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Biomedical subjects

Brian Diffey

Publications and source records attributed to Brian Diffey.

10 recordsLinked to original sources
PubMed2006

The contribution of medical physics to the development of psoralen photochemotherapy (PUVA) in the UK: a personal reminiscence.

Psoralen photochemotherapy (PUVA) is the combined treatment of skin disorders with a photosensitizing drug (Psoralen) and UltraViolet A radiation. The introduction of PUVA therapy has arguably been the most important development in dermatology over the past 30 years and from the first days of the treatment being introduced in the UK, British medical physicists were an integral part of the effort to establish it. Medical physicists have contributed to this development in a number of ways, from designing irradiation units in the early days of the technique, through to collaborating with dermatologists in prosecuting clinical and experimental studies aimed at improving patient outcomes. That the dose of UVA radiation is administered quantitatively, and not qualitatively, has probably been the single most important contribution made by several medical physicists over this period. However, despite concerns that were expressed almost 30 years ago about the accuracy with which UVA doses are administered to patients, the medical physics community still has some way to go before we can be satisfied that statements about UVA irradiance and dose can be made with confidence.

Ficusin↗
PubMed2005

Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation.

Pheomelanin is widely thought to be causally related to susceptibility to the harmful effects of ultraviolet radiation: epidemiological studies show that those with a higher ratio of pheomelanin to eumelanin in hair have higher rates of melanoma, and work in mouse and cell culture shows that pheomelanin generates excess free radicals after UVR exposure. By contrast, based on measurements of eumelanin and pheomelanin in human skin, before and following irradiation, we now report that both pheomelanin and eumelanin are positively related to skin colour, and by inference, inversely with cancer susceptibility. The ratio of melanin classes is similar in people with widely different cancer rates and UVR sensitivity. Although our numbers are small, our results extend previous work in man, and lead us to speculate that factors other than the amount of pheomelanin may be important in determining UVR susceptibility in persons with red hair.

Epidermis↗
PubMed2005

The photoadaptive response to ultraviolet exposure in human skin using ultraviolet spectrophotometry.

BACKGROUND: Both pigmentation and non-pigmentary processes contribute to the development of photoadaptation yet the exact contribution of either in the resting state and in response to ultraviolet (UV) radiation is unclear. The purpose of this study was to estimate independently these changes occurring in the epidermis following repeated exposure to UV in two groups with differing degrees of constitutive pigmentation. METHODS: We describe a mathematical model for explaining the spectral absorbance of excised human epidermis based on the absorbance of constituent chromophores. The model was applied to spectral absorbance data measured on samples of epidermis excised from pre-irradiated skin and from skin obtained following UV irradiation on 3 successive days. RESULTS: We found that in Asian skin there was only a mild photoadaptive response, principally by a small increase in pigmentation. On the other hand, the significant adaptive response in Caucasian skin was through hyperplasia of the epidermis, with tanning contributing only to a much smaller degree. CONCLUSION: This study has enabled us to study independently the pigmentary and non-pigmentary pathways and has shown that in those people with a lower degree of constitutive pigment, the primary mechanism of photoadaptation is via the non-pigmentary route.

Adaptation, Physiological↗
PubMed2004

Climate change, ozone depletion and the impact on ultraviolet exposure of human skin.

For 30 years there has been concern that anthropogenic damage to the Earth's stratospheric ozone layer will lead to an increase of solar ultraviolet (UV) radiation reaching the Earth's surface, with a consequent adverse impact on human health, especially to the skin. More recently, there has been an increased awareness of the interactions between ozone depletion and climate change (global warming), which could also impact on human exposure to terrestrial UV. The most serious effect of changing UV exposure of human skin is the potential rise in incidence of skin cancers. Risk estimates of this disease associated with ozone depletion suggest that an additional peak incidence of 5000 cases of skin cancer per year in the UK would occur around the mid-part of this century. Climate change, which is predicted to lead to an increased frequency of extreme temperature events and high summer temperatures, will become more frequent in the UK. This could impact on human UV exposure by encouraging people to spend more time in the sun. Whilst future social trends remain uncertain, it is likely that over this century behaviour associated with climate change, rather than ozone depletion, will be the largest determinant of sun exposure, and consequent impact on skin cancer, of the UK population.

Atmosphere↗
PubMed2004

The development of an objective method for measuring scratch in children with atopic dermatitis suitable for clinical use.

Itch is a major symptom of skin disease and remains poorly studied. We have used limb-worn digital accelerometers, and infrared video of patients as a gold standard, on children with atopic dermatitis and control subjects in their own homes at night. Video analysis shows that nocturnal scratching and restlessness are more complex than we first thought, with many movements that potentially damage the skin not conforming to stereotypical scratch movements. Children with atopic dermatitis spent a mean of 46 minutes less time motionless or sleeping at night than control subjects (468 +/- 3 [SEM] vs 422 +/- 37 [SEM], P<.001). Children with atopic dermatitis showed 2 to 3 times as much scratching or restlessness activity as control subjects, with little overlap between groups (P<.01). Scratching and restlessness were highly correlated with each other (0.94, P<.01). Accelerometer scores were highly correlated with video results (rho>0.02, P<.01, for scratching, restlessness, and sleeping time). Individual limb scores were highly correlated with each other (rho approximately 0.87-0.98), suggesting that little information would be lost if only 1 limb was measured. There was little relation between parental assessment of scratch and objective measured scratch. Accelerometers provide a useful and practical way of assessing scratching at night in the patient's own home and could be used as an objective measure of disease activity both in clinical trials and in everyday clinical practice.

Behavior↗
PubMed2004

The time course of photoadaptation and pigmentation studied using a novel method to distinguish pigmentation from erythema.

The dynamics of human pigmentation in response to ultraviolet radiation (UVR) remain poorly characterized. In part, this is attributable to methodological issues relating to the overlap in spectra of hemoglobin and melanin. We describe a new method, based on the recording of reflectance properties following iontophoresis of a potent vasoconstrictor, noradrenaline. This removes the influence of blood, allowing measurement of pigmentation, represented as L* on the L*a*b* scale. Blood flow was separately assessed using laser Doppler flowmetry. We show that there is a clear dose response with the dose of UVR administered, that pigmentation peaks at 1 wk and declines over the following 10 wk, but does not return to baseline within this period. We show clear differences in the degree, but not the temporal pattern of pigmentation between different pigmentary groups. We also report that the relation between facultative pigment and constitutive pigment is incomplete, with a wide scatter of responses for the development of pigmentation irrespective of constitutive levels. For comparison we also document overall photoadaptation and relate changes in pigmentation to the overall changes in photoadaptation.

Adaptation, Physiological↗
PubMed2003

Enhanced epidermal ultraviolet responses in chronically sun-exposed skin are dependent on previous sun exposure.

The p53 protein plays a key role in protecting cells from acquiring manifest mutations by inducing cell cycle arrest or apoptosis. The mechanisms for differences in epidermal responses to ultraviolet irradiation are unclear, although they have been shown to be related to both genetic events and environmental factors. In this study, we compared epidermal ultraviolet responses in chronically sun-exposed and non-sun-exposed skin using immunohistochemistry with antibodies recognizing thymine dimers and p53 protein. Six healthy volunteers were subjected to both artificial ultraviolet irradiation and natural sunlight, with and without photoprotection. A smaller number of thymine dimer-positive keratinocytes were detected 24 h after ultraviolet exposure in chronically sun-exposed skin compared to non-sun-exposed skin. Further, the p53 response was more variable in chronically sun-exposed skin. A significant correlation between total ultraviolet dose and number of p53-immunoreactive keratinocytes was found after natural sun exposure. Our findings suggest that repair of DNA damage is more efficient in chronically sun-exposed skin than in non-sun-exposed skin.

Aged↗