bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonism by salvianolic acid B of lipopolysaccharide‐induced disseminated intravascular coagulation in rabbits
Authors: Wu Zheng , Li Jian‐nan , Bai Zhi‐quan , Lin Xi 
Published: April 2014

SummaryThe aim of the present study was to investigate the effects of salvianolic acid B on lipopolysaccharide (LPS)‐induced disseminated intravascular coagulation (DIC) in rabbits. Continuous infusion of LPS was used to induce a DIC model in rabbits. Treatment with salvianolic acid B (1, 3 or 6 mg/kg) was started simultaneously with LPS infusion (0.5 mg/kg LPS in 60 mL saline; 10 mL/h over a period of 6 h) through the contralateral marginal ear vein. Activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count and fibrinogen concentration were determined, as were plasma levels of fibrin–fibrinogen degradation products (FDP), alanine aminotransferase (ALT), blood urea nitrogen (BUN), protein C activity, antithrombin III (ATIII) and tumour necrosis factor (TNF)‐α concentration. The gradual impairment of haemostatic parameters was induced by continuous infusion of LPS. There were marked increases in APTT, PT, BUN, ALT and plasma TNF‐α and marked decreases in the platelet count, fibrinogen, FDP, protein C and ATIII. The intravenous administration of 1, 3 or 6 mg/kg salvianolic acid B attenuated the increases in APTT, PT, BUN, ALT and plasma TNF‐α and the decreases in fibrinogen, platelet, FDP, protein C and ATIII induced by LPS infusion. These observations indicate that salvianolic acid B has an effect against LPS‐induced DIC in rabbits.
Impact of short‐term low‐dose atorvastatin on low‐density lipoprotein and high‐density lipoprotein subfraction phenotype
Authors: Xu Rui‐Xia , Guo Yuan‐Lin , Li Xiao‐Lin , Li Sha , Li Jian‐Jun 
Published: April 2014

SummaryStatins can significantly reduce low‐density lipoprotein–cholesterol (LDL‐C) and modestly raise or not alter high‐density lipoprotein–cholesterol (HDL‐C). However, their impact on high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) subfractions has been less examined. The aim of the present study was to investigate the short‐term impact of low‐dose atorvastatin on HDL and LDL subfractions in humans. In this randomized study, data from 52 subjects were analysed. Thirty‐seven patients with atherosclerosis were randomized to treatment with atorvastatin 10 mg/day (n = 17) or 20 mg/day (n = 20) for 8 weeks, with 15 healthy subjects without therapy used as a control group. The lipid profile and lipoprotein subfractions were determined using the Lipoprint system at baseline and at 8 weeks. The data suggest that atorvastatin treatment (10 and 20 mg/day) for 8 weeks significantly decreases LDL‐C levels and reduces the cholesterol concentration of all LDL subfractions, which is accompanied by an increase of the mean LDL particle size. Although 10 mg/day atorvastatin treatment for 8 weeks had no impact on the HDL subfraction, 20 mg/day atorvastatin for 8 weeks significantly increased the cholesterol concentration of large HDL particles and decreased the cholesterol concentration of small HDL particles without changing serum HDL‐C levels in patients with atherosclerosis. Therefore, the results suggest that 20 mg/day atorvastatin treatment for 8 weeks may result in a favourable modification of the HDL subfraction phenotype in addition to its effects on the cholesterol concentration of all LDL subfractions and mean LDL particle size.
Using genotyping data to assign markers to their chromosome type and to infer the sex of individuals: a Bayesian model‐based classifier
Authors: Gautier Mathieu 
Published: April 2014

AbstractThe recent democratization of next‐generation‐sequencing‐based approaches towards nonmodel species has made it cost‐effective to produce large genotyping data sets for a wider range of species. However, when no detailed genome assembly is available, poor knowledge about the organization of the markers within the genome might hamper the optimal use of this abundant information. At the most basic level of genomic organization, the type of chromosome (autosomes, sex chromosomes, mitochondria or chloroplast in plants) may remain unknown for most markers which might be limiting or even misleading in some applications, particularly in population genetics. Conversely, the characterization of sex‐linked markers allows molecular sexing of the individuals. In this study, we propose a Bayesian model‐based classifier named detsex, to assign markers to their chromosome type and/or to perform sexing of individuals based on genotyping data. The performance of detsex is further evaluated by a comprehensive simulation study and by the analysis of real data sets from various origins (microsatellite and SNP data derived from genotyping assay designs and NGS experiments). Irrespective of the origin of the markers or the size of the data set, detsex was proved efficient (i) to identify the sex‐linked markers, (ii) to perform molecular sexing of the individuals and (iii) to perform basic quality check of the genotyping data sets. The underlying structure of the model also allows to consider each of these potential applications either separately or jointly.
Lessons to be learnt in managing the breech presentation at term: An 11‐year single‐centre retrospective study
Authors: Borbolla Foster Ailsa , Bagust Annalise , Bisits Andrew , Holland Matthew , Welsh Alec 
Published: April 2014

BackgroundThe 2000 publication of the Term Breech Trial significantly impacted obstetric practice in Australia with a rapid increase in delivery of term breech singletons by caesarean section. More reassuring data from European centres who continued to offer vaginal breech deliveries to carefully selected women have led to a softening of international guidelines which now support an individualised approach to management. The application of this principle to an Australian population, particularly in the wake of such a major change in obstetric practice, has not previously been demonstrated.AimTo compare short‐term neonatal and maternal morbidity for infants with a singleton breech presentation born after 37 weeks, according to planned mode of delivery.Materials and MethodsEleven‐year single‐centre retrospective study with intention‐to‐treat analysis based on intended mode of delivery.ResultsTwo hundred and forty‐three of 766 (31.7%) eligible women elected for planned vaginal breech delivery. The overall success rate in this group was 58%. Morbidity rates were low and compare favourably with similar international studies. However, there was a nonsignificant trend towards higher rates of short‐term serious neonatal and maternal morbidity in the planned vaginal delivery group (1.6 vs 0.4%, P = 0.08 and 8.2 vs 4.8%, P = 0.06, respectively).ConclusionsAttempted vaginal delivery for breech presentation remains an option in carefully selected women under strict obstetric protocols.
The KITD816V allele burden predicts survival in patients with mastocytosis and correlates with the WHO type of the disease
Authors: Hoermann G. , Gleixner K. V. , Dinu G. E. , Kundi M. , Greiner G. , Wimazal F. , Hadzijusufovic E. , Mitterbauer G. , Mannhalter C. , Valent P. , Sperr W. R. 
Published: April 2014

AbstractKIT D816V is present in a majority of patients with systemic mastocytosis (SM). We determined the KIT D816V allele burden by quantitative real‐time PCR in bone marrow and peripheral blood of 105 patients with mastocytosis. KIT D816V was detected in 92/105 patients (88%). Significant differences in the median allele burden were observed between disease subgroups: cutaneous mastocytosis (0.042%), indolent SM (0.285%), smoldering SM (5.991%), aggressive SM (9.346%), and SM with associated hematologic non‐mast cell lineage disease (3.761%) (P < 0.001). The KIT D816V burden also correlated with serum tryptase (R = 0.5, P < 0.005) but not with mast cell infiltration in bone marrow or mediator symptoms. Moreover, the allele burden was of prognostic significance regarding survival (P < 0.01). Patients responding to cytoreductive therapy showed a significant decrease in KIT D816V (P < 0.05). To conclude, the KIT D816V burden correlates with the variant of mastocytosis, predicts survival, and is a valuable follow‐up parameter in SM.
A novel technique to determine an ‘apparent ke0’ value for use with the Marsh pharmacokinetic model for propofol
Authors: Thomson A. J. , Nimmo A. F. , Engbers F. H. M. , Glen J. B. 
Published: April 2014

SummaryDebate continues over the most appropriate blood–brain equilibration rate constant (ke0) for use with the Marsh pharmacokinetic model for propofol. We aimed to define the optimal ke0 value. Sixty‐four patients were sedated with incremental increases in effect‐site target concentration of propofol while using six different ke0 values within the range 0.2–1.2 min−1. Depth of sedation was assessed by measuring visual reaction time. A median ‘apparent ke0’ value of 0.61 min−1 (95% CI 0.37–0.78 min–1) led to the greatest probability of achieving a stable clinical effect when the effect‐site target was fixed at the effect‐site concentration displayed by the target‐controlled infusion system, at the time when a desired depth of sedation had been reached. By utilising a clinically relevant endpoint to derive this value, inter‐individual pharmacokinetic and pharmacodynamic variability may be accounted for.
Induction of general anaesthesia by effect‐site target‐controlled infusion of propofol: influence of pharmacokinetic model and ke0 value
Authors: Thomson A. J. , Morrison G. , Thomson E. , Beattie C. , Nimmo A. F. , Glen J. B. 
Published: April 2014

SummaryWe studied the use of a new ke0 value (0.6 min−1) for the Marsh pharmacokinetic model for propofol. Speed of induction and side‐effects produced were compared with three other target‐controlled infusion systems. Eighty patients of ASA physical status 1–2 were studied in four groups in a prospective, randomised study. Median (IQR [range]) induction times were shorter with the Marsh model in effect‐site control mode with a ke0 of either 0.6 min−1 (81 (61–101 [49–302])s, p < 0.01), or 1.2 min−1 (78 (68–208 [51–325])s, p < 0.05), than with the Marsh model in blood concentration control (132 (90–246 [57–435])). The Schnider model in effect‐site control produced induction times that were longer (298 (282–398 [58–513])s) than those observed with the Marsh model in blood control (p < 0.05), or either effect‐site control mode (p < 0.001). There were no differences in the magnitude of blood pressure changes or frequency of apnoea between groups.
Fetal effects of combined spinal‐epidural vs epidural labour analgesia: a prospective, randomised double‐blind study
Authors: Patel N. P. , El‐Wahab N. , Fernando R. , Wilson S. , Robson S. C. , Columb M. O. , Lyons G. R. 
Published: April 2014

SummaryWe have compared fetal heart rate patterns, Apgar scores and umbilical cord gas values following initiation of labour analgesia using either combined spinal‐epidural or epidural. One hundred and fifteen healthy women requesting neuraxial analgesia in the first stage of labour were randomly assigned to receive either combined spinal‐epidural (n = 62) or epidural analgesia (n = 53). Fetal heart rate traces, recorded for 30 min before and 60 min after neuraxial block, were categorised as normal, suspicious or pathological according to national guidelines. Sixty‐one fetal heart rate tracings were analysed in the combined spinal‐epidural group and 52 in the epidural group. No significant differences were found in fetal heart rate patterns, Apgar scores or umbilical artery and vein acid‐base status between groups. However, in both combined spinal‐epidural and epidural groups, there was a significant increase in the incidence of abnormal fetal heart rate patterns following neuraxial analgesia (p < 0.0001); two before compared with eight after analgesia in the combined spinal‐epidural group and zero before compared with 11 after in the epidural group. These changes comprised increased decelerations (p = 0.0045) (combined spinal‐epidural group nine before and 14 after analgesia, epidural group four before and 16 after), increased late decelerations (p < 0.0001) (combined spinal‐epidural group zero before and seven after analgesia, epidural group zero before and eight after), and a reduction in acceleration rate (p = 0.034) (combined spinal‐epidural group mean (SD) 12.2 (6.7) h−1 before and 9.9 (6.1) h−1 after analgesia, epidural group 11.0 (7.3) h−1 before and 8.4 (5.9) h−1 after). These fetal heart rate changes did not affect neonatal outcome in this healthy population.
The effect of audible alarms on anaesthesiologists' response times to adverse events in a simulated anaesthesia environment: a randomised trial
Authors: de Man F. R. , Erwteman M. , van Groeningen D. , Ziedses des Plantes P. V. , Boer C. , Loer S. A. , Krage R. 
Published: April 2014

SummaryAlarms are ubiquitous in anaesthetic practice, but their net effect on anaesthesiologists' performance and patient safety is debated. In this study, 27 anaesthesiologists performed two simulation sessions in random order; one session was programmed to include an alarm condition, with a standard, frequent, clearly audible alarm sound. During these sessions, adverse events were simulated and anaesthesiologists' response times to these events were recorded. Perceived workload was assessed with the NASA Task Load Index. Response times to adverse events and perceived workload were similar in both groups. Pooled response times to atrial fibrillation and desaturation were fast, with a median (range [IQR]) of 8 (4–14 [1–41]) s and 9 (6–16 [1–44]) s, respectively. Pooled response times to an ST segment elevation on the ECG and an obstructed intravenous line were significantly slower, with median (IQR[range]) times of 34 (21–76[4–300]) s and 227 (95–399 [2–600]) s, respectively (p < 0.001). This study shows that in a simulated anaesthesia environment, response times to adverse events are similar in the absence or presence of an audible alarm, and that response times to various critical events differ.
Relationship of Electrocardiographic Left Ventricular Hypertrophy to the Presence of Diastolic Dysfunction
Authors: Krepp Joseph M. , Lin Fay , Min James K. , Devereux Richard B. , Okin Peter M. 
Published: April 2014

BackgroundLeft ventricular (LV) diastolic dysfunction (DD) is a known predictor of poor cardiovascular outcomes. Although ECG LV hypertrophy (LVH) is strongly associated with LV systolic dysfunction and heart failure, the relation of LV DD to ECG LVH is unclear.MethodsECG LVH by Cornell product (CP) criteria was examined in a cohort of 185 patients who underwent both cardiac computed tomographic angiography and transthoracic echocardiography with complete evaluation of diastolic function. The presence of DD was determined via evaluation of mitral inflow velocities, tissue Doppler imaging, deceleration time, isovolumic relaxation time, pulmonary venous systolic: diastolic ratio, and left atrial enlargement.ResultsAmong the 185 patients (56% female, mean age 54.6 ± 15.6), 105 (57%) had DD. In univariate logistic regression analysis, patients in the upper quartile of CP (≥1595 mm·ms) had a >5‐fold greater odds of DD (odds ratio [OR] 5.1, 95% confidence interval [CI] 2.2–11.7, P < 0.001). In alternative analyses treating CP as a continuous variable, each 1 SD increase in CP (664 mm·ms) was associated with an OR of 1.9 for DD (95% CI 1.3–2.7, P < 0.001). In multivariate logistic regression analyses adjusting for univariate predictors of DD, the highest quartile of CP remained associated with a 5.9‐fold increased odds of DD (95% CI 2.3–15.4, P = 0.001), and each 1 SD of CP with a 1.7‐fold increased odds of DD (95% CI 1.2–2.5, P = 0.005).ConclusionsCP LVH is a strong predictor of DD, even after adjustment for other potential risk factors and ECG variables.
Assessment of human baroreflex function using carotid ultrasonography: what have we learnt?
Authors: Taylor C. E. , Willie C. K. , Ainslie P. N. , Tzeng Y.‐C. 
Published: April 2014

AbstractThe arterial baroreflex is critical to both short‐ and long‐term regulation of blood pressure. However, human baroreflex research has been largely limited to the association between blood pressure and cardiac period (or heart rate) or indices of vascular sympathetic function. Over the past decade, emerging techniques based on carotid ultrasound imaging have allowed new means of understanding and measuring the baroreflex. In this review, we describe the assessment of the mechanical and neural components of the baroreflex through the use of carotid ultrasound imaging. The mechanical component refers to the change in carotid artery diameter in response to changes in arterial pressure, and the neural component refers to the change in R‐R interval (cardiac baroreflex) or muscle sympathetic nerve activity (sympathetic baroreflex) in response to this barosensory vessel stretch. The key analytical concepts and techniques are discussed, with a focus on the assessment of baroreflex sensitivity via the modified Oxford method. We illustrate how the application of carotid ultrasound imaging has contributed to a greater understanding of baroreflex physiology in humans, covering topics such as ageing and diurnal variation, and physiological challenges including exercise, postural changes and mental stress.
Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non‐alcoholic steatohepatitis
Authors: Alisi A. , Bedogni G. , Baviera G. , Giorgio V. , Porro E. , Paris C. , Giammaria P. , Reali L. , Anania F. , Nobili V. 
Published: April 2014

SummaryBackgroundGut microbiota modifiers may have beneficial effects of non‐alcoholic fatty liver disease (NAFLD) but randomised controlled trials (RCT) are lacking in children.AimTo perform a double‐blind RCT of VSL#3 vs. placebo in obese children with biopsy‐proven NAFLD.MethodsOf 48 randomised children, 44 (22 VSL#3 and 22 placebo) completed the study. The main outcome was the change in fatty liver severity at 4 months as detected by ultrasonography. Secondary outcomes were the changes in triglycerides, insulin resistance as detected by the homoeostasis model assessment (HOMA), alanine transaminase (ALT), body mass index (BMI), glucagon‐like peptide 1 (GLP‐1) and activated GLP‐1 (aGLP‐1). Ordinal and linear models with cluster confidence intervals were used to evaluate the efficacy of VSL#3 vs. placebo at 4 months.ResultsAt baseline, moderate and severe NAFLD were present in 64% and 36% of PLA children and in 55% and 45% of VSL#3 children. The probability that children supplemented with VSL#3 had none, light, moderate or severe FL at the end of the study was 21%, 70%, 9% and 0% respectively with corresponding values of 0%, 7%, 76% and 17% for the placebo group (P < 0.001). No between‐group differences were detected in triglycerides, HOMA and ALT while BMI decreased and GLP‐1 and aGLP1 increased in the VSL#3 group (P < 0.001 for all comparisons).ConclusionsA 4‐month supplement of VSL#3 significantly improves NAFLD in children. The VSL#3‐dependent GLP‐1 increase could be responsible for these beneficial effects. Trial identifier: NCT01650025 (www.clinicaltrial.gov)
Minimal residual disease monitoring in chronic lymphocytic leukaemia patients. A comparative analysis of flow cytometry and ASO IgH RQ‐PCR
Authors: Raponi Sara , Della Starza Irene , De Propris Maria S. , Del Giudice Ilaria , Mauro Francesca R. , Marinelli Marilisa , Di Maio Valeria , Piciocchi Alfonso , Foà Robin , Guarini Anna 
Published: April 2014

SummaryMinimal residual disease (MRD) is becoming increasingly important in chronic lymphocytic leukaemia (CLL) as treatment strategies are progressively improving. The primary objective of this study was to compare the applicability of three different flow cytometric approaches: basic 4‐colour analysis, European Research Initiative in CLL (ERIC) consensus method and 8‐colour analysis. Secondly, we investigated the sensitivity and specificity of flow cytometry (FC) compared to molecular analyses for MRD detection. A total of 462 CLL samples were evaluated by basic FC; in 143, ERIC consensus method was also performed and all three FC methodologies were applied in a subgroup of 10 cases. No discordance in defining MRD‐positive/negative samples was observed between the FC methods; within positive samples, the ERIC consensus method and 8‐colour analysis showed the most accurate results. MRD was analysed by FC and polymerase chain reaction (PCR) in 243 cases: concordant results were obtained in 199/243 samples (81·9%); 42/243 were FC−/PCR+. Overall, the sensitivity and specificity of FC compared to PCR was 96·5% and 77·2%, respectively. Both FC and PCR proved suitable for the detection of MRD and prediction of progression‐free survival, which was significantly reduced in MRD‐positive patients, regardless of the methodology. These results offer the rationale for a strategy to monitor MRD in CLL patients.
Serine proteases and protease‐activated receptor 2 mediate the proinflammatory and algesic actions of diverse stimulants
Authors: Cattaruzza F , Amadesi S , Carlsson J F , Murphy J E , Lyo V , Kirkwood K , Cottrell G S , Bogyo M , Knecht W , Bunnett N W 
Published: April 2014

Background and PurposeAlthough serine proteases and agonists of protease‐activated receptor 2 (PAR2) cause inflammation and pain, the spectrum of proteases that are activated by proinflammatory and algesic stimuli and their contribution to inflammatory pain are uncertain.Experimental ApproachEnzymic assays and selective inhibitors were used to characterize protease activity in mice after intraplantar injections of formalin, bradykinin, PAR2 activating peptide (AP) or vehicle. The capacity of these proteases and of recombinant mouse trypsin 4 to cleave fragments of PAR2 and to activate PAR2 in cell lines was determined. Protease inhibitors and par2−/− mice were used to assess the contributions of proteases and PAR2 to pain and inflammation.Key ResultsIntraplantar injection of formalin, bradykinin or PAR2‐AP led to the activation of proteases that were susceptible to the serine protease inhibitor melagatran but resistant to soybean trypsin inhibitor (SBTI). Melagatran inhibited mouse trypsin 4, which degraded SBTI. Proteases generated in inflamed tissues cleaved PAR2‐derived peptides. These proteases and trypsin 4 increased [Ca2+]i in PAR2‐transfected but not in untransfected cells, and melagatran suppressed this activity. Melagatran or PAR2 deletion suppressed oedema and mechanical hypersensitivity induced by intraplantar formalin, bradykinin and PAR2‐AP, but had no effect on capsaicin‐induced pain.Conclusions and ImplicationsDiverse proinflammatory and algesic agents activate melagatran‐sensitive serine proteases that cause inflammation and pain by a PAR2‐mediated mechanism. By inducing self‐activating proteases, PAR2 amplifies and sustains inflammation and pain. Serine protease inhibitors can attenuate the inflammatory and algesic effects of diverse stimuli, representing a useful therapeutic strategy.