Split-face study of melasma patients treated with non-ablative fractionated photothermolysis (1540 nm).

BACKGROUND: Melasma treatment remains challenging despite various laser systems available, because of potential side-effects and high recurrence rates. OBJECTIVE: Non-ablative fractionated photothermolysis (FP) is a promising therapeutic method, long-time results comparing treated vs. non-treated site are lacking. METHODS: A total of 14 patients were treated with FP in a split-face mode with standardized adjustments in three sessions (weeks 0, 3-4, 6-8, follow-up: 26-28). At each consultation, improvement was evaluated by patients and physicians. Objective assessment was performed using digital photographs and the pigment imaging tool SIAscope(®). RESULTS: Melasma improvement was registered in 83% and 75% of the cases 26-28 weeks after the first treatment based on two evaluations: by patient and by physician, respectively. Digital photography and SIAscope(®) revealed improvement in 54% and 85% after the first, 61% and 85% after the second, 41% and 58% after the third treatment, accordingly, mostly due to reduction of the outline sharpness. Patients with lighter skin complexions revealed significant improvement ranged from slight to moderate (P=0.03). Postinflammatory hyperpigmentation occurred in two cases with skin types III and IV. CONCLUSION: Non-ablative FP can be considered as a valuable treatment option with short-term improvement in terms of mild reduction and softening the edges of melasma in patients with skin types I/II, if prior topical therapies failed. Treatment of patients with skin types III+ should be critically questioned.

Increased spontaneous formation of micronuclei in cultured fibroblasts of first-degree relatives of familial melanoma patients.

The phenomenon of spontaneous increased micronuclei and enhanced UV-sensitivity, which is known for familial cutaneous malignant melanoma (CMM) patients, could be demonstrated again in fibroblasts of 17 familial CMM patients. In order to determine if close relatives of familial CMM patients show both a comparable spontaneous chromosomal instability and enhanced UV-sensitivity, cultured fibroblasts of 24 healthy, first-degree relatives of patients with familial malignant melanoma were investigated. The cytokinesis-block micronucleous technique was used to detect enhanced chromosomal instability. Fibroblasts of the investigated relatives showed a significantly increased spontaneous formation of micronuclei, in comparison to 19 healthy controls, but no enhanced UV-sensitivity was evident. We conclude that chromosomal instability might be a hereditary trait and a causative factor in developing familial malignant melanoma. This supports the concept of a genetic predisposition to familial CMM and may help to identify high-risk family members at a cytogenetic level in addition to the common clinicopathological traits.

Fibroblast cultures of patients with basal cell epithelioma exhibit a normal sensitivity to the genotoxic effect of ultraviolet irradiation.

Fibroblast cultures of 16 basal cell epithelioma (basalioma, BCE) patients with an unusually young age at onset of disease (29-51 years; 42.5 +/- 7.04), and healthy normal controls (27-55 years; 40.73 +/- 9.52) were studied for chromosome instability induced by ultraviolet rays (UV). We used an UV source that emitted predominantly UV-A and UV-B at an intensity of 375 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). Young basalioma patients and normal controls showed no significant differences in MN and SCE frequencies, neither with respect to spontaneous nor to UV-induced values (MN spontaneous: 10.80 +/- 5.65 vs. 11.32 +/- 8.21; UV-induced increase: 7.36 +/- 4.40 vs. 9.93 +/- 7.55; SCE spontaneous: 10.28 +/- 1.61 vs. 10.72 +/- 1.09; UV-induced increase: 7.30 +/- 2.19 vs. 7.55 +/- 2.14). We conclude from these data that an enhanced UV sensitivity as observed in cells from patients with cutaneous malignant melanoma and xeroderma pigmentosum is not a constitutive risk factor in basalioma patients.

Increased mutagen sensitivity in human cultured fibroblasts with constitutively high micronucleus levels.

The induction of micronuclei (MN) by incubation with different mutagenic agents was tested in diploid fibroblast cultures obtained from 15 probands with constitutively high MN rates (15.75-77.25 MN/500 cells; average 36.27 +/- 17.60 MN) and 15 probands (controls) with low MN rates (4-13.75 MN/500 cells; average 8.97 +/- 2.73 MN). In order to find out whether fibroblast cultures of individuals with increased spontaneous MN levels exhibit an increased sensitivity to various agents with different genotoxic mechanisms, we studied the induction of MN in these cell cultures by ultraviolet (UV) irradiation, mitomycin C (MMC), N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and benzo-(a)pyrene-diol-expoxid (BPDE). In addition, we tested aphidicolin (APC), a polymerase alpha inhibitor, which is a potent inducer of common fragile sites. Probands with spontaneously high MN showed an significantly increased sensitivity to UV (p less than or equal to 0.005), MMC (p less than or equal to 0.005), and BPDE (p less than or equal to 0.005). No significant differences were found for MNNG and APC as compared to controls.

Constitutively increased micronuclei are predominantly caused by acentric fragments.

The frequency of kinetochore (centromere)-positive micronuclei (MN) was determined in 32 fibroblast cell lines. We tested 16 probands with spontaneously high MN levels (greater than or equal to 20 MN/500 cells (4%] and 8 probands (controls) with low MN levels (less than or equal to 13 MN/500 cells (2.6%]. To study whether the elevation of MN levels is due to increased chromosomal breakage we used the antikinetochore antibody fluorescent staining method. Probands with spontaneously high MN had kinetochore-positive MN increased by a factor 2.1 compared to the controls whereas the kinetochore-negative MN were increased by a factor 6.14. This shows that spontaneous elevation of MN is mainly caused by increased chromosomal breakage and only in a minor proportion by chromosome segregation errors as a consequence of spindle defects.