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Background— Loss-of-function mutations in CHD7 cause Coloboma, Heart Disease, Atresia of Choanae, Retardation of Growth and/or Development, Genital Hypoplasia, and Ear Abnormalities With or Without Deafness (CHARGE) syndrome, a variable combination of multiple congenital malformations including heart defects. Heart defects are reported in 70% to 92% of patients with a CHD7 mutation, but most studies are small and do not provide a detailed classification of the defects. We present the first, detailed, descriptive study on the cardiac phenotype of 299 patients with a CHD7 mutation and discuss the role of CHD7 in cardiac development. Methods and Results— We collected information on congenital heart defects in 299 patients with a pathogenic CHD7 mutation, of whom 220 (74%) had a congenital heart defect. Detailed information on the heart defects was available for 202 of these patients. We classified the heart defects based on embryonic cardiac development and compared the distribution to 1007 equally classified nonsyndromic heart defects of patients registered by EUROCAT, a European Registry of Congenital Anomalies. Heart defects are highly variable in patients with CHD7 mutations, but atrioventricular septal defects and conotruncal heart defects are over-represented. Sex did not have an effect on the presence of heart defects, but truncating CHD7 mutations resulted in a heart defect significantly more often than missense or splice-site mutations (χ 2 , P Conclusions— CHD7 plays an important role in cardiac development, given that we found a wide range of heart defects in 74% of a large cohort of patients with a CHD7 mutation. Conotruncal defects and atrioventricular septal defects are over-represented in patients with CHD7 mutations compared with patients with nonsyndromic heart defects.

Item does not contain fulltext PURPOSE: Early detection of infectious endocarditis is challenging. For diagnosing infectious endocarditis, the revised Duke criteria are the gold standard. Evidence of endocardial involvement on echocardiography is a major criterion, but sensitivity and specificity of echocardiography are not optimal. Here we investigated the utility of (18)F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) to diagnose infectious endocarditis in patients with gram-positive bacteraemia. METHODS: Seventy-two patients with gram-positive bacteraemia were prospectively included. Patients with a positive blood culture growing Staphylococcus aureus, Streptococcus species or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. Infectious endocarditis was defined according to the revised Duke criteria. All patients underwent (18)F-FDG PET/CT and echocardiography. (18)F-FDG uptake in or around the heart valves was evaluated independently by two nuclear medicine physicians. RESULTS: Sensitivity for diagnosing infectious endocarditis with (18)F-FDG PET/CT was 39% and specificity was 93%. The positive predictive value was 64% and negative predictive value was 82%. The mortality rate in patients without infectious endocarditis and without increased (18)F-FDG uptake in or around the heart valves was 18%, and in patients without infectious endocarditis but with high (18)F-FDG uptake in or around the heart valves the mortality rate was 50% (p = 0.181). CONCLUSION: (18)F-FDG PET/CT is currently not sufficiently adequate for the diagnosis of infectious endocarditis because of its low sensitivity. Improvements such as patient preparation with low carbohydrate-fat allowed diet and technical advances in the newest PET/CT scanners may increase sensitivity in future studies.

Item does not contain fulltext BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an association between inflammatory features of the adipose tissue and liver fat content. OBJECTIVE: To analyse associations between inflammatory features of the adipose tissue and liver fat content. DESIGN: A cross-sectional study. PATIENTS: Twenty-seven obese patients with insulin-treated T2DM were studied. MEASUREMENTS: LFAT content was measured by proton magnetic resonance spectroscopy. A subcutaneous (sc) fat biopsy was obtained to determine morphology and protein levels within adipose tissue. In addition to fat cell size, the percentage of macrophages and the presence of crown-like structures (CLSs) within sc fat were assessed by CD68-immunohistochemical staining. RESULTS: Mean LFAT percentage was 11.1 +/- 1.7% (range: 0.75-32.9%); 63% of the patients were diagnosed with an elevated LFAT (upper range of normal

SummaryAim: Cardiac 123I metaiodobenzylguanidine (MIBG) imaging can be influenced by several factors. We evaluated the relationship between catecholamine measurements and cardiac 123I MIBG uptake in neuroblastoma patients. Patients, methods: 30 neuroblastoma patients were retrospectively assessed on cardiac 123I MIBG uptake and urinary catecholamine dopamine and metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA). Cardiac 123I MIBG uptake was quantified by heart-to-mediastinum (H/M) ratios, which were calculated into standard deviation scores (SDS) using age-specific reference values. Results: In 17 (57%) and 12 patients (40%) H/M ratio measurements were below –1.0 and –2.0 SDS at diagnosis. A significant inverse correlation between the average of urine metabolites HVA and VMA, and H/M ratio SDS was observed (r -.39, p = 0.04). Furthermore, there was a significant correlation between the urinary catecholamine metabolite HVA and H/M ratio SDS (r -.40, p = 0.04). Conclusion: Routine calculation of H/M ratios in 123I MIBG scintigrams of neuroblastoma patients is not helpful because it will not identify cardiac ventricular dysfunction in this patient category. A low H/M ratio on 123I MIBG scintigraphy is explained by increased cathecholamine levels secreted by neuroblastoma tumours.

Item does not contain fulltext Mid-aortic syndrome is characterized by narrowing of the abdominal aorta, usually with the involvement of renal arteries and other visceral branches. The combination of the presence of an abdominal bruit, diminished or absent pulsations of the lower extremities, and a blood pressure discrepancy between upper and lower extremities is the classic triad associated with mid-aortic syndrome. However, it has a wide variety of clinical symptoms, and awareness of the variable presentation can lead to early diagnosis of the vascular anomaly. We report three cases presenting at three different stages of this disease, such as hydrops fetalis, refractory hypertension, and intracerebral bleeding. In conclusion, these cases highlight the importance of blood pressure measurements in all patients and accurate physical examination for early recognition of a mid-aortic syndrome. 01 maart 2013

Item does not contain fulltext Chemotherapy and particularly anthracycline exposure are associated with acute and chronic cardiotoxicity. Few data exist on the effect of cardiac function after in utero exposure to maternal chemotherapy. Our recently published multicenter prospective study showed no significant changes in systolic function using conventional echocardiographic parameters. The purpose of this study was to further investigate whether early functional changes can be detected using tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (STE). Sixty-two children (median/range age 1.7 (1-9.8) years) exposed to chemotherapy during fetal life were enrolled and compared to 62 age- and gender-matched controls. TDI velocities were measured at the basal interventricular septum (IVS) and right and left ventricular (LV) free walls. LV global longitudinal and circumferential systolic strains were derived using 2D STE. We found small but significant differences between the groups (patients versus controls) in LV fractional shortening [35 (29-46)% versus 39 (28-53)%, p < 0.001], LV ejection fraction [66 (57-79)% versus 70 (57-83)%, p < 0.001], LV posterior wall thickness z score [-0.15 (-2.32-1.81) versus -0.10 (-1.9-2.0), p < 0.001], and IVS thickness z score [-1.06 (-2.6-1.3) versus -0.5 (-2.1-1.7), p < 0.001]. No significant differences in TDI velocities or LV global strains were observed. Within the patient group, the cardiac functional parameters did not correlate to the number of cycles of anthracycline or the cumulative anthracycline dose. Children exposed to fetal chemotherapy have a lower normal fractional shortening and mildly lower left ventricular wall thickness. Tissue Doppler and strain measurements are within normal range and not statistically different from normal controls. The long-term implications of these findings will be further studied in this prospective cohort study.

Contains fulltext : 108770.pdf (Publisher’s version ) (Closed access) We report on four families affected by a clinical presentation of complex hereditary spastic paraplegia (HSP) due to recessive mutations in DDHD2, encoding one of the three mammalian intracellular phospholipases A(1) (iPLA(1)). The core phenotype of this HSP syndrome consists of very early-onset (

Item does not contain fulltext BACKGROUND: Data on myocardial deformation during the internationally widely used second-trimester screening are scarce and confusing. Reference values of time to peak strain are missing. The aims of this study were to assess reference values derived from two-dimensional speckle-tracking echocardiography for global and regional longitudinal right ventricular (RV) and left ventricular (LV) strain, strain rate, and time to peak global strain and to determine the influence of heart rate and gender on these strain parameters. METHODS: Seventy-five healthy fetuses were enrolled during second-trimester ultrasound (20-24 weeks). Clips with high frame rates (mean, 132 frames/sec) and two-dimensional (B-mode) grayscale images of apical or basal four-chamber views of both ventricles were used for offline analyses. RESULTS: There were no statistically significant differences in global strain and strain rate between both ventricles (P = .679 and P = .734, respectively) or among the RV, septal, and LV free walls. Regional measurements, modeled also as an interaction of wall and segment (basal mid and apical), showed only a small, statistically significant difference between the basal RV and LV free walls. Strain and strain rate values were independent of heart rate. The mean time to peak LV global strain adjusted for heart rate was statistically significantly shorter than the RV value (P < .0001]). Strain, strain rate, and time to peak global strain were not found to be associated with gender. CONCLUSIONS: The establishment of second-trimester two-dimensional speckle-tracking echocardiographic reference values for global and regional strain, strain rate, and time to peak global strain in a healthy fetal cohort is a mandatory prerequisite for its use in evaluating (pathologic) changes in both ventricular functions during pregnancy.

Item does not contain fulltext Cardiac pathologies are the major aspect in the treatment strategies for Marfan syndrome (MFS). In this progressive disease, less is known about manifestations and progression of cardiovascular symptoms in children. To define a certain decision regarding therapeutic options, knowledge concerning the onset of cardiovascular findings is essential. From 1998 to 2011, suspected pediatric Marfan patients were subjected to a standardized diagnostic program. Cardiovascular findings were analyzed in terms of age at first clinical manifestation, prevalence and gender differences, morbidity, mortality, and treatment. Marfan syndrome was diagnosed in 82 patients (46 boys; mean age at diagnosis, 9.0 +/- 5.7 years). At first presentation, aortic root dilation was found in 56 % of patients, mitral valve prolapse in 31 %, whereas pulmonary artery dilation was detected in 22 % and tricuspid valve prolapse in only 17 % of patients. Aortic (2.5 %) and mitral valve regurgitations (22 %) are significantly correlated with aortic root dilation (p < 0.01) and mitral valve prolapse (p < 0.05) but without relevant progression during childhood. Prophylactic medication was initiated for 42 % of the patients (mean age, 8.0 +/- 4.5 years) because of progressive aortic root dilation. Aortic dissection did not appear. Aortic root surgery was needed for 4 % of the patients. Gender-specific differences in cardiovascular findings, progression of disease, or treatment did not appear. Comparable with adults, aortic root dilation is the most frequent cardiovascular finding in children and associated with relevant morbidity, whereas aortic and mitral valve regurgitation are of minor clinical relevance. Manifestation at an early age and slow progression of cardiovascular findings underscore the necessity of repeated echocardiographic examinations for early diagnosis and start of prophylactic treatment. 01 april 2013

Objectives: To develop prediction models for long-term respiratory morbidity. To explore if respiratory distress syndrome (RDS) is a risk-indicator for long-term respiratory morbidity and to identify other perinatal risk-indicators for long-term respiratory morbidity. Study design: In the Dutch POPS cohort 1338 live born infants delivered in The Netherlands in 1983, either before 32 completed weeks gestation and/or with a birth weight below 1500 g, were followed prospectively. We used multivariable logistic regression analyses to construct three prediction models for respiratory morbidity at 2, 5 and 19 years of age. Results: At 2 years of age, maternal smoking (adjusted OR 1.5, 95% CI 1.0-2.4), prolonged rupture of membranes (adjusted OR 2.3, 95% CI 1.3-4.1), pre-eclampsia (adjusted OR 1.9, 95% CI 1.1-4.1), male gender (adjusted OR 1.5, 95% CI 1.1-2.0) and BPD (adjusted OR 1.9, 95% CI 1.1-3.2) were significantly associated with respiratory morbidity. Prolonged rupture of membranes (adjusted OR 3.7, 95% CI 1.6-8.5), family history of asthma (adjusted OR 5.9, 95% CI2.7-13.0) and BPD (adjusted OR 1.8, 95% CI1.1-3.0) were significantly associated with respiratory morbidity at 5 years of age. At 19 years of age only higher social class was associated with decreased respiratory morbidity (adjusted OR 0.64, 95% CI 0.41-0.99). The areas under the curves (AUC) were 0.65, 0.71 and 0.61 respectively. The prediction models for respiratory morbidity at 2 and 5 years of age showed a good calibration, while the calibration plot for respiratory morbidity at 19 year was less optimal. Conclusions: RDS is not a risk-indicator for long-term respiratory morbidity at 2, 5 and 19 years in this cohort (OR 1.2, 95% 0.88-1.7; 1.3, 95% 0.88-2.0; OR 0.91, 95% 0.56-1.5 respectively). Future obstetric studies interested in the effect of a specific perinatal intervention on long-term respiratory morbidity, should consider taking bronchopulmonary dysplasia (BPD) as primary outcome instead of RDS. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Item does not contain fulltext This review article gives a state-of-the-art synopsis of current pathophysiological concepts in Sjogren-Larsson syndrome (SLS) mainly based upon original research data of the authors in one of the world's largest clinical SLS study cohorts. Clinical features are discussed in order of appearance, and diagnostic tests are set out to guide the clinician toward the diagnosis SLS. Furthermore, current and future treatment strategies are discussed to render a comprehensive review of the topic.

Item does not contain fulltext BACKGROUND: Pediatric physical therapists assess the quantity and quality of children's motor skills. Several quantitative motor tests are currently available, but a concise measurement tool of observable movement quality (OMQ) is lacking. OBJECTIVE: The purpose of this study was to develop an OMQ measurement tool for children from the perspective of pediatric physical therapists. DESIGN: A qualitative, 3-phase study involving pediatric physical therapists was conducted. METHODS: The first phase consisted of 7 semistructured interviews. The second phase comprised a structured meeting using a nominal group technique, with the interviewees required to identify the most relevant OMQ aspects. The third phase comprised a Delphi technique involving 61 pediatric physical therapy experts with the aim of achieving at least 80% agreement on relevance, terminology, and definitions of OMQ aspects. RESULTS: Across all 3 phases, 32 aspects based on different theoretical constructs were considered. Fifteen aspects were included in the measurement. The pediatric physical therapy experts achieved at least 80% agreement on the definitions of 14 OMQ aspects: automated movements, asymmetry in movements, variation in movements, appropriate gross motor movements, fluency of movements, reduced muscle tone, increased muscle tone, involuntary movements, accuracy, slow/delayed movements, accelerated/abrupt movements, tremors, strength regulation, and stereotyped movements. The definition of appropriate fine motor movements achieved 75% agreement. This aspect was included because gross and fine motor movements are complementary. The aspects were scored using a 5-point Likert scale, with a total score ranging from 15 to 75 and with a higher score indicating a better OMQ. CONCLUSION: The OMQ scale, a concise measurement tool with 15 defined aspects, was developed. Content validity was obtained, but before the OMQ scale can be used in clinical practice, studies on reliability, construct validity, and responsiveness are needed. 01 april 2012

Item does not contain fulltext There is increasing evidence that supports the hypothesis that elevated cyclic shear strain in the adventitia of the common carotid artery promotes plaque progression. In this article, we estimated cyclic shear strain in the carotid arterial wall in 16 asymptomatic human participants using radio-frequency (RF) ultrasound. In each participant, we acquired two separate RF ultrasound recordings. We correlated the cyclic shear strain with the distension waveform (representing the blood pressure waveform) of the carotid artery and the brachial blood pressure. There were no significant differences between the shear strains estimated from the two separate RF ultrasound recordings. The point-in-time of the maximum shear strain showed a significant correlation with that of the dicrotic notch in the distension waveform (Spearman's coefficient = 0.7, p < 0.001). The pulse shear strain (difference between maximum and minimum shear strain) was significantly correlated with the pulse pressure as measured in the brachial artery (Spearman's coefficient = 0.4, p < 0.01). In this study, we show that the cyclic shear strain in the adventitia of the common carotid artery can be estimated using RF ultrasound. We found indications that the estimated cyclic shear strain was induced by the pulsating blood pressure and it was found to be higher in participants with an elevated pulse pressure.

Item does not contain fulltext BACKGROUND: The aim of this study was to investige serial changes of myocardial deformation using two-dimensional speckle-tracking echocardiographic (2DSTE) imaging in children undergoing balloon valvuloplasty for congenital valvular aortic stenosis (VAS). METHODS: Thirty-seven children with isolated congenital VAS were enrolled in this study prospectively. Patients underwent echocardiographic evaluation at three instances: before balloon valvuloplasty, 6 months after intervention, and 3 years after intervention. Longitudinal, circumferential, and radial peak systolic strain values were determined, as well as systolic strain rate and the time to peak global systolic strain. Linear mixed statistical models were used to assess changes in 2DSTE parameters after balloon intervention. Using one-way analysis of variance, 2DSTE results at 3-year follow-up were compared with 2DSTE measurements in 74 healthy age-matched children and 76 children with uncorrected VAS whose severity of stenosis corresponded to residual stenosis of study subjects at 3-year follow-up. RESULTS: Global peak strain and strain rate measurements in all three directions were decreased before intervention compared with healthy children. Global peak strain and strain rate measurements increased significantly (P < .001) several months after balloon valvuloplasty and continued to increase at 3-year follow-up. However, at 3-year follow-up, global peak strain and strain rate in the longitudinal and circumferential directions were significantly lower (P < .001) compared with both control groups. Measurements of time to peak global systolic strain were significantly shorter at early follow-up compared with measurements before intervention (P < .05). CONCLUSIONS: Shortly after balloon valvuloplasty for severe congenital VAS, there is an improvement in systolic myocardial deformation. However, 2DSTE parameters do not return to normal at 3-year follow-up. These abnormalities in systolic deformation cannot be fully attributed to residual stenosis or aortic regurgitation. 01 mei 2012

Contains fulltext : 97020.pdf (Publisher’s version ) (Closed access) OBJECTIVE: : To estimate whether normotensive women who were born small for gestational age have low plasma volume in adult life, which is associated with later chronic hypertension. METHODS: : In 280 normotensive women with a history of hypertension in pregnancy, we recorded recalled gestational age and weight at birth and measured plasma volume (I-human serum albumin indicator dilution method). To correct for possible confounders, we recorded recent obstetric history and measured in each individual all constituents of the metabolic syndrome (World Health Organization criteria), sex hormones (progesterone and estradiol), renal function, and cardiac performance at rest (echocardiography). We estimated daily activity level with a validated questionnaire (Short Questionnaire to Assess Health-enhancing physical activity). We studied the relation between women's own birth weight centile and her adult plasma volume (mL) and adjusted for the effects of confounding variables using multiple linear regression analysis. RESULTS: : Birth weight correlated positively with adult plasma volume (P

Contains fulltext : 95780.pdf (Publisher’s version ) (Closed access) Recent evidence implies that impaired metabolism of glutathione has a role in the pathogenesis of nephropathic cystinosis. This recessive inherited disorder is characterized by lysosomal cystine accumulation and results in renal Fanconi syndrome progressing to end stage renal disease in the majority of patients. The most common treatment involves intracellular cystine depletion by cysteamine, delaying the development of end stage renal disease by a yet elusive mechanism. However, cystine depletion does not arrest the disease nor cures Fanconi syndrome in patients, indicating involvement of other yet unknown pathologic pathways. Using a newly developed proximal tubular epithelial cell model from cystinotic patients, we investigate the effect of cystine accumulation and cysteamine on both glutathione and ATP metabolism. In addition to the expected increase in cystine and defective sodium-dependent phosphate reabsorption, we observed less negative glutathione redox status and decreased intracellular ATP levels. No differences between control and cystinosis cell lines were observed with respect to protein turnover, albumin uptake, cytosolic and mitochondrial ATP production, total glutathione levels, protein oxidation and lipid peroxidation. Cysteamine treatment increased total glutathione in both control and cystinotic cells and normalized cystine levels and glutathione redox status in cystinotic cells. However, cysteamine did not improve decreased sodium-dependent phosphate uptake. Our data implicate that cysteamine increases total glutathione and restores glutathione redox status in cystinosis, which is a positive side-effect of this agent next to cystine depletion. This beneficial effect points to a potential role of cysteamine as anti-oxidant for other renal disorders associated with enhanced oxidative stress.

Contains fulltext : 97926.pdf (Publisher’s version ) (Closed access) BACKGROUND: To evaluate the safety of ICSI with epididymal sperm, this study compared children born after ICSI treatment with epididymal sperm and children conceived after IVF and ICSI with ejaculated sperm. Additionally, the results of a multidisciplinary, multicentre follow-up of the children conceived with epididymal sperm at 2 years of age are described. METHODS: This follow-up study included 378 children conceived after ICSI with epididymal sperm (percutaneous epididymal sperm aspiration: PESA group) and a control group of 1192 IVF and 1126 ICSI (with ejaculated sperm) children, all with a gestational age of 20 weeks or more. Questionnaires were sent at birth, 1 year and 4 years of age, collecting data on parental, pregnancy and child factors. A total of 148 PESA children were assessed at 2 years of age for motor performance, mental- and language development and compared with the Dutch norms. RESULTS: PESA children showed no increased risks for stillbirths, total deaths and malformations. They also did not differ from IVF and ICSI children in gender rate, birthweight and gestational age. The mental Bayley score was higher (P < 0.05) for PESA singletons and parents reported fewer (P < 0.05) behavioural problems in the PESA group than the Dutch reference group. The scores for syntactic and lexical development for the PESA singletons were better (P < 0.05) than the Dutch standards. CONCLUSIONS: ICSI with epididymal sperm does not lead to more stillbirths or congenital malformations in comparison to IVF and ICSI with ejaculated sperm and does not lead to poor development in comparison with the Dutch reference group.

Item does not contain fulltext This is the first report that presents renal transplantation after bilateral nephrectomy as the final treatment for severe renovascular hypertension due to fibromuscular dysplasia (FMD). We describe the history of a 1-year-old girl who suffered from renovascular hypertension due to FMD. Imaging revealed multiple bilateral stenoses of the renal artery extending into the distal branches. The hypertension proved unresponsive to pharmacologic treatment and the intrarenal peripherally located stenoses rendered a conventional approach such as transluminal or surgical angioplasty not feasible. At the age of 5 years, a unilateral nephrectomy of the most affected kidney was performed, but she remained hypertensive and developed progressive cardiomyopathy and retinopathy. At the age of 6 years the remaining kidney was removed, followed by a living related renal transplantation with a kidney donated by her mother. Posttransplantation, she developed mild hypertension due to a postanastomotic stenosis, which was easily controlled with antihypertensives. Now 8 years after transplantation, she has experienced no further blood pressure related problems. Although there is a risk of recurrence of FMD after performing a living related transplantation, our report suggests that this procedure is relatively safe, provided appropriate preoperative evaluation and follow up is performed.

OBJECTIVE To investigate the effect of acute insulin-induced hypoglycemia on cerebral glucose metabolism in healthy humans, measured by 13C magnetic resonance spectroscopy (MRS). RESEARCH DESIGN AND METHODS Hyperinsulinemic glucose clamps were performed at plasma glucose levels of 5 mmol/L (euglycemia) or 3 mmol/L (hypoglycemia) in random order in eight healthy subjects (four women) on two occasions, separated by at least 3 weeks. Enriched [1-13C]glucose 20% w/w was used for the clamps to maintain stable plasma glucose labeling. The levels of the 13C-labeled glucose metabolites glutamate C4 and C3 were measured over time in the occipital cortex during the clamp by continuous 13C MRS in a 3T magnetic resonance scanner. Time courses of glutamate C4 and C3 labeling were fitted using a one-compartment model to calculate metabolic rates in the brain. RESULTS Plasma glucose 13C isotopic enrichment was stable at 35.1 ± 1.8% during euglycemia and at 30.2 ± 5.5% during hypoglycemia. Hypoglycemia stimulated release of counterregulatory hormones (all P < 0.05) and tended to increase plasma lactate levels (P = 0.07). After correction for the ambient 13C enrichment values, label incorporation into glucose metabolites was virtually identical under both glycemic conditions. Calculated tricarboxylic acid cycle rates (VTCA) were 0.48 ± 0.03 μmol/g/min during euglycemia and 0.43 ± 0.08 μmol/g/min during hypoglycemia (P = 0.42). CONCLUSIONS These results indicate that acute moderate hypoglycemia does not affect fluxes through the main pathways of glucose metabolism in the brain of healthy nondiabetic subjects.

Item does not contain fulltext BACKGROUND: There is a gap in the knowledge of longterm outcome of mild to moderate prematures compared to the extreme prematures or very low birth weight infants. AIM: Determine health-related quality of life (HRQoL) and prevalence of emotional and behavioral problems in (pre-)school age children born at 32 to 36weeks' gestation. STUDY DESIGN: A descriptive cohort study in a non-Neonatal Intensive Care Unit. Patient characteristics, diagnoses, treatment and social economic status (SES) were analyzed. Study tools were the TNO-AZL Preschool Quality of Life (TAPQoL) and Child Behavior Checklist (CBCL). SUBJECTS: 362 children born between 32 and 36weeks' gestation who had a follow-up evaluation at 2-5years of age. OUTCOME MEASURE: Health-related quality of life and the occurrence of emotional and behavioral problems. RESULTS: Main characteristics (mean+/-SD) were: gestation 34.7+/-1weeks and birth weight 2360+/-444g. Most families were two-parent middle-class households with parents employed at their educational level. Questionnaire response rate was 62.7%. The 12-item TAPQoL showed significantly lower scores for stomach and liveliness, while scores for behavior, communication and sleep were significantly higher compared to the general population. The TAPQoL subscale score for lung problems was significantly lower for children who had received continuous positive airway pressure (CPAP). CBCL scores were within the validated normal range although the study-population scored higher on emotionally reactive, somatic complaints and attention problems compared to their full-term peers. CONCLUSION: Children born at 32 to 36weeks' gestational age do not experience an overall lower HR-QoL at 2 to 5years of age. CPAP results in lower HRQoL scores for lung problems. The overall occurrence of behavioral and emotional problems does not differ from the general term-born pediatric population. Several subitems need further attention.

ContextPatients with congenital adrenal hyperplasia (CAH) are chronically treated with supraphysiological doses of glucocorticoids, which are known to induce insulin resistance. Thiazolidinediones might reverse this effect and improve insulin sensitivity.ObjectivesTo assess insulin sensitivity in CAH patients and the effect of pioglitazone treatment on insulin sensitivity in CAH patients. Secondary objectives were the effects of treatment with pioglitazone on blood pressure, body fat distribution, lipid, and steroid profiles.DesignRandomized placebo controlled crossover trial.ParticipantsTwelve CAH patients and 12 body mass and age-matched control subjects.InterventionSixteen-week treatment with pioglitazone (45 mg/day) or placebo.Main outcome measureInsulin sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further measures were 24-h blood pressure profiles, body fat distribution measured by magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and steroid profiles.ResultsCAH patients were insulin resistant compared with healthy controls. Treatment with pioglitazone significantly improved insulin sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5±11.6 to 38.9±11.0 μmol/kg per min, P=0.000, GIR in controls 46.2±23.4 μmol/kg per min, PPPConclusionsCAH patients are insulin resistant compared with matched control subjects. Treatment with pioglitazone improves insulin sensitivity and decreases blood pressure in CAH patients.

Contains fulltext : 80217.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: The success of home parenteral nutrition (HPN) programs is compromised by complications of central venous catheters (CVCs), such as occlusions and bloodstream infections. We performed a retrospective analysis of complication rates of arteriovenous fistulae versus CVCs in patients on long-term HPN. METHODS: Data were collected from 127 consecutive patients who received HPN between January 2000 and October 2006, comprising 344 access years of CVCs and 194 access years of arteriovenous fistulae. We evaluated access-related bloodstream infection and occlusion incidence rates (number of complications per access year) using Poisson-normal regression analysis. Complication incidence rate ratios were calculated by dividing complication incidence rates of CVCs by those of arteriovenous fistulae, adjusting for HPN frequency, medication use, infusion fluid composition, and underlying diseases. RESULTS: Bloodstream infection incidence rates were 0.03/year for arteriovenous fistulae, 1.37/year for long-term CVCs (Port-a-Caths and tunneled catheters), and 3.12/year for short-term CVCs (nontunneled catheters). Occlusion incidence rates were 0.60/year for arteriovenous fistulae, 0.35/year for long-term CVCs, and 0.93/year for shortterm CVCs. Adjusted incidence rate ratios of long-term CVCs over arteriovenous fistulae were 47 (95% confidence interval, 19-117) for bloodstream infections and 0.53 (95% confidence interval, 0.31-0.89) for occlusions. CONCLUSIONS: The occlusion incidence rate was higher for arteriovenous fistulae than for certain types of CVCs. The incidence rate of the most serious access-related complication (bloodstream infections) was much lower for arteriovenous fistulae than for all types of CVCs. Thus, arteriovenous fistulae are safe and valuable alternatives to CVCs for patients requiring long-term HPN.

Item does not contain fulltext OBJECTIVE: To evaluate the effect of furosemide on renal function and water balance in preterm infants treated with indomethacin (3 x 0.2 mg/kg at 12-h intervals) for symptomatic patent ductus arteriosus. Patients and METHODS: We performed a retrospective multi-centre double cohort study in preterm infants

Agouti-related protein (AGRP) is a homolog of the agouti protein and acts as an antagonist of peptides derived from propiomelanocortin through melanocortin receptors. This peptide is produced mainly in the hypothalamus, particularly during negative energy balance and influences increased food intake. In the hypothalamus, this peptide is co-expressed in arcuate nuclei with neuropeptide Y, another important peptide that regulates energy metabolisms. In our study, we analyzed changes in the Agrp mRNA level in the hypothalamus as well as mRNA and protein levels in placenta during different stages of rat pregnancy. We also investigated the AGRP level in the blood serum. In this study, we found the AGRP level in serum increased, while its gene expression in the hypothalamus increased only up to the 13th day of pregnancy, and decreased on the 18th day. This study demonstrates that AGRP is expressed during late pregnancy in placenta. Moreover, we found that AGRP expression is higher on the 18th than on the 13th day of pregnancy. Our results indicate that AGRP may play an important role during pregnancy in the mother's and, possibly, also in the fetus's energy balance.

Contains fulltext : 80120.pdf (Publisher’s version ) (Closed access) Myocardial strain imaging with 2-D echocardiography is a relatively new noninvasive method to assess myocardial deformation. To determine the interobserver, intraobserver and intrapatient reliability scores, we evaluated myocardial strain measurements of 10 asymptomatic survivors of childhood cancer. Ten patients were selected randomly out of a follow-up cohort of childhood cancer survivors. All 10 patients underwent a transthoracic echocardiographic examination. Two-dimensional gray scale images were made in parasternal apical four-chamber, apical two-chamber, midcavity short-axis and basal short-axis views. Offline analysis was performed using software for echocardiographic quantification (Echopac 6.1.0, GE Medical Systems, Horten, Norway). All echocardiographic studies were analyzed offline by three observers, separately (A.M., G.W., M.P.). A custom-made software package was designed for averaging the strain curves of three consecutive cardiac cycles. Values of peak systolic strain, time-to-peak strain and time-to-end systole of the different segments of the left ventricle were used for statistical analysis. Interobserver, intraobserver and intrapatient reliability were expressed as intraclass correlation coefficients (ICCs). Interobserver ICCs of peak strain, time to peak strain and time to aortic valve closure (AVC) were generally good to very good in all views and segments, except for in the two-chamber view. Intraobserver ICCs were rated as very good for almost all segments, except for the longitudinal peak strain values of the two-chamber view. Intrapatient ICCs were generally good for the two-chamber, four-chamber and midcavity short-axis views, but fair to moderate for the segments of the basal short-axis view (SaxMV). We recommend use of the four-chamber view for longitudinal peak strain values, and the basal and midcavity short-axis views for radial and circumferential peak strain values. Furthermore, we strongly recommend using the average of three cardiac cycles for peak strain values in clinical studies.

Contains fulltext : 79835.pdf (Publisher’s version ) (Closed access) Patient adherence to medical treatment for dyspepsia is disappointing, whereas adherence is crucial for a proper evaluation of treatment. This prospective study used elements of the Integrated Change Model and Weiner's Attribution Theory to describe patients' important cognitions and their interrelationships regarding self-perceived adherence to short-term medical treatment for dyspepsia. Patient questionnaires measured the predictors before treatment and self-perceived adherence after treatment. Approximately one-quarter of the patients indicated that they were non-adherent (n = 347). Univariate and multiple linear regression analyses revealed several significant predictors that explained 44% of the variance in self-perceived adherence. Patients with a low educational level, patients who claimed to regularly forget their medication in general, patients with a low self-efficacy or a low intention were less likely to be adherent. These results may indicate targets for interventions designed to improve adherence to medical treatment for dyspepsia. For instance, asking about expected difficulties in taking acid suppressants (e.g. forgetfulness or medication use at weekends) and making action plans to overcome these difficulties (e.g. using reminders) may result in improved adherence rates. Such an approach may reach a substantial number of patients since one in five patients in our study experienced some difficulties in taking medication.

Contains fulltext : 81905.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To investigate the value of the observed to expected fetal lung area to head circumference ratio (o/e LHR) and liver position in the prediction of neonatal morbidity in survivors with congenital diaphragmatic hernia (CDH). METHODS: Neonatal morbidity was recorded in 100 consecutive cases with isolated CDH diagnosed in fetal medicine units, which were expectantly managed in the prenatal period, were delivered after 30 weeks and survived until discharge from hospital. Regression analysis was used to identify the significant predictors of morbidity, including prenatal and immediate neonatal findings. RESULTS: The o/e LHR provided significant prediction of the need for prosthetic patch repair, duration of assisted ventilation, need for supplemental oxygen at 28 days, and incidence of feeding problems. An additional independent prenatal predictor of the need for patch repair was the presence of fetal liver in the chest. CONCLUSIONS: In isolated CDH the prenatally assessed size of the contralateral lung is a significant predictor of the need for prosthetic patch repair, the functional consequences of impaired lung development and occurrence of feeding problems.

Contains fulltext : 71402.pdf (Publisher’s version ) (Closed access) AIMS: Although neurocognitive problems after open-heart surgery for congenital heart disease are frequent, due to a shortage of prospective studies assessing neurocognitive functioning both before and after the procedure, the exact nature of the deficits usually remains unknown. The present study aims at assessing the neurocognitive effects of, in particular, cardiopulmonary bypass at school age. In addition, surgery-related risk factors for reduced neurocognitive outcome are explored. METHODS AND RESULTS: Participants were aged between 6 and 16 years. Forty-three children indicated for open-heart surgery and a comparison group of 19 children scheduled for interventional cardiac catheterization completed a neurocognitive assessment battery before and 1 year after their procedures. Forty healthy matched controls did so at a 1 year interval. The baseline-to-follow-up outcomes were similar in all three groups. The observed improvements most likely resulted from increased age and the repeated neurocognitive assessment. No risk factors for postsurgical neurocognitive deficits were identified. CONCLUSION: The present study demonstrates that at school age cardiac surgery using full-flow cardiopulmonary bypass does not affect neurocognitive functioning.

Contains fulltext : 69726.pdf (Publisher’s version ) (Closed access) The aim of this cross-sectional study was to determine the influence of test-taking behaviour and risk factors for delayed motor performance in 437 preterm infants (244 males, 193 females; < or = 32 weeks of gestation) at the corrected age of 2 to 3 years (mean 29mo [SD 3.3]). Other mean (SD) sample demographics were: postmenstrual age 29(+5) weeks (1(+5)), range 25(+0)-32(+0); birthweight 1213.7g (331.7), range 468-2350; and days in the neonatal intensive care unit 21.1 (21.3), range 1-165. Children (n=23) with a severe disability were excluded. We assessed motor performance and behaviour during testing with the Motor Scale and the Behaviour Rating Scale (BRS) of the Bayley Scales of Infant Development, 2nd edition (BSID-II). Risk factors were tested against delayed motor performance as the dependent variable in binary logistic regression analysis. Median score on the Motor Scale in terms of the BSID-II Psychomotor Developmental Index (PDI) was 86. 'Delayed' motor performance was observed in 46.5% of the children tested, and behaviour was 'not-optimal' in 31.4%. The Motor Scale and BRS scores were significantly correlated (r(s)=0.62, p

Contains fulltext : 69621.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The objective of this study was to determine the relationship between the frequency and total volume of intravascular volume administration and the development of intracranial hemorrhage during venoarterial extracorporeal membrane oxygenation. METHODS: In a retrospective, matched, case-control study, 24 newborns who developed an intracranial hemorrhage during venoarterial extracorporeal membrane oxygenation treatment were compared with 40 control subjects. Both groups were analyzed for gestational age, gender, race, Apgar scores at 1 and 5 minutes, birth weight, cardiopulmonary resuscitation before venoarterial extracorporeal membrane oxygenation, age at the start of treatment, duration of treatment, worst arterial blood gas sample preceding treatment, activated clotting time values, need for platelet transfusions, mean blood pressure, and the use of inotropics and steroids before the treatment. For both groups, total number and volume of intravascular infusions of normal saline, pasteurized plasma protein solution, erythrocytes, and platelets during the first 24 hours of treatment were determined. Variables were analyzed in their relationship to intracranial hemorrhage by using univariate and multivariate conditional logistic regression. RESULTS: The only statistically significant difference in patient characteristics between the case patients and control subjects was arterial blood gas values. Newborns who developed intracranial hemorrhage during the treatment received both a statistically significantly higher number and a statistically significantly higher total volume of intravascular volume administrations compared with control patients. After adjustment for pH, Paco(2), and Pao(2) in the multivariate analysis, we found a significant relation between the development of intracranial hemorrhage and >8 infusions or >300 mL of volume infusion in the first 8 hours and >10 infusions in the first 24 hours of treatment. CONCLUSIONS: The number and total volume of intravascular volume administration in the first 8 and 24 hours of venoarterial extracorporeal membrane oxygenation treatment are statistically significantly related to the development of intracranial hemorrhage.

Contains fulltext : 70116.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Advances in perinatal medicine increased survival after very preterm birth in all countries, but comparative population-based data on these births are not readily available. This analysis contrasts the rates and short-term outcome of live births before 32 weeks of gestation in 10 European regions. METHODS: The Models of Organizing Access to Intensive Care for Very Preterm Births (MOSAIC) study collected prospective data on all very preterm births in 10 European regions covering 494,463 total live births in 2003. The analysis sample was live births between 24 and 31 weeks of gestation without lethal congenital anomalies (N = 4908). Outcomes were rates of preterm birth, in-hospital mortality, intraventricular hemorrhage grades III and IV or cystic periventricular leukomalacia and bronchopulmonary dysplasia. Mortality and morbidity rates were standardized for gestational age and gender. RESULTS: Live births between 24 and 31 weeks of gestation were 9.9 per 1000 total live births with a range from 7.6 to 13.0 in the MOSAIC regions. Standardized mortality was doubled in high versus low mortality regions (18%-20% vs 7%-9%) and differed for infants < or = 28 weeks of gestation as well as 28 to 31 weeks of gestation. Morbidity among survivors also varied (intraventricular hemorrhage/periventricular leukomalacia ranged from 2.6% to < or = 10% and bronchopulmonary dysplasia from 10.5% to 21.5%) but differed from mortality rankings. A total of 85.2 very preterm infants per 10,000 total live births were discharged from the hospital alive with a range from 64.1 to 117.1; the range was 10 to 31 per 10,000 live births for infants discharged with a diagnosis of neurologic or respiratory morbidity. CONCLUSIONS: Very preterm mortality and morbidity differed between European regions, raising questions about variability in treatment provided to these infants. Comparative follow-up studies are necessary to evaluate the impact of these differences on rates of cerebral palsy and other disabilities associated with preterm birth.

Item does not contain fulltext PURPOSE: To assess pulmonary artery (PA) size, flow variables, and wall shear stress (WSS) in patients after Fontan operation at a young age. MATERIALS AND METHODS: Flow in the branch PA was obtained with phase contrast velocity-encoded cardiovascular magnetic resonance imaging in 14 patients before and after low-dose dobutamine stress (7.5 microg/kg/min) and in 17 healthy controls at rest. RESULTS: At rest, stroke index, total flow, average, and peak flow rate were all statistically significantly lower in patients than in controls (P

Contains fulltext : 69461.pdf (Publisher’s version ) (Closed access) After Fontan operation, patients are limited in increasing cardiac output and in exercise capacity. This has been related to impaired preload or other factors leading to decreased global ventricular performance with stress. To study these factors, the stress responses of functionally univentricular hearts were assessed at rest and during low-dose dobutamine stress using cardiovascular magnetic resonance imaging. Thirty-two patients after Fontan completion at young age were included (27 with total cavopulmonary connection, 5 with atriopulmonary connection; mean age 13.3 years, range 7.5 to 22.2; 23 male patients; median follow-up after Fontan operation 8.1 years, range 5.2 to 17.8). A multiphase short-axis stack of 10 to 12 contiguous slices of the systemic ventricle was obtained at rest and during low-dose dobutamine stress cardiovascular magnetic resonance imaging (maximum 7.5 microg/kg/min). With stress-testing, heart rate, ejection fraction, and cardiac index increased adequately (p

Contains fulltext : 69748.pdf (Publisher’s version ) (Closed access) Congenital diaphragmatic hernia (CDH) is a disorder of the development of the lung and diaphragm and is associated with pulmonary hypoplasia and pulmonary hypertension. Denys-Drash syndrome (DDS) is a well-known syndrome caused by several different germline mutations in the WT1-gene. CDH in DDS is rare. We present the third case of CDH with clinical features of DDS and the same, rare Arg366His mutation in the WT1-gene, as reported in the other two known cases. This report provides additional evidence that WT1 mutations can result in diaphragmatic hernia.

Contains fulltext : 71270.pdf (Publisher’s version ) (Closed access) Intestinal malrotation (IM) and cardiovascular defects (CCVD) are both common congenital defects. We investigated the prevalence and types of CCVD in a 25-year IM population, and its association with post-IM-operative morbidity and mortality. Data on the type of CCVD, other congenital defects, syndromes, associations, post-IM-operative morbidity and mortality were retrospectively reviewed from the records of IM patients born between 1980 and 2005. Data were analyzed on (significant) differences between CCVD subgroups, and risk factors for both morbidity and mortality were calculated. Seventy-seven of 284 IM patients (27.1%) were diagnosed with a major or minor CCVD (37 and 40 patients, respectively). Syndromes and associations were more frequently diagnosed in patients with major than with a minor CCVD (67.6 vs. 40%, respectively). Post-IM-operative complications, although frequently observed (61%), did not differ between patients with major and minor CCVD. Physical CCVD signs before IM surgery increased post-IM-operative morbidity significantly (OR 4.0, 95% CI 1.4-11.0). Fifteen patients died (19.5%), seven due to cardiovascular cause. Mortality risk was increased by intestinal ischemia and post-IM-operative complications and by major CCVD after correction for age at weight at the time of IM operation. Congenital cardiovascular defects in children with intestinal malrotation are common, with high morbidity and mortality rates after IM operation. Elective IM surgery in young patients with CCVD should be performed in a centre with adequate paediatric cardiac care. Benefits of laparoscopic intervention need further study.

Purpose: Although metabolic changes make diagnosis of insulinoma relatively easy, surgical removal is hampered by difficulties in locating it, and there is no efficient treatment for malignant insulinoma. We have previously shown that the high density of glucagon-like peptide-1 receptors (GLP-1R) in human insulinoma cells provides an attractive target for molecular imaging and internal radiotherapy. In this study, we investigated the therapeutic potential of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4, an 111In-labeled agonist of GLP-1, in a transgenic mouse model of human insulinoma. Experimental Design: [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 was assessed in the Rip1Tag2 mouse model of pancreatic β-cell carcinogenesis, which exhibits a GLP-1R expression comparable with human insulinoma. Mice were injected with 1.1, 5.6, or 28 MBq of the radiopeptide and sacrificed 7 days after injection. Tumor uptake and response, the mechanism of action of the radiopeptide, and therapy toxicity were investigated. Results: Tumor uptake was >200% injected activity per gram, with a dose deposition of 3 Gy/MBq at 40 pmol [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4. Other GLP-1R–positive organs showed ≥30 times lower dose deposition. A single injection of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 resulted in a reduction of the tumor volume by up to 94% in a dose-dependent manner without significant acute organ toxicity. The therapeutic effect was due to increased tumor cell apoptosis and necrosis and decreased proliferation. Conclusions: The results suggest that [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 is a promising radiopeptide capable of selectively targeting insulinoma. Furthermore, Auger-emitting radiopharmaceuticals such as 111In are able to produce a marked therapeutic effect if a high tumor uptake is achieved.

Objective: To investigate the feasibility of echographic imaging of healthy and reconstructed cleft lip and to estimate tissue dimensions and normalized echo level. Methods: Echographic images of the upper lip were made on three healthy subjects and two patients using a linear array transducer (7 to 11 MHz bandwidth) and a noncontact gel coupling. Tissue dimensions were measured using calipers. Echo levels were calibrated and were corrected for beam characteristics, gel path, and tissue attenuation using a tissue-mimicking phantom. Results: At the central position of the philtrum, mean thickness (SD) of lip loose connective tissue layer, orbicularis oris muscle, and dense connective layer was 4.0 (0.1) mm, 2.3 (0.7) mm, and 2.2 (0.7) mm, respectively, in healthy lip at rest; and 4.1 (0.9) mm, 3.8 (1.7) mm, and 2.6 (0.6) mm, respectively, in contracted lip. Mean (SD) echo level of muscle and dense connective tissue layer with respect to echo level of lip loose connective tissue layer was −19.3 (0.6) dB and −10.7 (4.0) dB, respectively, in relaxed condition and −20.7 (1.5) dB and −7.7 (2.3) dB, respectively, in contracted state. Color mode echo images were calculated, showing lip tissues in separate colors and highlighting details like discontinuity of the orbicularis oris muscle and presence of scar tissue. Conclusions: Quantitative assessment of thickness and echo level of various lip tissues is feasible after proper echographic equipment calibration. Diagnostic potentials of this method for noninvasive evaluation of cleft lip reconstruction outcome are promising.

Contains fulltext : 53641.pdf (Publisher’s version ) (Closed access) BACKGROUND: Periconceptional folic acid supplementation may protect against congenital heart defects (CHDs). Identification of candidate genes in folate metabolism has suggested that the 677C-->T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene may be particularly associated with the risk of CHDs. AIM: To assess the relationship between MTHFR 677C-->T and CHDs by literature review and meta-analysis. METHODS: Studies were identified by searches of electronic literature for papers focussing on MTHFR 677C-->T and the risk of any type of CHD. Both case-control comparisons and transmission-disequilibrium tests (TDTs) in family-based designs were included. RESULTS: We found 13 eligible studies. Of 10 case-control studies, four focused on the fetal polymorphism, two studied the maternal polymorphism, and a further four investigated both. Three further publications used a family-based association study to assess the effect of the T allele on cardiac development. Overall analysis yielded odds ratios of 1.3 (95%CI 0.97-1.73) and 1.2 (95%CI 0.83-1.74) for fetal and maternal MTHFR TT genotypes, respectively. TDTs revealed no association between fetal 677T allele and CHDs. DISCUSSION: This relatively small meta-analysis found no substantial evidence of increased CHD risk in individuals with MTHFR 677CT and TT genotypes. Heterogeneity regarding population background, study design and type of heart defects complicates the pooling and comparison of the studies. The effect of modification by periconceptional folic acid intake should be taken into account. Further larger studies and well-defined phenotypic subcategory analyses are needed to decide whether the MTHFR 677C-->T polymorphism of the affected child and/or their mother is truly a risk factor for the development of CHDs.

Item does not contain fulltext AIMS: Stenting has become an established interventional cardiology procedure for congenital heart disease. Although most stent procedures are completed successfully, complications may occur. This multicentre study evaluated early complications after stenting in patients with congenital heart disease, including potential risk factors. METHODS AND RESULTS: In this combined Dutch-Belgian retrospective study, 309 consecutive patients had undergone 366 catheterizations and received 464 stents in 13 different anatomical positions (418 sites). Seventy-two stenting-related complications (19%) occurred, of which 24 (5.7%) were major. Seven procedure-related deaths were documented (2.3%). Stent malpositioning and embolization were most common (7.7%). The use of non-premounted stents tended to be associated with higher complication rates. Centre inexperience with stenting and stenting of native vs. post-surgical stenosis tended to be associated with increased major complication rates. CONCLUSION: After stenting, complications are common for congenital heart disease. The vast diversity of stenotic sites combined with relatively small patient populations makes these procedures sensitive to complications. Combining operator experience may reduce the risks of stenting in congenital heart disease. The availability of premounted stents for greater vessel diameters will likely reduce incidences of stent migration and embolization.

Contains fulltext : 49608.pdf (Publisher’s version ) (Closed access) AIM: To renew the echocardiographic reference values of heart dimensions in healthy children. METHODS AND RESULTS: Group 1 consisted of 587 children, of which 361 boys and 226 girls, age from birth to 18 years, body weight over 2500 g, who visited the Pediatric Cardiology outclinic during the period January 2000 till March 2004. All included children were diagnosed as normal, or as having innocent heart murmur. The second group was taken from an earlier study and comprised 160 children (77 boys and 83 girls). The echocardiographic measures were taken from conventional M-mode recording of the left ventricle (LV) parasternal long axis view. End diastolic septal (IVS) and LV posterior wall thickness (LVPW) and end diastolic as well as end systolic LV intracavity dimensions were retrospectively analyzed. The regression lines from all measured sizes are significantly different from those collected in the early eighties. Especially the thickness of the IVS is smaller. The regression lines are independent of gender. CONCLUSIONS: New reference values have been found which should replace the presently used ones. There is no difference between boys and girls. Why the muscular wall thicknesses are thinner than found 20 years ago needs to be further explored.

Contains fulltext : 51383.pdf (Publisher’s version ) (Closed access) BACKGROUND: CHARGE syndrome is a non-random clustering of congenital anomalies including coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. A consistent feature in CHARGE syndrome is semicircular canal hypoplasia resulting in vestibular areflexia. Other commonly associated congenital anomalies are facial nerve palsy, cleft lip/palate, and tracheo-oesophageal fistula. Specific behavioural problems, including autistic-like behaviour, have been described. The CHD7 gene on chromosome 8q12.1 was recently discovered as a major gene involved in the aetiology of this syndrome. METHODS: The coding regions of CHD7 were screened for mutations in 107 index patients with clinical features suggestive of CHARGE syndrome. Clinical data of the mutation positive patients were sampled to study the phenotypic spectrum of mutations in the CHD7 gene. RESULTS: Mutations were identified in 69 patients. Here we describe the clinical features of 47 of these patients, including two sib pairs. Most mutations were unique and were scattered throughout the gene. All patients but one fulfilled the current diagnostic criteria for CHARGE syndrome. No genotype-phenotype correlations were apparent in this cohort, which is best demonstrated by the differences in clinical presentation in sib pairs with identical mutations. Somatic mosaicism was detected in the unaffected mother of a sib pair, supporting the existence of germline mosaicism. CONCLUSIONS: CHD7 mutations account for the majority of the cases with CHARGE syndrome, with a broad clinical variability and without an obvious genotype-phenotype correlation. In one case evidence for germline mosaicism was provided.

Contains fulltext : 47626reimer.pdf (Publisher’s version ) (Closed access) To evaluate the indications, underlying cardiac disorders, efficacy and complications involved with implantable cardioverter-defibrillators (ICDs) in paediatric patients in The Netherlands, the records of all patients aged 18 years or younger who underwent ICD placement were reviewed retrospectively. Between January 1995 and September 2002, 23 patients (11 males, 12 females; median age 12 years, range 6 months to 16 years) underwent ICD implantation. The ICD was implanted for aborted sudden cardiac death ( n = 14), syncope ( n = 5) or for primary prevention of sudden cardiac death ( n = 4). Underlying cardiac disorders were electrical diseases ( n = 16), hypertrophic or dilated cardiomyopathy ( n = 4) and congenital cardiac malformations ( n = 3). Five patients had an epicardially placed ICD, while 18 underwent a transvenous approach. The generator was placed in an abdominal position in eight patients, whereas it was placed in the subpectoral region in 15. There was no early mortality. Median hospital stay was 5 days (range 2-30 days). Median follow-up time was 29 months (range 1 month to 7 years). Seven patients experienced an inappropriate shock after a median period of 7 months; five patients an appropriate shock after a median period of 3 months. The reasons for inappropriate shock were supraventricular tachycardia ( n = 1), sinus tachycardia ( n = 4) or T-wave sensing (n = 2). One patient with malignant long QT syndrome died of intractable arrhythmias and irreversible cardiomyopathy. Generator replacement was necessary in four patients after 28, 44, 51 and 54 months respectively. CONCLUSION: Implantable cardioverter-defibrillator implantation in paediatric patients is a safe procedure with a good medium-term outcome. The most serious problem is the occurrence of a significant number of inappropriate shocks.

Item does not contain fulltext The fetal brain develops rapidly during the last trimester of pregnancy. Therefore, the brain of infants who are born preterm is vulnerable to changes in oxygen and nutrient supply in the neonatal period. The objective was to determine the effect of gestational age (GA) on the cerebral O2 supply threshold level for preservation of brain function during hypotension in near-term-born lambs. Lambs were delivered at 141 or 127 d of gestation. Hypotension was induced by stepwise withdrawal of blood. Mean arterial blood pressure (MABP) baseline levels were 63.2 (6.4) in 141-d and 54.4 (15.5) mm Hg in 127-d lambs. The MABP threshold below which MABP and blood flow in the left carotid artery were linearly related was 36.1 (13.1) mm Hg in 141-d lambs. In 127-d lambs, MABP and blood flow in the left carotid artery were linearly related over the whole range of recorded MABP values. Electrocortical brain activity (ECBA) was used as a measure of brain function. Thresholds of MABP for maintenance of ECBA were reached at, respectively, 31.6% (4.9%) of baseline in 141-d and 61.9% (13.0%) of baseline MABP in 127-d lambs. However, thresholds of cerebral O2 supply for maintenance of ECBA were similar in both GA groups. We conclude that thresholds of cerebral O2 supply for maintenance of brain cell function are independent of GA but are reached at higher MABP levels in 127-d than in 141-d lambs and therefore places the sick preterm infant easily at risk for ischemic cerebral injury.

Contains fulltext : 49100.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain.METHODS: Intramuscular tramadol (100--250 mg) was administered to 22 mothers giving birth who requested pain relief. At the time of birth (1.5--6.0 h after last tramadol dose), maternal and umbilical blood samples were taken. Another venous blood sample was drawn from each neonate, and at the same time from its mother, at 1, 2, 3, 6 or 12 h post-partum, providing the data for a population pharmacokinetic evaluation of tramadol and its metabolite M1. Routine APGAR scores and a standard neurological and adaptive capacity test were considered for evaluation of the effect of tramadol on the neonates.RESULTS: Serum tramadol concentrations at the time of birth (t(0)) were 243+/-102 ng/ml (mean+/-SD, umbilical vein), 258+/-103 ng/ml (umbilical artery) and 250+/-113 ng/ml (maternal vein). Serum M1 concentrations were 52+/-27 ng/ml (umbilical vein), 47+/-24 ng/ml (umbilical artery) and 56+/-21 ng/ml (maternal vein). The two-compartment type elimination profiles during the first 12 h post-partum for neonates (and mothers, respectively) were characterised by terminal t(1/2) (tramadol)=7.0 (7.2) h and t(1/2) (metabolite M1)=85.0 (5.5) h.CONCLUSION: The intramuscular application of tramadol in birth-giving mothers almost freely reaches the neonate, confirming a high degree of placental permeability. The neonates already possess the complete hepatic capacity for the metabolism of tramadol into its active metabolite. However, the renal elimination of the active tramadol metabolite M1 is delayed, in line with the slow maturation process of renal function in neonates. Despite this difference in pharmacokinetics between neonates and adults, the intramuscular application of tramadol at the recommended dosage range during delivery appears to effective in the relief of labour pain.

Item does not contain fulltext Monochorionic dizygous twins are probably more frequent than considered previously as many cases remain unrecognized, especially when the children have the same sex. Here we present a pair of dizygous, sex-discordant monochorionic twins who were conceived after artificial insemination. Histological examination of the placenta and extensive genetic studies of the healthy boy and girl clearly proved that they indeed were monochorionic dizygous twins with a fully joined blood circulation. We conclude that when counseling parents expecting monochorionic twins of discordant sex, not only a disorder of sexual differentiation in one of the twins should be addressed but also the possibility of dizygosity with a completely normal (sexual) development of both children.

Contains fulltext : 119288.pdf (Publisher’s version ) (Closed access) 01 juli 2013

ObjectiveShort stature is a prominent feature of Turner syndrome (TS), which is partially overcome by GH treatment. We have previously reported the results of a trial on the effect of oxandrolone (Ox) in girls with TS. Ox in a dose of 0.03 mg/kg per day (Ox 0.03) significantly increased adult height gain, whereas Ox mg/kg per day (0.06) did not, at the cost of deceleration of breast development and mild virilization. The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment.Design and methodsDuring the previous randomized controlled trial, 133 girls were treated with GH combined with placebo (Pl), Ox 0.03, or Ox 0.06 from 8 years of age and estrogen from 12 years. Sixty-eight women (Pl,n=23; Ox 0.03,n=27; and Ox 0.06,n=18) participated in the double-blind follow-up study (mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years). We assessed height, body proportions, breast size, virilization, and body composition.ResultsHeight gain (final minus predicted adult height) was maintained at follow-up (Ox 0.03 10.2±4.9 cm, Ox 0.06 9.7±4.4 cm vs Pl 8.0±4.6 cm). Breast size, Tanner breast stage, and body composition were not different between groups. Ox-treated women reported more subjective virilization and had a lower voice frequency.ConclusionOx 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients. Despite previously reported deceleration of breast development during Ox 0.03 treatment, adult breast size is not affected. Mild virilization persists in only a small minority of patients. The long-term evaluation indicates that Ox 0.03 treatment is effective and safe.

Item does not contain fulltext 01 februari 2013

Background: Therapeutic hypothermia was introduced in the Netherlands and Flanders, Belgium, in 2008. Since then, an increasing number of patients has been treated - up to 166 in 2010. Complications and outcome were registered in an online database. Objectives: The aim of this study was to analyse complications and outcome after implementation. Methods: Data were retrieved from an online database to which all centres had contributed. Results: In 3 years, 332 patients were treated. Excluding 24 patients with congenital abnormalities or metabolic disorders, mortality was 31.8%. Of the 210 survivors without congenital malformations, 21 had cerebral palsy, another 19 a developmental delay of more than 3 months at the age of at least 24 months, and 2 had severe hearing loss. The total adverse outcome, combining death and adverse neurodevelopment, in 308 patients without congenital malformations is 45.5%, which is similar to that of the large trials. Conclusions: The introduction of therapeutic hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders has been rapid and successful, with results similar to findings in the randomised controlled trials.

Item does not contain fulltext OBJECTIVE: To reduce the risk of bronchopulmonary dysplasia, preterm infants receive neonatal treatment with glucocorticoids, mostly dexamethasone (DEX). Compared to current protocols, treatment regimens of the late 1980s - early 1990s prescribed high doses of DEX for an extensive period up to 6 weeks. Worldwide at least one million children have been treated with this dose regimen. Previous studies have shown adverse effects of neonatal treatment with the glucocorticoid dexamethasone (DEX) on outcome in children aged 7-10 years. On the other hand, treatment with another glucocorticoid, hydrocortisone (HC), was not related to adverse effects in childhood. In the current study we determined the consequences of early life intervention with DEX or HC in adolescents (age 14-17 years). Besides motor function and intellectual capacities, we also examined fundamental neuropsychological functions which have so far received little attention. METHODS: In an observational cohort study we compared 14-17 year-old adolescents who received DEX (.5 mg/kg/day tapering off to .1 mg/kg/day over 21 days, n=63), or HC (5 mg/kg/day tapering off to 1 mg/kg/day over 22 days, n=67), or did not receive neonatal glucocorticoids (untreated, n=71) after premature birth (gestational age