Comparison of Calculated with Measured Oxygen Consumption in Children Undergoing Cardiac Catheterization

Our objective was to compare calculated (LaFarge) with measured oxygen consumption (VO2) using the AS/3 TM Compact Airway Module M-CAiOVX (Datex-Ohmeda, Helsinki, Finland; AS/3 TM) in children without cardiac shunts in a prospective, observational study. VO2 was determined at the end of the routine diagnostic and/or interventional catheterization. VO2was calculated according to the formula of LaFarge and Miettinen for each child and compared with the measured VO2. Data were compared using simple regression and Bland Altman analysis. Fifty-two children aged from 0.5 to 16years (median, 6.9years) and weighing 3.4 to 59.4kg (median, 22.9kg) were investigated. Calculated VO2values ranged from 59.0 to 230.8ml/min, and measured VO2 values from 62.7 to 282.2ml/min. Comparison of calculated versus measured VO2 values revealed a significant correlation (r=0.90, p<0.0001). Bias and precision were 8.9 and 48.3ml/min, respectively (95% limits of agreement: −39.4 to 57.2ml/min). Comparison of calculated VO2 in children older than 3 years (n=41), as restricted to the formula, with measured VO2, revealed a slightly reduced correlation (r=0.86, p<0.0001). Bias and precision were 10.0 and 52.5ml/min, respectively (95% limits of agreement: -42.4 to 62.5ml/min). We conclude that calculation of VO2 by the LaFarge formula does not provide reliable values compared to measured values. In clinical routine, measured rather than calculated VO2 values should be used for the estimation of cardiac output and related variable

Tumor Evasion from T Cell Surveillance

An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells

Cardiac output measurement in children: comparison of the Ultrasound Cardiac Output Monitor with thermodilution cardiac output measurement

Objective: To compare the assessment of cardiac output (CO) in children using the noninvasive Ultrasound Cardiac Output Monitor (USCOM) with the invasive pulmonary artery catheter (PAC) thermodilution cardiac output measurement. Design and setting: Prospective observational study in atertiary center for pediatric cardiology of auniversity children's hospital. Patients: Twenty-four pediatric patients with congenital heart disease without shunt undergoing cardiac catheterization under general anesthesia. Measurements and results: CO was measured by USCOM using asuprasternal CO Doppler probe in children undergoing cardiac catheterization. USCOM data were compared to CO simultaneously measured by PAC thermodilution technique. Measurements were repeated three times within 5 min in each patient. Amean percentage error not exceeding 30% was defined as indicating clinical useful reliability of the USCOM. CO values measured by PAC ranged from 1.3 to 5.3 l/min (median 3.6 l/min). Bias and precision were −0.13 and 1.34 l/min, respectively. The mean percentage error of CO measurement by the USCOM compared to PAC thermodilution technique was 36.4% for USCOM. Conclusions: Our preliminary data demonstrate that cardiac output measurement in children using the USCOM does not reliably represent absolute CO values as compared to PAC thermodilution. Further studies must evaluate the impact of incorporating effective aortic valve diameters on CO measurement using the USCO

Cerebral lesions on magnetic resonance imaging correlate with preoperative neurological status in neonates undergoing cardiopulmonary bypass surgery

OBJECTIVES To determine the prevalence, spectrum and course of cerebral lesions in neonates with congenital heart disease (CHD) undergoing full flow cardiopulmonary bypass (CPB) surgery using magnetic resonance imaging (MRI) and to examine the correlation between cerebral lesions and clinical neurological abnormalities. METHODS Prospective cohort study of neonates with d-transposition of the great arteries (n = 22), univentricular heart malformation with hypoplastic aortic arch (n = 6) and aortic arch obstructions (n = 2) undergoing CPB. Neonates underwent cerebral MRI and blinded standardized neurological examination before (median day 6) and after surgery (day 13). The MRI findings were compared with those of 20 healthy controls. RESULTS Preoperative cerebral lesions were present in 7 of 30 patients (23%) with isolated mild or moderate white matter injury (WMI) (n = 4), isolated small cerebral stroke (n = 1) and combined WMI and stroke (n = 2). None of the healthy controls had cerebral lesions on MRI. CHD neonates with preoperative cerebral lesions had more neurological abnormalities (P = 0.01) than neonates without cerebral lesions. Low arterial oxygen saturation (P = 0.03) was a risk factor for preoperative cerebral lesions, while balloon atrioseptostomy (P = 0.19) was not. After surgery, preoperative cerebral lesions persisted in 5 of 7 neonates, and 2 neonates (7%) showed signs of additional WMI in their postoperative MRI. CONCLUSIONS In neonates with severe CHD, WMI was the predominant preoperative finding, while cerebral strokes were less frequent. New postoperative lesions were rare. Preoperative neurological abnormalities correlated with the presence of cerebral lesions on MR

Sex-Dependent Differences in Symptom-Related Disability Due to Lumbar Spinal Stenosis

Study Design: Retrospective observational study. Objective: The objective of this study is to identify possible sex-dependent differences in symptom-related disability in patients with lumbar spinal stenosis. Methods: 103 consecutive outpatients (42 men and 61 women) with lumbar spinal stenosis were assessed on the basis of their medical history, the physical examination, and a series of questionnaires including the Oswestry Disability Index (ODI), the Roland Morris Disability Questionnaire (RMDQ), the Patient Health Questionnaire module 9 (PHQ-9), and the Depression Anxiety Stress Scales (DASS). Narrowing of the spinal canal was graded according to the method established by Schizas. Parameters were statistically analyzed according to the biological sex of the patients. The influence of the variables on the disability scores was analyzed by means of a multivariate regression model. Results: Symptom severity was equally distributed between men and women. Female patients showed higher RMDQ and ODI scores as well as significantly higher intermediate depression scores. The confounding variables age, pain chronicity, and psychological affection as well as the symptoms level of pain and paresis were dependent on patient sex. Conclusion: The study shows sex-depended differences in the perception of symptoms of lumbar spinal stenosis and disability of life. The findings suggest that the main mediators are pain perception and psychological influences on the quality of life

Fat in the skin: Triacylglycerol metabolism in keratinocytes and its role in the development of neutral lipid storage disease

Keratinocyte differentiation is essential for skin development and the formation of the skin permeability barrier. This process involves an orchestrated remodeling of lipids. The cleavage of precursor lipids from lamellar bodies by β-glucocerebrosidase, sphingomyelinase, phospholipases and sterol sulfatase generates ceramides, non-esterified fatty acids and cholesterol for the lipid-containing extracellular matrix, the lamellar membranes in the stratum corneum. The importance of triacylglycerol (TAG) hydrolysis for the formation of a functional permeability barrier was only recently appreciated. Mice with defects in TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2-knock-out) or TAG catabolism (comparative gene identification-58, -CGI-58-knock-out) develop severe permeability barrier defects and die soon after birth because of desiccation. In humans, mutations in the CGI-58 gene also cause (non-lethal) neutral lipid storage disease with ichthyosis. As a result of defective TAG synthesis or catabolism, humans and mice lack ω-(O)-acylceramides, which are essential lipid precursors for the formation of the corneocyte lipid envelope. This structure plays an important role in linking the lipid-enriched lamellar membranes to highly cross-linked corneocyte proteins. This review focuses on the current knowledge of biochemical mechanisms that are essential for epidermal neutral lipid metabolism and the formation of a functional skin permeability barrier

Normal right- and left ventricular volumes and myocardial mass in children measured by steady state free precession cardiovascular magnetic resonance

BACKGROUND: Quantification of ventricular volume by steady state free precession (SSFP) cardiovascular magnetic resonance is accurate and reproducible. Normal values exist for adults, but are lacking for children.We sought to establish normal values for left and right ventricular volumes, mass and function in healthy children by using SSFP. METHODS AND RESULTS: Fifty children (27 females, 23 males) without cardiovascular disease were evaluated. Median age was 11 years (range 7 months - 18 years), weight 35 kg (range 7-77 kg), height 146 cm (range 66-181 cm). Thirty-six examinations were performed with breath holding, 14 in freely breathing sedated children.Ventricular volumes and mass were measured in the end systolic and end diastolic phase on SSFP cine images acquired in a short axis plane as a stack of 12 contiguous slices covering full length of both ventricles. Regression analysis showed an exponential relationship between body surface area (BSA) and ventricular volumes and mass (normal value = a*BSAb). Normative curves for males and females are presented in relation to BSA for the end-diastolic volume, end-systolic volume and mass of both ventricles. Intra- and interobserver variability of the measurements was within the limits of 2% and 7% respectively, except for right ventricular mass (10%). CONCLUSION: The exponential equation for calculation of normal values for each ventricular parameter and graphical display of normative curves for data acquired in healthy children by SSFP cardiovascular magnetic resonance are provided

A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)

Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767-777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

Reception Test of Petals for the End Cap TEC+ of the CMS Silicon Strip Tracker

The silicon strip tracker of the CMS experiment has been completed and was inserted into the CMS detector in late 2007. The largest sub system of the tracker are its end caps, comprising two large end caps (TEC) each containing 3200 silicon strip modules. To ease construction, the end caps feature a modular design: groups of about 20 silicon modules are placed on sub-assemblies called petals and these self-contained elements are then mounted onto the TEC support structures. Each end cap consists of 144 such petals, which were built and fully qualified by several institutes across Europe. Fro