A review of responsive MRI contrast agents: 2005–2014

This review focuses on MRI contrast agents that are responsive to a change in a physiological biomarker. The response mechanisms are dependent on six physicochemical characteristics, including the accessibility of water to the agent, tumbling time, proton exchange rate, electron spin state, MR frequency or superparamagnetism of the agent. These characteristics can be affected by changes in concentrations or activities of enzymes, proteins, nucleic acids, metabolites, or metal ions, or changes in redox state, pH, temperature, or light. A total of 117 examples are presented, including ones that employ nuclei other than ¹H, which attests to the creativity of multidisciplinary research efforts to develop responsive MRI contrast agents. Copyright © 2014 John Wiley & Sons, Ltd.     

Review article: Inotrope and vasopressor use in the emergency department

Shock is a common presentation to the ED, with the incidence of septic shock increasing in Australasia over the last decade. The choice of inotropic agent is likely dependent on previous experience and local practices of the emergency and other critical care departments. The relatively short duration of stay in the ED before transfer leaves little room for evaluating the appropriateness of and response to the agent chosen. Delays in transfer to inpatient facilities means that patients receive advanced critical care within the ED for longer, requiring initiation and titration of vasoactive agents in the ED. This article discusses the general concepts of shock and the indicators for inotrope and vasopressor use, revises the various agents available and reviews the current evidence for their use.     

2009-2010年某医院抗感染药物应用情况分析R978

【目的】分析本院抗感染药物应用现状、趋势,为临床合理用药和降低医药费用提供参考。【方法】对2009～2010年本院抗感染药物应用的品种、数量、用药金额、用药频度（DDDs）、限定日费用（DDDc）等进行统计、分析。【结果】抗感染药物用药金额占全部药物用药金额比例呈下降趋势;注射剂型抗感染药物的用药金额比例呈下降趋势,抗感染药物金额所占比例平均为22．01％,此值低于全国医院27．97％的平均水平。【结论】本院抗感染药物临床应用总体来说较为合理。但注射剂型用药金额比例仍然偏大,头孢菌素类用药金额和DDDs偏大,故应进一步加强管理,做到合理使用。     

Effect of mucolytic and bronchodilator aerosol therapy on airway resistance in mechanically ventilated patients

Nebulisation of a 10% solution of Mesna (Mistabron) in 10 postoperatively ventilated patients without preexisting pulmonary disease caused a significant increase in inspiratory resistance. This increase is effectively blocked by addition of a bronchodilator (i.e. Salbutamol) to the aerosol. No significant changes in airway resistance were observed in the 10 patients receiving salbutamol alone or isotonic saline. The expiratory resistance did not change suggesting that only the larger airways are involved in the constrictive effect of the drug. Although no patient showed clinical signs of bronchospasm, it is worth considering that even in patients without history of obstructive pulmonary disease nebulisation of Mesna should be performed in combination with a bronchodilator.     

免疫抑制剂结合生物制剂治疗类风湿关节炎效果

目的：探讨免疫抑制剂结合生物制剂对类风湿关节炎（RA）患者的作用。方法：选取2019年8月至2021年10月医院治疗的98例RA患者作为研究对象，随机分为观察组和对照组，各49例。对照组采用来氟米特治疗，观察组在对照组基础上联合阿达木单抗注射液治疗，两组均治疗8周。比较两组患者的治疗效果、免疫相关指标、炎症相关指标、骨代谢相关指标、血清相关标志物。结果：治疗8周后，两组患者中医症状评分、晨僵具体时间、关节压痛数量、肿胀关节数量以及RA患者病情评价（DAS28）评分均显著改善，且观察组优于对照组（P＜0.05）；两组患者免疫系统补体C3、补体C4、免疫球蛋白（Ig）A、IgG、IgM均显著升高，且观察组高于对照组（P＜0.05）；两组患者血清指标[骨桥蛋白（OPN）、类风湿因子（RF）、抗环瓜氨酸多肽抗体（anti-CCP）]、炎症相关指标[白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、降钙素原（PCT）]均显著下降，且观察组低于对照组（P＜0.05）；两组患者骨代谢指标[碱性磷酸酶（ALP）、Ⅰ型胶原羧基末端肽（ⅠCTP）、Ⅰ型前胶原羧基端肽（PⅠCP）及骨钙素（BGP）]均显著下降，且观察组低于对照组（P＜0.05）。结论：采用免疫抑制剂结合生物制剂对RA患者进行治疗，患者的骨代谢以及血清学指标和炎症相关指标显著改善，治疗效果显著。     

The pH sensitivity of –NH exchange in LnDOTA–tetraamide complexes varies with amide substituent

The amide proton exchange rates in various lanthanide(III) DOTA–tetraamide complexes were investigated by CEST as a function of variable chemical structures and charges on the amide substituents. Comparisons were made between YbDOTA–(gly)₄^? (Yb‐1), YbDOTA–(NHCH₂PO₃)₄^5? (Yb‐2) and YbDOTA–(NHCH₂PO₃Et₂)₄³⁺ (Yb‐3). The general shapes of the CEST vs pH profiles were similar for the three complexes but they showed maximum CEST intensities at different pH values, pH 8.3, 8.8 and 6.9 for Yb‐1, Yb‐2 and Yb‐3, respectively. This indicates that a more negatively charged substituent on the amide helps stabilize the partial positive charge on the amide nitrogen and consequently more base is required to catalyze proton exchange. The chemical shifts of the –NH protons in Yb‐1 and Yb‐2 were similar (?17 ppm) while the –NH proton in Yb‐3 was at ?13 ppm. This shows that the crystal field produced by the amide oxygen donor atoms in Yb‐3 is substantially weaker than that in the other two complexes. In an effort to expand the useful range of pH values that might be measured using these complexes as CEST agents, the shapes of the CEST vs pH curves were also determined for two thulium(III) complexes with much larger hyperfine shifted –NH proton resonances. The ratio of CEST from –NH exchange in Tm‐1 compared with CEST from –NH exchange in Tm‐3 was found to be linear over an extended pH range, from 6.3 to 7.4. This demonstrates a potential advantage of using mixtures of lanthanide(III) DOTA–tetraamides for mapping tissue pH by use of ratiometric CEST imaging. Copyright © 2011 John Wiley & Sons, Ltd.     

Immunomodulatory effects of antimicrobial agents. Part II: antiparasitic and antifungal agents

Antiparasitic and antifungal drugs have not received the same high level of recognition as antimicrobial drugs. They are comparatively few in number, the great majority of them were developed more than a century ago, they have many adverse side effects and are subject to the emergence of drug resistance. The second part of the review, devoted to the immunomodulatory effects of antimicrobial agents, addresses the interference of antiparasitic and antifungal agents with the host natural defenses and the deleterious or beneficial consequences of these properties.     

2-(8'-羟基喹啉-5'-磺酸-7'-偶氮)-变色酸络合解离法测定血清钙

目的建立灵敏度高、选择性好的２（８′羟基喹啉５′磺酸７′偶氮）变色酸（简称８Ｑ５ＳＡＣ）血清钙络合解离测定法。方法在甘氨酸ＮａＯＨ缓冲介质中，８Ｑ５ＳＡＣ与钙、镁等金属离子络合显色，加入ＥＧＴＡ使８Ｑ５ＳＡＣ与钙解离，以测定吸光度的下降值分析血清钙。对反应条件、方法性能进行系统研究。结果该法线性０～５ｍｍｏｌ／Ｌ，平均回收率９９３％，变异系数０５６％～１８１％。与邻甲酚酞络合酮法对照，ｒ＝０９９８，Ｐ＞０５；与甲基百里酚蓝法对照，ｒ＝０９９３，Ｐ＞００５。结论该法试剂稳定，灵敏度、选择性及测试线性均优于或相当于邻甲酚酞络合酮法和ＭＴＢ法，可用于血清钙的常规分析，尤其适合于自动分析     

FFAs对人网膜脂肪细胞脂联素分泌的影响及罗格列酮的干预作用

[目的]观察游离脂肪酸(FFAs)对人成熟网膜脂肪细胞脂联素分泌的影响及罗格列酮(RSG)干预的效果.[方法]取6名外科手术女性患者的网膜脂肪组织,胶原酶消化分离纯化成熟脂肪细胞.细胞在FFAs(油酸∶软脂酸,2∶1)和(或)加用RSG的培基中培养不同的时间,酶联免疫吸附法测定培基中脂联素浓度.[结果]FFAs呈剂量及时间依赖性抑制网膜脂肪细胞脂联素分泌,各个干预组与对照组相比,脂联素降低有统计学意义;RSG可逆转此种抑制作用,高浓度(10 μmol/L)时逆转作用更强.[结论]FFAs能抑制体外培养的人网膜脂肪细胞脂联素分泌,但此种抑制作用可被RSG逆转.     

某院门诊2008～2010年口服降糖药应用情况分析

【目的】了解本院门诊近3年来口服降糖药应用现状及其变化趋势,为临床合理使用降糖药提供参考。【方法】对本院门诊药房2008-2010年口服降糖药的用药频度（DDDs）、销售金额、日用药金额（DDC）等数据进行统计、分析。【结果】3年来本院口服降糖药销售金额持续增长。销售金额,DDDs排序居第1位的始终是阿卡波糖（拜糖平）,销售金额排序与DDDs排序比值在0．5～3．5之间。【结论】本院口服降糖药使用基本合理。     

护士职业接触烷化剂类化疗药防护情况的调查分析

目的了解护士接触烷化剂类化疗药自我防护知识、措施落实情况。方法对接触烷化剂类化疗药物的30名院本部肿瘤科护士和24名院外门诊部护士采用自行设计的调查表及直接观察法评估防护知识的掌握及措施落实情况。结果院本部肿瘤科护士对防护知识的掌握及防护措施的落实较院外门诊部护士好(P0.05)。结论护士接触烷化剂类化疗药应通过岗前培训掌握化疗相关知识及防护措施,特别是对院外门诊部护士的岗前培训和在职教育不容忽视,应引起管理者的高度重视。     

Evidence-based interventions to improve patient compliance with antihypertensive and lipid-lowering medications

The MEDLINE database was searched from 1972 to June 2002 to identify studies of interventions designed to improve compliance with antihypertensive or lipid-lowering medications. Studies were required to employ a controlled design, follow patients for >or=6 months and measure compliance by a method other than patient self-report. The literature review yielded 62 studies describing 79 interventions. Overall, 56% of interventions were reported to improve patient compliance. When only those studies meeting minimum criteria for methodological quality were considered, 22 interventions remained and 12 were recommended, because they demonstrated a significant improvement in compliance. Recommended interventions included fixed-dose combination drugs, once-daily or once-weekly dosing schedules, unit-dose packaging, educational counselling by telephone, case management by pharmacists, treatment in pharmacist- or nurse-operated disease management clinics, mailed refill reminders, self-monitoring, dose-tailoring, rewards and various combination strategies. Personalised, patient-focused programs that involved frequent contact with health professionals or a combination of interventions were the most effective at improving compliance. Less-intensive strategies, such as prescribing products that simplify the medication regimen or sending refill reminders, achieved smaller improvements in compliance but may be cost-effective due to their low cost.     

Medicinal chemistry strategies toward host targeting antiviral agents

Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed.     

清洁手术抗菌药物预防性用药调查

目的了解外科清洁手术围手术期抗菌药物预防使用情况,加强抗菌药物使用管理。方法采用回顾性调查方法,对医院外科部分清洁(Ⅰ类切口)手术围手术期预防性用药情况进行调查与分析。结果在调查的94例清洁手术患者中,抗菌药物预防性使用率94.68%,其中无指征用药占79.78%。预防用药开始时间在术前0.5～2h内执行占61.70%,术后24h内停药仅占13.82%。结论该医院Ⅰ类切口手术预防用药比例较大,用药起点较高,存在抗菌药物使用不合理现象。     

Acute right ventricular failure—from pathophysiology to new treatments

The right ventricle (RV) provides sustained low-pressure perfusion of the pulmonary vasculature, but is sensitive to changes in loading conditions and intrinsic contractility. Factors that affect right ventricular preload, afterload or left ventricular function can adversely influence the functioning of the RV, causing ischaemia and right ventricular failure (RVF). As RVF progresses, a pronounced tricuspid regurgitation further decreases cardiac output and worsens organ congestion. This can degenerate into an irreversible vicious cycle.The effective diagnosis of RVF is optimally performed by a combination of techniques including echocardiography and catheterisation, which can also be used to monitor treatment efficacy. Treatment of RVF focuses on alleviating congestion, improving right ventricular contractility and right coronary artery perfusion and reducing right ventricular afterload. As part of the treatment, inhaled nitric oxide or prostacyclin effectively reduces afterload by vasodilating the pulmonary vasculature. Traditional positive inotropic drugs enhance contractility by increasing the intracellular calcium concentration and oxygen consumption of cardiac myocytes, while vasopressors such as norepinephrine increase arterial blood pressure, which improves cardiac perfusion but increases afterload. A new treatment, the calcium sensitiser, levosimendan, increases cardiac contractility without increasing myocardial oxygen demand, while preserving myocardial relaxation. Furthermore, it increases coronary perfusion and decreases afterload. Conversely, traditional treatments of circulatory failure, such as mechanical ventilation and volume loading, could be harmful in the case of RVF. This review outlines the pathophysiology, diagnosis and treatment of RVF, illustrated with clinical case studies.Electronic Supplementary Material Supplementary material is available in the online version of this article at