Prognostic molecular markers in pediatric liver disease – Are there any?

Pediatric liver disease (PLD) is a major cause of severe morbidity and prolonged hospitalizations in children. Stratifying patients in terms of prognosis remains challenging. The limited knowledge about molecular mechanisms causing and accompanying PLD remains the main obstacle in a search for reliable prognostic biomarkers. A systematic search of MEDLINE via PubMed and Embase via OVID was conducted on studies published between August 2007 and August 2017. Molecular markers with a prognostic potential in terms of survival, need for liver transplantation or disease progression/regression were selected. In general, identified studies were single center smaller case-control studies or case series with a low level of evidence and a high risk of bias. Only 23 studies comprising 898 patients could be included, mostly focusing on biliary atresia, non-alcoholic fatty liver disease, viral hepatitis, and LT; and markers related to morphogenesis and fibrosis. Furthermore, molecular markers in metabolic pathways and inflammation shown to be relevant, however requiring further validation. Hence, further biological and clinical studies are needed to gain greater molecular insight into PLD.     

Halothane Anesthesia Affects NMDA-Stimulated Cholinergic and GABAergic Modulation of Striatal Dopamine Efflux and Metabolism in the Rat In Vivo

Microdialysis of the striatum of halothane-anesthetized rats was used to study the participation of local cholinergic and GABAergic neurotransmission in NMDA receptor-modulated striatal dopamine release and metabolism. Reverse dialysis.of NMDA (1 mM) evoked a 10-fold increase in dopamine efflux and reduced DOPAC and HVA to > 20% of basal values. The effect of NMDA on dopamine efflux was abolished by atropine (10 microM) but unaffected by (+)-bicuculline (50 microM). NMDA-induced decrease in DOPAC (but not HVA) efflux was potentiated by atropine, whereas (+)-bicuculline attenuated the decrease in DOPAC and HVA. Compared to our previous studies in unanesthetised rats, our data suggest that halothane anesthesia alters the balance between NMDA-stimulated cholinergic and GABAergic influences on striatal dopamine release and metabolism. Differential sensitivity to halothane of NMDA receptors expressed by the neurones mediating these modulatory influences, or loss of specific NMDA receptor populations through voltage-dependent Mg2+ block under anesthesia, could underlie these observations.     

Solubility, adsorption, and the thermodynamics of the cutoff effect

For many years, the expression "cutoff effect of anesthesia," has been used to denote the failure of the higher alcohols or paraffins to produce anesthesia. As such, it is used to assess the plausibility of specific models, proposed for anesthesia. However, the uses were shown, in many respects, to be problematic. This article augments the notion of the cutoff to fit for all cases in which only some of the molecules in a homologous series are anesthetics. We find that the location of the cutoff points is affected by three free energy quantities: that of the adsorption of the agent to the anesthetic "site" (f(sl,site)), that of the perturbation of the site (f(ll,site)), and that of the evaporation of the agent from its pure condensed phase (Deltamu degrees (evaporation)). This outcome indicates that the cutoff cannot be attributed to a single parameter. In addition, the analyses that attribute the cutoff to the failure of compounds to obey the much-used Meyer-Overton correlation will have to be amended. This article shows that cutoff results can be used to elucidate the structure of a site.     

The involvement of nitric oxide in the analgesic effects of ketamine

We investigated the contribution of NO-cyclic GMP (cGMP) pathway to the antinociceptive effects of ketamine in mice by using the nitric oxide synthase inhibitor, nitro(g)- L-arginine methyl ester (L-NAME). Intraperitoneal (i.p.) (1, 5 or 10 mg/kg) or intrathecal (i.th.) (10, 30 or 60 microg/mouse) administration of ketamine produced dose-dependent antinociceptive effects in the acetic acid-induced writhing and formalin tests but not in the tail-flick nor in hot-plate tests. Pretreatment of mice with L-NAME (10 mg/kg, i.p.) which produced no antinociception on its own, significantly inhibited the antinociceptive effect of ketamine (1, 5 or 10 mg/kg, i.p.). However, L-NAME (30 microg/mouse) was given intrathecally, it neither modified the antinociceptive effect of i.th. ketamine (10, 30 or 60 microg/mouse) nor did it produce an antinociceptive effect alone. These data suggest that the activation of the NO-cGMP pathway probably at the supraspinal level, but not spinal level, contributes to the antinociceptive effects of ketamine.     

Reversal of Ketamine/Xylazine combination anesthesia by Atipamezole in olive baboons (Papio anubis)

Background  The potential of Atipamezole (ATI) to reverse Ketamine/Xylazine (KET/XYL) anesthesia in the Olive baboon ( Papio anubis ) was studied.
Methods  Anesthesia was induced with 10 mg/kg KET and 0.5 mg/kg XYL intramuscularly. Mean arousal time (MAT), heart rate (HR), systolic arterial blood pressure (SAP), rectal temperature, respiratory rate (RR), and hemoglobin oxygen saturation (SpO₂) were monitored. Baboons were treated with: KET/XYL only, KET/XYL followed by 100 μg/kg ATI or by 200 μg/kg ATI administered 25 minutes after KET/XYL.
Results  Atipamezole rapidly reversed depressed HR and SAP (10 ± 5.2 minutes), RR (5 ± 2 minutes) and SpO₂ (3 ± 6 minutes) and significantly decreased MAT (13 ± 2.2 minutes) vs. KET/XYL alone (35 ± 5 minutes). Emesis was absent and salivation was observed after administration of 200 μg/kg ATI only.
Conclusions  Atipamezole at 100 μg/kg is sufficient for rapid and smooth reversal of KET/XYL anesthesia in the Olive baboon with minimal side effects.     

动态心电图在小儿心律失常与心率变异性诊断中的意义

目的：研究动态心电图（DCG）诊断小儿心律失常及心率变异性（HVR）的临床价值。方法：560 例患者均进行常规心电图和动 态心电图的检查,由两组专业人员分别对心电图（ECG）和动态心电图（DCG）的检查结果进行（评价）,比较两种检查手段的不同 类型的心律失常的诊出率;评价不同类型心律失常的HVR。结果：ECG对各型心律失常的总诊出率为25.00%,对不同类型心率失 常的诊出率分别为5.71%、1.43%、9.29%、6.43%和2.14%;DCG 总诊出率为62.85%,对不同类型心率失常的诊出率分别为 16.43%、6.43%、17.86%、14.29%和7.86%,二者具有统计学差异（P＜0.05）。不同类型的心律失常的HVR不同,其中室性心动过速 和室性期前收缩的各项指标均明显低于其他类型（P＜0.05）。结论：DCG对不同心律失常的诊出率明显高于ECG,并能有效反应 不同类型心率失常的HVR,在小儿心律失常的诊断中具有一定的临床价值。     

硬膜外复合全麻对老年高血压患者腹部手术后并发症的影响

目的：探讨硬膜外复合全麻对老年高血压患者腹部手术后并发生的影响。方法：收集2013 年6 月-2015 年6 月在两家医院 接受腹部手术的老年高血压患者100 例,根据麻醉方法不同分为研究组和对照组。研究组患者给予硬膜外复合麻醉,对照组给予 全凭静脉麻醉。观察并比较两组患者的麻醉时间、药物用量以及术后并发症的发生率。结果：两组麻醉时间比较,差异无统计学意 义（P>0.05）;研究组麻醉药物用量低于对照组,差异具有统计学意义（P<0.05）;两组患者手术时间比较,差异无统计学意义（P>0. 05）;研究组患者术后苏醒时间、拔管时间以及住院时间均短于对照组,差异具有统计学意义（P<0.05）;研究组术后并发症的发生 率低于对照组,差异具有统计学意义（P<0.05）。结论：硬膜外复合全麻用于老年高血压患者腹部手术能够减少麻醉药物用量,降低 术后并发症的发生率,安全性较高。     

老年患者全身麻醉术后认知功能障碍的影响因素分析

目的：探讨分析老年非心脏手术患者全身麻醉术后认知功能障碍(POCD)的影响因素。方法：选择我院80 例老年行非心脏手 术患者,所有患者均给予全身麻醉手术,于术前及术后1、3 d 分别使用简易智能状态检查法（MMSE）评估患者认知功能,同时记 录行不同手术种类患者POCD 发生率并分析其年龄、麻醉时间、术中出血量、并发症情况及受教育程度等指标与POCD发生的相 关性。结果：80 例患者POCD发生率为30.0%,且不同种类手术中的发生率比较差异无统计学意义（P＞0.05）;POCD 组术后1d MMSE 评分为较术前分明显下降,比较差异具有统计学意义（P＜0.05);POCD组术后3 d及非POCD 组术后1、3 d MMSE 评分与 术前比较差异无统计学意义（P＞0.05）;Logistic 回归分析显示,患者年龄、文化程度、麻醉持续时间≥ 3 h、术中出血量≥ 350 mL及 合并高血压与POCD的发生具有显著相关性（P＜0.05）。结论：行全麻手术患者术后POCD 发病率较高,且患者高龄、文化程度 低、高血压合并症及麻醉持续时间长等是引起POCD发生的重要影响因素。     

Monitoring depth of anesthesia using combination of EEG measure and hemodynamic variables

Monitoring depth of anesthesia (DOA) via vital signs is a major ongoing challenge for anesthetists. A number of electroencephalogram (EEG)-based monitors such as the Bispectral (BIS) index have been proposed. However, anesthesia is related to central and autonomic nervous system functions whereas the EEG signal originates only from the central nervous system. This paper proposes an automated DOA detection system which consists of three steps. Initially, we introduce multiscale modified permutation entropy index which is robust in the characterization of the burst suppression pattern and combine multiscale information. This index quantifies the amount of complexity in EEG data and is computationally efficient, conceptually simple and artifact resistant. Then, autonomic nervous system activity is quantified with heart rate and mean arterial pressure which are easily acquired using routine monitoring machine. Finally, the extracted features are used as input to a linear discriminate analyzer (LDA). The method is validated with data obtained from 25 patients during the cardiac surgery requiring cardiopulmonary bypass. The experimental results indicate that an overall accuracy of 89.4 % can be obtained using combination of EEG measure and hemodynamic variables, together with LDA to classify the vital sign into awake, light, surgical and deep anesthetised states. The results demonstrate that the proposed method can estimate DOA more effectively than the commercial BIS index with a stronger artifact-resistance.