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Biomedical subjects

R Marks

Publications and source records attributed to R Marks.

At least 253 records · Page 14Linked to original sources
PubMed1990

Investigations on the percutaneous absorption of the antidepressant rolipram in vitro and in vivo.

In vitro experiments using full-thickness human skin showed that it was feasible to deliver therapeutic amounts of the new antidepressant drug rolipram. Simple transdermal devices were constructed, and the presence of isopropyl myristate (IPM) in a silicone adhesive (Dow Corning X7-2920) enhanced the flux across excised human skin. The steady-state fluxes from adhesive mixtures containing 0, 5, and 10% IPM were 3, 5.2, and 6 micrograms/cm2/hr, respectively. The in vitro experiments were confirmed in a clinical study involving six healthy male volunteers. The formulations tested were an alcoholic solution and adhesive patches containing 5 and 10% IPM. The dose of drug administered was 0.5 mg/cm2 and the device size 25 cm2. Blood samples were withdrawn over a 24-hr period and analyzed using radioimmunoassay. The topical applications were well tolerated, with only mild or no side effects. A lag time of approximately 2 hr was found for the detection of rolipram in the plasma (detection limit, 50 pg/ml). Interindividual variations both for the peak drug levels and throughout the delivery were quite high but this magnitude of variation has been observed in many other transdermal studies. Plasma levels between 1 and 2 ng/ml were found for all formulations and the AUC0-30 hr was significantly higher for the patch containing 5% IPM.

Administration, Cutaneous↗
PubMed1990

The effects of an abrasive agent on normal skin and on photoaged skin in comparison with topical tretinoin.

Two studies were designed to assess the effect of abrasive preparations on the skin and to test the specificity of the effect of topical tretinoin in the management of chronic photodamage to the skin. In the first study two abrasive preparations (Brasivol fine and Brasivol medium) were compared with white soft paraffin and no treatment in eight volunteer subjects for their effects on the epidermis. The study was conducted over 3 days and measurements were taken of the effects on dansyl chloride-induced fluorescence to assess desquamation, epidermal thickness, and the tritiated thymidine autoradiographic labelling index. The abrasives were found to increase the desquamation rate significantly and to increase epidermal thickness and the epidermal labelling index compared to white soft paraffin and no treatment. In the second study the effect of one of the abrasive preparations (Brasivol medium) was compared with 0.05% tretinoin cream (Retin A) on the photodamaged skin of the dorsal aspects of the forearms of 12 subjects over an 8-week period. Cutaneous blood flow measured by the laser-Doppler flowmeter was found to be significantly increased in the abrasive-treated sites, but there was only a non-significant trend to increased blood flow in the tretinoin-treated sites. Measurements of skin thickness using pulsed A-scan ultrasound demonstrated that both treatments produced significant increases in thickness over the 8-week period but the increase was greater for the abrasive treated site. Measurements of the skin extensibility at the treated sites were made using a uniaxial extensometer. Forces needed for 30% skin extension were increased in the abrasive-treated sites only. Measurements of epidermal thickness and of [3H]-thymidine autoradiographic labelling indices showed greater increases in the abrasive-treated sites than in tretinoin-treated sites compared to untreated sites, but these increases were not statistically significant. No significant inflammation and no changes in the degree of elastosis or the presence of a 'repair zone' were found in any of the post-treatment biopsies. The results indicate that some of the changes produced in the skin by topical tretinoin that are taken to indicate a specific antiphotoageing effect may not in fact be specific and can be achieved by an abrasive preparation.

Adult↗
PubMed1990

An immunoradiometric assay for von Willebrand factor antigen to assess angiogenesis.

A method of determining the degree of vascularization of tissues would be of great value in dermatological research such as the investigation of neoangiogenesis in wounds and in the study of the vascular abnormality in psoriasis. We describe an adaptation of an immunoradiometric assay (IRMA) for von Willebrand factor antigen for this purpose. The results show that in endothelial cells in culture there was a good relationship between the number of cells and von Willebrand factor antigen measured by the IRMA. The relationships between the numbers of endothelial cells in biopsies of normal and healing wound skin as estimated by the histometric technique and the IRMA are less good (r = 0.45 and 0.32, respectively) but suggest that there is a positive and proportionate variation. There is a much stronger relationship (r = 0.79) between the biochemical and histometric methods in psoriatic skin.

Adolescent↗
PubMed1990

Epidermal growth factor receptors in human epidermal tumours.

Immunolocalization studies using the strepavidin/biotin peroxidase system were used to identify epidermal growth factor receptors in 10 samples of normal skin, 13 seborrhoeic warts (SW), five lesions of Bowen's disease (BD), 11 solar keratoses (SK), 22 basal cell carcinomas (BCC) and five squamous cell carcinomas (SCC). The intensity of cell membrane staining was assessed using the 10-cm visual analogue scale technique and the results analysed using non-parametric statistics. The cell membranes in BCC showed significantly less intense staining when compared to normal epidermal cells (P less than 0.001) and the constituent cells of SW (P less than 0.001), SK (P less than 0.001), BD (P less than 0.01), and SCC (P less than 0.001). Classification of the specimens into normal, benign, premalignant and malignant indicated that cell membranes of malignant tumours showed significantly less staining than the other groups (P less than 0.001). The observed reduction in the epidermal growth factor receptors in malignant tumours may be due to occupation and down regulation in response to autocrine secretion of growth factors.

Adult↗
PubMed1990

Topical retinoic acid for treatment of solar damage.

Twenty patients with chronic solar damage of the skin were entered in a double-blind, within-patient trial to compare the effect of 0.05% tretinoin cream with a placebo applied once daily for 12 weeks. Sixteen completed the study. Clinical assessment of the individual signs of solar damage were recorded on separate visual analogue scales. After 12 weeks, there were significant improvements in fine wrinkling around the eyes, crease lines around the mouth and cheeks, wrinkling on the dorsum of the hands and yellow discoloration. Overall, 14 of the tretinoin-treated sides were judged to have improved compared to only two of the placebo-treated sides (P = 0.011). Measurement of skin thickness by pulsed A-scan ultrasound revealed that the sides treated with tretinoin were significantly thicker than the placebo-treated sides (P = 0.019). Skin biopsies taken before and after treatment showed an increase in mean epidermal thickness with tretinoin treatment (P = 0.019). The clinical signs of improvement persisted at the follow-up assessment performed 4 weeks after cessation of therapy.

Administration, Topical↗
PubMed1990

The effect of cyclosporin on human epidermal keratinocytes in vitro.

Cyclosporin A has been shown to be effective in the treatment of severe, recalcitrant psoriasis, but it is uncertain whether the mode of action is primarily by immune suppression or by other mechanisms. Cyclosporin-dependent growth-inhibition has recently been demonstrated in vitro using several non-human and transformed epithelial cell lines. In this study the effect of cyclosporin on human epidermal keratinocytes and skin fibroblasts was investigated. Secondary cultures of human epidermal keratinocytes were grown on collagen-coated dishes in the presence of increasing concentrations of cyclosporin. Inhibition of growth was observed at 6-8 microM. An almost identical dose-response curve was obtained for the cytotoxic drug, cis-platin. Short-term exposure (I h) to cyclosporin did not have any effect on epidermal cell growth, suggesting that direct membrane-related effects were not involved. Analysis of cellular proteins by SDS-PAGE indicated no effect of continuous cyclosporin exposure on in vitro differentiation. The observation that human epidermal keratinocyte growth is inhibited by cyclosporin suggests that a topical form of therapy for psoriasis may be an effective alternative to oral treatment.

Adult↗
PubMed1990

Dose-response relationships for topically applied antigens.

Patch-test responses to serially diluted nickel sulphate and potassium dichromate solutions in patients with nickel and chrome sensitivity were assessed by pulsed A-scan ultrasound to determine skin thickness and laser-Doppler flowmeter techniques to evaluate blood flow, as well as clinical scoring. There was a relationship between the dose of antigen and the test responses as measured by ultrasound and laser-Doppler flowmeter techniques in both nickel and chrome sensitive patients. Our data suggest that both techniques may be useful in the detection of allergic contact dermatitis in which there is a doubtful patch-test reaction as well as in experimental sensitization studies.

Chromium↗
PubMed1990

Solar keratoses.

Solar keratoses are premalignant epidermal lesions that rarely transform to squamous cell carcinoma and occur even in temperate European climates much more frequently than has been previously supposed. Some lesions of solar keratosis may spontaneously regress due to immune rejection, but immunological influences do not appear to be responsible for keeping them from progressing to frank malignancy. Their frequency, accessibility and various morphological forms provide the basis of excellent models for carcinogenesis.

Adult↗
PubMed1990

Studies on the effects of topical retinoic acid on photoageing.

Tretinoin has been previously shown in animal and clinical studies to stimulate epidermal cell production and to be effective in the treatment of solar keratoses. A double-blind, placebo-controlled study confirmed that topical tretinoin produced an overall improvement in photoaged skin and decreased solar keratoses. There is no evidence that tretinoin has an irritative effect, nor is there any evidence that the improvement in appearance is due to oedema.

Administration, Topical↗
PubMed1990

Assessment of disease severity and outcome in the gravitational syndrome using pulsed A-scan ultrasound to measure skin thickness.

In order to investigate the prognostic significance of skin thickening in the gravitational syndrome, 54 patients and 10 normal control subjects were studied. Patients were investigated using a standard questionnaire, as well as recording the results of clinical history and a physical examination. To quantify the severity of the syndrome, an index of disease severity was devised on the basis of the clinical findings. Skin thickness was measured using pulsed A-scan ultrasound on standardized sites on the lower leg in patients and controls. The results indicated that skin thickness determined non-invasively by pulsed A-scan ultrasound can be used to provide prognostic information in the gravitational syndrome.

Adult↗
PubMed1990

Do all melanomas come from "moles"? A study of the histological association between melanocytic naevi and melanoma.

Histological examination of 1101 melanomas (990 superficial spreading and 111 nodular melanomas) from 1098 people revealed that 23.3% showed an associated melanocytic naevus. Of these, 56.5% were classified histologically as common acquired, 37.7% as dysplastic and 5.8% as congenital. Of the superficial spreading melanomas, 25.7% showed an associated naevus. By contrast, only 2.7% of nodular melanomas showed histological evidence of a coexisting naevus. When the superficial spreading melanomas were analysed by level, the presence of a naevus varied from 31.3% of level I melanomas to 21.3% of level IV melanomas. When thickness was measured, an associated naevus was found in 27.0% of superficial spreading melanomas less than 1.0 mm thick, and 14.8% of melanomas with a thickness of 1.0 mm or greater. These data suggest that most melanomas do not arise in pre-existing naevi, and accordingly public educational programs for the early detection of melanoma should focus on looking for changes in previously normal skin as well as in pre-existing moles.

Female↗
PubMed1990

Current views on the aetiology, pathogenesis and treatment of acne vulgaris.

Acne may vary from a relatively trivial condition to a severe disfiguring disease and management must be tailored to suit individuals. Pathogenetic factors that may be addressed by treatment include increased sebum secretion, abnormal follicular keratinisation, bacterial colonisation and local inflammation. Mild acne can be controlled with topical preparations alone but many patients with more severe disease require oral therapy with antibiotics, antiandrogens or retinoids. Combinations of topical and systemic treatments are often appropriate. The choice of drug requires knowledge of their efficacy, ease of use and possible adverse effects.

Acne Vulgaris↗
PubMed1990

Influence of obesity, impaired glucose tolerance, and NIDDM on LDL structure and composition. Possible link between hyperinsulinemia and atherosclerosis.

The possible causes of the enhanced risk for coronary heart disease (CHD) were examined in morbidly obese women with normoglycemia, impaired glucose tolerance (IGT), and non-insulin-dependent diabetes mellitus (NIDDM) before and after gastric bypass surgery. Compared with age-matched lean women, plasma lipid and apolipoprotein concentrations of the obese women before surgery favored atherogenesis. The risk for CHD may further be exacerbated in the IGT and NIDDM groups by the prevalence of smaller and denser low-density-lipoprotein (LDL) particles. LDL size correlated negatively with plasma insulin levels independent of triglyceride levels, age, or body mass index (BMI). After surgery, BMI, plasma insulin, and triglyceride levels decreased, but LDL size increased, and LDL density decreased. Neither cholesterol nor LDL cholesterol levels were affected after surgery, but high-density-lipoprotein cholesterol was increased in all patients after surgery. Although the mechanisms underlying the changes in the properties of LDL could not be determined from this study, these changes appear to be of benefit in reducing CHD risk in these patients.

Adult↗
PubMed1990

Methods for the assessment of the effects of topical retinoic acid in photo-ageing and actinic keratoses.

Quantitative techniques for assessing the effects of tretinoin on photo-aged skin mainly involve humans, although hairless mice were used in initial studies. Ideally techniques should be non-invasive but occasionally biopsies have to be taken, especially when studying the effects of tretinoin on different skin compartments. Characteristic features of photo-aged skin, including the development of fine and coarse wrinkles, skin discoloration, rosy cheeks and telangiectasis, have been assessed subjectively using a visual analogue scale. Effects of tretinoin on wrinkle depth have been measured non-invasively by quantifying contours of silicone rubber replicas using either a mechanical tracking device or an optical technique employing an image-analysing computer. Changes in skin colour have been measured using an erythema meter and the stimulatory effect of tretinoin on blood flow has been established by laser doppler flowmetry. Skin thickness has been measured non-invasively using pulsed A-scan ultrasound which showed that tropical tretinoin increased thickness. Biopsies have also been used but no changes in the thickness of the dermal repair zone have been noted in humans, in contrast to the situation in hairless mice. Epidermal dysplasia has been measured by a visual analogue scale or by objective image analysis.

Humans↗
PubMed1990

The effects of the detergent action of cleansing agents on the skin.

Detergent substances are important components of cleansing materials. Their detergent cleansing action may also result in skin toxicity. Methods for the evaluation of their toxic effect on the skin surface are reviewed stressing the usefulness of the soap chamber test, and newer in vitro cultural techniques. The action of detergents in promoting desquamation and removing intercorneocyte materials is also discussed. Finally, the point is made that cleansing can also be accomplished with non-detergent containing cleaners.

Detergents↗