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Biomedical subjects

P M Farr

Publications and source records attributed to P M Farr.

At least 55 records · Page 3Linked to original sources

Wavelength specific patterns of p53 induction in human skin following exposure to UV radiation.

We report that, in human skin, exposure to equally erythemogenic doses of UVA, UVB, and UVC increases immunocytochemically detected p53 in a wavelength-specific pattern. UVC produced immunostaining confined to the upper epidermis. With UVB, staining was seen throughout the epidermis, whereas with UVA staining predominated in the basal layer. The results with UVB and UVC are understandable on the basis of their known differences in penetration, whereas those with UVA are not. This suggests that within one cell type the pattern of p53 response to UV radiation is wavelength dependent.

Adult↗

Response of psoriasis to psoralen-UVB photochemotherapy.

The effect of psoralen in combination with 311 nm (UVB) radiation was studied in five subjects with normal skin and 10 patients with psoriasis involving both forearms. Treatment with oral 8-methoxypsoralen augmented the UVB erythemal response at 6 h after irradiation, but had no effect at 24-72 h. In eight of the nine patients who completed the trial, lesions of psoriasis on the arms treated with psoralen-UVB cleared before lesions on the arms treated with UVB alone. This study has shown that psoralen in combination with UVB has an erythemal effect on normal skin, and a therapeutic effect in psoriasis which is greater than the response to UVB alone.

Adult↗

The study of plaques of psoriasis using a scanning laser-Doppler velocimeter.

A scanning laser-Doppler velocimeter, able to measure blood flux over a large area without contact with the skin surface, was used for the objective measurement of the vascular changes in psoriasis. Individual plaques were scanned, and tracings of the visible plaque edge taken on to a cellulose-acetate sheet from which area measurements were made using a digitizing tablet. Mean blood flux within plaques was increased fourfold compared with mean background flux. There was a highly significant linear correlation between plaque area measured by tracing and scanning, but area measured by scanning was greater. Detailed study of blood flux outside the visible plaque edge with the scanner, and with a conventional laser-Doppler instrument, showed this was due to a 2-4 mm rim of increased blood flux around plaques. The scanning laser-Doppler velocimeter allows rapid measurement of psoriasis in terms of mean blood flux and area of increased blood flux, and should be useful in the assessment of psoriasis severity and the response to treatment.

Adolescent↗

PUVA erythemal sensitivity depends on plasma psoralen concentration and UVA sensitivity.

The variation in erythemal sensitivity of the skin during PUVA therapy with oral 8-methoxypsoralen (8-MOP) was examined by measuring both UVA and PUVA erythemal responses, together with plasma 8-MOP concentration, in 27 patients about to start PUVA therapy for psoriasis. The erythema responses were judged visually, and also measured using a reflectance instrument in order to construct dose-response curves. No significant association was found between the UVA and PUVA minimal erythema responses. The plasma psoralen concentration showed significant association with the slope of the PUVA erythema dose-response curve. The slopes of the UVA and PUVA erythema dose-response curves were significantly associated, and this association became much stronger when allowance was made for plasma psoralen concentration. These results show that erythemal sensitivity during PUVA therapy is related to both plasma psoralen concentration and inherent UVA sensitivity, but that this relationship is not apparent when sensitivity is judged visually as the minimal erythema response. The association between PUVA and UVA erythemal sensitivity suggests a common pathway in the vascular response induced by UVA radiation, with or without psoralen.

Adult↗

A device for phototesting patients before PUVA therapy.

A device is described and validated for rapid and easy phototesting of patients at the start of a course of PUVA therapy. The phototesting template consists of metal foil with four apertures of 10 mm diameter, mounted in pliable polyurethane. One aperture is open, and the other three each incorporate a grid of hexagonal holes of differing size which attenuate the radiation, resulting in relative intensities at the skin surface of 1, 2, 4 and 8. Thus, a single exposure through the foil of, for example, 8 J/cm2, would allow the minimal phototoxic dose to be determined as either 1, 2, 4, 8, or > 8 J/cm2. The device was validated by comparison with a metal foil with four open apertures, but otherwise identical construction, in which the dose was controlled by varying the exposure time. In 11 subjects, tested with one device on each arm, the minimal phototoxic dose, judged visually, was identical. Reflectance measurements of erythema at each of the test sites showed no systematic difference between the two methods. The device has no moving parts, requires no source of electrical power, will not change its optical transmission with age, and is robust and easy to use. It should, therefore, allow much wider application of the useful technique of minimal phototoxic dose determination before PUVA therapy.

Dermatitis, Phototoxic↗

Response of psoriasis to twice weekly PUVA.

In the U.K., PUVA treatment for psoriasis is usually given three times weekly, with the starting dose of UVA chosen according to the skin type of the patient. Observations on the time-course and dose-response characteristics of PUVA erythema suggest that larger doses of UVA could be used safely, provided that the frequency of PUVA treatment is reduced. We have examined this by treating 100 patients with chronic plaque-type psoriasis with a PUVA protocol in which treatment using oral 8-methoxypsoralen was given twice weekly, with the starting dose of UVA based on each patient's minimal phototoxic dose, and with weekly UVA dose increments calculated as a percentage of the dose used in the previous treatment. Clearance of psoriasis was achieved in 92% of patients. The median number of treatments required for clearance was 12, and the median cumulative UVA dose for clearance was 52J/cm2. Although erythema occurred at some stage during the course of PUVA in 48% of patients, in only 16% of cases was the erythema of sufficient intensity to result in more than one treatment being missed. These results compare favourably with previous studies in which treatment was given three or four times weekly. Thus, twice weekly PUVA treatment for psoriasis is at least as effective as treatment given more frequently, and may be safer, as lower cumulative UVA doses are required for clearance. It also allows for more efficient operation of a PUVA unit and is more convenient for patients.

Adolescent↗

Quantification of contact allergic inflammation: a comparison of existing methods with a scanning laser Doppler velocimeter.

Responses to a range of doses of common contact dermatitis-producing allergens were measured using a novel scanning laser Doppler velocimeter and three commonly used conventional measurement techniques. The techniques were compared in terms of sensitivity, measurement error, range of the linear portion of the dose-response curve and ease of use. The detection thresholds of the objective methods did not differ significantly and did not detect responses at concentrations less than those required to produce a visible response. Of the objective methods the range of linearity was greatest when reactions were measured using change in skin fold thickness, erythema or area of inflammation. Measurement error was greatest with measurements made using the conventional laser Doppler velocimeter. Present instrumental methods are no more sensitive than visual assessment in the reading of patch test reactions. The conventional laser Doppler velocimeter was least suited for measurement of allergic contact hypersensitivity reactions as readings are time-consuming, show detectable changes over a more limited range of allergen concentration, and have a larger measurement error than the other methods. There is no single best method for measuring allergic contact hypersensitivity reactions. Useful data over a wide range of allergen concentrations can best be obtained by measurement of skin fold thickness, erythema or area of reaction using the scanning laser Doppler velocimeter. The scanning laser Doppler velocimeter has the added advantages of being able to measure area of reaction without contact with the skin surface and to measure reactions at all skin sites.

Dermatitis, Allergic Contact↗

The relationship between chronological age and the erythemal response to ultraviolet B radiation.

To investigate whether erythemal responses to ultraviolet radiation alter with age, we have reviewed the results of monochromator phototesting in adults and children, and have measured the dose-response curves for UVB erythema in a further 38 subjects. There was no significant difference between adults and children in minimal erythema dose (MED) at 300 nm; the median MED in 254 adults was 34 mJ/cm2 (range 14-80 mJ/cm2) and in 24 children aged less than 15 years was 30 mJ/cm2 (range 10-80 mJ/cm2). Objective measurements of UVB-induced erythema were performed in 15 subjects aged below 25 years and 23 subjects aged above 60 years. A dose-response curve for UVB erythema was constructed for each subject and the slope of the steepest part of each curve calculated by logit regression; the values in the young subjects were greater than in the older group (P less than 0.02). However, there was no difference between the two groups in either the visually assessed MED or the calculated UVB dose required to produce a constant degree of mild erythema.

Adult↗

Neutrophilic alveolitis in Sweet's syndrome.

In a case of Sweet's syndrome (acute febrile neutrophilic dermatosis) neutrophilic alveolitis was found by lung biopsy. Pulmonary disease in this condition may be underrecognised yet, like the dermatological features, it responds rapidly to corticosteroids.

Aged↗

A dose-response study of irritant reactions to sodium lauryl sulphate in patients with seborrhoeic dermatitis and atopic eczema.

The susceptibility of the skin of patients with seborrhoeic dermatitis to surfactant irritation was investigated and compared to that of a group of normal subjects and patients with a history of atopic eczema. Responses to six concentrations of sodium lauryl sulphate (SLS), applied to forearm skin, were assessed clinically and measured by laser Doppler flowmetry. Analysis of dose-response curves showed statistically significant increased susceptibility to SLS-induced irritation in patients with seborrhoeic dermatitis and atopic eczema compared with normal subjects. Increased susceptibility to chemical irritation may be important in the pathogenesis of seborrhoeic dermatitis.

Adolescent↗