Nitric oxide precursors and congenital heart surgery: A randomized controlled trial of oral citrulline

ObjectiveThe study sought to determine whether citrulline supplementation, a precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma citrulline concentrations and decreasing the risk of postoperative pulmonary hypertension.Study DesignForty children, undergoing cardiopulmonary bypass and at risk for pulmonary hypertension, were randomized to receive 5 perioperative doses (1.9 g/m2 per dose) of either oral citrulline or placebo. Plasma citrulline and arginine concentrations were measured at 5 time points. Measurements of systemic blood pressure and presence of pulmonary hypertension were collected.ResultsMedian citrulline concentrations were significantly higher in the citrulline group versus the placebo group immediately postoperatively (36 μmol/L vs 26 μmol/L, P = .012) and at 12 hours postoperatively (37 μmol/L vs 20 μmol/L, P = .015). Mean plasma arginine concentrations were significantly higher in the citrulline group versus the placebo group by 12 hours postoperatively (36 μmol/L vs 23 μmol/L, P = .037). Mean systemic blood pressure did not differ between groups (P = .53). Postoperative pulmonary hypertension developed in 9 patients, 6 of 20 (30%) in the placebo group and 3 of 20 (15%) in the citrulline group (P = .451), all of whom had plasma citrulline concentrations less than age-specific norms. Postoperative pulmonary hypertension did not develop in patients who demonstrated plasma citrulline concentrations in excess of 37 μmol/L (P = .036).ConclusionsOral citrulline supplementation safely increased plasma citrulline and arginine concentrations compared with placebo after cardiopulmonary bypass. Postoperative pulmonary hypertension did not occur in children with naturally elevated citrulline levels or elevations through supplementation. Oral citrulline supplementation may be effective in reducing postoperative pulmonary hypertension

The role of Kelvin-Helmholtz instability in the internal structure of relativistic outflows. The case of the jet in 3C 273

Relativistic outflows represent one of the best-suited tools to probe the physics of AGN. Numerical modelling of internal structure of the relativistic outflows on parsec scales provides important clues about the conditions and dynamics of the material in the immediate vicinity of the central black holes in AGN. We investigate possible causes of the structural patterns and regularities observed in the parsec-scale jet of the well-known quasar 3C 273. We present here the results from a 3D relativistic hydrodynamics numerical simulation based on the parameters given for the jet by Lobanov & Zensus (2001), and one in which the effects of jet precession and the injection of discrete components have been taken into account. We compare the model with the structures observed in 3C 273 using very long baseline interferometry and constrain the basic properties of the flow. We find growing perturbation modes in the simulation with similar wavelengths to those observed, but with a different set of wave speeds and mode identification. If the observed longest helical structure is produced by the precession of the flow, longer precession periods should be expected. Our results show that some of the observed structures could be explained by growing Kelvin-Helmholtz instabilities in a slow moving region of the jet. However, we point towards possible errors in the mode identification that show the need of more complete linear analysis in order to interpret the observations. We conclude that, with the given viewing angle, superluminal components and jet precession cannot explain the observed structures.Comment: Accepted for publication in Astronomy & Astrophysics. 14 pages. Higher resolution plots available on request to [email protected] and at http://www.mpifr-bonn.mpg.de/staff/mperuch

Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: Potential therapy for postoperative pulmonary hypertension

ObjectivePulmonary hypertension may complicate surgical correction of congenital heart defects, resulting in increased morbidity and mortality. We have previously shown that plasma levels of the nitric oxide precursors citrulline and arginine drop precipitously after congenital cardiac surgery and that oral citrulline supplementation may be protective against the development of pulmonary hypertension. In this study, we assessed the safety and pharmacokinetic profile of intravenous citrulline as a potential therapy for postoperative pulmonary hypertension.MethodsThe initial phase of this investigation was a dose-escalation study of intravenously administered citrulline in infants and children undergoing one of five congenital cardiac surgical procedures (phase 1). The primary safety outcome was a 20% drop in mean arterial blood pressure from the baseline pressure recorded after admission to the intensive care unit. Based on our previous work, the target circulating plasma citrulline trough was 80 to 100 μmol/L. Each patient was given two separate doses of citrulline: the first in the operating room immediately after initiation of cardiopulmonary bypass and the second 4 hours later in the pediatric intensive care unit. Stepwise dose escalations included 50 mg/kg, 100 mg/kg, and 150 mg/kg. After model-dependent pharmacokinetic analysis, we enrolled an additional 9 patients (phase 2) in an optimized dosing protocol that replaced the postoperative dose with a continuous infusion of citrulline at 9 mg/(kg·h) for 48 hours postoperatively.ResultsThe initial stepwise escalation protocol (phase 1) revealed that an intravenous citrulline dose of 150 mg/kg given after initiation of cardiopulmonary bypass yielded a trough level of in the target range of approximately 80 to 100 μmol/L 4 hours later. The postoperative dose revealed that the clearance of intravenously administered citrulline was 0.6 L/(h·kg), with a volume of distribution of 0.9 L/kg and estimated half-life of 60 minutes. Because of the short half-life, we altered the protocol to replace the postoperative dose with a continuous infusion of 9 mg/(kg·h). An additional 9 patients were studied with this continuous infusion protocol (phase 2). Mean plasma citrulline levels were maintained at approximately 125 μmol/L, with a calculated clearance of 0.52 L/(h·kg). None of the 17 patients studied had a 20% drop in mean arterial blood pressure from baseline.ConclusionsIn this first report of the use of intravenous citrulline in humans, we found citrulline to be both safe and well tolerated in infants and young children undergoing congenital cardiac surgery. Because of the rapid clearance, the optimal dosing regimen was identified as an initial bolus of 150 mg/kg given at the initiation of cardiopulmonary bypass, followed 4 hours later by a postoperative infusion of 9 mg/(kg·h) continued up to 48 hours. Using this regimen, plasma arginine, citrulline, and nitric oxide metabolite levels were well maintained. Intravenous citrulline needs to be studied further as a potential therapy for postoperative pulmonary hypertension

Revealing gendered identity and agency in dementia

As identity and agency are central to the well-being of people with dementia, this paper explores whether their dialogue conveys a gendered sense of identity and agency. The author discusses whether they demonstrate not just a subjective sense of being, but also an understanding of their relational selves. Findings are presented from a qualitative study in the North of England which examined the everyday decisions made by married couples when one partner had dementia. Ethnographic methods were used, including participant observation and interviews. Whilst dialogical analysis usually centres on the subjective self, it was also used to examine intersubjectivity. Comparisons are made between the dialogue of women and men in order to draw conclusions about the gendered nature of identity and agency. The study found that the women and men defined themselves according to their social and gender identities. The literature had suggested that agency might be a gendered concept and the study confirmed that men were somewhat individualistic and rational in their concerns, whereas women were more relational and even spiritual. Yet, women and men demonstrated emotional reflexivity. Since national and international health policy prioritises living well with dementia, more systematic attention should be given to the role of gender in influencing wellbeing in dementia. Health and social care staff should recognise and facilitate the gender identity and related social roles of people with dementia (e.g. parent, carer, worker) in order to enhance their quality of life

Current concepts of the management of dental extractions for patients taking warfarin

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Controversy has surrounded the correct management of patients therapeutically anticoagulated with warfarin who require dental extractions. The risk of bleeding must be weighed up against the risk of thromboembolism when deciding whether to interfere with a patient's warfarin regimen. An improved understanding of the importance of fibrinolytic mechanisms in the oral cavity has resulted in the development of various local measures to enable these patients to be treated on an outpatient basis. Methods: A review of the literature was undertaken. This was supplemented by the authors' clinical trials and extensive clinical experience with anticoagulated patients. Results: Various protocols for treating patients taking warfarin have been reviewed and summarized and an overview of the haemostatic and fibrinolytic systems is presented. A protocol for management of warfarinized patients requiring dental extractions in the outpatient setting is proposed. Conclusions: Patients therapeutically anticoagulated with warfarin can be treated on an ambulatory basis, without interruption of their warfarin regimen provided appropriate local measures are used.G Carter, AN Goss, JV Lloyd, R Tocchett

Social Class

Discussion of class structure in fifth-century Athens, historical constitution of theater audiences, and the changes in the comic representation of class antagonism from Aristophanes to Menander

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

The Canine Oral Microbiome

Determining the bacterial composition of the canine oral microbiome is of interest for two primary reasons. First, while the human oral microbiome has been well studied using molecular techniques, the oral microbiomes of other mammals have not been studied in equal depth using culture independent methods. This study allows a comparison of the number of bacterial taxa, based on 16S rRNA-gene sequence comparison, shared between humans and dogs, two divergent mammalian species. Second, canine oral bacteria are of interest to veterinary and human medical communities for understanding their roles in health and infectious diseases. The bacteria involved are mostly unnamed and not linked by 16S rRNA-gene sequence identity to a taxonomic scheme. This manuscript describes the analysis of 5,958 16S rRNA-gene sequences from 65 clone libraries. Full length 16S rRNA reference sequences have been obtained for 353 canine bacterial taxa, which were placed in 14 bacterial phyla, 23 classes, 37 orders, 66 families, and 148 genera. Eighty percent of the taxa are currently unnamed. The bacterial taxa identified in dogs are markedly different from those of humans with only 16.4% of oral taxa are shared between dogs and humans based on a 98.5% 16S rRNA sequence similarity cutoff. This indicates that there is a large divergence in the bacteria comprising the oral microbiomes of divergent mammalian species. The historic practice of identifying animal associated bacteria based on phenotypic similarities to human bacteria is generally invalid. This report describes the diversity of the canine oral microbiome and provides a provisional 16S rRNA based taxonomic scheme for naming and identifying unnamed canine bacterial taxa