributed to R Marks.

At least 235 records · Page 13Linked to original sources

Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis.

A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.

Adolescent↗

"Goodbye Sunshine": effects of a television program about melanoma on beliefs, behavior, and melanoma thickness.

Of 333 persons interviewed after a television show about the effects of melanoma, 113 (34%) saw the show and 73% believed that the sun protection/skin examination message applied to them. Fifty-six percent of persons examined their own skin and 36% examined someone else's skin after seeing the program. Fifteen persons (4.5% of the total sample) planned to visit a doctor for an abnormal skin spot as a result of the program, of whom three actually did so within 4 weeks of the show. An increase of 167% was observed in the number of melanomas diagnosed in the 3 months after the show, compared with those diagnosed in the same period the year before. There was a significant shift in the proportion of tumors removed in the thin, easily cured stage. The high rate of diagnosis of new tumors and the high proportion of thin tumors was maintained a year after the program. By extrapolation from these figures, it is estimated that 208,000 Victorians out of a total population of 4.1 million intended to seek a consultation after a single television program. Of these, it is estimated that about 27,000 actually sought attention in the month after the viewing.

Adolescent↗

The effect of dermatophyte species and density of infection on the pathology of ringworm.

In this study we have measured the mean hyphal length as a function of the density of infection in skin surface biopsies from patients suffering from infection with different species of dermatophyte. The tissue response in the epidermis and dermis of these patients was evaluated for the degree of eczematization (epidermal thickening, spongiosis and dermal infiltrate) in periodic acid Schiff stained histological sections, employing visual analogue scales. There was no correlation between mean hyphal density and the degree of eczematization.

Adult↗

Heat shock proteins in cultured human keratinocytes and fibroblasts.

Heat shock induces in cells the synthesis of specific proteins called heat-shock proteins. We have compared the induction of these proteins in human keratinocytes, skin fibroblasts, and a human epithelial tumor cell line following exposure to weak and strong inducing agents (heat, cadmium sulphate, and sodium arsenite). The induction of heat shock proteins was measured in cells by one-dimensional gel electrophoresis of [35S] methionine-labeled proteins and by immunofluorescence using a specific HSP72 monoclonal antibody. Both HSP90 and HSP116 were constitutively expressed in these cell types. Exposure of these cells to weak inducing agents such as heat or cadmium sulphate resulted in the synthesis of HSP72 and HSP90, whereas HSP28 and HSP116 synthesis was detected in keratinocytes and fibroblasts following exposure to the strong inducing agent sodium arsenite. In addition, sodium arsenite induced the synthesis of HSP46 in human keratinocytes. Immunofluorescence demonstrated a rapid and reversible accumulation of the 72-kD heat shock protein within the nucleolus of heat-stressed human keratinocytes and fibroblasts.

Arsenic↗

Phenytoin has little effect on in-vitro models of wound healing.

It has been reported that phenytoin induces gingival and connective tissue hyperplasia and may be of use in wound healing. In this study the effect of phenytoin on human epidermal keratinocytes and skin fibroblasts has been investigated in vitro. Cell cultures were exposed to increasing concentrations of phenytoin from 10(-9) to 10(-4) M in the presence of 1 and 10% serum supplemented medium. In addition the effect of phenytoin on epidermal cell migration (epiboly) has been investigated using organ culture of human skin. No stimulation of cell growth was observed, and only a mild toxicity affecting keratinocytes was seen at the highest concentrations. Similarly, no effect on epidermal cell migration in vitro was observed. The lack of a direct effect in vitro suggests that any in-vivo effect was not the result of interaction between phenytoin and keratinocytes or fibroblasts but possibly due to indirect modulation via other cell types, such as inflammatory or lymphoreticular cells.

Adult↗

The effect of area of application on the intensity of response to a cutaneous irritant.

The intensity of the cutaneous response was assessed after application of a standard irritant to increasing areas of normal forearm skin. Twenty subjects were tested to determine the minimal irritant dose (MID) to dilutions of aqueous sodium dodecyl sulphate. Each subject was then treated under occlusion for a period of 24 h with different areas of filter paper (9, 25, 100, 225 and 400 mm2) soaked with the concentration required to give the individual's MID. At 25 and 48 h the degree of erythema was assessed using a 0-4 arbitrary scale, a 10-cm visual analogue scale (VAS) and an erythema meter. Cutaneous blood flow was measured with a laser-Doppler device and cutaneous oedema measured by pulsed A-scan ultrasound. The results at 25 and 48 h were almost identical. Both forms of visual assessment (arbitrary scale and VAS) showed an increase in perceived erythema with increasing area and this was confirmed by the erythema meter. Further area-related changes were noted with both cutaneous blood flow and ultrasound measurements.

Administration, Cutaneous↗

Efficacy of topical dimetindene in experimentally induced pruritus and weal and flare reactions.

Double-blind, placebo-controlled studies were performed to assess the effect of 0.1% dimetindene gel on the itch threshold to intracutaneous histamine and on the weal and flare reaction after intracutaneous injection of histamine in normal volunteer subjects. Treatment of the forearm skin in 20 volunteers resulted in an increase in itch threshold with dimetindene gel compared to placebo. Treatment of the forearm skin with dimetindene gel in 32 volunteers had no significant effect on weal thickness in subjects treated for 10, 30 or 60 min, but there was a significant reduction in weal thickness in those subjects treated for 120 min. Topical dimetindene may be of value in treating conditions mediated through histamine release.

Administration, Topical↗

Topical retinoid treatment for skin cancer: a review.

There is laboratory and clinical evidence to suggest that retinoids have a potentially important place in the management of neoplastic and preneoplastic disorders of the epidermis. Topical administration avoids the side-effects of orally administered retinoids, but doubts remain over their efficacy. Evidence from clinical studies suggests that although topical retinoids have some effect in treating established skin cancers, alternative treatments are more effective. Topical retinoids appear more effective in the treatment of solar keratoses and epidermal dysplasia in photodamaged skin.

Administration, Topical↗

The effect of platinum complexes on human skin cells in vivo and in vitro.

The effects of platinum complexes on human fibroblasts and keratinocytes have been investigated. Cytotoxic effects were observed at approximately 4 microM (cisplatin), 10 microM (carboplatin) and 15 microM (JM9) when cells were grown continuously in these agents. When applied topically to hairless mouse skin in vitro carboplatin was shown to penetrate the skin and give levels where a cytotoxic effect would be apparent. Using an in vivo model of epidermal hyperproliferation in the mouse, an antimitotic effect of a 1% and 5% topical carboplatin preparation was demonstrated. These results suggest that topical platinum complexes are of potential in the therapy of hyperproliferative skin diseases.

Administration, Topical↗

Dose-response relationship between objective measures of histamine-induced weals and dose of terfenadine.

Terfenadine is a safe non-sedative H1-receptor antagonist. This study aimed to quantify the relative reduction in weal and flare area, thickness and erythema at 4, 8, 12 and 24 h following a single but variable oral dose of terfenadine compared with pre-treatment measurements, in order to compare the dose-effect relationship and time course of the different dosages. In a double-blind randomized cross-over study, 12 healthy volunteers were given 60, 120 or 240 mg of terfenadine or placebo. Twenty micrograms of histamine acid phosphate was then injected intradermally at 4, 8, 12 and 24 h. The weal and flare areas were measured by planimetry, the thickness of the weal by an A-scan pulsed ultrasound device and the redness of both the weal and flare by an erythema-meter. A definite dose-response relationship was demonstrated between the weal and flare areas and the three active treatments. For the weal area, there was a significant difference between 60 mg and 240 mg of terfenadine at 4 h (p less than 0.01), at 8 and 12 h (p less than 0.05). For the flare area there was a similar significant difference at 4 h (p less than 0.01) and at 8 h (p less than 0.05). A dose-response relationship was demonstrated between weal erythema and 120 mg or 240 mg and 60 mg of terfenadine (p less than 0.05). There was a correlation between the plasma levels of the major metabolite and the initial dose of terfenadine, demonstrating their expected proportionality. This metabolite was also demonstrated in tissue fluid.

Adult↗

Stucco keratoses. A clinico-pathological study.

Stucco keratoses are benign acquired papular warty lesions which usually occur on the distal parts of the lower limbs of elderly men. Their nature and pathogenesis are uncertain. Eight patients with multiple stucco keratoses who presented to the Cardiff Dermatology Department over an 18-month period were studied in an attempt to characterize these lesions. All subjects were male, with ages ranging from 50 to 72 years. Their lesions were most numerous over the fronts of the lower legs, but were also evident over other areas of the limbs. Most patients had a history of prolonged solar exposure, but the relationship of this to the development of the lesions was uncertain. Histologically there were no dysplastic changes and a characteristic regular 'church spire' type retention hyperkeratosis without marked acanthosis was evident. Lack of a marked increase in the epidermal cell population size is reflected in the normal in vitro tritiated thymidine autoradiographic labelling indices (7.81 +/- 1.67%, normal range 5 to 9%). Ultrastructurally no viral particles were evident and a normal pattern of epidermal differentiation with hypergranulosis was present. Two of the patients with myriads of lesions who were treated for 2 months with etretinate showed a dramatic clinical improvement which, however, lasted for 6 months only.

Aged↗

Increasing cervical screening in women of more than 40 years of age: an intervention in general practice.

An intervention that was aimed at increasing cervical screening in women of more than 40 years of age was undertaken, with general practitioners as the primary point of contact. The intervention consisted of the practice receptionist giving female patients pamphlets about Papanicolaou smear-tests and the general practitioner offering a Papanicolaou smear-test. Nineteen general practitioners and their female patients (n = 466) of more than 40 years of age who presented for consultation over a 10-day period were involved in this study. Each woman in the study was asked when she had last undergone a Papanicolaou smear-test. All women who were found to be "at risk", that is, who had not undergone a Papanicolaou smear-test in the previous two years (57% of those women who were asked) were offered cervical screening. Over-all about 50% of the women who were found to be "at risk" underwent a Papanicolaou smear-test at the general practitioner initiated request, either at the same consultation (26% of those "at risk") or on their return at a later date (23% of those "at risk"). Therefore, the intervention appears to have been effective in encouraging a relatively high-risk group of patients to undergo Papanicolaou smear-tests. However, the strategy was differentially effective depending on age: more women of less than 65 years of age underwent a Papanicolaou smear-test than did women of more than 65 years of age. The feasibility of using the intervention in everyday general practice depends on the willingness of medical practitioners to ask female patients to undergo a Papanicolaou smear-test, the ability to take a Papanicolaou smear during the consultation or soon after, and the acceptance of the invitation by women as based on an understanding of the need.

Adult↗

The role of childhood exposure to sunlight in the development of solar keratoses and non-melanocytic skin cancer.

The age-standardized proportion of persons with solar keratoses in 1232 Australian-born persons who were aged 40 years and older was 44.5% compared with a proportion of 15.7% in 1332 British persons who had migrated to Australia at various ages. Stratification of the British migrants into those who had arrived in Australia between one and 20 years of age and those who had arrived in Australia after the age of 20 years revealed that the proportion of persons with solar keratoses in the latter group never reached the proportion in Australian-born persons of the same age, in spite of many years in Australia after migration. Those persons who arrived in Australia between one and 20 years of age showed a lower proportion with solar keratoses in the younger age-groups, but with increasing age the proportion with solar keratoses equalled or exceeded that which was seen in Australians. These results suggest that a reduction in exposure to sunlight in childhood will reduce substantially the incidence of solar keratoses, and by implication, squamous-cell carcinomas, in adulthood.

Adult↗