Molecular epidemiology has linked ultraviolet-induced DNA damage with mutagenesis and skin carcinogenesis. Ultraviolet radiation may damage DNA in one of two ways: either directly, leading to lesions such as cyclobutane thymine dimers (T<>T), or indirectly, via photosensitizers that generate free radical species that may ultimately produce such oxidative lesions as 8-oxo-2'-deoxyguanosine. We report the results of a pilot, case control study in which seven, healthy, human volunteers (skin type II; aged 23-56 y; three male, four female) received a suberythemal dose of whole body irradiation from ultraviolet-A-emitting fluorescent tubes used in psoralen plus ultraviolet A therapy. First void, mid-stream urine samples were collected pre-exposure and daily postexposure, for up to 13 d. Analysis of urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers was by competitive enzyme-linked immunosorbent assay (interassay coefficient of variation < or = 10%) and compared with a matched, control group of unirradiated individuals. A maximal increase in levels of urinary 8-oxo-2'-deoxyguanosine was seen 4 d post-ultraviolet exposure. A subsequent reduction was noted, before finally returning to baseline. Similarly, cyclobutane thymine dimer levels peaked 3 d postexposure, before returning to baseline. In contrast to the 8-oxo-2'-deoxyguanosine analysis, however, a second peak was noted at days 9-11, before again returning to baseline. This is the first report examining urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers following ultraviolet exposure of healthy human subjects. This work illustrates the induction and time course for excretion of ultraviolet-induced lesions, perhaps alluding to repair and ultimately offering the potential to define psoralen plus ultraviolet A dosage regimes in terms of minimizing DNA damage and hence cancer risk.
Acquired haemophilia is rare and potentially fatal, with a mortality of 20% if left untreated. There is a strong association with other autoimmune diseases. This report describes a patient with rheumatoid arthritis, vitiligo, and bullous pemphigoid where the diagnosis of acquired haemophilia was made after an extensive bleed into a bullous lesion in the buccal mucosa. This case highlights some of the potential complications of acquired haemophilia and its treatment.
We report the results of a study of the ruby laser in normal mode for treatment of hirsutism in 43 patients with skin types I-IV. A pulse width of 950 microseconds, a 4 mm spot and a fluence sufficient to produce minimal whitening of the epidermis were used (mean 48 J/cm2). In each patient, one site was treated once only, and a second site received four treatments at monthly intervals. After a single treatment, hair counts had reduced to a mean of 46% (median 67, reduced to 26) of the pretreatment values at 1 month, but increased to 80% (median 42) at 3 months and were 66% (median 37) at 6 months. One month after three treatments, hair counts had reduced to a mean of 29% (median 60, reduced to 15) of pretreatment values, and 3 months after four treatments at the same site, counts had increased to 44% (median 21). Patient tolerance of the treatment was good and higher fluences tended to be tolerated at consecutive visits. The first treatment was followed by mild, short-lived erythema and swelling in 60% (25 of 42) patients. Fourteen per cent (six of 42) experienced mild blistering and 33% (14 of 42) crusting. More severe reactions were seen infrequently. These results indicate that normal mode ruby laser treatment is well tolerated. Sustained reduction in hair counts can be achieved for at least 6 months, and multiple treatments produce greater clinical effects.
Psoralen in conjunction with UVA (PUVA) is perhaps the most effective treatment for psoriasis. It is, however, a risk factor for skin cancer in these patients and there is a need to develop non-invasive assays reflective of treatment-induced DNA damage. We report here the assessment of two important lesions, thymine dimer (TG Gf fT) and 8-oxo-2P P-deoxyguanosine (8-OHdG), in the urine of psoriasis patients. It was found that, once corrected for urine concentration, the psoriatic group had significantly higher (P6 6 0.0001) urinary levels of thymine dimers compared to the control group. No significant differences in urinary 8-OHdG levels were noted between the psoriatic, atopic dermatitis and control groups. Therefore biomonitoring of therapy from the very start with this simple and non-invasive assay could perhaps be an effective measure of the risk involved with the treatment allowing optimization for minimal-risk therapy.z 1999 Federation of European Biochemical Societies.
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