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BACKGROUND: It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis.METHODS: In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133.FINDINGS: Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64-1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04-0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group.INTERPRETATION: In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis.FUNDING: The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.

Land plants can grow to exceptional body sizes, with the most complex specialized structures. Directional cell division has a fundamental role throughout the tremendous plant growth processes, yet its molecular regulation is still largely unknown. Chapter 1 of this thesis discusses mechanisms and sub-cellular structures known to be involved in plant cell division orientation control, and explores tools used for dissection of this complex mechanism.Dissecting the complex plant cell division control mechanisms requires a simple and highly predictable in vivo model system. The highly predictable a relatively simple development of the Arabidopsis embryo makes it suitable for studying plant cell division regulation. In Chapter 2, we explore the cellular basis -, cell division patterns -, and regulatory pathways underlying early plant embryogenesis. We describe previous research showing that most cell divisions in the Arabidopsis embryo divide according a geometry- based “shortest-wall” principle, except for formative, asymmetric divisions. When auxin- signalling is disabled by overexpression of the dominant negative response inhibitor BODENLOS (BDL; bdl-mutant) all divisions in the embryo switch to “shortest-wall” divisions, suggesting auxin-signalling based control of oriented cell divisions.Since the microtubule (MT) cytoskeleton is a possible factor regulating cell division orientation downstream of auxin, dissecting its dynamics and regulatory mechanisms is crucial to understand cell division regulation. Combining high-resolution imaging of cell walls and MTs with a modelling strategy for MT organisation, in Chapter 3, we show that the cortical MT array is crucial for division plane orientation control in de Arabidopsis embryo. In our model, MT-dynamics are confined by cell shape -, MT stability at cell edges-, and local MT stability by auxin. Additionally, comparison of cell-biology in wild-type - and bdl-mutant embryos in Chapter 4 reveals that F-actin organisation and cell expansion are affected in the mutant. These results suggest a function for the cytoskeleton and cell shape regulation in plant cell division orientation control downstream of BDL-mediated auxin-signalling.Transcripts of factors regulating cytoskeletal structures and cell shape downstream of auxin should be differentially expressed in the bdl-mutant background. To allow for the identification of these factors, in Chapter 5, we establish and optimize a pipeline to generate high-quality embryo transcriptomes for the earliest embryonic stages. As a proof of concept, we use this pipeline to generate a reference transcriptome for early Arabidopsis embryogenesis which can be used as a tool in future developmental embryonic research.Since the role of auxin-signalling in cell division control is inferred from overexpression of a dominant response inhibitor, it is not clear if endogenous auxin truly regulates division orientation. In Chapter 6, we show that the segregating tir1/afb hexuple – and bdl-mutant embryos have similar division plane defects, suggesting that cell division regulation is regulated by auxin. However, we were not able to verify an overlap in transcriptomic regulation between the two auxin-insensitive mutants, possibly due to the small number of true mutants in the tir1/afb-mutant. Using the bdl-mutant transcriptome we identified IQ-domain 6 as a possible target of BDL-mediated auxin-signalling involved in cell division plane control. We show that the IQD6-8 protein family subclade localizes to MTs, and IQD6 binds cytoskeletal structures and calmodulins, in vivo. Loss of function of the IQD6-8 subclade results in skewed division planes in the embryo and roots, suggesting a role in cell division control, possible through Ca2+-mediated cytoskeletal regulation.Finally, in Chapter 7, we discuss future challenges in research focused on plant cell division orientation control, and the most important findings of this thesis are placed in a broader cell biological – and plant developmental framework.

A growing body of literature has reported the effects of dual tasks on gait performance in people with Parkinson’s disease (PD). The purpose of this meta-analysis was to synthesize the existing literature and quantify the overall influence of dual tasks on gait performance in PD. A thorough literature search was conducted, and 19 studies met the stringent inclusion criteria. Two moderator variable analyses examined the dual-task effect by: (a) mean single-task gait speed for each study (≥ 1.1 m/s or < 1.1 m/s), and (b) the type of dual task (arithmetic, language, memory, and motor). Three main findings were revealed by a random effects model analysis. First, a strong negative effect of dual tasks on walking performance (SMD = −0.68) confirmed that gait performance is adversely affected by dual tasks in people with PD. Second, the significant negative effect of dual tasks is present regardless of the mean level of single-task gait speed in a study. Third, dual-task walking speed deteriorates regardless of the type of dual task. Together, these results confirm that dual tasks severely affect walking performances in people with PD.

Background: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted.Methods: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years.Results: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years.Discussion: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies. Copyright (C) 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

Item does not contain fulltext BackgroundThe use of therapeutic monoclonal antibodies for clinical purposes has significantly increased in recent years, and so has the need to monitor antibody concentrations. This may be achieved using the well-established enzyme linked immunoassay (ELISA) methods; however, these assays are subject to a variety of interferences.MethodsIn the present study, the authors have tested ELISA methods for quantifying bevacizumab (BVZ) to investigate this interference. Three different ELISA methods were used and exhibited similar characteristics.ResultsThe detection limits of the ELISA methods varied from 0.05 ng/ml to 0.07 ng/ml. To monitor assay performance BVZ was measured in a control sample during each run. The BVZ concentration in the control sample was 15.4 µg/ml, the within-run imprecision (CV) and between-run CV were 4.3\% and 10.4\% (Direct ELISA), 5.2\% and 12.9\% (Indirect/Rabbit ELISA) and 3.9\% and 9.1\% (Indirect/Chicken ELISA). The assays exhibited good precision and parallelism in serial dilutions of samples and a mean recovery of 98 (range: 78-118)\%.ConclusionThe authors show that the degree of interference by using direct and indirect target immobilization depends heavily on the method of target immobilisation on the surface of the ELISA plate, and is patient specific. The results highlight pitfalls of potential relevance to sandwich-type assays, as well as an approach to rectify such problems.This approach will yield a valid assay protocol for the measurement of monoclonal therapeutic antibodies in case no target is available for direct immobilization.

Background Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients. Methods/Design The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation. Discussion The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications. Trial registration Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012) Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1132-0) contains supplementary material, which is available to authorized users.

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials. © 2016 The Authors

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA - disseminated and implemented in over 70 countries globally - is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease. © 2016 The Author(s).

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards. © 2015 John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Headache and epilepsy often co-occur. Epidemiologic studies conducted in the past few years reinforce the notion of a bi-directional association between migraine and epilepsy. Data on an association between headache (in general) and epilepsy, however, are less clear. Peri-ictal headache often presents with migraine-like symptoms and can be severe. A correct diagnosis and management are paramount. It was demonstrated that cortical hyperexcitability may underlie both epilepsy and migraine. A recent study linked spreading depolarisation, the supposed underlying pathophysiological mechanism of migraine with aura, to epilepsy. Although this study was carried out in patients who had suffered a subarachnoid haemorrhage, the finding may shed light on pathophysiological mechanisms common to epilepsy and migraine.

Background. Smoking is considered as an addiction to nicotine for most subjects consuming 10 cigarettes or more per day. Hence, nicotine replacement therapy by way of gum, patch, or spray has been advocated. The rationale of this study is to evaluate the possible beneficial effects of adding nicotine gum to the routine of subjects using the nicotine patch. The effect of the nicotine patch against the placebo, both groups receiving placebo nicotine gum, has also been assessed. Methods. Healthy subjects (374) were randomized at their work-setting in a 1-year double-blind placebo-controlled trial: 149 subjects to active nicotine patch + active gum (group 1), 150 to active nicotine patch + placebo gum (group 2), and 75 to placebo patch + gum (group 3). Treatment duration was 12 weeks with a 16-hr transdermal patch of 15 mg, followed by a 6 + B-weeks weaning period on respectively 10 and 5 mg patches. Gum use was not restricted during the first 6 months, with recommendations to use at least four pieces a day. A strict definition of smoking abstinence was used in this study, which did not allow smoking any cigarette after Week 1. Nonsmoking status at each visit, as reported by the subjects, was verified by CO below 10 ppm in expired air. Results. Abstinence rates in group 1 against group 2 were 34.2 and 22.7% (P = 0.027) at 12 weeks, 27.5 and 15.3% (P = 0.010) at 24 weeks, and 18.1 and 12.7% (P = 0.191) at 52 weeks. In group 3, abstinence rates were 17.3, 14.7, and 13.3% respectively at 12, 24, and 52 weeks. Using logistic regression with adjustment for six baseline covariates, odds ratios for abstinence (with 95% CI) were computed. For group 1/group 2, OR at 12, 24, and 52 weeks were 1.72 (1.03-2.94) (P = 0.039), 2.04 (1.14-3.57) (P = 0.018), and 1.47 (0.76-2.76) (P = 0.125). No significant differences in OR were observed when comparing groups 2 and 3. Time to relapse is significantly longer in group 1 as compared to that of group 2 (P = 0.041), whereas no significant differences between groups 2 and 3 were observed. No significant differences between the three groups in systemic and local adverse drug events were observed. Conclusion. Adding active gum use to active patch use in subjects smoking 10 cigarettes or more a day increased abstinence rates, which are statistically significant up to 24 weeks.

BACKGROUND: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. OBJECTIVES: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. METHODS: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother-child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. RESULTS: Questionnaires were completed by 37 cohort studies of > 350,000 mother-child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. CONCLUSION: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.

Item does not contain fulltext Weight loss, cachexia and sarcopenia are profound problems in the frail oncologic patients. With the development and increasing use of angiogenesis inhibitors in metastatic cancer patients, the question arises as to their influence on body weight and composition. Angiogenesis is not only important for the growth, development and metastatic potential of tumors but also for physiological processes in adipogenesis. A less known approach of angiogenesis inhibitors is their experimental use in obese models. This review focuses on the effects on the body weight and composition of angiogenesis inhibitors, especially of those targeting the vascular endothelial growth factor pathway. 01 februari 2012

Background. Capsule endoscopy (CE) is a relatively new diagnostic modality in the evaluation of patients with suspected small bowel pathology. It is unclear to what extent physicians are able to predict the clinical consequences of CE on patient management.Methods. In this prospective study, 180 consecutive CE examinations were analysed. Prior to CE, referring physicians were asked to indicate the consequences of CE according to potential different CE outcomes. The influence of CE on patient management was determined with at least I year follow-up. Management consequences were defined as major (surgical or endoscopic intervention, or medical therapy) or minor (nonspecific therapy, including iron supplementation, or no further diagnostic tests).Results. CE led to major management consequences in 32% of cases. Of patients with obscure gastrointestinal bleeding and normal CE findings, 91% were independent of blood transfusions and experienced no further bleeding episodes during a mean follow-up of 33 months. In 78% of 118 cases that were evaluated, the actual consequences of CE matched the consequences predicted by the referring physicians.Conclusion. CE had a major impact on patient management in about one third of investigations. In the majority of cases, physicians adequately predicted the clinical consequences of CE. (C) 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background Muscle weakness in cystic fibrosis (CF) is reported to be reduced. Influencing factors are still not well defined. Aim This study correlates muscle strength measurements: handgrip force (HGF), quadriceps force (QF) and 6 minute walking distance (6MWD) in adult CF patients with physical activity (PA), pulmonary function and decline, colonization status, and number of hospitalization over the past year. Methods A handheld dynamometer (HHD) was used for HGF, a knee shuttle with HHD for the isometric voluntary QF and a standard 6MWD was performed. Results are expressed as % of normal. PA is measured using Sensewear Pro® armband [Moderate PA (mPA) = 4.8–7.2 metabolic equivalents (MET), vigorous PA (vPA) MET >7.2). Pulmonary function (FVC%, FEV1%) and number of hospitalization were retrieved from the medical file. Results are given as median (interquartile range). Results 31 patients (aged 25 (22–33)years) (12 female(38.7%))(12 chronically colonized(38.7%)) with a FEV1% of 75.4(57–84.7)% participated. Muscle strength was not related to pulmonary function or pulmonary function decline or pseudomonas colonization. 21 patients measured PA. They had an average MET of 1.7 (1.55–2.1), a mPA of 26′/day (19–68.5) and a m-vPA of 40′/day (22–98). The 6MWD was 72.7% (66.9–77.8), the QF% was 46% (40.2–57.4) and the HGF 97.4% (79.8–106.5). Pseudomonas negative patients were more PA (p = 0.034). None of the muscle strength measurements correlated with the PA. The number of hospitalizations correlated with the QF (p = 0.001), the HGF (p = 0.0001) and 6MWD (p = 0.007). Conclusion Muscle weakness in CF was only influenced by the number of hospitalizations over the past year.

Coeliac disease is a common disorder, but most persons with coeliac disease remain undetected because they have only mild aspecific symptoms or are free of symptoms. For a definitive diagnosis small bowel biopsies showing partial or (sub)total villous atrophy are required. The presence of anti-endomysium and/or anti-tissue-transglutaminase antibodies in serum is strongly predictive for coeliac disease. In case of clear clinical suspicion the most straightforward way to diagnose or exclude coeliac disease is by taking endoscopic biopsies from the distal duodenum. When the suspicion is low, determination of the above mentioned antibodies as a first step suffices. At present there are insufficient reasons to initiate population-wide screening for coeliac disease by means of serological testing or individual screening by taking duodenal biopsies during each gastroscopy.

Three men, aged 20, 24 and 42 years, reported difficulties in passing food through the oesophagus. The diagnosis of eosinophilic oesophagitis was made after endoscopic investigation, laboratory tests and histological tests. In all three patients the symptoms disappeared: respectively spontaneously, during systemic treatment with corticosteroids due to a kidney complaint, and after topical corticosteroid treatment lasting 6 weeks. Eosinophilic oesophagitis occurs in particular in young men. There are complaints about the passage of food through the oesophagus, with frequent food impaction, also without any obvious stenosis. Endoscopic features are subtle and comprise a vulnerable oesophageal mucosa with a ringed appearance or small white spots on the oesophageal mucosa. Histopathology reveals an eosinophilic infection infiltrate in the oesophageal epithelium. Food allergies may play a causal role. With respect to the treatment, favourable results have been described for oral fluticasone, while endoscopic treatment may consist of dilation.

Fast simulation techniques are applied to estimate error rates of coherent M-ary phase shift keying (PSK) in the presence of co-channel interference (CCI) and additive white Gaussian noise (AWGN). This type of interference occurs often in wireless systems that employ frequency reuse. Error rates are frequently calculated assuming that CCI can be modelled as Gaussian. It is shown that this assumption is valid only in noise dominated environments. Simulation techniques based on adaptive importance sampling (IS) are developed for this problem. Several new numerical results are presented and used to calculate cellular capacities.

The authors conducted 3 studies in which Turkish and other adolescents in the Netherlands completed questionnaires that addressed the importance of collectivist cultural values for achievement motivation and educational outcomes. Compared with other minority group students and Dutch students, the Turkish students had stronger family-oriented achievement motivation. In addition, only among the Turks was ethnic identification positively related to family motivation. Furthermore, there were no differences in individual achievement motivation between the Turks and Dutch, and only among the former group was a combination of family motivation and individual motivation found. Also, for the Turks, family motivation was positively related to task-goal orientation, which mediated the relationship between family motivation and academic performance. Individual motivation was an independent predictor of performance. For the other ethnic minority groups and the Dutch, family motivation was not related to task-goal orientation and performance. In addition, for these groups, task-goal orientation mediated the relationship between individual achievement motivation and performance.

Topiramate (TPM) is a new anti-epileptic drug with proven efficacy against partial seizures in adults. Its use in children is less well documented. In a retrospective study, 41 patients with intractable childhood epilepsy were treated with TPM as add-on therapy for an average period of 15 months. They were classified according to seizure type and etiology. The dose was titrated for effect and ranged between 2 and 24 mg/kg/d. Of the 41 patients being treated, six became seizure free, ten had a seizure reduction of more than 75% and eight a seizure reduction of between 50 and 75%. The most remarkable effect was seen in seven patients with West syndrome. Of these, four patients became seizure free and one had more than 75% seizure reduction. Adverse effects including sedation, fatigue, difficulties with verbal expression and anorexia were noted in 15 patients. None of these effects were important enough to interrupt treatment. We conclude that TPM as adjunctive therapy is a promising drug in children with intractable epilepsy, especially in the patients with West syndrome.

Aim: Sunitinib, a VEGFR tyrosine kinase inhibitor (TKI) is registered in metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumor (GIST) and pancreatic neuroendocrine tumors. In patients with diabetes who were treated with sunitinib, a decrease in blood glucose levels and symptomatic hypoglycemias have been reported. Some preclinical studies suggest that improved insulin sensitivity may be the underlying mechanism. Therefore we studied the early effects of sunitinib on insulin sensitivity and insulin steady-state concentrations. Methods: In 10 mRCC patients, after an overnight fast, a 120 minutes hyperinsulinemic euglycemic clamp (insulin infusion rate 60 mE.m-2.min-1; steady state 90-120 minutes) was performed before and one week (7-10 days) after start of sunitinib 50mg per day. Insulin levels were measured using a radio-immune assay. Insulin sensitivity index (SI) was defined as glucose disposal rate normalized for steady state blood glucose concentration divided by the steady-state plasma insulin. Results: One patient with diabetes (treated with metformin) and 9 patients without diabetes were included in the study protocol (Female/Male: 1/9). Co-medication did not change during the study. The insulin sensitivity index decreased from 0.22 ± 0.04 µmol/kg-1 . min-1 .(mE insulin/L)-1 before to 0.18 ± 0.02 µmol/kg-1 . min-1 . (mE insulin /L)-1 (p Conclusions: Sunitinib increased steady-state insulin concentrations by 30% most likely as a result of impaired insulin clearance. In our study group, mostly without diabetes, insulin sensitivity decreased. These alterations were already observed as early as one week on sunitinib treatment. In patients using insulin or insulin-secretion stimulating agents the effect of sunitinib on insulin clearance could result in overexposure to insulin and thereby induce hypoglycemia. Intense blood glucose monitoring in patients with diabetes is therefore essential in the first week after starting sunitinib. Disclosure: All authors have declared no conflicts of interest.

Nous rapportons la synthese des 1667 reponses a un questionnaire postal auto-administre, adresse par la BELTA a un echantillon de 4643 medecins belges , en contact professionnel avec des patients (taux de reponses: 35,9%), dont 17,3% etaient des fumeurs. Les liens entre tabagisme et maladie sont consideres comme demontres par 98,8% des medecins pour ce qui est du tabagisme actif, par 85,3% pour le tabagisme passif, par 96,4% pour les consequences foetales du tabagisme gravidique, par 83,3% pour la dependance nicotinique. Les interactions du tabagisme sur le metabolisme des medicaments ne sont pas assez connues. Les medecins ne percoivent pas suffisamment l'approche specifique de l'arret en fonction des divers stades du cycle de cessation, du degre de dependance nicotinique et de l'etat psychique du patient. Moins de la moitie des medecins determinent le statut tabagique de tous leurs patients, alors que pres de 90% affirment informer leurs patients fumeurs sur les risques-sante du tabagisme, et que 84,2% declarent aborder avec eux le probleme de l'arret. Leur intervention se limite le plus souvent a un ferme conseil, qui n'est complete par la prescription d'une substitution nicotinique (surtout gomme et timbre) qu'au maximum chez 50% des fumeurs. Le recours a des structures specialisees n'est pas frequent (10-20%) et le suivi apres le conseil d'arret nettement deficient. Dans cette etude retrospective de leurs modalites d'approche, les declarations des medecins pourraient refleter davantage leurs intentions que leur pratique effective. Les problemes du tabagisme et des techniques d'arret devraient etre enseignes de facon plus approfondie au niveau gradue et postgradue, afin d'obtenir une attitude plus interventionniste des professionnels de la sante dans la lutte contre le tabagisme.

Background: Triple therapy involving a proton pump inhibitor and two antibiotics has been suggested as an effective treatment for Helicobacter pylori infection. The impact of imidazole resistance on the efficacy of such regimens is largely unknown. Methods: One hundred patients with culture proven H. pylori infection were treated with omeprazole 40 mg b.d., amoxycillin 1000 mg b.d., and tinidazole 500 mg b.d. for one week. Pre-treatment imidazole susceptibility was measured by disk diffusion. Resistance was confirmed by E-test. Eradication was assessed by endoscopy 6–8 weeks after the end of treatment. In cases of doubt a 13C-urea breath test was performed. Side-effects were scored using a semiquantitative scale. Results: H. pylori was eradicated in 95% of the patients with an imidazole-susceptible strain and in 69% of the patients with a resistant strain (P

To assess the accuracy of six commonly used diagnostic tests for Helicobacter pylori in a prospective study without using any specific test as the gold standard (the patient was regarded as H. pylori-infected if two or more tests, whatever their nature, were positive).In 105 outpatients undergoing upper GI endoscopy, 62 without significant abnormalities, 28 with gastroesophageal reflux disease, 19 with peptic ulcer, one with erosive gastritis, and one with atrophic gastritis (some patients had more than one diagnosis), antral biopsy specimens were taken for culture, polymerase chain reaction, histological examination (hematoxylineosin and Giemsa stains), and rapid urease test. Corpus biopsy specimens were taken for histological examination. Serology (ELISA) and a 13C-urea breath test were also performed. Consistency of diagnosis between two pathologists was assessed by kappa statistics.Sensitivity and specificity, respectively, were as follows: culture, 98.4 and 100%; polymerase chain reaction, 96.7 and 100%; histological examination (antrum), 96 and 98.8%; histological examination (antrum + corpus), 98.4 and 98.8%; rapid urease test, 90.2 and 100%; 13C-urea breath test, 100 and 100%; and serological examination, 98.4 and 88.4% (95% in those who had not been previously treated for H. pylori). All H. pylori-positive cases were detected by culture and rapid urease test. In 86.4% of these cases all antral biopsy-based tests were positive. Agreement between pathologists was good, with a kappa coefficient around 0.90 for antral biopsy specimens.All antral biopsy-based tests, as well as the 13C-urea breath test, are accurate for the diagnosis of H. pylori infection. Sampling error is a problem of minor importance. The lower specificity of serological tests may be largely explained by previous treatment of H. pylori.

Setting the two hypotheses of complete neglect and full use of base rates against each other is inappropriate. The proper question concerns the degree to which base rates are used (or neglected), and under what conditions. We outline alternative approaches and recommend regression analysis. Koehler's conclusion that we have been oversold on the base rate fallacy seems to be premature.

This study analyses the 13C-urea breath test with the aim of determining the optimal time interval between dosing and breath sampling and examines the feasibility of having patients perform the test without supervision at home.Prospective study comparing the 13C-urea breath test with four antral biopsy-based tests in a random population undergoing upper gastrointestinal endoscopy.One university hospital and one general hospital.One hundred and four patients were included; 61 were Helicobacter pylori-positive and 43 H. pylori-negative according to biopsy-based tests.The 13C-urea breath test was performed at home by collecting a baseline and two post-dosing samples; the next day it was performed clinically by collecting a baseline and six post-dosing samples. A 100 mg dose of 13C-urea and a test meal were used.The breath samples collected were analysed. Excess delta 13CO2/12CO2 values above five per million were considered positive.The specificity of the clinical test was 100% whereas that of the home-based test was 95.1%. The sensitivity of the clinical test depended on the time interval between dosing and collection of the evaluated sample. Sensitivity was 100% if the sample was taken 50 min or more after dosing. The home-based test had a sensitivity of 94.8%.To obtain maximum sensitivity (100%) using the single-sample technique the sample has to be collected at least 50 min after dosing. It is feasible to have the test performed at home. Patient selection and thorough instruction are necessary.

Introduction: Angiogenesis inhibitors have remarkably improved the outcome of patients with several types of cancer. One of the most reported side effects of angiogenesis inhibitors is hypertension. In patients treated with bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), hypertension has an overall incidence up to 32%. Understanding the pathogenesis of this side effect is essential for optimal treatment with this class of drugs. Microvascular endothelial dysfunction is involved in the pathogenesis of hypertension. Our hypothesis is that bevacizumab (BVZ) induced hypertension is caused by an acute reduction of endothelium-mediated vasodilation. Methods: BVZ was infused intra-arterially to separate direct local effects of VEGF inhibition from systemic actions, such as hypertension, that could indirectly interfere with endothelial function. At first, in seven volunteers the acute vasomotor effect of BVZ was studied. During 15 minutes BVZ 144 μg/dl forearm volume/min was infused in the brachial artery of the non-dominant arm while assessing forearm blood flow (FBF) with venous strain gauge plethysmography. During BVZ infusion venous blood was collected from both arms to measure local and systemic concentrations of BVZ. Subsequently the acute vasodilator response to intra-arterial acetylcholine (Ach, endothelium-dependent vasodilator) alone and during simultaneous infusion of BVZ was studied, in another group of 12 volunteers. Finally, the effect of BVZ on the response to an endothelium-independent vasodilator nitroprusside (SNP) was studied in a similar experimental set up, in a third group of 12 volunteers. Results: In the experimental arm during infusion BVZ reached a concentration of 135±10,7μg/ml (± SD; n=8), resembling systemic exposure to BVZ in patients treated with 5mg BVZ i.v./kg. BVZ concentration in the control arm was 6,7±1,1 μg/ml (n=10). Intra-arterial BVZ did not directly alter forearm vascular tone. Infusion of BVZ significantly reduced the percentage increase in forearm blood flow during infusion of two dosages of acetylcholine from (mean±SE) 440±157 and 926±252 to 169±154 and 612±40 (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1693. doi:1538-7445.AM2012-1693

We studied in 20 splenectomised dogs the incidence of early intravascular hepatic pooling after administration of E. coli endotoxin. Autologous red cells were labelled in vitro with 99mTc. Bloodpool imaging and haemodynamic measurements were performed simultaneously. Changes in hepatic red cell volume were estimated from alterations in hepatic activity. In 10 dogs, hepatic red cell activity increased considerably (156 to 359% of the basal value). In the remaining animals the hepatic activity did not change markedly or even decreased. The decline in arterial pressure and cardiac output seemed more pronounced in dogs with clear evidence of hepatic pooling. However no significant differences in absolute haemodynamic values could be demonstrated between dogs with and without pooling. It is concluded that an hepatic outflow block is not a constant feature of canine endotoxin shock. Absolute haemodynamic values do not depend on the presence of an outflow block. Thus the presence of hepatic pooling need not make the canine model inappropriate for studies on human sepsis.

An accurate numerical procedure is presented for calculating the normal mode parameters of symmetrical coupled microstrip lines. The Green's function approach leads to a singular integral equation of the first kind which is reduced to an equivalent Fredholm equation of the second kind. It is shown that this equation may be approximated by a set of linear equations. The solution of these equations gives the charge distribution on the strips from which the normal mode parameters are computed. Results for the characteristic impedance and the effective relative permittivity are compared with those obtained by other authors.

During administration of ketanserin, a selective 5-HT2-receptor blocker, intracranial pressure (ICP) was measured in dogs without (group 1) and with (group 2) intracranial hypertension (ICP greater than 20 mm Hg). A bolus of 1 mg/kg body weight and subsequent infusion of 13.25 +/- 1.2 mg/kg of ketanserin decreased mean arterial pressure 35% +/- 18% in group 1 and 35% +/- 19% in group 2. In both groups, there was no change in ICP or in ventricular volume-pressure response curves (intracranial compliance [ICC]) after the administration of ketanserin. Ketanserin may be a safe antihypertensive drug for avoiding and treating hypertension in neurosurgical patients.