Apolipoprotein E allelic frequency in elderly smokers.

Susceptibility genes for human diseases (e.g., cancer and atherosclerosis) increase disease risk by altering the metabolic activation of exogenous (e.g., carcinogens) and endogenous (e.g., cholesterol) compounds. The function of these genes, and subsequent risk, can be adversely affected by polymorphisms. This study tests the hypothesis that if specific genetic polymorphisms are related to mortality, then in elderly heavy smokers, there should be a decreased frequency of "at risk" alleles and an increased frequency of "protective" alleles, i.e., a survival effect. One such potential polymorphism is in the apolipoprotein E (apoE) gene, which is involved in cholesterol metabolism, where the epsilon4 allele is associated with an increased risk of coronary artery disease and is under represented in elderly populations. In this study, ApoE variant alleles were determined in 81 living, elderly current smokers (mean age: 72.5; range: 65-94; mean pack-years: 78; range: 13-192) and in 82 younger autopsy donors (mean age: 33; range: 1-58). There was a borderline difference in the apoE 4 allelic frequencies among the groups (11% in the elderly and 18% in the comparable younger group [df = 1; chi(2) = 4.02; P = 0.05]). A significant difference was found for age when stratified as a continuous variable by genotype in the elderly smokers (P = 0.03; mean age for persons with and without epsilon4 was 69.9 and 73.2, respectively). Pack-years of cigarette smokers did not differ by genotype, indicating no selective effect. These results confirm earlier associations for differences in the apoE allelic frequencies in the elderly and extend it to smokers, who generally have increased mortality at younger ages.

Efficiency of acitretin in combination with UV-B in the treatment of severe psoriasis.

Compared with the antipsoriatic retinoid etretinate, the new aromatic retinoid acitretin represents an important advance due to its rapid elimination kinetics. Since in psoriasis vulgaris retinoids are used predominantly in combination regimens, we investigated the therapeutic efficacy of acitretin and UV-B compared with placebo and UV-B in a double-blind, randomized multicenter trial in 82 patients with severe psoriasis. They were treated with 35 mg of the study medication during the first 4 weeks of therapy and 25 mg thereafter, concomitantly with UV-B irradiation in increasing energy doses. Forty patients who underwent therapy with acitretin and UV-B and 38 patients who underwent therapy with placebo and UV-B were evaluated for efficacy. The target variables--psoriasis severity index and total UV-B dose--were reported at intervals of 2 weeks over a maximum period of 8 weeks. At the end of treatment, the psoriasis severity index decrease was 79% in the acitretin and UV-B group and 35% in the placebo and UV-B group. The response rate, defined as greater than or equal to a 75% decrease of the psoriasis severity index, was 60% for the combination treatment and only 24% for the control treatment. This treatment response was achieved with markedly lower cumulative UV-B energy. The median cumulative UV-B energy applied to reach 75% clinical improvement was 11.8 J/cm2 vs 6.9 J/cm2. Side effects showed a similar pattern in both groups. Our data show that the acitretin dramatically improves the results of UV-B treatment in patients with severe psoriasis. In addition, it markedly decreases the effective cumulative UV-B dose, thereby reducing the potential long-term hazards of UV irradiation. We conclude that the acitretin plus UV-B combination treatment represents a highly effective therapeutic regimen in severe psoriasis.