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Item does not contain fulltext Hydroxynitrile lyases (HNLs), which catalyse the decomposition of cyanohydrins, are found mainly in plants. In vitro, they are able to catalyse the synthesis of enantiopure cyanohydrins, which are versatile building blocks in the chemical industry. Recently, HNLs have also been discovered in bacteria. Here, we report on the detailed biochemical and structural characterization of a hydroxynitrile lyase from Granulicella tundricola (GtHNL), which was successfully heterologously expressed in Escherichia coli. The crystal structure was solved at a crystallographic resolution of 2.5 A and exhibits a cupin fold. As GtHNL does not show any sequence or structural similarity to any other HNL and does not contain conserved motifs typical of HNLs, cupins represent a new class of HNLs. GtHNL is metal-dependent, as confirmed by inductively coupled plasma/optical emission spectroscopy, and in the crystal structure, manganese is bound to three histidine and one glutamine residue. GtHNL displayed a specific activity of 1.74 U.mg(-1) at pH 6 with (R)-mandelonitrile, and synthesized (R)-mandelonitrile with 90% enantiomeric excess at 80% conversion using 0.5 m benzaldehyde in a biphasic reaction system with methyl tertiary butyl ether. 01 november 2013

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 OBJECTIVE: To evaluate phototherapy practices by measuring the irradiance levels of phototherapy (PT) devices. DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care units. PATIENTS: None. INTERVENTIONS: Irradiance levels of PT devices used in the 10 Dutch Neonatal Intensive Care Units (NICUs) were measured according to the local PT practice patterns. The irradiance levels of all overhead and fibre-optic PT devices were measured with a radiometer using an infant silhouette model. RESULTS: Eight different PT devices were used in the 10 NICUs; five were overhead devices and three fibre-optic pads. The median (range) irradiance level for overhead PT devices was 9.7 (4.3-32.6) microW/cm(2)/nm and for fibre-optic pads 6.8 (0.8-15.6) microW/cm(2)/nm. Approximately 50% of PT devices failed to meet the minimal recommended irradiance level of 10 microW/cm(2)/nm. Maximal irradiance levels for overhead PT spot lights were inversely related to the distance between device and infant model (R2=0.33). The distances ranged from 37 cm to 65 cm. CONCLUSIONS: PT devices in the Dutch NICUs show considerable variability with often too low irradiance levels. These results indicate that suboptimal PT is frequently applied and may even be ineffective towards reducing total serum bilirubin levels. These results underline the need for greater awareness among all healthcare workers towards the requirements for effective PT including measurements of irradiance and distance. 01 maart 2013

Item does not contain fulltext Proper functioning of pancreatic islets requires that numerous beta-cells are properly coordinated. With evolution, many mechanisms have converged, which now allow individual beta-cells to sense the state of activity of their neighbors as well as the changes taking place in the extracellular medium, and to regulate accordingly their own function. Here, we review one such mechanism for intercellular coordination, which depends on connexins. These integral membrane proteins accumulate at sites of close apposition between adjacent islet cell membranes, referred to as gap junctions. Recent evidence demonstrates that connexin-dependent signaling is relevant for the in vivo control of insulin biosynthesis and release, as well as for the survival of beta-cells under stressing conditions. The data suggest that alterations of this signaling may be implicated in the beta-cell alterations which characterize most forms of diabetes, raising the tantalizing possibility that targeting of the direct intercellular communications beta-cells establish within each pancreatic islet may provide a novel, therapeutically useful strategy.

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.

Background: Neonatal extracorporeal membrane oxygenation (ECMO) is a lifesaving therapeutic approach in newborns suffering from severe, but potentially reversible, respiratory insufficiency, mostly complicated by neonatal persistent pulmonary hypertension. However, cerebral damage, intracerebral hemorrhage as well as ischemia belong to the most devastating complications of ECMO. Objectives: The objectives are to give insights into what is known from the literature concerning cerebral damage related to neonatal ECMO treatment for pulmonary reasons. Methods: A short introduction to ECMO indications and technical aspects of ECMO are provided for a better understanding of the process. The remainder of this review focuses on outcome and especially on (potential) risk factors for cerebral hemorrhage and ischemia during ECMO treatment. Results: Although neonatal ECMO treatment shows improved outcome compared to conservative treatment in cases of severe respiratory insufficiency, it is related to disturbances in various aspects of neurodevelopmental outcome. Risk factors for cerebral damage are either related to the patient's disease, EMCO treatment itself, or a combination of both. Conclusion: It is of ongoing importance to further understand pathophysiological mechanisms resulting in cerebral hemorrhage and ischemia due to ECMO and to develop neuroprotective strategies and approaches.

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.

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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 (

Contains fulltext : 108353.pdf (Publisher’s version ) (Closed access) BACKGROUND: /st> Transpulmonary ultrasound dilution (TPUD) is a promising method for cardiac output (CO) measurement in severely ill neonates. The incidence of lung injury in this population is high, which might influence CO measurement using TPUD because of altered lung perfusion. We evaluated the influence of lung injury on the accuracy and precision of CO measurement using TPUD in an animal model. METHODS: /st> In nine neonatal lambs, central venous and arterial catheters were inserted and connected to the TPUD monitor. Repeated lavages with warmed isotonic saline were performed to gradually induce lung injury. CO measurements with TPUD (COtpud) were compared with those obtained by an ultrasonic transit-time flow probe around the main pulmonary artery (COufp). An increase in oxygenation index was used as an indicator of induced lung injury during the experiment. Post-mortem lung injury was confirmed by histopathological examination. RESULTS: /st> Fifty-five sessions of three paired CO measurements were analysed. The mean COufp was 1.53 litre min(-1) (range 0.66-2.35 litre min(-1)), and the mean COtpud was 1.65 litre min(-1) (range 0.78-2.91 litre min(-1)). The mean bias (standard deviation) between the two methods was 0.13 (0.15) litre min(-1) with limits of agreement of +/-0.29 litre min(-1). The overall percentage error was 19.1%. The accuracy and precision did not change significantly during progressive lung injury. Histopathological severity scores were consistent with heterogeneous lung injury. The capability to track changes in CO using TPUD was moderate to good. CONCLUSIONS: /st> The accuracy and precision of CO measurement using TPUD is not influenced in the presence of heterogeneous lung injury in an animal model.

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.

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Item does not contain fulltext Recombinant AciX9_0562 from Acidobacterium sp. MP5ACTX9 (UniProt ID E8WYN5) containing sequence motifs characteristic of the RmlC-type cupins superfamily and containing Pfam motif PF07883 has been successfully cloned, expressed and purified. AciX9_0562 crystallized in a number of conditions from the Morpheus protein crystallization screen. The best crystal diffracted to 2.7 A resolution (space group C222(1); unit-cell parameters a = 125.29, b = 254.63, c = 82.99 A). Structure solution was facilitated by the automated molecular-replacement pipeline BALBES. The initial solution was automatically rebuilt using the PHENIX AutoBuild wizard, with final R and R(free) values of 0.23 and 0.26, respectively. The structure is currently undergoing manual refinement.

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

Item does not contain fulltext During the treatment of colorectal liver metastases, evaluation of treatment efficacy is of the utmost importance for decision making. The aim of the present study was to explore the ability of preclinical imaging modalities to detect experimental liver metastases. Nine male Wag/Rij rats underwent a laparotomy with intraportal injection of CC531 tumor cells. On days 7, 10, and 14 after tumor induction, sequential positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) scans were acquired of each rat. At each time point, three rats were euthanized and the metastases in the liver were documented histologically. Topographically, the liver was divided into eight segments and the image findings were compared on a segment-by-segment basis with the histopathologic findings. Sixty-four liver segments were analyzed, 20 of which contained tumor deposits. The overall sensitivity of PET, CT, and MRI was 30%, 25%, and 20%, respectively. For the detection of tumors with a histologic diameter exceeding 1 mm (n = 8), the sensitivity of PET, CT, and MRI was 63%, 38%, and 38%, respectively. The overall specificity of PET, CT, and MRI was 98%, 100%, and 93%, respectively. This study showed encouraging detectability and sensitivity for preclinical imaging of small liver tumors and provides valuable information on the imaging techniques for designing future protocols.

For more than a decade, researchers have been trying to develop non-invasive imaging techniques for the in vivo measurement of viable pancreatic beta cells. However, in spite of intense research efforts, only one tracer for positron emission tomography (PET) imaging is currently under clinical evaluation. To many diabetologists it may remain unclear why the imaging world struggles to develop an effective method for non-invasive beta cell imaging (BCI), which could be useful for both research and clinical purposes. Here, we provide a concise overview of the obstacles and challenges encountered on the way to such BCI, in both native and transplanted islets. We discuss the major difficulties posed by the anatomical and cell biological features of pancreatic islets, as well as the chemical and physical limits of the main imaging modalities, with special focus on PET, SPECT and MRI. We conclude by indicating new avenues for future research in the field, based on several remarkable recent results., Journal Article, Research Support, Non-U.S. Gov't, Review, SCOPUS: re.j, info:eu-repo/semantics/published

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.

Contains fulltext : 96811.pdf (Publisher’s version ) (Closed access) Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disorder characterized by hepatitis in neonates, childhood and adulthood (protease inhibitor (PI)*ZZ) and emphysema with or without hepatitis (PI*ZZ)/(PI*SS,SZ or null) in adulthood. We report the case of a female neonate born at 40 weeks of gestation who presented with vitamin K deficiency-related intracranial bleeding and cholestasis of which she died at 28 days of age. At autopsy, the infant was found to have intracranial bleeding, hepatomegaly, and cholestasis with paucity of bile ducts in the liver. Small periodic acid-Schiff diastase positive intrahepatic granules and positive staining with antibodies against AAT protein suggested an AAT deficiency. AAT is a glycoprotein that has a protease inhibitor function. Its deficiency can be the result of various point mutations in Serpin 1 located on chromosome 14. The diagnosis AAT deficiency was confirmed by mutation analysis showing the PI*ZZ genotype in the neonate. In conclusion, AAT deficiency is a rare genetic disorder that can lead to a serious bleeding disorder in the neonatal period if not recognised on time. Pathological diagnosis together with verifying molecular analysis can be used to identify index patients.

Item does not contain fulltext AIM: To evaluate 10-year quality assurance of newborn hearing screening (NHS) in Dutch neonatal intensive care units (NICU). METHODS: Results of the two-stage automated auditory brainstem response (AABR) screening and diagnostic examination in NICU graduates were centrally registered between October 1998 and December 2008. This registration facilitates screening, tracking and follow-up after abnormal screening results. Outcome measures are referral rates, prevalence rate of hearing loss and (trends of) coverage rates and timeliness of follow-up. RESULTS: Thirty-two thousand one hundred and two infants have been screened. Referral rates were 9.2% at the first and 26.3% at the second stage. Hearing loss was diagnosed in 728 infants (2.2%). Coverage rates were 98.7% at the first, 92.1% at the second stage, 92.3% for the diagnostic examination and 97.9% for the complete programme. After correction for gestational age, 95.8% of the infants had their first AABR

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 OBJECT: To increase the signal-to-noise ratio (SNR) efficiency of hepatic fat signals in proton magnetic resonance spectroscopy (1H MRS) at 3 T, in order to improve the quantitation of hepatic fat and allow fast, single breath-hold T2 relaxometry of hepatic water and fat. MATERIALS AND METHODS: Since the T1 of lipid protons is relatively short, we hypothesized that it could be possible to increase the lipid SNR efficiency by choosing a TR shorter than that typically employed (>/=1.5 s). The lipid SNR per unit-time was calculated using published values of lipid (CH2)n protons' T1 at 3 T. 1H MRS PRESS spectra were acquired from VOIs located in the right lobe of the liver in 28 healthy volunteers. At the short TR of 0.6 s, fast T2 relaxometry with the acquisition of 16 echo times (30, 40, ..., 180 ms), was performed in a single breath-hold measurement using a modified PRESS sequence. RESULTS: Good agreement was observed between simulated and experimental data, with the shortening of TR to 0.6 s yielding an ~50% SNR improvement of hepatic lipid (CH2)n resonances, compared to the SNR at TR=2 s. The T2 relaxation time of water and lipid (CH2)n protons at 3 T was 25.8+/-1.1 ms and 55.4+/-3.9 ms, respectively, across five healthy volunteers. CONCLUSION: The short-TR approach allows for an improved SNR efficiency of lipids and for fast T2 relaxometry of hepatic water and fat, with a detailed coverage of the T2 relaxation decay curve, within a single breath-hold experiment. 01 december 2011

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.

Contains fulltext : 87739.pdf (Publisher’s version ) (Closed access) This simulation study is concerned with: 1) the feasibility of measuring rotation and 2) the assessment of the performance of strain estimation in shearing and rotating structures. The performance of 3 different radio frequency (RF) based methods is investigated. Linear array ultrasound data of a deforming block were simulated (axial shear strain = 2.0, 4.0, and 6.0%, vertical strain = 0.0, 1.0, and 2.0%). Furthermore, data of a rotating block were simulated over an angular range of 0.5 degrees to 10 degrees . Local displacements were estimated using a coarse-to-fine algorithm using 1-D and 2-D precompression kernels. A new estimation method was developed in which axial displacements were used to correct the search area for local axial motion. The study revealed that this so-called free-shape 2-D method outperformed the other 2 methods and produced more accurate displacement images. For higher axial shear strains, the variance of the axial strain and the axial shear strain reduced by a factor of 4 to 5. Rotations could be accurately measured up to 4.0 to 5.0 degrees . Again, the free-shape 2-D method yielded the most accurate results. After reconstruction of the rotation angle, the mean angles were slightly underestimated. The precision of the strain estimates decreased with increasing rotation angles. In conclusion, the proposed free-shape 2-D method enhances the measurement of (axial shear) strains and rotation. Experimental validation of the new method still has to be performed. 01 april 2010

Background: It remains a great challenge to measure systemic blood flow in critically ill newborns. In a former study we validated the modified carbon dioxide Fick (mCO2F) method for measurement of cardiac output in a newborn lamb model. In this new study we studied the influence of a left-to-right shunt on the accuracy of the mCO2F method. Objective: To analyze the influence of a left-to-right shunt on the agreement between cardiac output measurement with the mCO2F method and ultrasonic transit time pulmonary blood flow in a lamb model. Methods: The study was approved by the Ethical Committee on Animal Research of the Radboud University Nijmegen and performed in 8 random-bred lambs. A Gore-Tex® shunt was placed between the left pulmonary artery and the descending aorta. This aortopulmonary shunt was intermittently opened and closed, while cardiac output was manipulated by creating hemorrhagic hypotension. Cardiac output measurement with the mCO2F method (QmCO2F) was compared with pulmonary blood flow obtained by a transit time ultrasonic flow probe positioned around the common pulmonary artery (QAPC). Results: Bias, defined as QmCO2F – QAPC, was calculated for each measurement. With an open shunt there was a significant left-to-right shunt (mean Qp/Qs ratio 2.26; range 1.56–3.69). Mean bias (SD) was –12.3 (50.4) ml·kg–1·min–1 and –12.3 (42.7) ml·kg–1·min–1 for measurements with a closed and open shunt, respectively (no statistical significant difference). Conclusions: Cardiac output measurement with the mCO2F method is reliable and easily applicable in ventilated newborn lambs, also in the presence of a significant left-to-right shunt.

Contains fulltext : 88270.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Analysis of cerebral and systemic hemodynamic consequences of ultrasound dilution cardiac output measurements. DESIGN: : Prospective, experimental piglet study. SETTING: Animal laboratory. SUBJECTS: Nine piglets. INTERVENTIONS: Ultrasound dilution cardiac output measurements were performed in ventilated, anesthetized piglets. Interventions that are required for ultrasound dilution cardiac output measurement were evaluated for its effect on cerebral and systemic circulation and oxygenation. MEASUREMENTS AND MAIN RESULTS: DeltacHbD and DeltactHb, representing changes in cerebral blood flow and cerebral blood volume, respectively, were measured with near infrared spectrophotometry. Pulmonary artery (Q) and left carotid artery (Q) blood flow were assessed with transit time flow probes. Starting and/or stopping blood flowing through the arteriovenous loop did not cause relevant hemodynamic changes. Fast injection of isotonic saline caused a biphasic change in DeltacHbD and DeltactHb. After injection of 0.5 mL/kg, the mean (sd) increase in DeltacHbD and DeltactHb was 0.175 (0.213) micromol/L and 0.122 (0.148) micromol/L, respectively, with a subsequent mean decrease of -0.191 (0.299) micromol/L and -0.312 (0.266) micromol/L. Injection of 1.0 mL/kg caused a mean increase in DeltacHbD and DeltactHb of 0.237 (0.203) micromol/L and 0.179 (0.162) followed by a mean decrease of -0.334 (0.407) micromol/L and -0.523 (0.335) micromol/L, respectively. Q and Q changed shortly with a mean increase of 5.9 (3.0) mL/kg/min and 0.23 (0.10) mL/kg/min after injection of 0.5 mL/kg and with 12.0 (4.2) mL/kg/min and 0.44 (0.18) mL/kg/min after injection of 1.0 mL/kg, respectively. The observed changes were more profound after an injection volume of 1.0 mL/kg compared with 0.5 mL/kg for DeltacHbD (p = .06), DeltactHb (p = .09), Q, and Q (p < .01). No relevant changes in mean arterial blood pressure or heart rate were detected in response to the indicator injection. CONCLUSIONS: Cardiac output measurement by ultrasound dilution does not cause clinically relevant changes in cerebral and systemic circulation and oxygenation in a piglet model. 01 september 2010

Contains fulltext : 88176.pdf (Publisher’s version ) (Open Access) In this study, first we propose a biplane strain imaging method using a commercial ultrasound system, yielding estimation of the strain in three orthogonal directions. Secondly, an animal model of a child's heart was introduced that is suitable to simulate congenital heart disease and was used to test the method in vivo. The proposed approach can serve as a framework to monitor the development of cardiac hypertrophy and fibrosis. A 2D strain estimation technique using radio frequency (RF) ultrasound data was applied. Biplane image acquisition was performed at a relatively low frame rate (

Contains fulltext : 88821.pdf (Publisher’s version ) (Closed access) In this study, a multidimensional strain estimation method using biplane ultrasound is presented to assess local relative deformation (i.e., local strain) in three orthogonal directions in skeletal muscles during induced and voluntary contractions. The method was tested in the musculus biceps brachii of five healthy subjects for three different types of muscle contraction: 1) excitation of the muscle with a single electrical pulse via the musculocutaneous nerve, resulting in a so-called "twitch" contraction; 2) a train of five pulses at 10 Hz and 20 Hz, respectively, to obtain a submaximum tetanic contraction; and 3) voluntary contractions at 30, 60, and 100% of maximum contraction force. Results show that biplane ultrasound strain imaging is feasible. The method yielded adequate performance using the radio frequency data in tracking the tissue motion and enabled the measurement of local deformation in both the vertical direction (orthogonal to the arm) and in the horizontal directions (parallel and perpendicular to direction of the arm) in two orthogonal cross sections of the muscle. The twitch experiments appeared to be reproducible in all three directions, and high strains in vertical (25 to 30%) and horizontal (-20% to -10%) directions were measured. Visual inspection of both the ultrasound data, as well as the strain data, revealed a relaxation that was significantly slower than the force decay. The pulse train experiments nicely illustrated the performance of our technique: 1) similar patterns of force and strain waveforms were found; and 2) each stimulation frequency yielded a different strain pattern, e.g., peak vertical strain was 40% during 10-Hz stimulation and 60% during 20-Hz stimulation. The voluntary contraction patterns were found to be both practically feasible and reproducible, which will enable muscles and more natural contraction patterns to be examined without the need of electrical stimulation. 01 september 2010

Item does not contain fulltext Much research is being conducted on position-sensitive scintillation detectors for medical imaging, particularly for emission tomography. Monte Carlo simulations play an essential role in many of these research activities. As the scintillation process, the transport of scintillation photons through the crystal(s), and the conversion of these photons into electronic signals each have a major influence on the detector performance; all of these processes may need to be incorporated in the model to obtain accurate results. In this work the optical and scintillation models of the GEANT4 simulation toolkit are validated by comparing simulations and measurements on monolithic scintillator detectors for high-resolution positron emission tomography (PET). We have furthermore made the GEANT4 optical models available within the user-friendly GATE simulation platform (as of version 3.0). It is shown how the necessary optical input parameters can be determined with sufficient accuracy. The results show that the optical physics models of GATE/GEANT4 enable accurate prediction of the spatial and energy resolution of monolithic scintillator PET detectors.

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.

To determine the effects of bladderbox alarms during venoarterial extracorporeal membrane oxygenation (va-ECMO) on cerebral oxygenation and hemodynamics, six lambs were prospectively treated with va-ECMO and bladderbox alarms were simulated. Changes in concentrations of oxyhemoglobin (deltacO2Hb), deoxyhemoglobin (deltacHHb), and total Hb (deltactHb) were measured using near infrared spectrophotometry. Fluctuations in Hb oxygenation index (deltaHbD) and cerebral blood volume (deltaCBV) were calculated. Heart rate (HR), mean arterial pressure (MAP), blood flow in the left carotid artery (Qcar), and central venous pressure (CVP) were registered. Bladderbox alarms were simulated by increasing the ECMO flow or partially clamping the venous cannula and resolved by decreasing the ECMO flow, unclamping the cannula, or intravascular volume administration. CBV, HbD, MAP, and Qcar decreased significantly during bladderbox alarms, whereas HR and CVP increased. After the bladderbox alarms, CBV and HbD increased significantly to values above baseline. For HbD, this increase was higher during intravascular volume administration.MAP, Qcar, and CVP recovered to preexperiment values but increased further with volume administration. HR was increased at the end of our measurements. We conclude that Bladderbox alarms during va-ECMO treatment result in significant fluctuations in cerebral oxygenation and hemodynamics, a possible risk factor for intracranial lesions.

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.

Contains fulltext : 81308.pdf (Publisher’s version ) (Closed access) This study evaluated the relation between prior inhaled nitric oxide (iNO) and the time to initiation and duration of treatment with veno-arterial extracorporeal membrane oxygenation (ECMO) and the occurrence of hemorrhagic complications. A retrospective study was conducted in 59 human newborns treated for respiratory insufficiency with ECMO over a 5-year period. Patients received iNO before ECMO (iNO group) or not (control group). Both groups were compared for patient characteristics, postnatal age at the initiation of ECMO, duration of ECMO treatment, and hemorrhagic complications. There were no significant differences between the iNO group and the control group for patient characteristics and medication use before the ECMO treatment, except for norepinephrine. There was no significant difference for postnatal age at the initiation of ECMO and mean duration of ECMO treatment. We found no statistically significant difference in hemorrhagic complications between both groups. This persisted after correction for diagnosis and ECMO run-time in linear logistic regression analysis. Inhaled nitric oxide before ECMO did not result in a significant delay in the initiation of ECMO or longer duration of the ECMO. There was no significant relationship between the use of prior iNO and the occurrence of hemorrhagic complications during the ECMO treatment.

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 : 81678.pdf (Publisher’s version ) (Closed access) Web-based virtual microscopy has enabled new applications within pathology. Here, we introduce and evaluate a network of academic servers, designed to maximize image accessibility to users from all regions of Europe. Whole-slide imaging was utilized to digitize the entire slide set (n = 154) for the slide seminars of the 21st European Congress of Pathology. The virtual slides were mirrored to five academic servers across Europe using a novel propagation method. Functionality was implemented that automatically selects the fastest server connection in order to optimize the slide-viewing speed ( http://www.webmicroscope.net/ECP2007). Results show that during 6 months of monitoring the uptime of the network was 100%. The average viewing speed with the network was 3.1 Mbit/s, as compared to 1.9 Mbit/s using single servers. A good viewing speed (>2Mbit/s) was observed in 32 of 37 countries (86%), compared to 25 of 37 (68%) using single servers. Our study shows that implementing a virtual microscopy network spanning a large geographical area is technically feasible. By utilizing existing academic networks and cost-minimizing image compression, it is also economically feasible.

Contains fulltext : 81813.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: Lipid-induced immune modulation might contribute to the increased infection rate that is observed in patients using parenteral nutrition. We previously showed that emulsions containing medium-chain triglycerides (LCT/MCTs or pure MCTs), but not pure long-chain triglycerides (LCTs), impair neutrophil functions, modulate cell-signaling and induce neutrophil activation in vitro. It has recently been shown that medium-chain fatty acids are ligands for GPR84, a pertussis toxin (PT)-sensitive G-protein-coupled receptor (GPCR). This finding urged us to investigate whether MCT-induced neutrophil activation is mediated by PT-sensitive GPCRs. METHODS: Neutrophils isolated from blood of healthy volunteers were pre-incubated with PT (0.5-1 microg/mL, 1.5 h) and analyzed for the effect of this pre-incubation on LCT/MCT (2.5 mmol/L)-dependent modulation of serum-treated zymosan (STZ)-induced intracellular Ca(2+) mobilization and on LCT/MCT (5 mmol/L)-induced expression of cell surface adhesion (CD11b) and degranulation (CD66b) markers and oxygen radical (ROS) production. RESULTS: PT did not inhibit the effects of LCT/MCT on the STZ-induced increase in cytosolic free Ca(2+) concentration. LCT/MCT increased ROS production to 146% of unstimulated cells. However, pre-incubation with PT did not inhibit the LCT/MCT-induced ROS production. Furthermore, the LCT/MCT-induced increase in CD11b and CD66b expression (196% and 235% of unstimulated cells, respectively) was not inhibited by pre-incubation with PT. CONCLUSION: LCT/MCT-induced neutrophil activation does not involve the action of a PT-sensitive G-protein-coupled receptor.

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 : 81914.pdf (Publisher’s version ) (Closed access) The goal of this study was to investigate the applicability of conventional 2-D displacement and strain imaging techniques to phased array radiofrequency (RF) data. Furthermore, the possible advantages of aligning and stretching techniques for the reduction of decorrelation artefacts was examined. Data from both realistic simulations and phantoms were used in this study. Recently, the used processing concepts were successfully applied to linear array data. However, their applicability to sector scan data is not trivial because of the polar grid. Homogeneous and inhomogeneous tissue phantoms were simulated at a range of strains (0 to 5%) using Field II((c)). The inhomogeneous phantom, a commonly used tumor/lesion model, was also constructed using gelatin/agar solutions. A coarse-to-fine displacement algorithm was applied, using aligning and stretching to enhance re-correlation. Vertical and horizontal strains were reconstructed from the axial and lateral displacements. Results revealed that the error on displacement estimates was lower when using 2-D data windows rather than 1-D windows. For regions at large depths and large insonification angles, the allowed lateral window size was limited. Still, 1-D windows resulted in larger errors. The re-correlation techniques resulted in a significant increase in the elastographic signal-to-noise ratio (SNRe) and elastographic contrast-to-noise ratio (CNRe) of the vertical and horizontal strain components. An increase of the SNRe of 5-20 dB was observed over a range of strains (0.5 to 5.0%). In the inhomogeneous phantom, a vertical SNRe of 27.7 dB and a horizontal SNRe of 16.7 dB were measured in the background. The vertical and horizontal CNRe were 35 dB and 23.1 dB, respectively. For the experimental data, lower SNRe (vertical: 19.1 dB; horizontal: 11.4 dB) and CNRe (vertical: 33.3 dB; horizontal: 12.5 dB) were found. In conclusion, 2-D window matching of sector scan data is feasible and outperforms 1-D window matching. Furthermore, the use of re-correlation techniques enhances both precision and contrast of strain images.