[Genodermatoses with malignant skin tumors]. / Genodermatosen mit malignen Hauttumoren.

Cutaneous malignancies can manifest as isolated and sporadic tumors as well as multiple and disseminated tumors. In the latter case they often point to a genetic disease, which either can be restricted to the skin exclusively or also involve extracutaneous organs in the context of a hereditary tumor syndrome. Such hereditary tumor syndromes are clinically and genetically very heterogeneous. Therefore, the prevailing specific skin tumors play an important diagnostic role in the case of complex symptom constellations. Elucidation of the genetic basis of rare monogenetically inherited disorders and syndromes can contribute to a better understanding of the pathogenesis of frequently occurring cutaneous malignancies because the mutated genes often encode proteins, which have a key position in metabolic signaling pathways that are of high significance for the development of targeted therapies. Here we provide an overview of genodermatoses, which are associated with basal cell carcinomas, sebaceous carcinomas, keratoacanthomas, squamous cell carcinomas and malignant melanomas.

Effects of exercise on lipoprotein(a).

Lipoprotein(a) [Lp(a)] is a unique lipoprotein complex in the blood. At high levels (> 30 mg/dl), Lp(a) is considered an independent risk factor for cardiovascular diseases. Serum Lp(a) levels are largely genetically determined, remain relatively constant within a given individual, and do not appear to be altered by factors known to influence other lipoproteins (e.g. lipid-lowering drugs, dietary modification and change in body mass). Since regular exercise is associated with favourable changes in lipoproteins in the blood, recent attention has focused on whether serum Lp(a) levels are also influenced by physical activity. Population and cross-sectional studies consistently show a lack of association between serum Lp(a) levels and regular moderate physical activity. Moreover, exercise intervention studies extending from 12 weeks to 4 years indicate that serum Lp(a) levels do not change in response to moderate exercise training, despite improvements in fitness level and other lipoprotein levels in the blood. However, recent studies suggest the possibility that serum Lp(a) levels may increase in response to intense load-bearing exercise training, such as distance running or weight lifting, over several months to years. Cross-sectional studies have reported abnormally high serum Lp(a) levels in experienced distance runners and body builders who train for 2 to 3 hours each day. However, the possible confounding influence of racial or ethnic factors in these studies cannot be discounted. Recent intervention studies also suggest that 9 to 12 months of intense exercise training may elevate serum Lp(a) levels. However, these changes are generally modest (10 to 15%) and, in most individuals, serum Lp(a) levels remain within the recommended range. It is unclear whether increased serum Lp(a) levels after intense exercise training are of clinical relevance, and whether certain Lp(a) isoforms are more sensitive to the effects of exercise training. Since elevation of both low density lipoprotein cholesterol (LDL-C) and Lp(a) levels in the blood exerts a synergistic effect on cardiovascular disease risk, attention should focus on changing lifestyle factors to decrease LDL-C (e.g. dietary intervention) and increase high density lipoprotein cholesterol (e.g. exercise) levels in the blood.

Effects of physical activity and diet on lipoprotein(a).

Lipoprotein(a) [Lp(a)] represents a class of lipoproteins with some structural similarity to low density lipoprotein (LDL), but containing a unique apoprotein, apoprotein(a). First reported in 1963, Lp(a) is now considered to have an independent role in the development of atherosclerotic lesions. The level of Lp(a) in the blood is under strong genetic influence and does not appear to be alterable by lifestyle factors known to influence other lipoproteins. Regular moderate exercise has been shown to favorably alter other lipoproteins, and recent attention has focused on whether Lp(a) level can be influenced by physical activity. Current data from cross-sectional and intervention studies show little effect of moderate exercise on serum Lp(a) concentration. One possible exception may be an elevation of serum Lp(a) concentration in adult endurance and power athletes who exercise intensely on a daily basis. However, not all studies have taken into account possible racial or ethnic differences in Lp(a) concentrations and the skewed distribution observed within most populations. Standard dietary intervention such as a low fat diet recommended for weight loss and control of other blood lipids has little effect on serum Lp(a) level. At present, serum Lp(a) concentration does not appear to be significantly altered by realistic dietary changes and moderate physical activity as recommended for health. The synergistic effect on cardiovascular disease risk when both LDL-cholesterol and Lp(a) are elevated highlight the importance of attending to those risk factors that can be modified by exercise and other lifestyle changes.

Acute effects of treadmill running on lipoprotein(a) levels in males and females.

This investigation examined the acute response of serum lipoprotein(a) (Lp(a)) concentration immediately after, and during several days following, level and downhill motorized treadmill running. Eight males ran for 1 h on a level motorized treadmill at an intensity producing 90% maximum heart rate (MHR). On a separate occasion, three males and three females performed downhill (negative 13.4% incline) treadmill running at an intensity producing 75-80% MHR. For both protocols, serial blood samples were taken pre- and post-exercise and at the same time of day 1, 3, 5, and 7 days following exercise. Levels of Lp(a), creatine kinase (CK), C-reactive protein (CRP), and ferritin were measured. Repeated measures statistical analysis (Friedman ANOVA) showed no significant change in the median level of Lp(a) (level run, 5.0 mg.dl-1; downhill run, 7.45 mg.dl-1) across time following either protocol. After level running, ferritin levels 5 and 7 d post-exercise were significantly (P < 0.05) lower compared with immediately and 1 d post-exercise measures (Friedman ANOVA). Following level running, the Wilcoxon signed rank test showed significant (P < 0.05) elevations in CK levels immediately, 1 and 5 d post-exercise compared with pre-exercise values. Following downhill running. CK level was significantly elevated up to 3 d post-exercise (Wilcoxon signed rank). Calculated plasma volume did not change significantly following either protocol. These data suggest that Lp(a) does not change acutely in response to level or downhill treadmill running up to 60 min duration.

The effect of endurance training on lipoprotein(a) [Lp(a)] levels in middle-aged males.

Serum lipoprotein(a) [Lp(a)] levels were measured before and after a 12-wk program of moderate-intensity endurance training. The training program consisted of walking and/or jogging, at least three sessions.wk-1 of at least 30 min duration, at an intensity producing 60-85% HRmax reserve. Twenty-eight previously sedentary middle-aged Caucasian males matched for age, body mass, and body mass index (BMI) were randomly allocated to either an exercise (N = 17, mean age +/- SEM = 51.57 +/- 1.25 yr) or a control (N = 11, mean age +/- SEM = 50.0 +/- 1.15 yr) group. Pre- and post-training median Lp(a) levels, measured by immunoturbidimetric analysis, were not significantly different in either the exercise (pre 13.0, post 15.0 mg.dl-1) or the control subjects (pre 14.0, post 12.0 mg.dl-1) (P > 0.05). Kendall Rank correlation analysis revealed no significant relationship between the level of Lp(a) and any other variable in either group before or after training. In the exercisers, a significant increase (P < 0.05) was recorded in the estimated mean VO2max (pre 33.39 +/- 1.70, post 37.7 +/- 1.75 ml.kg-1 min-1). These data indicate that the level of Lp(a) was not influenced by a 12-wk program of moderate-intensity endurance training, and are consistent with previous reports suggesting that Lp(a) level is not altered by lifestyle factors.

Lipoprotein(a) [Lp(a)] levels in middle-aged male runners and sedentary controls.

Serum Lipoprotein(a) [Lp(a)] concentration was compared between middle-aged well-trained Caucasian male endurance runners (N = 57), (mean age +/- SEM 47.8 +/- 0.7 yr) and age-, body mass-, and body mass index (BMI)-matched male nonathletic control subjects (N = 62), (mean age +/- SEM 48.7 +/- 0.8). The mean weekly training distance of the runners was (60.7 +/- 2.8 km.wk-1) at the time of testing. Median Lp(a) levels were not significantly different (P > 0.05) between the runners (15.0 mg.dl-1) and the control subjects (12.5 mg.dl-1). As expected, compared with control subjects, in runners levels of other lipoproteins and apoproteins were significantly more favorable for cardiovascular health (all P < 0.01). There was no significant relationship between Lp(a) and any other measured variable (lipid, anthropometric, or dietary) in the runners group. In the control group, the significant positive correlation between Lp(a) and LDL-C was no longer significant after correction for the estimated contribution of Lp(a) cholesterol to LDL-C. These cross-sectional data suggest that a lifestyle of moderate to intense exercise training does not exert a significant impact on the Lp(a) level.

The acute effect of 30 min of moderate exercise on high density lipoprotein cholesterol in untrained middle-aged men.

Fifteen middle-aged, untrained (defined as no regular exercise) men (mean age 49.9 years, range 42-67) cycled on a cycle ergometer at 50 rpm for 30 min at an intensity producing 60% predicted maximum heart rate [(fc,max), where fc,max = 220 - age]. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (Tg) concentrations were measured from fasting fingertip capillary blood samples collected at rest, after 15 and 30 min of exercise, and at 15 min post-exercise. The mean HDL-C level increased significantly from the resting level of 0.85 mmol.l-1 to 0.97 mmol.l-1 (P < 0.05) after 15 min of exercise, increased further to 1.08 mmol.l-1 (P < 0.01) after 30 min of exercise and remained elevated at 1.07 mmol.l-1 (P < 0.01) at 15 min post-exercise. These increases represented changes above the mean resting level of 14.1%, 27.1% and 25.9% respectively. The HDL-C/LDL-C ratio increased significantly from a resting ratio of 0.20 to 0.26 after 30 min of exercise (P < 0.01) and to 0.24 at 15 min post-exercise (P < 0.05). The mean Tg level increased significantly from a resting level of 0.88 mmol.l-1 to 1.05 mmol.l-1 after 15 min, and to 1.06 mmol.l-1 after 30 min of exercise (P < 0.05 at each time). The TC/HDL-C ratio decreased significantly (P = 0.05) after 30 min of exercise and at 15 min post-exercise by 18.8% and 14%, respectively. No significant changes were observed in the levels of TC or LDL-C over time.(ABSTRACT TRUNCATED AT 250 WORDS)