Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Respiratory support in children

Respiratory failure is defined by the inability of the respiratory system to adequately deliver oxygen or remove carbon dioxide from the pulmonary circulation resulting in hypoxemia, hypercapnia or both. A wide variety of disease processes can lead to respiratory failure in children. Multiple interventions can support the paediatric patient with respiratory failure, from simple oxygen delivery devices to high frequency oscillatory ventilation and extracorporeal membrane oxygenation. This article will review available devices to improve oxygenation and ventilation, their advantages and disadvantages, and help guide physicians in the management of children with respiratory failure.     

COPD机械通气病人下呼吸道感染致病菌分布特点

①目的 探讨慢性阻塞性肺病(COPD)病人机械通气后下呼吸道感染致病菌的特点。②方法 取32例COPD并发呼吸衰竭行机械通气病人下呼吸道分泌物做痰细菌学培养，同时做药物敏感试验。③结果 32例病人共分离出菌株76株，阳性率71．7％，其中混合感染10例次。其中革兰阴性杆菌(GNB)58株，占76．3％；阳性球菌10株，占13．2％；真菌8株，占10．5％。常见致病菌以铜绿假单胞菌、鲍曼不动杆菌和肺炎杆菌为主，GNB中铜绿假单胞菌和不动杆菌的耐药率高。④结论 COPD应用机械通气病人下呼吸道感染以革兰阴性杆菌为主，耐药性高。     

CPAP对化疗后单肺通气时氧合及肺内分流的影响

[目的] 探讨应用一种新的持续气道正压 (CPAP)系统,对肺癌化疗后病人单肺通气时氧合和肺内分流的影响.[方法] 择期行肺癌手术病人 22例,按美国麻醉医师协会( ASA)分级, Ⅰ～Ⅲ级;随机分为对照组 (A组 )和 CPAP组 (B组 ),每组各 11例.A组在单肺麻醉期间非通气侧肺的支气管导管直接开口于大气中; B组单肺通气期间非通气侧持续给予 CPAP( P= 0.2 kPa),仰卧双肺通气 20 min, 仰卧单肺通气 20 min,侧卧单肺通气 30 min, 60 min,于关闭胸腔双肺通气时 ,分别采取动脉血样作血气分析,计算肺内分流率 (Qs/ Qt).[结果] 于单肺通气后 30 min和 60 min时 ,B组氧合明显高于 A组 (P < 0.01), B组分流率 (Qs/ Qt)明显低于 A组 (P < 0.05).[结论] 化疗后病人单肺通气期间 , 非通气侧持续 CPAP,有助于提高氧合 ,减少肺内分流 ,减少低氧血症的发生率.     

INTERACTIONS BETWEEN THE CIRCULATORY EFFECTS OF CENTRAL HYPOVOLAEMIA AND ARTERIAL HYPOXIA IN CONSCIOUS RABBITS

1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval-cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min. 2. Caval-cuff inflations were performed after 10 min exposure to 100, 21, 12–14 and 8–10% O₂, with and without the addition of 3–4% CO₂, in randomized order. 3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased. 4. During Phase I, there were independent linear relationships between Pao₂ (but not Pao₂) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of Pao₂, the greater was the rate of fall of SVCI and the less the rate of fall of MAP. 5. There was an inverted U-shaped effect of Pao₂, on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O₂), Phase II occurred later than during normoxia (21% O₂); and (b) across the normoxic and hypoxic gas mixtures (21–8% O₂, with and without added CO₂), there was an independent linear relationship between Pao₂ (but not Pao₂ or Pao₂×Pao₂) and the level of CI at which Phase II occurred. That is, the lower the level of Pao₂, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia.     

Moving beyond empiric continuous positive airway pressure (CPAP) trials for central sleep apnea: a multi-modality titration study

There is no universally accepted method to determine effective therapy for central sleep apnea (CSA). Continuous positive airway pressure (CPAP) applied acutely most often does not eliminate apneas and hypopneas. We hypothesized that the application of two or more therapeutic modalities after the diagnostic phase of polysomnography, a multi-modality titration study (MMTS), would identify a successful CSA treatment more often than a standard split-night study (SNS) and obviate the need for additional polysomnograms to determine a successful therapy. We retrospectively analyzed polysomnograms of patients diagnosed with CSA at our Sleep Disorders Center. We defined a therapy trial that resulted in an apnea–hypopnea index < 10 with at least one treatment modality as a therapeutic success. One hundred fifteen patients with CSA were studied. Sixty-six patients (57.4%) underwent a SNS, and 49 patients (42.6%) underwent a MMTS. SNS yielded only 8/66 (12.1%) successes on the first night, whereas a MMTS yielded 19/49 (38.8%) successes (p = 0.001, two-tailed Fishers exact). Patients who underwent a SNS eventually had similar rate of success as patients studied with MMTS (60.6 vs 63.3%, NS), but required more testing. Adaptive servo-ventilation was the most successful modality tested, yielding 36/46 (78.3%) successes. Trials of additional modalities following a failed trial of CPAP often produce a successful option that may guide therapy in patients with CSA. This approach may lead to establishing the diagnosis and treatment plans faster, while reducing unnecessary testing.     

深部病原真菌菌种4453株分析

目的 分析深部病原真菌菌种分布。方法 收集1991-2003年我院门诊及住院病人6533例，对其标本按真菌培养分离鉴定步骤进行鉴定。结果 分离出白念珠菌3555株(85．44％)，克柔念珠菌309株(7．43％)，高里念珠菌239株(5．74％)；呼吸系统分离出真菌3004株(68．35％)；消化系统真菌1291株(29．37％)；泌尿生殖系统87株(1．98％)；神经系统8株(0．18％)；血液5株(0．11％)。结论 念珠菌属尤其白念珠菌是我院近13年间系统性真菌感染的重要致病菌；合理应用抗生素及早期诊断尤为重要。     

早期应用无创性通气治疗老年Ⅱ型呼吸衰竭的护理

目的　探讨应用无创性通气治疗老年Ⅱ型呼吸衰竭的护理。方法　在常规治疗的同时 ,实验组与对照组分别应用无创通气和呼吸兴奋剂治疗 ,观察 2组患者治疗前、后、治疗间歇期动脉血气变化及康复例数。结果　实验组患者治疗后血气明显改善 (P <0 .0 1) ,康复例数明显多于对照组 (P <0 .0 1)。结论　应用无创通气可促进呼吸衰竭患者的康复 ,护士要加强对患者的心理支持 ,严密监测生命体征 ,保持呼吸道通畅 ,熟练掌握无创通气呼吸机的性能、使用方法 ,防止并发症     

Invasive ventilation in the emergency department: Part 2: Implications for patient safety

The use of mechanical ventilation in the Emergency Department requires adequate resources in order to maintain patient safety and avoid potential risks. Moreover, developments in technology require increased knowledge of mechanical ventilation techniques to address the complexity of decision-making involved. Organisational issues and system factors have the potential to negatively impact on the ability of the emergency service to provide optimum care to patients receiving mechanical ventilation. These issues include staffing and skill-mix, demand on emergency services, role-delineation, scope of practice, and current mechanisms for monitoring of quality and safety. Furthermore, in response to advances in ventilator technology, current education programs for both nursing and medical staff require review to ensure that they provide comprehensive information about the types of ventilation techniques now available and the relative risks and benefits associated with their application.This article is the second in a two-part series and explores the educational and organisational factors that impact upon safety and quality of care delivered to patients receiving mechanical ventilation in the emergency department. Recommendations for future policy development, curriculum review and reporting mechanisms to support further research in the application of mechanical ventilation in the emergency department are made.