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Biomedical subjects

R Marks

Publications and source records attributed to R Marks.

At least 37 records · Page 2Linked to original sources

The epidemiology of non-melanoma skin cancer: who, why and what can we do about it.

Non-melanoma skin cancer (NMSC) comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common cancers in humans in many countries. Sunlight plays a major part in the development of these tumours which appear predominantly on areas of the most frequently exposed skin. The site distribution for BCC and SCC is not the same, with SCC being most common on the sites of very heavy exposure and BCC becoming more common on areas of only moderate exposure, e.g. upper trunk in men and women and lower leg in women. Incidence rates of NMSC, where they are being recorded, show rises over time. Mortality rates, on the other hand, have been dropping most of this century until they have been levelling out recently. The case fatality rate due to SCC appears to be between 1-2%. The malignant transformation rate of actinic keratoses to SCC appears to be very low. Studies on similar populations at different latitudes allow estimates to be made of increases which might occur with increasing exposure to ultraviolet radiation (UVR) over a life time. These have been used to estimate the possible increases in NMSC due to stratospheric ozone depletion. Finally, recent studies on the reduction of existing actinic keratoses and prevention of new ones with regular use of sunscreen augurs well for prevention of NMSC in the future.

Basal Cell Carcinoma

Fluticasone propionate 0.05% cream in the treatment of atopic eczema: a multicentre study comparing once-daily treatment and once-daily vehicle cream application versus twice-daily treatment.

The aim of this study was to compare the efficacy and safety of once-daily with twice-daily application of a 0.05% cream formulation of fluticasone propionate in the treatment of atopic eczema in adults and children. Two hundred and seventy patients with moderate to severe atopic eczema were enrolled in the study, and randomized to receive either once-daily or twice-daily fluticasone propionate 0.05% cream for 4 weeks. Patients randomized to the once-daily group also received the vehicle cream to ensure that the study remained blinded. The clinical response of a preselected target area of affected skin was assessed by investigators at weekly intervals and compared with the baseline. Analysis of the investigators' overall assessment of the response of the target area for both the 'intent-to-treat' population and the per protocol population showed that 79-85% of patients were judged a clinical success. For both populations, there was no statistically significant difference between the response to once-daily and twice-daily active treatment (intent-to-treat; P = 0.35; 95% confidence interval for difference -14.2 to +5.0 percentage points: per protocol; P = 0.42; 95% confidence interval for difference -14.7 to +6.2 percentage points.) The improvement in the signs and symptoms was judged a success in 95-97% of patients. There was an equal reduction in severity scores for disease activity in both groups, and the speed of symptom relief was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical

Protracted cutaneous disorders in association with low CD4+ lymphocyte counts.

We report two patients with skin disorders usually associated with severe immunosuppression, who had low CD4+ lymphocyte counts but normal immunoglobulin levels. The patients were HIV negative, and had CD4+ lymphocyte counts just above 300/mm3, but they presented with cutaneous manifestations of profound immunodeficiency. Idiopathic CD4+ lymphocyte deficiency is a recently described syndrome which may present with dermatological disease. We discuss the symptom complex of our patients in relationship to the diagnosis of idiopathic CD4+ lymphocyte deficiency.

Adult

The growth of ichthyotic epidermal cells in a 3-dimensional reconstruction of human skin, the skin equivalent.

We have studied the differentiation of ichthyotic epidermis in vitro using the skin equivalent model. The morphology of these ichthyotic cultures has been investigated using histopathological and histometric techniques including epidermal and stratum corneum thickness measurements. The skin equivalents have also been investigated for the presence of markers of differentiation using immunolocalization techniques. These markers include the 65.5 and 67 kDa keratins, desmoplakin, involucrin, laminin and filaggrin. It has been shown that the ichthyotic epidermis develops a fully differentiated epidermis and stratum corneum, equivalent to those seen in normal skin equivalents.

Cell Differentiation

Cancer of the skin in the next century.

One can confidently predict that the 21st century will be a span of intense activity in unraveling the precise molecular and biochemical events that lead to the various forms of cutaneous cancers. These discoveries will lead to new approaches in our therapeutic armamentarium that currently do not exist. Eventually, the incidence rates and mortality rates from cancers of the skin will markedly decline--the finite goal of all the combined endeavors of the scientific and practicing medical community.

Developing Countries

The effects of protective occlusive gloves on stratum corneum barrier properties.

Data suggests that protection from gloves is paradoxically reduced because of effects of occlusion on the skin. The aim of this study was to characterize these effects on physical and functional properties of stratum corneum. Volunteer trials were conducted using patches of polyvinyl chloride (PVC) glove material on the skin. Impairment of barrier function was assessed by measuring transepidermal water loss (TEWL). Hydration and water sorption-desorption was assessed using skin conductance. The major finding was a short-term impairment of barrier function, measured as an increase in TEWL of 1.7 gn-2h-1 (95% C.I. 0.4 to 2.6 gn-2h-1,p < 0.01). Temporary increases in hydration and water sorption were also observed. On this basis, the effects of wearing PVC gloves over 2 days on stratum corneum barrier properties on the dorsum of the hand were studied. TEWL measurements remained elevated by 1.5 gn-2h-1 the day after occlusive glove removal (95% C.I. 0.2 to 2.8 gn-2h-1, p < 0.01), indicating a possible cumulative effect. In conclusion, our studies demonstrate a potential hazard resulting from the repeated use of protective gloves.

Adult

A stepwise procedure for evaluating irritant materials in normal volunteer subjects.

1. The cutaneous response to a known irritant has been assessed in human volunteer subjects using both clinical scoring and two non-invasive instrumental methods; erythema measurement using an erythema meter and capillary blood flow using a laser Doppler device. 2. Aqueous solutions (0.5% and 1%) of sodium hydroxide were applied to back skin for 3, 15 and 60 min with assessments immediately after removal and at 1, 24 and 48 hours. 3. Increased erythema was seen with increasing duration of exposure and an increase was also seen at 1 h, 24 h and 48 h after removal of the patch. The results obtained with the erythema meter paralleled the clinical erythema scores. However, the laser Doppler device showed the greatest changes immediately after removal of the patch with subsequent readings showing a gradual decrease. 4. Statistical analysis of the data has been carried out to determine the accuracy and precision of the assessment procedures and to determine the minimum test panel size for detecting irritant reactions. 5. Comparison between back and forearm skin indicated a greater sensitivity to sodium hydroxide on the back. 6. The results of this study define an ethical approach to testing irritant materials in human subjects and provide the basis for the development of a classification system for cutaneous irritants.

Adolescent

Skin cancer. Recognition and treatment.

There is a worldwide increasing incidence of all forms of skin cancer among Whites as a result of increased sun exposure. Basal cell and squamous cell carcinomas, the most common tumours of the head and neck, are relatively benign neoplasms of elderly individuals. Malignant melanoma, however, has the potential for early metastasis and may occur in early adult life. The increase in malignant melanoma is particularly disturbing, and is a clear indication for skin screening clinics. Although surgical excision is the primary treatment of choice for skin tumours, various drugs may be of therapeutic value. Fluorouracil cream is a useful treatment for solar keratoses. Retinoids are particularly suitable for patients with large numbers of nonmelanoma skin cancer lesions and solar keratoses. For malignant melanoma, arterial limb perfusion with high concentrations of cytotoxic drugs may be performed both as an adjunctive and therapeutic manoeuvre. Treatment of metastatic melanoma with cytotoxic agents is associated with low response rates and high toxicity. However, trials with combined interferon-alpha, interleukin-2 and cytostatic drugs have produced promising preliminary results.

Bowen's Disease

The effect of regular sunscreen use on vitamin D levels in an Australian population. Results of a randomized controlled trial.

BACKGROUND AND DESIGN: Studies published have suggested a possibility that regular use of sunscreen to prevent skin cancer may put the population, particularly elderly people, at risk of vitamin D deficiency. We aimed to determine whether regular use of sunscreens in the normal adult population, as recommended by public health authorities for the prevention of skin cancer, may put individuals at risk of vitamin D deficiency. A randomized double-blind control trial of the daily use of a broad-spectrum sunscreen (sun protection factor [SPF] 17) vs placebo cream over a summer period in Australia was conducted in 113 people aged 40 years and over, with sampling stratified by age. All participants had at least one solar keratosis. Serum samples taken at the beginning and at the end of the study were analyzed for 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3. RESULTS: Mean levels of 25-hydroxyvitamin D3 rose significantly by the same amount in both groups over the period of the study (placebo, +12.8 mmol/L; sunscreen, +11.8 mmol/L). Mean levels of 1,25-dihydroxyvitamin D3 increased significantly in the placebo group only (placebo, +10.8 pmol/L; sunscreen, +1.3 pmol/L), but for no subject in either group was the level of 1,25-dihydroxyvitamin D3 outside the reference range either at the start or at the end of the study. There were no significant differences by age, sex, and skin type in the change in 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 over the study period. CONCLUSIONS: No person, including those aged 70 years and over, developed any vitamin D levels outside the normal reference range during the period of the study. The data suggest that over an Australian summer sufficient sunlight is received, probably through both the sunscreen itself and the lack of total skin cover at all times, to allow adequate vitamin D production in people who are recommended to use sunscreens regularly. More work is required to elucidate the relationship between 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3, particularly during the different seasons of the year.

Adult

Quadriceps femoris activation changes in genu varum: a possible biomechanical factor in the pathogenesis of osteoarthrosis.

This study was designed to determine whether the presence of an alignment deformity of the lower leg, known as genu varum, causes abnormalities in individual- or group-activation of the surrounding knee extensors, a situation which might accelerate knee deterioration. Nine healthy women with normal tibial alignment were compared with nine age-matched healthy women with genu varum. The outcome measure of maximal quadriceps femoris activity was recorded during successive maximal concentric isometric and isokinetic contractions of the knee extensors performed on a dynamometer using surface electromyography. The results showed that, taken as a whole, the percentage utilization of quadriceps motor units was higher for those subjects with genu varum (p < 0.01). These findings demonstrate that the extensors surrounding a varus knee might function less efficiently than those surrounding a normally aligned knee. As such they suggest that pathological force generation across a varus knee might be caused, in part, by associated alterations in quadriceps tension generating capacity.

Adult

Early detection of skin cancer. Knowledge, perceptions and practices of general practitioners in Victoria.

OBJECTIVE: To determine the current knowledge, perceptions and practices of general practitioners (GPs) in Victoria in the diagnosis and management of skin cancer. METHOD: A stratified random sample of 666 Victorian GPs was surveyed by postal questionnaire (a colour photographic quiz on 12 examples of benign and malignant skin tumours). RESULTS: GPs were better at recognising the 12 skin tumours as suspicious or benign than they were at providing the correct diagnosis. They were better at providing the correct diagnosis for benign lesions (75%) than for skin cancers (61%) or dysplastic lesions (61%). They had more difficulty in recognising early melanoma than late melanoma and were more likely to manage benign lesions (85%) and dysplastic lesions (34%) than skin cancers (4%). Knowledge of appropriate management was high for GPs who correctly identified tumours. Most perceived skin cancer as an important public and individual health concern. CONCLUSIONS: Overall, GPs had a good knowledge of diagnosis and management of skin cancer and related benign tumours. Several gaps in knowledge and practice were apparent and need specific targeting for educational programs.

Adolescent

Reliability and validity of self-paced walking time measures for knee osteoarthritis.

This study assessed the reliability and validity of self-paced walking time as an outcome measure for osteoarthritis (OA) of the knee. The 13-m timed walking tests were carried out twice on two separate occasions for 15 patients using photocells. Validity was examined by comparing the walking time data with results of other methodologies for evaluating osteoarthritic gait. As indicated by intra- and inter-day intraclass correlation coefficients of 0.97 and 0.88 the gait measurements were reliable. The measurements also compared favorably with a validated subjective functional index for knee OA (P < 0.01). The findings suggest that measurements of self-paced walking time can provide both reliable and valid data for evaluating functional performance in this patient population.

Adult

Expression of c-fos proto-oncogene mRNA in non-melanoma skin cancer.

c-fos is a member of the proto-oncogene family and is implicated in the modulation of cell proliferation and differentiation. Previous studies have shown that the c-fos gene expression is regulated in a tissue specific manner. In order to clarify the role of the c-fos gene in human epidermis, we have investigated c-fos mRNA expression in both normal skin and non-melanoma skin cancer. In normal skin the intensity of the c-fos mRNA expression in spinous cells was found to be stronger than that observed in basal cells. In lesions of solar keratosis and Bowen's disease the spinous cells also showed stronger c-fos mRNA expression than in basal cells. In two of four cases of Bowen's disease some upper spinous cells showed very strong mRNA expression of the c-fos gene. In squamous cell carcinomas studied there was considerable variation in the intensity of c-fos mRNA expression. Our findings indicate that the degree of c-fos mRNA expression is related to the degree of dysplasia present. In all cases of basal cell carcinoma examined the c-fos mRNA expression was markedly decreased. These results suggest that c-fos expression may be involved in the differentiation of human keratinocytes in vivo rather than in the neoplastic process itself.

3T3 Cells

An investigation of the influence of age, clinical status, pain and position sense on stair walking in women with osteoarthrosis.

The objective of this study was to determine the extent to which stair walking in persons with osteoarthrosis of the knee is influenced by age, weight, height, pain, clinical status, and position sense. The subjects were six women with severe knee joint disease who attended a single test session at which clinical status, disease severity, pain, position sense and stair-walking time was assessed. The results of correlation analyses revealed significant correlations of r = 0.84 and r = 0.95 (p < 0.05) between the measurements of stair-walking time and pain and between the measurements of stair-walking time and position sense, respectively. There was no relationship between stair-walking time and age, height, weight, clinical status or disease severity. It is concluded that knee pain and positional sense are strong determinants of the stair-walking ability of individual osteoarthrotic patients. In treating stair-walking problems in this group, it is recommended that effort be directed to improving proprioception as well as to reducing pain.

Aged

Melanoma prevention: is it possible to change a population's behavior in the sun?

With the highest incidence and mortality rates of melanoma in the world, Australia has been running carefully designed primary prevention programs for more than 10 years. These have included public education programs aimed at all ages but concentrating particularly on young people. The programs have also included structural changes such as provision of shade in open space, rescheduling work and sport activities, removal of sales tax from approved sunscreens, and provision of cheap sunscreens. There have been substantial changes in knowledge, attitudes, and beliefs about melanoma, sunlight, and suntans. There have been significant increases in sun protective behavior reflected in the reduced proportions of people sunburnt at the weekend in summer in recent years. The incidence rate of melanoma continues to rise, as expected. Although there has been considerable success so far, we still have a long way to go.

Australia