主动脉内球囊反搏在低射血分数患者非体外循环冠状动脉旁路移植术中应用的必要性探讨

目的探讨对低射血分数患者施行非体外循环冠状动脉旁路移植术(off-pump coronary artery bypass grafting, OPCAB)预防性应用主动脉内球囊反搏(intraaortic balloon pump, IABP)辅助的必要性. 方法 2001 年1 月～2004年10月对64例低射血分数(LVEF≤40%)施行OPCAB,将64例分为2组:术前或术中预防性应用IABP辅助者列为IABP组,共19例;未应用IABP者列为对照组,共45例. 结果 IABP组与对照组在术后并发症手术死亡、脑血管意外、肾功能衰竭衰血滤、围手术期心肌梗死等方面无显著差异(χ2=0.000,P=1.000).IABP组术后需要延长呼吸机带机时间(超过24 h)的比例显著高于对照组(IABP组8例,对照组3例; χ2=9.429,P=0.002);IABP组术后监护时间延长(超过48 h)的比例显著高于对照组(IABP组14例,对照组19例; χ2=4.110,P=0.043). 结论在无IABP辅助的情况下,为低射血分数患者实施OPCAB手术是可行的.     

沙丁胺醇加布地奈德微量泵吸入治疗小儿毛细支气管炎的疗效观察

目的 :评价沙丁胺醇 (喘乐宁 )加布地奈德 (普米克令舒 )微量泵吸入治疗小儿毛细支气管炎的疗效。方法 :随机将 72例患儿分为两组。对照组在综合疗法基础上单用喘乐宁微量泵吸入治疗 ,治疗组加用喘乐宁及普米克令舒微量泵吸入治疗。观察两组疗效及气急缓解和喘鸣音消失时间。结果 :显效率治疗组为 94.4% ,对照组为 72 .2 % ,两者相比有显著性差异 ( χ2 =4.9,P <0 .0 5 ) ;治疗组气急缓解、喘鸣音消失时间均较对照组短。结论 :喘乐宁加普米克令舒微量泵吸入治疗小儿毛细支气管炎较单用喘乐宁有较好疗效。     

Imbalance of plasma membrane ion leak and pump relationship as a new aetiological basis of certain disease states

The basis for life is the ability of the cell to maintain ion gradients across biological membranes. Such gradients are created by specific membrane-bound ion pumps [adenosine triphosphatases (ATPases)]. According to physicochemical rules passive forces equilibrate (dissipate) ion gradients. The cholesterol/phospholipid ratio of the membrane and the degree of saturation of phospholipid fatty acids are important factors for membrane molecular order and herewith a determinant of the degree of non-specific membrane leakiness. Other operative principles, i.e. specific ion channels can be opened and closed according to mechanisms that are specific to the cell. Certain compounds called ionophores can be integrated in the plasma membrane and permit specific inorganic ions to pass. Irrespective of which mechanism ions leak across the plasma membrane the homeostasis may be kept by increasing ion pumping (ATPase activity) in an attempt to restore the physiological ion gradient. The energy source for this work seems to be glycolytically derived ATP formation. Thus an increase in ion pumping is reflected by increased ATP hydrolysis and rate of glycolysis. This can be measured as an accumulation of breakdown products of ATP and end-products of anaerobic glycolysis (lactate). In certain disease entities, the balance between ATP formation and ion pumping may be disordered resulting in a decrease in inter alia (i.a.) cellular energy charge, and an increase in lactate formation and catabolites of adenylates. Cardiac syndrome X is proposed to be due to an excessive leakage of potassium ions, leading to electrocardiographic (ECG) changes, abnormal Tl-scintigraphy of the heart and anginal pain (induced by adenosine). Cocksackie B3 infections, a common agent in myocarditis might also induce an ionophore-like effect. Moreover, Alzheimer's disease is characterized by the formation of extracellular amyloid deposits in the brain of patients. Perturbation of cellular membranes by the amyloid peptide during the development of Alzheimer's disease is one of several mechanisms proposed to account for the toxicity of this peptide on neuronal membranes. We have studied the effects of the peptide and fragments thereof on 45Ca2+-uptake in human erythrocytes and the energetic consequences. Treatment of erythrocytes with the beta 1-40 peptide, results in qualitatively similar nucleotide pattern and decrease of energy charge as the treatment with Ca2+-ionophore A23187. Finally, in recent studies we have revealed and published in this journal that a rare condition, Tarui's disease or glycogenosis type VII, primarily associated with a defect M-subunit of phosphofructokinase, demonstrates as a cophenomenon an increased leak of Ca2+ into erythrocytes.     

The “pumpgate” incident: Stigma against lactating mothers in the U.S. workplace

ABSTRACT

Studies conclude that breastfeeding for six months is associated with better lifelong health for the mother and the child. Mothers in the U.S. returning to work after maternity leave report difficulty with the need to take frequent breaks to pump breastmilk so many stop breastfeeding. Factors discouraging pumping breastmilk in the workplace motivated a content analysis of public comments posted in response to a legal deposition that occurred in January of 2011 in which an attorney who was a new mother was challenged about taking a break to pump breastmilk. A total of 899 public comments posted on Yahoo in 2015–2016 in response to this earlier incident were analyzed for content. Of these, only 336 mentioned breastfeeding. Overall, 148 comments showed support for breastfeeding or pumping breastmilk at work, while 182 comments showed moderate to strong disapproval (six unclassified). The majority of disapproving comments were critical of pumping breastmilk in the workplace. Implications of these findings for the duration of breastfeeding after returning to work are discussed.     

主动脉内球囊反搏支持下急性心肌梗死经皮冠状动脉介入治疗的临床应用

目的：观察急性心肌梗死（AMI）合并心功能不全高危患者在主动脉球囊反搏（IABP）支持下行经皮冠状动脉介入治疗（PCI）对早期病死率及心功能的影响。方法选择第四军医大学西京医院2012年9月至2013年2月收治的20例AMI患者于发病3~12 h内在IABP支持下行急诊冠状动脉造影术,并行经皮冠状动脉腔内血管成形术及支架置入术。观察IABP置入前后的血压变化,并于1周内行心脏超声心功能检查。结果患者应用IABP 24 h后,平均心率由（120.0±15.8）次/分降至（84.3±5.7）次/分,1周内心功能射血分数由（36±5）％改善为（44±4）％,患者术后收缩压和舒张压均有明显改善,差异有统计学意义（P＜0.05）。1例因肺部感染、呼吸衰竭而放弃治疗自动出院;出院后1个月死亡率为5％（1/20）。结论 IABP作为辅助手段可在AMI患者PCI术前早期预防性短期应用,以减少并发症的发生,降低病死率,改善术后近期心功能。     

Characterizing asthma from a drop of blood using neutrophil chemotaxis

Asthma is a chronic inflammatory disorder that affects more than 300 million people worldwide. Asthma management would benefit from additional tools that establish biomarkers to identify phenotypes of asthma. We present a microfluidic solution that discriminates asthma from allergic rhinitis based on a patient’s neutrophil chemotactic function. The handheld diagnostic device sorts neutrophils from whole blood within 5 min, and generates a gradient of chemoattractant in the microchannels by placing a lid with chemoattractant onto the base of the device. This technology was used in a clinical setting to assay 34 asthmatic (n = 23) and nonasthmatic, allergic rhinitis (n = 11) patients to establish domains for asthma diagnosis based on neutrophil chemotaxis. We determined that neutrophils from asthmatic patients migrate significantly more slowly toward the chemoattractant compared with nonasthmatic patients (P = 0.002). Analysis of the receiver operator characteristics of the patient data revealed that using a chemotaxis velocity of 1.55 μm/min for asthma yields a diagnostic sensitivity and specificity of 96% and 73%, respectively. This study identifies neutrophil chemotaxis velocity as a potential biomarker for asthma, and we demonstrate a microfluidic technology that was used in a clinical setting to perform these measurements.Asthma is a chronic inflammatory disorder of the lungs that is associated with airway hyperresponsiveness (AHR) and obstructed airflow (1), affecting more than 300 million people worldwide (2). Over the past 30 y, asthma prevalence has increased significantly in many populations, with some indications that prevalence may be reaching a plateau in the developed world. Significant progress has been made in identifying primary mediators involved in the pathophysiology of asthma. Several cell types, such as T helper cells (T_H1/T_H2), dendritic cells, mast cells, macrophages, eosinophils, and neutrophils play central roles in the pathology of asthma (4–7). Additionally, various cytokines that regulate the leukocyte trafficking, such as interleukins, IFN-γ, and TNF-α, have been identified and targeted in drug therapies. The recruitment of leukocytes to the lungs, particularly eosinophils and neutrophils, is central to the pathogenesis of asthma. Increased numbers of eosinophils are prominently observed in the lung tissue and bronchoalveolar lavage (BAL) fluid for most asthmatics (5). Neutrophils play a more critical role in severe asthma, where elevated counts of neutrophils are often observed in the BAL fluid (7). An overview of the role of neutrophils in asthma is shown in Fig. 1A. Although significant progress has been made in uncovering mediators in the pathology of asthma, these gains have not yet greatly improved our ability to define clinically relevant phenotypes of asthma in patients.Open in a separate windowFig. 1.Overview of different diagnostic techniques and the role of neutrophils in the pathology of asthma. (A) Summary of the role of neutrophils in the pathology of asthma, showing neutrophil adhesion and transendothelial migration; chemotaxis mediated by macrophages and T-helper cells; and neutrophilia in the lung tissue that leads to airway remodeling and airflow obstruction. (B) Proposed microfluidic method (more details in Fig. S1) for phenotyping asthma patients by measuring upstream of the asthma pathology with rapid neutrophil sorting on a P-selectin–coated surface (1); neutrophil chemotaxis monitored with high-throughput microscopy and automatically tracked with software (2); and asthma characterization on the basis of chemotaxis outputs (3). (C) Traditional clinical asthma diagnostic methods occur downstream of the asthma pathophysiology by measuring the effect of leukocyte inflammation on airway obstruction, nitric oxide output, or clinical symptoms.Asthma is diagnosed clinically by physicians, informed by the patient’s medical history, spirometry tests that measure lung function, reversibility of AHR, and several other potential metrics (8). These diagnostic techniques measure the effects of the inflammatory response in the lung by assessing airway constriction, nitric oxide production, and the resulting clinical symptoms. However, all of these diagnostic tests require patient compliance, which can be challenging when diagnosing children or the elderly (9). Additionally, many asthma diagnostic tests partially rely on the patient experiencing clinical symptoms that are variable during or around the visit to the physician. Perhaps these common characteristics of current diagnostic techniques contribute to difficulties in diagnosing asthma, particularly in certain subpopulations. For example, in a recent Canadian study involving ∼500 obese and nonobese subjects, Aaron et al. (10) found that ∼30% of the test subjects had been falsely diagnosed with asthma by physicians. Additionally, it is well established that the elderly are consistently underdiagnosed for asthma (11, 12). Therefore, additional tools are needed to improve the diagnosis of asthma. Furthermore, current asthma assessments do not inform the clinician of disease severity, expected clinical course, and risk of exacerbations.To improve characterization of asthma in the clinic, we have developed a handheld microfluidic chip that can identify functional measures of asthma from a drop of whole blood. Microfluidic systems have several characteristics that make them well-suited for clinical use, including low sample-volume requirements (13, 14); simple integration with automated fluid handling systems (15); and diffusion-dominant laminar fluidic phenomena that allow for precise control of a cell’s microenvironment (16–18). Indeed, microfluidic-based tools are increasingly being used in clinical research for diagnostic purposes (19–26). Neutrophils have been used to diagnose clinical conditions in human patients based on proteomic and genomic analysis (22) and chemotaxis behavior (23, 27), demonstrating that assays measuring cell function can be used for diagnostics. In this work, we assay the neutrophil chemotactic function in a blind study to identify quantitative domains that can be used to discriminate asthma from nonasthmatic allergic rhinitis. This approach of directly measuring the effector cell in the pathology of asthma differs from traditional diagnostic tests, which measure the variable effect of inflammation on airway constriction (Fig. 1 B and C and Table S1). Importantly, we developed methods to simplify the sample preparation, assay protocol, and data analysis that offer significant time savings over traditional macroscale (28–30) and microscale (18) chemotaxis techniques, allowing for the translation of the technology into the clinic. We analyzed 34 patients, and discovered that neutrophil chemotaxis can be used to discriminate asthma from nonasthmatic, allergic rhinitis patients with sensitivity and specificity of 96% and 73%, respectively. The results of the clinical application of our microfluidic device represent a first step demonstration of how asthma can potentially be diagnosed and managed based on cellular function, rather than largely by clinical observations.