Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy

Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, are associated with the risk of atherothrombosis. Plasma levels of these markers of inflammation are affected by hormone replacement therapy (HRT) and modulated by smoking. We studied whether genetic variation in the estrogen receptor- 1 (ESR1), CRP and fibrinogen-beta genes influences the plasma levels of inflammation markers after HRT. Plasma CRP and fibrinogen were measured after five years follow-up in healthy postmenopausal women (per-protocol group) who were randomised to hormone therapy (n=187) or no treatment (n=249). The effect of HRT, smoking and genetic variations in ESR1 (PvuII and XbaI), CRP (1444C/T) and fibrinogen-beta (FGB, -455G/A) were determined. The plasma concentration of CRP was higher in the HRT group than in the control group (2.03 mg/l and 1.41 mg/l, respectively; p < 0.001), while the concentration of fibrinogen was lower in the HRT group than in the control group (3.02 g/l and 3.20 g/l, respectively; p < 0.001), indicating that it is unlikely that inflammation is the common underlying pathway. There was a significant interaction between smoking and HRT on the fibrinogen (p=0.02), but not on the CRP concentration (n.s.). Genetic polymorphisms in ESR1, CRP and fibrinogen were not associated with an effect of HRT on the CRP and fibrinogen plasma levels, and no significant interaction with smoking was observed. In conclusion, higher plasma levels of CRP and lower plasma levels of fibrinogen were observed in women using HRT; however, genetic polymorphisms in ESR1, CRP and FGB were not associated with these effects of HRT.     

Inhibition of lipolysis stimulates peripheral glucose uptake but has no effect on endogenous glucose production in HIV lipodystrophy

HIV-infected patients with lipodystrophy (HIV lipodystrophy) are insulin resistant and have elevated plasma free fatty acid (FFA) concentrations. We aimed to explore the mechanisms underlying FFA-induced insulin resistance in patients with HIV lipodystrophy. Using a randomized, placebo-controlled, cross-over design, we studied the effects of an overnight acipimox-induced suppression of FFAs on glucose and FFA metabolism by using stable isotope-labeled tracer techniques during basal conditions and a two-stage euglycemic-hyperinsulinemic clamp (20 and 50 mU insulin/m(2) per min, respectively) in nine patients with nondiabetic HIV lipodystrophy. All patients received antiretroviral therapy. Biopsies from the vastus lateralis muscle were obtained during each stage of the clamp. Acipimox treatment reduced basal FFA rate of appearance by 68.9% (95% CI 52.6-79.5) and decreased plasma FFA concentration by 51.6% (42.0-58.9) (both, P < 0.0001). Endogenous glucose production was not influenced by acipimox. During the clamp, the increase in glucose uptake was significantly greater after acipimox treatment compared with placebo (acipimox: 26.85 micromol x kg(-1) x min(-1) [18.09-39.86] vs. placebo: 20.30 micromol x kg(-1) x min(-1) [13.67-30.13]; P < 0.01). Insulin increased phosphorylation of Akt Thr(308) and glycogen synthase kinase-3beta Ser(9), decreased phosphorylation of glycogen synthase (GS) site 3a + b, and increased GS activity (percent I-form) in skeletal muscle (P < 0.01). Acipimox decreased phosphorylation of GS (site 3a + b) (P < 0.02) and increased GS activity (P < 0.01) in muscle. The present study provides direct evidence that suppression of lipolysis in patients with HIV lipodystrophy improves insulin-stimulated peripheral glucose uptake. The increased glucose uptake may in part be explained by increased dephosphorylation of GS (site 3a + b), resulting in increased GS activity.     

Use of Pornography in a Random Sample of Norwegian Heterosexual Couples

This study examined the use of pornography in couple relationships to enhance the sex-life. The study contained a representative sample of 398 heterosexual couples aged 22–67 years. Data collection was carried out by self-administered postal questionnaires. The majority (77%) of the couples did not report any kind of pornography use to enhance the sex-life. In 15% of the couples, both had used pornography; in 3% of the couples, only the female partner had used pornography; and, in 5% of the couples, only the male partner had used pornography for this purpose. Based on the results of a discriminant function analysis, it is suggested that couples where one or both used pornography had a more permissive erotic climate compared to the couples who did not use pornography. In couples where only one partner used pornography, we found more problems related to arousal (male) and negative (female) self-perception. These findings could be of importance for clinicians who work with couples.     

Effects of multi-source feedback on developmental plans for leaders of postgraduate medical education

Objectives  Multi-source feedback (MSF) is a widely used developmental tool for leaders in organisations including those dealing with health care. This study was performed to examine the effects of an MSF process on developmental plans made by leaders of postgraduate medical education (PGME) in clinical departments.
Methods  An MSF instrument was developed based on literature on the subject and previous investigations. The instrument was used by consultants responsible for PGME in clinical departments (CREs). Apart from CREs' self-ratings, MSF responses were collected from heads of departments, consultants and young doctors-in-training. The MSF process included individual feedback as well as guidance on drafting developmental plans for both the department and the CREs. Themes emerging in the developmental plans were analysed and compared with the areas in need of improvement identified by the MSF process.
Results  The MSF instrument was found to be feasible, valid and reliable (Cronbach's α = 0.98). The study included 52 CREs from various specialties and 498 MSF respondents. The response rate was 84%. Low ratings and negative gaps between others' ratings and self-ratings were identified for both management and leadership performance areas. The developmental plans mainly focused on management initiatives, whereas plans for the development of leadership performance were few. Areas rated low by all respondents were scarcely represented in CREs' developmental plans.
Conclusions  An MSF process might in itself lead to development in administrative areas. However, MSF carried through as a single stand-alone procedure was not sufficient to foster plans for the development of leadership performance.     

Risk factors and predictors of Torsade de pointes ventricular tachycardia in patients with left ventricular systolic dysfunction receiving Dofetilide

The purpose of this study was to identify risk factors of Torsade de pointes (TdP) ventricular tachycardia in patients medicated with a class III antiarrhythmic drug (dofetilide) and left ventricular systolic dysfunction with heart failure (HF) or recent myocardial infarction (MI). The 2 Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) studies enrolled patients with HF (DIAMOND-HF) or MI (DIAMOND-MI) and left ventricular systolic dysfunction. The present analysis includes only patients treated solely with dofetilide. The incidence of TdP was 2.1% (32 of 1,511). Twenty-five of the incidences occurred in the DIAMOND-HF study and 7 cases in the DIAMOND-MI study (p = 0.0015). TdP was more frequent in women than in men (47% vs 28%, p = 0.02). Risk factors for developing TdP were female gender (odds ratio 2.2, 95% confidence interval [CI] 1.0 to 5.0), MI within 8 weeks (odds ratio 0.3, 95% CI 0.1 to 0.7), being in New York Heart Association class III or IV (odds ratio 3.2, 95% CI 1.2 to 8.6), and baseline QTc duration (odds ratio 1.14, 95% CI 1.00 to 1.30) per 10 ms. Women with chronic HF, QTc duration >400 ms. and New York Heart Association class III or IV had a risk of TdP of 10%, whereas no TdP episodes were observed in patients with QTc duration <400 ms. In conclusion, severity of HF, female gender, and QTc duration make it possible to identify patients with a high risk of early TdP when treated with dofetilide. Patients with recent MI less often had TdP compared with patients with chronic HF.     

Disease activity in pregnant women with Crohn's disease and birth outcomes: a regional Danish cohort study

OBJECTIVES: CD is associated with increased risk of adverse birth outcomes, but existing studies have not assessed the impact of disease activity during pregnancy. We examined the impact of disease activity on birth outcomes: LBW, preterm birth, LBW at term, and CAs. METHODS: All births by CD women in North Jutland County, Denmark, from January 1, 1977 to December 31, 2005, were evaluated in a cohort study based on linkage between the Danish National Registry of Patients and the Medical Birth Registry. After identification of all births by CD women, review of medical records allowed collection of clinical details (including disease activity and drug therapy during pregnancy). The exposed cohort (N = 71) constituted pregnancies with low/moderate-high disease activity during pregnancy, and the unexposed cohort (N = 86) those with inactive disease. Logistic regression analyses were used to estimate the adjusted relative risks (with 95% confidence intervals) for adverse birth outcomes associated with disease activity in CD pregnancies. In subanalysis, we examined the impact of moderate-high activity. RESULTS: In women with disease activity, the adjusted risks of LBW, LBW at term, preterm birth, and CAs were 0.2 (0.0-2.6), 0.4 (0.0-3.7), 2.4 (0.6-9.5), and 0.8 (0.2-3.8), respectively. The crude risk of preterm birth was 3.4 (1.1-10.6) in those with moderate-high disease activity. CONCLUSIONS: Disease activity during pregnancy only increased the risk of preterm birth (especially in those with high disease activity). Further research is needed to assess the critical impact of disease activity in larger cohorts of CD women.     

Birth outcome in Danish women with cutaneous malignant melanoma

Several factors may affect birth outcome in women with cutaneous malignant melanoma. We examined whether maternal cutaneous malignant melanoma affects birth outcome (preterm birth, low birth weight at term, stillbirth, congenital abnormalities, mean birth weight, and male proportion of newborns) in a nationwide cohort study of 1059 births from 1973 to 2002 to women with cutaneous melanoma, compared with 50,794 births from a cohort of mothers without cancer. We found no increased risk of adverse birth outcome for the 620 newborns born to women with a diagnosis of melanoma before pregnancy or the 88 newborns born to women diagnosed during pregnancy. Among 351 births of women diagnosed with melanoma within 2 years from the time of delivery, the prevalence odds ratio of stillbirth was 4.6 (95% confidence interval: 1.7; 12). This estimate was, however, based on only five stillbirths in the exposed group and was an unexpected finding. With this exception, our data suggest no substantially increased risk of adverse birth outcome for women with melanoma.