http://repub.eur.nl/res/aut/39614/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/35044/ 2012-01-01T00:00:00Z Huntington's disease (HD) is known to have a negative impact on family life. Offspring of HD patients may be exposed to adversity in childhood because of the parent's disease and its psychological consequences. BRCA1/2 hereditary breast and ovarian cancer (BRCA1/2) increases the risk for offspring of being exposed to parental disease or loss. Childhood adversity is associated with psychopathology and various other problems in later life. Adverse childhood experiences (ACEs) before age 16 were assessed in adults at 50% risk for HD (n = 74) or BRCA1/2 (n = 82) and in controls (n = 101), using the Negative Life Events Scale. Mean number and occurrence of ACEs were compared between groups. The odds of having experienced adversity in childhood were higher in HD offspring and BRCA1/2 offspring than in controls. HD offspring reported a higher mean number of ACEs than controls or BRCA1/2 offspring. In HD offspring, the prevalence of parental disease and parental dysfunction experienced before age 16 was higher than in controls. In BRCA1/2 offspring, the prevalence of parental loss before age 16 was higher than in controls. This study indicates that 53% of HD offspring and 45% of BRCA1/2 offspring are exposed to adversity in childhood or adolescence. The relevance of these findings for counseling in predictive testing programs, reproductive decision-making, and child rearing matters is discussed. http://repub.eur.nl/res/pub/27915/ 2010-10-01T00:00:00Z This paper contains detailed results of a sub-population of the prospective randomized RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study. Objective: Statin treatment results in substantially decreased incidence of cardiovascular events but the exact pathophysiological mechanism of their beneficial effect is yet unclear. We aimed to examine the effects of up-titrated doses of two widely used statins (atorvastatin (ATOR) and rosuvastatin (ROSU)) on parameters involved in lipoprotein metabolism, in patients with low high density lipoprotein cholesterol values (HDL-C). Research design and methods: In this RADAR substudy, 80 patients, aged 4080 years, with known cardiovascular disease and low HDL-C (<1.0mmol/l), were randomized to receive, after an initial 6 week dietary run-in phase, either ATOR 20mg (n41) or ROSU 10mg (n39). The doses were up-titrated (in 6 week intervals) to 80mg of ATOR or 40mg of ROSU at 12 weeks. Serum lipoproteins and lipoprotein metabolism parameters were measured at baseline and at 6 and 18 weeks of follow up. Results: Both statins significantly reduced total cholesterol (TChol) and non-HDL-C values with ROSU being more effective for the doses studied (p<0.05). No statistically significant effect on HDL-C was observed for either statin. Apolipoproteins (apo) B, CI, CIII, AV and E were significantly reduced in both groups (p<0.05), while the ratio of HDL particles containing both apoAI and apoAII (LpAI-AII) over HDL containing apoAI alone (LpAI) was changed for both statins with the decrease of LpAI being more prominent in the ATOR group (p=0.028). Cholesterol ester transfer protein (CETP) mass and activity, phospholipid transfer protein (PLTP) activity and lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity were all significantly reduced in both treatment groups over the follow-up period (p<0.001). ATOR displayed a more prominent decrease of PLTP activity compared to ROSU (p=0.043), while ROSU displayed a more prominent decrease of Lp-PLA2 activity compared to ATOR (p=0.04). Both statins effectively reduced, in a dose-dependent way, high sensitivity C-reactive protein values over time, while no effect on the levels of circulating inter cellular adhesion molecule 1 (cICAM-1) was observed. Conclusions: The effects of statin treatment extend further and beyond a mere TChol and LDL cholesterol reduction, as demonstrated by the aforementioned alterations of lipoproteins, enzymes and lipid transfer proteins involved in lipoprotein metabolism and pro-atherogenic and inflammatory molecules. ROSU and ATOR displayed a similar pattern of effect on lipid metabolism with discrete differences in the magnitude of this effect in certain variables. Despite the limitations of small population size and lack of clinical end points, reported data provide an insight for the possible pathophysiological mechanisms implicated in the effect of increasing dosages of different statin treatments. http://repub.eur.nl/res/pub/32437/ 2008-09-01T00:00:00Z Objective: To compare voice quality after radiotherapy or endoscopic laser surgery in patients with similar T1a midcord glottic carcinomas according to a validated multidimensional protocol. Design: Retrospective cohort study. Setting: University cancer referral center. Patients: Two cohorts of consecutive patients willing to participate after treatment for primary Tla midcord glottic carcinoma with laser surgery (18 of 23 eligible) or radiotherapy (16 of 18 eligible). Main Outcome Measures: Posttreatment voice quality was evaluated according to a multidimensional voice protocol based on validated European Laryngological Society recommendations, including perceptual, acoustic, aerodynamic, and stroboscopic analyses, together with patient self-assessment using the Voice Handicap Index. Results: Approximately half of the patients had mild to moderate voice dysfunction in the perceptual analysis (53% [8 of 15] in the radiotherapy group and 61% [11 of 18] in the laser surgery group) and on the Voice Handicap Index (44% [7 of 16] in the radiotherapy group and 56% [10 of 18] in the laser surgery group). The voice profile in the laser surgery group was mainly breathy; in the radiotherapy group, it was equally breathy and rough, with a trend for more jitter in the acoustic analysis. There was no statistical difference in the severity of voice dysfunction between the groups in any of the variables. Conclusions: Endoscopic laser surgery offers overall voice quality equivalent to that of radiotherapy for patients with Tla midcord glottic carcinoma, although specific voice profiles may ultimately be different for the 2 modalities. We believe that endoscopic laser surgery is the preferred treatment in these patients because it provides oncologic control similar to that of radiotherapy and the additional benefits of lower costs, shorter treatment time, and the possibility of successive procedures.