C.S.P.M. Uiterwaal

Hogeschool Utrecht, Utrecht, Utrecht, Netherlands

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Publications (373)1600.8 Total impact

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    ABSTRACT: Using data on weight and height at 6 and 11 months of age and primary care electronic health records data from 1960 children participating in the WHISTLER birth cohort study, we found that BMIat 6 and 11 months of age was not associated with otitis media occurrenceduring the first 4 years of life.
    The Pediatric Infectious Disease Journal 09/2015; DOI:10.1097/INF.0000000000000936 · 2.72 Impact Factor
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    ABSTRACT: Probiotics are used by women in the perinatal period and may improve balance of microbiota, with possible health benefits for both mother and baby. Characteristics and (health) behaviour patterns of mothers using probiotics during pregnancy, and health effects on their offspring, were investigated. Differences between mothers using probiotics during pregnancy and those who did not, were assessed. In total, 341 out of 2491 (13.7 %) mothers reported use of probiotics during pregnancy. There were no significant differences in maternal features (gestation, age, ethnicity, education) between users and non-users. Logistic regression analyses showed that consumption of probiotics was significantly associated with use of homeopathic products [odds ratio (OR) 1.65, 95 % confidence interval (CI) 1.17-2.33, p = 0.005], maternal history of smoking (OR 1.72, 95 % CI 1.25-2.37, p = 0.001) and paternal history of smoking (OR 1.39, 95 % CI 1.01-1.89, p = 0.05). Common disease symptoms during the first year of life in the offspring did not differ between both groups. The use of probiotics or other health-related products without doctor's prescription during pregnancy might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not seem to induce positive health effects in the offspring in an unselected population. What is Known: • Aberrant microbiota compositions have been detected during critical periods when early programming occurs including pregnancy and early neonatal life. • Probiotics modulate intestinal microbiota composition and are associated with positive health effects. What is New: • The use of probiotics or other health-related products without doctor's prescription during pregnancy is associated with and might point to compensation for types of less favourable behaviour. • Probiotic use during pregnancy does not induce positive health effects in the offspring in this unselected population.
    European Journal of Pediatrics 08/2015; DOI:10.1007/s00431-015-2618-1 · 1.89 Impact Factor
  • Jacobien B Eising · Cuno S.P.M. Uiterwaal · Cornelis K van der Ent ·
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    ABSTRACT: Recent studies have shown that maternal obesity is associated with increased risk of wheezing in the offspring. We assessed whether impaired neonatal lung function could explain this association.We measured neonatal lung function in 2606 children of our prospective birth cohort. Information about daily symptoms of wheezing was obtained using questionnaires. Consultations and prescriptions for wheezing illnesses were derived from general practitioner patient files.Higher maternal body mass index (BMI) was associated with increased risk of wheezing in the first year of life and more consultations and prescriptions for wheezing illnesses until the age of 5 years. Lung function could partially explain the association with wheezing in the first year of life. Adding respiratory resistance to the model decreased the incidence rate ratio from 1.023 (95% CI 1.008-1.039) to 1.015 (95% CI 0.998-1.032). Anthropometrics of the 5-year-olds largely explained the association with consultations. Intermediates or confounders could not explain the association with prescriptions.There is an association between higher maternal BMI and increased risk of wheezing illnesses. In the first year of life, it is largely explained by an impaired lung function in early life, especially in children of nonatopic mothers. At the age of 5 years, infant lung function is of minor influence in this association. Copyright ©ERS 2015.
    European Respiratory Journal 08/2015; 46(5). DOI:10.1183/13993003.00784-2014 · 7.64 Impact Factor
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    Atherosclerosis 07/2015; 241(1):e50-e51. DOI:10.1016/j.atherosclerosis.2015.04.181 · 3.99 Impact Factor
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    ABSTRACT: Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop study, we showed that timing of AED withdrawal does not majorly influence long-term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative IQ, and change in IQ (delta IQ) following pediatric epilepsy surgery. We collected IQscores of children from the TTS cohort with both pre- and postoperative neuropsychological assessments (NPA) (n=301) and analysed whether reduction of AEDs prior to the latest NPA was related to postoperative IQ and delta IQ, using linear regression analyses. Factors previously identified to independently relate to (delta) IQ, and currently identified predictors of (delta) IQ, were considered possible confounders and used for adjustment. Additionally, we adjusted for a compound propensity score that contained previously identified determinants of timing of AED withdrawal. Mean interval to latest NPA was 19.8±18.9 months. Reduction of AEDs at latest NPA significantly improved postoperative IQ and delta IQ (adjusted RC 3.4(0.6, 6.2), p=0.018, and 4.5(1.7, 7.4), p=0.002), as did complete withdrawal (4.8(1.4, 8.3), p=0.006 and 5.1(1.5, 8.7), p=0.006). AED reduction also predicted ≥10 points IQ increase (p=0.019). The higher the number of AEDs reduced, the higher the IQ (gain) after surgery (2.2(0.6, 3.7), p= 0.007 and 2.6(1.0, 4.2), p=0.001, IQ points per AED reduced). Start of AED withdrawal, number of AEDs reduced, and complete AED withdrawal were associated with improved postoperative IQ scores and gain in IQ, independent of other determinants of cognitive outcome. This article is protected by copyright. All rights reserved. © 2015 American Neurological Association.
    Annals of Neurology 04/2015; 78(1). DOI:10.1002/ana.24427 · 9.98 Impact Factor
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    ABSTRACT: Background: Most estimates of the incidence of acute otitis media (AOM) are based on general practitioner (GP) or pediatrician diagnoses. It is likely that these figures underestimate the community incidence of AOM since parents do not visit their doctor every time their child suffers from acute ear symptoms. The impact of these symptom episodes may be substantial since they affect the child's quality of life and parents' productivity. Methods: To determine AOM symptoms in the community, we measured parent-reported AOM symptoms daily for 12 consecutive months in 1,260 children participating in a prospective birth cohort in the Netherlands. The mean age of these children was at study enrollment 0.9 months (standard deviation 0.6). A parent-reported AOM symptom episode was defined as fever (temperature 38˚C or above) plus at least one of the following symptoms: ear pain and ear discharge. These febrile AOM symptom episodes were linked to GP-consultations and diagnoses in the GP electronic health records. Results: With an estimated 624 parent-reported symptom episodes per 1,000 child-years (95% CI: 577 to 674) incidence of febrile AOM symptoms during the child's first year is high. The GP was consulted in half of these symptom episodes and AOM was diagnosed in 49% of these consultations. Conclusions and relevance: The incidence of febrile AOM symptoms in the first year of life is high in Dutch children and leads to a GP-consultation in only half of the cases. This suggests that AOM symptomatology in the community is underestimated when focusing on GP-diagnosed AOM episodes alone, since a considerable proportion of febrile AOM symptom episodes are treated symptomatically by parents at home and do not come to the attention of the GP. Having data on community AOM symptomatology available for each country is important when the potential impact of preventive and therapeutic interventions for AOM are studied.
    PLoS ONE 04/2015; 10(4):e0121572. DOI:10.1371/journal.pone.0121572 · 3.23 Impact Factor
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    ABSTRACT: Introduction Asthma control is considered the major goal of asthma management, while many determinants of control are difficult to modify. We studied the association between respiratory infection episodes (RTIs) of various types and asthma control. Methods Cross-sectional data were used from children aged 4-18 years with physician-diagnosed asthma who participated in a web-based electronic portal for children with asthma, allergies or infections. Asthma control was measured using the Childhood Asthma Control Test (C-ACT) or the Asthma Control Test (ACT). Linear regression was used to analyse the association between categories of numbers of various types of RTIs sustained in the preceding 12 months (categorized) and asthma control, adjusted for potential confounders. Results Asthma control was assessed in 654 children, and 68.5% were clinically well controlled (ACT≥20). Higher total numbers of RTIs in the last 12 months were strongly associated with a lower level of asthma control (ptrend<0.001). Similarly strong statistically significant associations were found for subtypes of RTI: ≥4 vs. 0 otitis episodes: coefficient -1.7 (95% CI -3.3 to -0.2); ≥5 vs.0 colds: coefficient -2.3 (95% CI -3.0 to -1.6); ≥3 vs. 0 bronchitis episodes: coefficient -3.1 (95% CI -4.0 to -2.3), each with ptrend <0.05. Conclusion Higher numbers of reported respiratory tract infections are associated with lower level of asthma control. The different type of respiratory tract infections contribute equally to less controlled asthma.
    Respiratory Medicine 10/2014; 108(10). DOI:10.1016/j.rmed.2014.07.007 · 3.09 Impact Factor
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    ABSTRACT: Background Atherosclerosis is a process that begins in childhood, develops over decades and underlies the majority of cardiovascular events in adulthood. Previously, we demonstrated in adults with cardiovascular disease that levels of extracellular vesicle (EV) proteins CD14, Serpin F2 and cystatin C predict vascular outcome. Here, we study for the first time whether these EV proteins are related to vascular characteristics in healthy, young children. Methods and results In 141 eight-year old children of the Wheezing-Illnesses-Studie-LEidsche-Rijn birth cohort, anthropometrics and blood pressure were measured. In addition, common carotid intima-media thickness, carotid distensibility and carotid Young's elastic modulus were obtained non-invasively using ultrasound imaging. A fasting lipid spectrum was obtained and EVs were isolated from plasma. Levels of EV proteins CD14, Serpin F2 and cystatin C were measured using a multiplex assay. In a multivariable linear regression model we assessed the relation between these EV proteins and the selected vascular characteristics. Of the studied EV proteins, CD14 levels were positively related to common carotid intima-media thickness (log transformed, beta = 7.31 ln(mm)/(ng/mg) (1.24, 13.38), p = 0.02). EV proteins Serpin F2 and cystatin C were not related to common carotid intima-media thickness. In addition, we found no relation between all three EV proteins and carotid distensibility or carotid Young's elastic modulus. Conclusion In healthy eight-year old children, extracellular vesicle protein CD14 levels seem positively related to common carotid intima-media thickness. This would point towards inflammatory vascular alterations inflicted by extracellular vesicle protein CD14 already in early life and warrants further investigation.
    Atherosclerosis 10/2014; 236(2):270–276. DOI:10.1016/j.atherosclerosis.2014.07.018 · 3.99 Impact Factor
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    ABSTRACT: Many Muslim women worldwide are pregnant during Ramadan and adhere to Ramadan fasting during pregnancy. In the present study, we determined whether maternal adherence to Ramadan fasting during pregnancy has an impact on the birth weight of the newborn, and whether the effects differed according to trimester in which Ramadan fasting took place. A prospective cohort study was conducted in 130 pregnant Muslim women who attended antenatal care in Amsterdam and Zaanstad, The Netherlands. Data on adherence to Ramadan fasting during pregnancy and demographics were self-reported by pregnant women, and the outcome of the newborn was retrieved from medical records after delivery. The results showed that half of all the women adhered to Ramadan fasting. With strict adherence to Ramadan fasting in pregnancy, the birth weight of newborns tended to be lower than that of newborns of non-fasting mothers, although this was not statistically significant ( - 198 g, 95 % CI - 447, 51, P= 0·12). Children of mothers who fasted in the first trimester of pregnancy were lighter at birth than those whose mothers had not fasted ( - 272 g, 95 % CI - 547, 3, P= 0·05). There were no differences in birth weight between children whose mothers had or had not fasted if Ramadan fasting had taken place later in pregnancy. Ramadan fasting during early pregnancy may lead to lower birth weight of newborns. These findings call for further confirmation in larger studies that should also investigate potential implications for perinatal and long-term morbidity and mortality.
    British Journal Of Nutrition 09/2014; 112(9):1-7. DOI:10.1017/S0007114514002219 · 3.45 Impact Factor
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    ABSTRACT: Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the EPIC study. Coffee and tea consumption was assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-CI: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, P-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 09/2014; 136(6). DOI:10.1002/ijc.29223 · 5.09 Impact Factor
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    Kim Boshuisen · Dieter Schmidt · Cuno S P M Uiterwaal · Alexis Arzimanoglou · Kees P J Braun ·
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    ABSTRACT: Aim: It was recently suggested that early postoperative seizure relapse implicates a failure to define and resect the epileptogenic zone, that late recurrences reflect the persistence or re-emergence of epileptogenic pathology, and that early recurrences are associated with poor treatment response. Timing of antiepileptic drugs withdrawal policies, however, have never been taken into account when investigating time to relapse following epilepsy surgery. Methods: Of the European paediatric epilepsy surgery cohort from the "TimeToStop" study, all 95 children with postoperative seizure recurrence following antiepileptic drug (AED) withdrawal were selected. We investigated how time intervals from surgery to AED withdrawal, as well as other previously suggested determinants of (timing of) seizure recurrence, related to time to relapse and to relapse treatability. Uni- and multivariable linear and logistic regression models were used. Results: Based on multivariable analysis, a shorter interval to AED reduction was the only independent predictor of a shorter time to relapse. Based on univariable analysis, incomplete resection of the epileptogenic zone related to a shorter time to recurrence. Timing of recurrence was not related to the chance of regaining seizure freedom after reinstallation of medical treatment. Conclusion: For children in whom AED reduction is initiated following epilepsy surgery, the time to relapse is largely influenced by the timing of AED withdrawal, rather than by disease or surgery-specific factors. We could not confirm a relationship between time to recurrence and treatment response. Timing of AED withdrawal should be taken into account when studying time to relapse following epilepsy surgery, as early withdrawal reveals more rapidly whether surgery had the intended curative effect, independently of the other factors involved.
    Epileptic disorders: international epilepsy journal with videotape 09/2014; 16(3). DOI:10.1684/epd.2014.0681 · 0.95 Impact Factor
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    ABSTRACT: To evaluate the feasibility and reproducibility of free fatty acid (FFA) measurement for diagnosing adipose tissue dysfunction by (1) H-magnetic resonance spectroscopy ((1) H-MRS) in different abdominal adipose tissue depots in healthy obese and lean subjects. Polyunsaturated fatty acids (PUFA), total unsaturated fatty acids (TUFA), triglycerides (TG), and their ratios were determined in three adipose tissue depots of 12 obese and 13 lean subjects. Subjects underwent two separate examinations to assess reproducibility. In lean subjects, 44% of measurements failed due to inclusion of nonadipose tissue in the spectroscopy voxel, as opposed to 23% in obese subjects. Reproducibility of PUFA, TUFA, and TG was moderate to good in obese subjects (intraclass correlation coefficients [ICCs] 0.18-0.75), and poor to moderate in lean subjects (ICCs -1.04-0.55) in subcutaneous and omental adipose tissue. In the perirenal adipose tissue, ICCs were poor in both lean and obese subjects (-0.794-0.013). PUFA/TUFA and PUFA/TG were higher in omental adipose tissue in obese vs. lean subjects (35*10(-3) vs. 0.16*10(-3) , P = 0.01 and 2.05*10(-3) vs. 0.01*10(-3) , P = 0.02, respectively). (1) H-MRS is a feasible and reproducible method for FFA profiling in abdominal adipose tissue in abdominally obese individuals. (1) H-MRS has potential as diagnostic tool for noninvasive identification of adipose tissue dysfunction. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 08/2014; 40(2). DOI:10.1002/jmri.24368 · 3.21 Impact Factor
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    ABSTRACT: Increases in human population size, dengue vector-density and human mobility cause rapid spread of dengue virus in Indonesia. We investigated the changes in dengue haemorrhagic fever (DHF) incidence in Indonesia over a 45-year period and determined age-specific trends in annual DHF incidence. Using an on-going nationwide dengue surveillance program starting in 1968, we evaluated all DHF cases and related deaths longitudinally up to 2013. Population demographics were used to calculate annual incidence and case fatality ratios (CFRs). Age-specific data on DHF available from 1993 onwards were used to assess trends in DHF age-distribution. Time-dependency of DHF incidence and CFRs was assessed using the Cochrane-Armitage trend test. The annual DHF incidence increased from 0.05/100,000 in 1968 to ~ 35-40/100,000 in 2013, with superimposed epidemics demonstrating a similar increasing trend with the highest epidemic occurring in 2010 (85.70/100,000; p < 0.01). The CFR declined from 41% in 1968 to 0.73% in 2013 (p < 0.01). Mean age of DHF cases increased during the observation period. Highest incidence of DHF was observed among children aged 5 to 14 years up to 1998, but declined thereafter (p < 0.01). In those aged 15 years or over, DHF incidence increased (p < 0.01) and surpassed that of 5 to 14 year olds from 1999 onwards. Incidence of DHF over the past 45 years in Indonesia increased rapidly with peak incidence shifting from young children to older age groups. The shifting age pattern should have consequences for targeted surveillance and prevention.
    BMC Infectious Diseases 07/2014; 14(1):412. DOI:10.1186/1471-2334-14-412 · 2.61 Impact Factor
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    ABSTRACT: It is unknown why respiratory syncytial virus (RSV) causes mild disease in some children and severe disease, requiring hospitalisation, in others. We aimed to assess whether diminished premorbid lung function in healthy term infants predisposes to hospitalisation during RSV bronchiolitis, and to post-RSV wheeze. In a prospective birth cohort study of unselected term healthy children, neonatal lung function was measured before the age of 2 months (n = 2133). From birth through the first year of life, respiratory symptoms were recorded in a diary, and general practitioner consultations and hospitalisations were documented. In a subgroup (n = 417) repeated nose and throat swabs were collected for PCR to detect RSV infections. Median neonatal respiratory system compliance (Crs) was significantly lower (41.2 versus 47.4 mL·kPa(-1), p = 0.03) and resistance (Rrs) was higher (8.2 versus 6.3 kPa·s·L(-1), p = 0.10) in hospitalised RSV patients (n = 18) compared with nonhospitalised RSV-positive infants (n = 84). Every 10 mL·kPa(-1) increase in Crs was associated with 55% less post-RSV wheeze (OR 0.56, 95% CI 0.35-0.90), and each kPa·s·L(-1) increase in Rrs was associated with 42% more post-RSV wheeze, which was only marginally explained by pre-RSV wheeze or severity of the RSV disease. This unselected birth cohort study shows for the first time that decreased lung function at birth predisposes to severe RSV disease, and to post-RSV wheeze.
    European Respiratory Journal 07/2014; 44(3). DOI:10.1183/09031936.00009314 · 7.64 Impact Factor
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    ABSTRACT: To compare whole-body magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), to computed tomography (CT) for staging newly diagnosed lymphoma. In all, 108 patients with newly diagnosed lymphoma prospectively underwent whole-body MRI (T1-weighted and T2-weighted short inversion time inversion recovery [n = 108], and DWI [n = 104]) and CT. Ann Arbor stages were assigned according to whole-body MRI and CT findings. Staging disagreements were resolved using bone marrow biopsy, FDG-PET, and follow-up studies. The results were descriptively analyzed. Staging results of whole-body MRI without DWI were equal to those of CT in 66.6%, higher in 24.1%, and lower in 9.3%, with correct/incorrect/unresolved higher staging and incorrect/unresolved lower staging relative to CT in 15/7/4 and 9/1 patient(s), respectively. Staging results of whole-body MRI with DWI were equal to those of CT in 65.4%, higher in 27.9%, and lower in 6.7%, with correct/incorrect/unresolved higher staging and incorrect/unresolved lower staging relative to CT in 18/6/5 and 6/1 patient(s), respectively. The results of this study suggest that whole-body MRI staging equals CT staging in the majority of patients with newly diagnosed lymphoma. No advantage of additional DWI was demonstrated. Whole-body MRI can be a good alternative to CT if radiation exposure should be avoided. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 07/2014; 40(1). DOI:10.1002/jmri.24356 · 3.21 Impact Factor

  • European Respiratory Journal 05/2014; 44(2). DOI:10.1183/09031936.00006814 · 7.64 Impact Factor
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    ABSTRACT: Background There is accumulating evidence of hypothalamic–pituitary–adrenal (HPA) axis hypofunction in chronic fatigue syndrome (CFS). However, knowledge of this hypofunction has so far come exclusively from research in adulthood, and its clinical significance remains unclear. The objective of the current study was to assess the role of the HPA-axis in adolescent CFS and recovery from adolescent CFS. Method Before treatment, we compared the salivary cortisol awakening response of 108 diagnosed adolescent CFS patients with that of a reference group of 38 healthy peers. Salivary cortisol awakening response was measured again after 6 months of treatment in CFS patients. Results Pre-treatment salivary cortisol levels were significantly lower in CFS-patients than in healthy controls. After treatment recovered patients had a significant rise in salivary cortisol output attaining normalization, whereas non-recovered patients improved slightly, but not significantly. The hypocortisolism found in CFS-patients was significantly correlated to the amount of sleep. Logistic regression analysis showed that an increase of one standard deviation in the difference between pre- and post-treatment salivary cortisol awakening response was associated with a 93% higher odds of recovery (adjusted OR 1.93 (1.18 to 3.17), p = 0.009). Pre-treatment salivary cortisol did not predict recovery. Conclusions Hypocortisolism is associated with adolescent CFS. It is not pre-treatment cortisol but its change to normalization that is associated with treatment success. We suggest that this finding may have clinical implications regarding the adaptation of future treatment strategies.
    Psychoneuroendocrinology 04/2014; 42:199–206. DOI:10.1016/j.psyneuen.2014.01.017 · 4.94 Impact Factor
  • Jacobien B Eising · Cuno S P M Uiterwaal · Cornelis K van der Ent ·
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    ABSTRACT: Rationale: Wheezing is a very common symptom in preschool children. Nocturnal wheezing is present in many asthmatic patients, due to enhanced airflow limitation overnight. We assessed the prevalence of nocturnal wheezing in young children and correlated this with respiratory system resistance and history of wheezing symptoms. Methods: Using a continuous overnight recording of respiratory sounds we analyzed wheeze rate (ratio between wheezing time and recorded breathing time), oxygen saturation and heart rate during one night in 59 three-year-old children of an ongoing birth cohort study, the WHISTLER-project. We associated the nocturnal measurements with the patient's history of wheezing symptoms and with measurement of respiratory system resistance (Rint). Results: Analysis of wheeze rate was successful in 44 children. The overall wheeze rate of these children was low, with the highest wheeze rate of 0.63% measured by the tracheal sensor during expiration. In total, 21/44 children had a wheeze rate of ≥ 5% during at least 1 min. There was no statistically significant difference in wheeze rate between the children with and without a history of wheezing. The wheeze rate of the tracheal sensor had a significant correlation with Rint (correlation coefficients of inspiration and expiration: 0.308 and 0.382, P-values 0.05 and 0.01, respectively). Conclusions: Overall, the wheeze rate in young children is low, but seems to increase over nighttime. Almost 50% of the children have sporadic wheeze during the night. Although higher nocturnal wheeze rates are related to increased respiratory system resistance, it is not related to clinical wheezing symptoms.
    Pediatric Pulmonology 03/2014; 49(3). DOI:10.1002/ppul.22803 · 2.70 Impact Factor
  • Anne C van der Gugten · Cornelis K van der Ent · Cuno S P M Uiterwaal ·
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    ABSTRACT: 10.1183/09031936.00172013
    European Respiratory Journal 03/2014; 43(3):921-2. DOI:10.1183/09031936.00172013 · 7.64 Impact Factor
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    ABSTRACT: Alterations in extracellular vesicles (EVs), including exosomes and microparticles, contribute to cardiovascular disease. We hypothesized that obesity could favour enhanced release of EVs from adipose tissue, and thereby contribute to cardiovascular risk via obesity-induced metabolic complications. The objectives of this study were: 1) to investigate the relation between the quantity, distribution and (dys) function of adipose tissue and plasma concentrations of atherothrombotic EV-markers; 2) to determine the relation between these EV-markers and the prevalence of the metabolic syndrome; and 3) to assess the contribution of EV markers to the risk of incident type 2 diabetes. In 1012 patients with clinically manifest vascular disease, subcutaneous and visceral fat thickness was measured ultrasonographically. Plasma EVs were isolated and levels of cystatin C, serpin G1, serpin F2 and CD14 were measured, as well as fasting metabolic parameters, hsCRP and adiponectin. The association between adiposity, EV-markers, and metabolic syndrome was tested by multivariable linear and logistic regression analyses. As sex influences body fat distribution, sex-stratified analyses between adipose tissue distribution and EV-markers were performed. The relation between EV-markers and type 2 diabetes was assessed with Cox regression analyses. Higher levels of hsCRP (β 5.59; 95% CI 3.00-8.18) and lower HDL-cholesterol levels (β-11.26; 95% CI -18.39 - -4.13) were related to increased EV-cystatin C levels, and EV-cystatin C levels were associated with a 57% higher odds of having the metabolic syndrome (OR 1.57; 95% CI 1.19-2.27). HDL-cholesterol levels were positively related to EV-CD14 levels (β 5.04; 95% CI 0.07-10.0), and EV-CD14 levels were associated with a relative risk reduction of 16% for development of type 2 diabetes (HR 0.84, 95% CI 0.75-0.94), during a median follow up of 6.5 years in which 42 patients developed type 2 diabetes. In patients with clinically manifest vascular disease, EV-cystatin C levels were positively related, and EV-CD14 levels were negatively related to metabolic complications of obesity.
    Cardiovascular Diabetology 02/2014; 13(1):37. DOI:10.1186/1475-2840-13-37 · 4.02 Impact Factor

Publication Stats

8k Citations
1,600.80 Total Impact Points


  • 2014
    • Hogeschool Utrecht
      Utrecht, Utrecht, Netherlands
  • 2001-2014
    • University Medical Center Utrecht
      • • Julius Center for Health Sciences and Primary Care
      • • Division of Pediatrics
      • • Urology
      Utrecht, Utrecht, Netherlands
  • 2010
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
  • 2009
    • Massachusetts General Hospital
      • Center for Human Genetic Research
      Boston, Massachusetts, United States
  • 2008
    • Maastricht University
      • Department of Biochemistry
      Maestricht, Limburg, Netherlands
  • 2001-2008
    • Utrecht University
      • • Julius Centre for Health Sciences and Primary Care
      • • Department of Epidemiology
      Utrecht, Utrecht, Netherlands
  • 1999-2007
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 2004
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2003
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1997
    • Erasmus Universiteit Rotterdam
      • Department of Epidemiology
      Rotterdam, South Holland, Netherlands