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Biomedical subjects

L J van Doornen

Publications and source records attributed to L J van Doornen.

At least 19 recordsLinked to original sources
PubMed2001

Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis.

OBJECTIVE: There is evidence that the hypothalamic pituitary adrenal (HPA) axis is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis responses to experimental stressors mimicking daily life challenges in patients with RA to determine whether HPA axis activity is associated with Th1 and Th2 activity. METHODS: ACTH and cortisol responses in reaction to the succession of a bicycle ergometer task, a cold pressor task, and a computerized Stroop Color-Word interference test, as well as basal Th1 and Th2 cell activity, were assessed in 29 patients (21 female, 8 male) with recently diagnosed RA (mean disease duration 29 wks, range 5-69), mean age 55.7 years, none receiving glucocorticoid treatment, and 30 (20 female, 10 male) healthy age and sex matched controls (mean age 54.1 yrs). RESULTS: Mean ACTH and cortisol levels did not differ between the groups (p > 0.10). Patients tended to have a less pronounced ACTH response (F2.50 = 2.7, p = 0.08) and had a significantly smaller cortisol response (P F2.50 = 6.1, p < 0.01) than healthy controls in reaction to the stressors. This difference in cortisol response was reduced, but remained significant when ACTH responsiveness was accounted for by entering it as a covariate (P F2.49 = 3.7, p = 0.03). ACTH and cortisol levels and responses were not associated (all p > 0.19) with basal interferon-gamma and interleukin 4 as reflections of Th1 and Th2 cell activity, respectively. HPA axis activity was not linked to current disease activity. CONCLUSION: Our findings show reduced HPA axis responsiveness in RA patients with recent diagnosis receiving longterm medication that is suggested to be located both at a hypothalamic/pituitary and at an adrenal level. It appears that common HPA axis activity accomplishes low amounts of cortisol release, which makes it difficult to determine an influence of endogenous cortisol changes on the Th1/Th2 balance.

Adrenocorticotropic Hormone↗
PubMed2000

Effects of work stress on ambulatory blood pressure, heart rate, and heart rate variability.

Work stress has repeatedly been associated with an increased risk for cardiovascular disease. This study tested whether this relationship could be explained by exaggerated cardiovascular reactivity to work or impaired recovery in leisure time. Vagal tone was assessed as a possible determinant of these work stress effects. Participants included 109 male white-collar workers (age, 47.2+/-5. 3) who were monitored on 2 workdays and 1 nonworkday for ambulatory blood pressure, heart rate, and heart rate variability. Chronic work stress was defined according to Siegrist's model as (1) high imbalance, a combination of high effort and low reward at work, or (2) high overcommitment, an exhaustive work-related coping style indexing the inability to unwind. All findings were adjusted for possible differences in posture and physical activity between the work stress groups. High imbalance was associated with a higher heart rate during work and directly after work, a higher systolic blood pressure during work and leisure time, and a lower 24-hour vagal tone on all 3 measurement days. Overcommitment was not associated with an unfavorable ambulatory profile. Logistic regression analysis revealed that heart rate [odds ratio 1-SD increase 1.95 (95% CI, 1.02 to 3.77)] and vagal tone [odds ratio 1-SD decrease 2.67 (95% CI, 1.24 to 5.75)] were independently associated with incident mild hypertension. Surprisingly, the values during sleep were more predictive for mild hypertension than the values during work. The results from the present study suggest that the detrimental effects of work stress are partly mediated by increased heart rate reactivity to a stressful workday, an increase in systolic blood pressure level, and lower vagal tone.

Adult↗
PubMed2000

Genetics of testosterone and the aggression-hostility-anger (AHA) syndrome: a study of middle-aged male twins.

The aim of this study was to determine the genetic contribution to the variation in testosterone and the aggression-hostility-anger (AHA) syndrome in middle-aged twins. Moreover, the relation between testosterone and this syndrome, and possible common genetic mechanisms were investigated. Towards this end, blood samples were collected at two time points; the AHA syndrome was measured using three questionnaires: the Buss-Durkee Hostility Inventory with seven subscales, the Jenkins Activity Survey and the Spielberger State-Trait Anger Scale. The results showed substantial heritabilities for testosterone (approximately 60%) and moderate to fair heritabilities for the nine measures of the AHA syndrome (23-53%). The best fitting model for testosterone at two time points included a small age component and additive genetic and unique environmental factors, while a multivariate analysis of the nine AHA subscales resulted in an independent pathway model with two common additive genetic and two common unique environmental factors. No correlation between the common genetic factor influencing testosterone and the AHA subscales was found. We did, however, detect a negative correlation between the common environmental factor underlying testosterone and both common environmental factors influencing the nine AHA subscales, which may reflect a tendency for testosterone levels to rise and hostility to drop (or vice versa) after repeatedly experiencing success (or failure).

Adult↗
PubMed1999

Bivariate genetic analysis of fasting insulin and glucose levels.

The main aim of this study was to estimate the relative influence of genes and environment on fasting insulin levels, which were considered a proxy of insulin resistance. Possible sex differences in genetic and environmental influences, and the origin of the covariance between fasting insulin and glucose were investigated. Subjects were 209 pairs of middle-aged twins, divided into 5 sex-by-zygosity groups. A general bivariate model and a reciprocal causation model including fasting insulin and glucose were used in the analyses. For both quantitative genetic models, a model specifying additive genetic and unique environmental factors, which were the same in males and females, showed the best fit to the data. Heritability estimates were modest and highly similar in both models: 20-25% of the variance in fasting insulin, and around 50% of the variance in fasting glucose levels could be attributed to genetic factors. The two models could not be discriminated on the basis of their fit to the data. A submodel of the general bivariate model suggested that the covariance between glucose and insulin has a unique environmental basis, whereas for the reciprocal causation model both causal paths were needed to explain the phenotypic correlation between insulin and glucose and estimates of the reciprocal paths were of opposite sign, an indication for the expected negative feedback loop.

Adult↗
PubMed1999

Dissecting the genetic architecture of lipids, lipoproteins, and apolipoproteins: lessons from twin studies.

We review the ways in which twin studies have been used to investigate the genetic architecture of lipids, lipoproteins, and apolipoproteins. We focus on the age dependency of genetic effects and the importance of pleiotropy for the lipid system. Finally, consequences are discussed of age dependency and pleiotropy for the design and power of twin studies aimed at detecting the actual quantitative trait loci (QTLs) involved. It is concluded that twin studies have played an important role and will remain highly valuable for the elucidation of the genetic architecture of lipids, lipoproteins, and apolipoproteins. Twins can efficiently be used to identify the location and function of QTLs. Taking account of pleiotropy and age-dependent gene expression in study design and data analysis will improve the power and efficiency to find these QTLs for components of the lipid system.

Apolipoproteins↗
PubMed1999

Light and diurnal cycle affect human heart rate: possible role for the circadian pacemaker.

Humans and animals demonstrate diurnal rhythms in physiology and behavior, which are generated by the circadian pacemaker, located in the supra-chiasmatic nucleus (SCN). The endogenous diurnal rhythm of the SCN is synchronized to the diurnal cycle most effectively by light. However, light also influences the SCN and its output instantaneously, as is demonstrated for the immediate effects of light on SCN neuronal firing frequency and on the output of the SCN to the pineal, inhibiting melatonin secretion. In addition to this, the circadian pacemaker modulates neuronally also other organs such as the adrenal. Therefore, the authors investigated the effect of this light input to the SCN on human heart rate, using light at different phases of the day-night cycle and light of different intensities. Resting heart rate (HR) was measured in volunteers between 20 and 40 years of age during supine, awake, resting conditions, and after 2 hours of fasting. In Experiment 1, HR was measured at different times over the day-night cycle at 0 lux and at indoor light. In Experiment 2, HR was measured at different times over the day-night cycle at controlled light intensities of 0 lux, 100 lux, and 800 lux. The authors demonstrate a clear diurnal rhythm in resting HR in complete darkness, similar to that measured under constant routine conditions. Second, it is demonstrated that light increases resting HR depending on the phase of the day-night cycle and on the intensity of light. These data strongly suggest that the circadian pacemaker modulates human HR.

Adult↗
PubMed1998

Serum lipids and cardiovascular reactivity to stress.

Several studies have reported an association between serum lipid levels and cardiovascular reactivity to laboratory stressors. Their findings, however, are equivocal. The inconsistencies may be due to shortcomings such as the small number of subjects, the inclusion of patient groups, no control for medication, and no control for age effects. Two studies are presented investigating the relationship in large groups of adolescent and middle-aged males and females. Cholesterol, triglycerides and HDL were measured. Subjects were exposed to mental stressors, and in one study also to a cold pressor test. In addition to heart rate and blood pressure, in one study impedance cardiography was used to measure pre-ejection period, stroke volume and total peripheral resistance. Canonical correlation analysis suggested an association between triglycerides and decreased cardiac reactivity to mental stressors in middle-aged females. Trends in the same direction were found in both middle-aged males and females with respect to reactivity to the cold pressor. These associations, however, were not confirmed when the extreme deciles of the triglyceride distributions were compared with respect to stress reactivity. The fact that associations were completely absent in youngsters but sometimes showed up in older persons suggested an age dependency of the association. In post hoc analyses, indeed, some evidence was found for stronger cardiac responsivity being associated with cholesterol specifically in relatively older males. In females, in contrast to this, the association between triglycerides and cardiac responsivity was stronger in the younger group. More detailed measurement techniques, of specifically vascular processes, may be needed to explore further the effects of sex and age on the association between lipids and stress reactivity.

Adolescent↗
PubMed1998

Heritability of blood pressure increases during mental stress.

We studied the influence of mental stress on the contributions of genes and environment to individual variation in systolic (SBP) and diastolic (DBP) blood pressure by structural equation modelling in 320 adolescent male and female twins. Blood pressure data were collected during rest and during a reaction time and a mental arithmetic task. Univariate analyses of SBP and DBP showed familial aggregation for blood pressure. A genetic explanation for this resemblance was most likely, although during rest conditions a model that attributed familial resemblance to shared environmental factors, also fitted the data. There was no evidence for sex differences in heritabilities. Multivariate analyses showed significant heterogeneity between sexes for the intercorrelations of the blood pressure data measured under different rest and task conditions. Multivariate genetic analyses were therefore carried out separately in males and females. For SBP and DBP in females and for SBP in males an increase in heritabilities was seen for blood pressure measured during stress, as compared to rest measurements. The influence of shared environmental factors decreased during stress. For DBP in males no significant contributions of shared environment were found. The multivariate analyses indicated that the same genetic and environmental influences are expressed during rest and stress conditions.

Adolescent↗
PubMed1997

The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins.

The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To that end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations.

Adolescent↗
PubMed1997

Association between alcohol use and smoking in adolescent and young adult twins: a bivariate genetic analysis.

The association between alcohol use and smoking was examined in a large population-based sample of Dutch twins consisting of three age groups; young adolescent twins aged 12-14 years (n = 650 twin pairs), 15-16-years-old adolescent twins (n = 705 twin pairs), and young adult twins aged 17-25 years (n = 1266 twin pairs). For all three age groups, alcohol use and smoking were correlated (r = 0.5-0.6). Adolescents and young adults who smoked were more likely to drink alcohol than nonsmokers. The relation between alcohol use and smoking was also found within a twin pair; alcohol use in one twin was correlated with smoking in the cotwin. This finding suggested that familial factors contribute to the association between alcohol and tobacco use. With a bivariate genetic model, it was examined to what extent the comorbidity was due to genetic and environmental factors that predispose to both alcohol use and smoking. The genetic analyses showed that the underlying factors that influence alcohol and tobacco use and cause their association were different for adolescent and young adult twins. Initiation of alcohol use and smoking in adolescents (aged 12-16 years) was substantially influenced by the same shared environmental features. Alcohol and tobacco use in young adults were associated due to the same genetic risk factors.

Adolescent↗
PubMed1996

The role of antioxidant vitamins and enzymes in the prevention of exercise-induced muscle damage.

A growing amount of evidence indicates that free radicals play an important role as mediators of skeletal muscle damage and inflammation after strenuous exercise. It has been postulated that the generation of oxygen free radicals is increased during exercise as a result of increases in mitochondrial oxygen consumption and electron transport flux, inducing lipid peroxidation. The literature suggests that dietary antioxidants are able to detoxify the peroxides produced during exercise, which could otherwise result in lipid peroxidation, and that they are capable of scavenging peroxyl radicals and therefore may prevent muscle damage. Endogenous antioxidant enzymes also play a protective role in the process of lipid peroxidation. The studies reviewed (rodent and human) show significant increases of malondialdehyde (a product of lipid peroxidation) after exercise to exhaustion, and also favourable changes in plasma antioxidant levels and in antioxidant enzyme activity. In trained individuals and trained rats, the antioxidant enzyme activity increases markedly. In this way, the increased oxidative stress induced by exercise is compromised by increased antioxidant activity, preventing lipid peroxidation. Human studies have shown that dietary supplementation with antioxidant vitamins has favourable effects on lipid peroxidation after exercise. Although several points of discussion still exist, the question whether antioxidant vitamins and antioxidant enzymes play a protective role in exercise-induced muscle damage can be answered affirmatively. The human studies reviewed indicate that antioxidant vitamin supplementation can be recommended to individuals performing regular heavy exercise. Moreover, trained individuals have an advantage compared with untrained individuals, as training results in increased activity of several major antioxidant enzymes and overall antioxidant status. However, future studies are needed in order to be able to give more specific information and recommendations on this topic.

Animals↗
PubMed1996

Cardiovascular response to physical stress in offspring of hypertensive parents: Dutch Hypertension and Offspring Study.

Blood pressure (BP) regulatory mechanisms were studied in youngsters with contrasting risks for hypertension, based on parental history, during physical stress. As a static exercise, an isometric handgrip task (22% of maximal force during 5 min) was used and a dynamic exercise task was performed on a bicycle ergometer. At rest and during stress, BP and heart rate were recorded. In order to study the adaptation of the cardiovascular system to physical stress, cardiac output and total peripheral resistance were measured in addition to indices of vagal and sympathetic influences on the heart. Heart rate and cardiac output declined significantly more in offspring of hypertensive parents during static exercise (difference in heart rate: -2.5 +/- 1.2 bpm, P = 0.04; difference in cardiac output: -9.0 +/- 4.6%, P = 0.05). This is most likely the result of a larger increase in the total peripheral resistance in youngsters at risk (difference: 13.2 +/- 6.8%, P = 0.06). No differences between the two groups were found in reactivity of BP or in the indices of sympathetic activation or vagal inhibition of the heart. The offspring of hypertensive parents showed an attenuated increase in stroke volume during the dynamic exercise task (difference at the first cycling level: -11.5 +/- 5.4%, P = 0.04), while no difference in neural activity or heart rate was found. Youngsters with a parental history of hypertension show an enhanced reactivity of total peripheral resistance during static exercise. This does not lead to a higher BP response in this group, most probably because of a larger decrease of the cardiac output. During dynamic exercise the physiological increase in stroke volume is blunted in offspring of hypertensive parents.

Adolescent↗
PubMed1995

Ambulatory measurement of respiratory sinus arrhythmia and respiration rate.

The present study describes a device (AMD43) for ambulatory measurement of respiration rate and respiratory sinus arrhythmia from the combined electrocardiogram (ECG) and thoracic impedance signals. Respiratory time intervals derived from this ambulatory device closely corresponds to those derived from simultaneous recordings with a 'classical' laboratory set-up. Good cross-instrument comparison was also found for respiratory sinus arrhythmia parameters derived with both the peak-to-trough and spectral analyses methods. It is discussed how simultaneous measurement of respiration rate, respiratory sinus arrhythmia may be used to assess cardiac vagal tone in real-life situations.

Adult↗
PubMed1995

A multivariate genetic analysis of sensation seeking.

The genetic architecture of sensation seeking was analyzed in 1591 adolescent twin pairs. Individual differences in sensation seeking were best explained by a simple additive genetic model. Between 48 and 63% of the total variance in sensation seeking subscales was attributable to genetic factors. There were no sex differences in the magnitude of the genetic and environmental effects. The different dimensions of sensation seeking were moderately correlated. The strongest correlations were between the subscales Thrill and Adventure Seeking and Experience Seeking (r = 0.4) and between Boredom Susceptibility and Disinhibition (r = 0.4 in males, r = 0.5 in females). A triangular decomposition showed that the correlations between the sensation seeking subscales were induced mainly by correlated genetic factors and, to a smaller extent, by correlated unique environmental factors. The genetic and environmental correlation structures differed between males and females. For females, higher genetic correlations for Experience Seeking with Boredom Susceptibility and Disinhibition and higher correlations among the unique environmental factors were found. There was no evidence that sex-specific genes influenced sensation seeking behavior in males and females.

Adolescent↗
PubMed1995

Cardiovascular response to mental stress in offspring of hypertensive parents: the Dutch Hypertension and Offspring Study.

OBJECTIVE: To compare blood pressure-regulating mechanisms during mental stress in two groups of offspring with contrasting risk for hypertension. DESIGN: Cardiovascular reactivity to two different types of mental stressors was studied in adolescents and young adults with two hypertensive or two normotensive parents. The two tasks used were intended to evoke either a predominantly adrenergic cardiac response (a memory search task) or a predominantly vascular response (a reaction-time task with visual search and tone avoidance). METHODS: Blood pressure and heart rate were recorded at rest and during stress. To study adaptations of the cardiovascular system to mental stress, cardiac output, total peripheral resistance and indices of vagal and sympathetic influences on the heart were measured. RESULTS: The reactivity of systolic blood pressure (SBP) to the memory search task was significantly higher in offspring of hypertensive parents, which resulted in a longer recovery after the task. In contrast, during the reaction-time task, offspring of hypertensive parents had a significantly enhanced reactivity of peripheral resistance, but no differences in heart rate or blood pressure response were observed. No differences between the two groups were found in sympathetic or vagal activity during either task measured by the ratio of pre-ejection time and left ventricular ejection time, and respiratory sinus arrhythmia, respectively. CONCLUSION: Apart from a higher reactivity of SBP during the memory search task, no other indications supporting the presence of hyperadrenergic activation of the heart in early primary hypertension were found. On the contrary, the results of the present study support the hypothesis that blood pressure responses in prehypertensive subjects are characterized by enhanced vasoconstriction rather than by increased cardiac output.

Adolescent↗
PubMed1994

Anthropometric measures, fitness and habitual physical activity in offspring of hypertensive parents. Dutch Hypertension and Offspring Study.

As part of the Dutch Hypertension and Offspring Study, subjects with contrasting risk for hypertension according to their parental history of hypertension were compared with respect to anthropometric measures and measures of fitness and physical activity. Body height, weight, two skinfolds, and blood pressure at rest were measured. Fitness was evaluated by a maximal exercise test, and habitual physical activity was assessed using a questionnaire. No differences were observed in body mass index after adjustment for slight differences in age and proportion of men between the groups (difference between groups: 0.74 kg/m2, 95% CI: -0.30, 1.78). Offspring of hypertensive parents, however, had significantly more central fat (difference between groups: 2.32 mm, 95% CI: 0.18, 4.46). No differences in fitness or physical activity were present between the two groups. The results of this study indicate a potential role for central fat in the etiology of primary hypertension. Fitness or habitual physical activity are, however, not different between groups of subjects at different risk for future hypertension.

Adolescent↗