[A woman with balls in the lower abdomen]. / Een vrouw met bolletjes in de onderbuik.

A 34-year old woman visited the general practitioner because of nausea and diarrhoea. A large abdominal swelling was palpable. Ultrasound showed a cyst containing 'floating balls', pathognomic for a mature teratoma. An ovariectomy was performed. Macroscopic the ovary contained greasy balls existing of hairs and sebum. Our diagnosis: Dermoid cyst.

Personality and stress appraisal in adults prenatally exposed to the Dutch famine.

BACKGROUND: Previous studies have shown that prenatal exposure to the Dutch famine is associated with an increased risk for several psychiatric disorders. Variation in personality characteristics and in stress appraisal may underlie mental disorders. AIMS: To investigate whether prenatal famine exposure is associated with personality characteristics and stress appraisal. STUDY DESIGN: Cohort study. SUBJECTS: Participants included a total of 572 men and women, born as term singletons in a local hospital in Amsterdam around the time of the 1944-1945 Dutch famine. OUTCOME MEASURES: Scores on the Big Five Inventory and the Perceived Stress Scale (PSS). RESULTS: There were no statistically significant differences in the personality traits openness, conscientiousness, extraversion, agreeableness and neuroticism or in PSS scores between those unexposed and those exposed to famine during early, mid or late gestation. However, there were statistically significant (P=0.01) and borderline significant interactions (P=0.07) respectively between exposure to famine during early gestation and sex on conscientiousness and agreeableness. Subsequent analyses showed that men exposed to famine during early gestation had lower conscientiousness scores and women exposed during early gestation had higher agreeableness scores. CONCLUSIONS: We conclude that conscientiousness and agreeableness may differ between men and women unexposed and exposed to famine during early gestation. As evidence was not very robust, future research should confirm the present findings.

Associations between DNA methylation of a glucocorticoid receptor promoter and acute stress responses in a large healthy adult population are largely explained by lifestyle and educational differences.

BACKGROUND: Glucocorticoids are the key regulators of the biological stress response and act by binding to glucocorticoid receptors (GR). Expression of GR is altered by DNA methylation. Methylation patterns in GR promoters have been shown to be highly variable between individuals, but little is known about the functional consequences of this variation for the acute stress response. The present study investigated associations between methylation status of the GR 1-C promoter and cortisol, cardiovascular and perceived stress responses to a psychosocial stress protocol in a large healthy adult population. METHODS: A total of 725 overall healthy men and women, aged 55-60 years, participated in a standardized psychosocial stress protocol consisting of three different stressors. At different stages during the stress protocol, salivary cortisol levels, continuous blood pressure and heart rate (HR) levels as well as perceived stress were measured. Stress reactivity was calculated as the increase between basal and peak measurements. Methylation status of the GR 1-C promoter was assessed in DNA isolated from peripheral blood samples using a methylation sensitive PCR assay for 675 of the 725 participants. RESULTS: A decrease in methylation of the GR 1-C promoter was associated with a decrease in stress reactivity as indicated by lower cortisol and lower HR reactivity. A 1% decrease in GR 1-C methylation corresponded with a cortisol decrease by 0.14% (95% CI: 0.03-0.25, p=0.02) and an HR decrease by 0.10 bpm (0.03-0.16, p=0.003). Adjusting for sex, lifestyle and education largely abolished these associations. A decrease in methylation of the GR 1-C promoter was also associated with an increase in stress perception as indicated by higher perceived stress (0.03 points [0.00-0.06, p=0.05]), lower perceived performance (-0.03 points [-0.05 to -0.01], p=0.02), and lower perceived control (-0.03 points [-0.05 to 0.00], p=0.04). After adjusting for sex and educational level the associations were no longer statistically significant. GR 1-C methylation status was not associated with blood pressure responses to the stress protocol. DISCUSSION: Although effects were small, variation in methylation status in the GR 1-C promoter was associated with physical and perceived acute stress responses. Interestingly, these associations could largely be explained by differences in lifestyle and education.

Survival effects of prenatal famine exposure.

BACKGROUND: Adverse intrauterine conditions are known to be associated with an increased risk of chronic diseases in adult life. Previously, we showed that prenatal famine exposure increased the incidence of cardiovascular and metabolic disease in adulthood. OBJECTIVE: We examined the association between prenatal famine exposure and adult mortality. DESIGN: We studied adult mortality among 1991 term singletons from the Dutch Famine Birth Cohort. We compared overall and cause-specific adult mortality among people exposed to famine in late, mid, and early gestation with those unexposed to famine in utero by using Cox proportional hazard models. RESULTS: A total of 206 persons (10%) had died by the end of follow-up. Compared with unexposed women, women exposed to famine in early gestation had a significantly higher risk of overall adult mortality (HR: 1.9; 95% CI: 1.1, 3.4), cardiovascular mortality (HR: 4.6; 95% CI: 1.2, 17.7), cancer mortality (HR: 2.3; 95% CI: 1.1, 4.7), and breast cancer mortality (HR: 8.3; 95% CI: 1.1, 63.0). In men exposed to famine in early gestation, these associations were as follows compared with unexposed men: overall adult mortality (HR: 0.4; 95% CI: 0.2, 1.1), cardiovascular mortality (HR: 0.9; 95% CI: 0.3, 3.1), and cancer mortality (HR: 0.3; 95% CI: 0.0, 1.9). CONCLUSIONS: Women exposed to famine in early gestation had a higher overall adult, cardiovascular, cancer, and breast cancer mortality risk than did women not exposed to famine. No such effects were observed in men exposed to famine in early gestation.

Biochemical cardiovascular risk factors after hypertensive pregnancy disorders: a systematic review and meta-analysis.

The objective of this study was to perform a systematic review and meta-analysis of studies assessing biochemical cardiovascular risk factors in women with previous hypertensive pregnancy disorders and women with previous normotensive pregnancies. Data were collected from PubMed and EMBASE (from inception to February 28, 2011) supplemented by manual searches of bibliographies. Included were cohort studies and case-control studies assessing biochemical cardiovascular risk factors in women with previous hypertensive pregnancy disorders compared with women with previous normotensive pregnancies. Of 2573 studies reviewed for eligibility, quality, and data extraction, 22 were included in the review, of which 15 could be meta-analyzed. The pooled mean differences for the outcomes of interest were 0.17 mmol/L (95% confidence interval [CI], 0.08-0.25 mmol/L) for glucose (10 studies), 3.46 mU/mL (95% CI, 2.34-4.58 mU/mL) for insulin (5 studies), 0.13 mmol/L (95% CI, 0.05-0.21) for triglycerides (10 studies), 0.22 mmol/L (95% CI, 0.11-0.33 mmol/L) for total cholesterol (11 studies), -0.11 mmol/L (95% CI, -0.18 to -0.04 mmol/L) for high-density lipoprotein cholesterol (10 studies), and 0.21 mmol/L (95% CI, 0.10-0.32) for low-density lipoprotein cholesterol (9 studies), all in the disadvantage in women with previous hypertensive pregnancy disorders. Analyses for preeclampsia alone showed similar results. CONTINUED LEARNING OBJECTIVES: After completing this CME activity, physicians should be better able to assess the long-term cardiovascular consequences after hypertensive pregnancy disorders, evaluate and interpret the evidence regarding biochemical cardiovascular risk factor assessment after pregnancy, and counsel women with a history of hypertensive pregnancy disorders as to the effectiveness of cardiovascular risk factor assessment in the primary prevention of cardiovascular disease. CONCLUSIONS: Women with previous hypertensive pregnancy disorders have higher glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels measured after pregnancy compared with women with previous normotensive pregnancies. These biochemical cardiovascular risk factors may identify women who will benefit from primary prevention of cardiovascular disease. TARGET AUDIENCE: Obstetricians and gynecologists, family physicians.

The fetal origins of hypertension: a systematic review and meta-analysis of the evidence from animal experiments of maternal undernutrition.

OBJECTIVE: Numerous experiments in animals have been performed to investigate the effect of prenatal undernutrition on the development of hypertension in later life, with inconclusive results. We systematically reviewed animal studies examining the effects of maternal undernutrition on SBP, DBP, and mean arterial blood pressure (BP) in offspring. METHODS: A search was performed in Medline and Embase to identify articles that reported on maternal undernutrition and hypertension in experimental animal studies. Summary estimates of the effect of undernutrition on SBP, DBP, and mean arterial BP were obtained through meta-analysis. RESULTS: Of the 6151 articles identified, 194 were considered eligible after screening titles and abstracts. After detailed evaluation, 101 met the inclusion criteria and were included in the review. Both maternal general and protein undernutrition increased SBP [general undernutrition: 14.5 mmHg, 95% confidence interval (CI) 10.8-18.3; protein undernutrition: 18.9 mmHg, 95% CI 16.1-21.8] and mean arterial BP (general undernutrition: 5.0 mmHg, 95% CI 1.4-8.6; protein undernutrition: 10.5 mmHg, 95% CI 6.7-14.2). There was substantial heterogeneity in the results. DBP was increased by protein undernutrition (9.5 mmHg, 95% CI 2.6-16.3), whereas general undernutrition had no significant effect. CONCLUSION: The results of this meta-analysis generally support the view that in animals, maternal undernutrition--both general and protein--results in increased SBP and mean arterial BP. DBP was only increased after protein undernutrition. The results depended strongly on the applied measurement technique and animal model.

Hungry in the womb: what are the consequences? Lessons from the Dutch famine.

An increasing body of evidence suggests that poor nutrition at the very beginning of life - even before birth - leads to large and long term negative consequences for both mental and physical health. This paper reviews the evidence from studies on the Dutch famine, which investigated the effects of prenatal undernutrition on later health. The effects of famine appeared to depend on its timing during gestation, and the organs and tissues undergoing critical periods of development at that time. Early gestation appeared to be the most vulnerable period. People who were conceived during the famine were at increased risk of schizophrenia and depression, they had a more atherogenic plasma lipid profile, were more responsive to stress and had a doubled rate of coronary heart disease. Also, they performed worse on cognitive tasks which may be a sign of accelerated ageing. People exposed during any period of gestation had more type 2 diabetes. Future investigation will expand on the finding that the effects of prenatal famine exposure may reach down across generations, possibly through epigenetic mechanisms. Recent evidence suggests that similar effects of prenatal undernutrition are found in Africa, where many are undernourished. Hunger is a major problem worldwide with one in seven inhabitants of this planet suffering from lack of food. Adequately feeding women before and during pregnancy may be a promising strategy in preventing chronic diseases worldwide.