Menogaril in the treatment of malignant mesothelioma: A phase II study

Summary Menogaril is a new semisynthetic anthracycline agent derived from the antitumor antibiotic Nogalomycin. Compared to doxorubicin it has similar or improved activity in anti-tumor cell line screening; human tumor cloning assays suggest modest anti-tumor activity as well. Menogaril is much less cardiotoxic than doxorubicin. We performed a phase II trial of this agent in 22 patients with advanced malignant mesothelioma. At a dose of 200 mg/m² iv every 4 weeks (160 mg/m² in previously radiated patients) only 1 of 22 (5%) evaluable patients had a partial remission lasting 4 months. (95% confidence limits 0.1–23%). The major toxic effects included pain at the site of infusion and granulocytopenia. While well tolerated, Menogaril has minimal activity in malignant mesothelioma. We do not plan further studies with Menogaril in this disease.     

液相色谱测定隐形眼镜保护药水中EDTA二钠和山梨酸钾的含量

采用反相高效液相色谱法,以0.02mol/L硼砂为流动相,YNG C_(16)H_(37),为固定相,检测波长288nm,测定隐形眼镜保护药水中EDTA二钠和山梨酸钾的含量。简便快速,结果准确可靠。回收率100.26％(EDTA)、100.36％(山梨酸钾)。相对标准偏差0.85％(EDTA)、0.41％(山梨酸钾)。     

Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A.

BACKGROUND: Major depressive disorder (MDD) shows increased coronary artery disease (CAD) risk of unknown mechanism(s). MDD is more common in women than men; CAD diagnosis can be difficult in women. Elevations of the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in populations; few data on these markers exist in MDD, particularly in remitted patients. METHODS: We measured fasting am serum CRP (high sensitivity, CRP(hs)) and SAA in 18 unmedicated, remitted women with MDD (mean age 41 +/- (SD)12, body mass index (BMI) 25.2 +/- 4.1 kg/m(2)) and 18 BMI-matched healthy control subjects (age 36 +/- 10, BMI 25.3 +/- 3.8 kg/m(2)) on 2 separate occasions, > or = 6 days apart. RESULTS: Repeat SAA and CRP(hs) measurements strongly correlated across study days (SAA: r = .83, p < .001; CRP(hs): r = .94, p < .001). Both SAA (5.30 +/- 3.39 vs. 2.84 +/- 1.87 mg/L, p < .005) and CRP(hs) (3.23 +/- 3.17 vs. 1.12 +/- 1.45 mg/L; p < .01) were significantly elevated in MDD women versus controls. CONCLUSIONS: Elevated SAA and CRP(hs) in remitted, unmedicated women with MDD indicate a pro-inflammatory state unrelated to current depressive symptoms or pharmacotherapy. These findings suggest that inflammatory mechanisms may in part underlie findings of increased CAD risk in MDD.     

Adaptive group sequential design for phase II clinical trials: A Bayesian decision theoretic approach

Bayesian decision theoretic approaches (BDTAs) have been widely studied in the literature as tools for designing and conducting phase II clinical trials. However, full Bayesian approaches that consider multiple endpoints are lacking. Since the monitoring of toxicity is a major goal of phase II trials, we propose an adaptive group sequential design using a BDTA, which characterizes efficacy and toxicity as correlated bivariate binary endpoints. We allow trade‐off between the two endpoints. Interim evaluations are conducted group sequentially, but the number of interim looks and the size of each group are chosen adaptively based on current observations. We utilize a loss function consisting of two components: the loss associated with accruing, treating, and monitoring patients, and the loss associated with making incorrect decisions. The performance of our Bayesian modeling, and the operating characteristics of decision rules under a wide range of loss function parameters are evaluated using seven scenarios in a simulation study. Our method is illustrated in the context of a single‐arm phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma. Copyright © 2009 John Wiley & Sons, Ltd.     

反相高效液相色谱-柱后衍生法分析检测鱿鱼中的生物胺

建立了水产品中多组分生物胺的反相高效液相色谱-柱后衍生-荧光检测方法。采用荧光试剂邻苯二甲醛（OPA）为柱后衍生化试剂,在Capcell Pak MG-C18色谱柱上,通过梯度洗脱使酪胺、腐胺、尸胺、组胺、胍丁胺、精胺和亚精胺等7种生物胺得到良好分离,在给定的浓度范围内,各组分生物胺呈现良好线性相关（R^2〉0.999）。在水产品中添加生物胺混合标准溶液,平均回收率为88.3%～110.1%,相对标准偏差RSD小于10%。结合水产品的感官鉴定、pH值和TVBN值测定等方法检测水产食品的新鲜程度,分析了鱿鱼在不同保藏温度、保藏时间下的生物胺种类及含量的变化。其中胍丁胺和尸胺在鱿鱼的保藏过程中发生最显著变化,可以作为其质量变化的参考指标。     

美罗培南在家兔胆汁中的药物浓度-时间分布的实验研究

目的研究美罗培南在家兔胆汁中的浓度及其分布规律,为预防和治疗胆道感染用药提供参考和依据。方法家兔行胆总管造瘘术,先留取空白胆汁,静脉注射美罗培南后分别于不同时间点采集胆汁标本。行专属性试验后,取空白胆汁加美罗培南对照品和流动相,配成0.5~500μg/ml不同浓度的系列胆汁样品,经高效液相色谱仪分析,采用外标法行药物色谱峰面积定量,以胆汁样品药物浓度对色谱峰面积进行线性回归,得回归方程。注射美罗培南后的家兔胆汁样品经预处理后用高效液相色谱仪测定峰面积,按标准曲线回归方程计算得出胆汁药物浓度,从而了解美罗培南的胆汁药物浓度-时间分布情况。结果专属性试验显示,在本研究的流动相色谱条件下测定药物,胆汁杂质峰、美罗培南药物色谱峰分离效果良好。标准曲线回归方程为S=2209.10C-1251.34,r=0.9999,美罗培南的最低定量限为0.5μg/ml。家兔静脉注射美罗培南(75mg/kg)后即时在胆汁中达(38.36±14.17)μg/ml,远远超过其对革兰阴性杆菌的最小抑菌浓度(MIC90)0.031~2μg/ml,之后美罗培南的胆汁药物浓度随时间而迅速降低。用药后180min,胆汁中的药物均被完全消除。结论美罗培南在胆汁中能达到较高的有效杀菌浓度,可作为预防和治疗胆道感染的较佳的药物。由于消除速度较快,临床用药应缩短间隔时间。     

Phase-sensitive cardiac tagging--REALTAG.

Fully inverting spins, instead of merely saturating them, provides superior contrast for tagging procedures. The resulting improvement in tag contrast-to-noise ratio (CNR) yields higher-precision tag detection. Also, thinner slices and hence reduced tag separations can be employed, providing displacement and strain measurements with better spatial resolution. Alternatively, the improved tag contrast can be used to obtain cine images covering a greater portion of the cardiac cycle. The use of standard magnitude reconstruction for images of these inversion tags causes rectification of the negative-valued signals from the tags, confounding the image interpretation. Therefore, a phase-sensitive reconstruction scheme of the inverted tags must be employed. Here we demonstrate the implementation of inverted tags with phase-sensitive reconstruction in a ramped-flip-angle, steady-state free precession (SSFP) sequence.     

Adiabatic refocusing pulses for volume selection in magnetic resonance spectroscopic imaging.

Because of their excellent slice profiles and high immunity to RF inhomogeneity, adiabatic full passage (AFP) pulses are ideal for use in spatial localization. The nonlinear, position-dependent phase of a single AFP pulse generated during refocusing of transverse magnetization traditionally is eliminated by using identical pairs of AFP pulses, at the expense of increased RF power deposition and increased echo time (TE). Here it is shown that one can achieve significant phase refocusing by executing single AFP pulses along non-equivalent spatial axes. When used for volume selection in MR spectroscopic imaging (MRSI) the remaining nonlinear phase becomes inconsequential when the phase across a spectroscopic volume is small. Selection of rectangular and octagonal volumes is demonstrated with half the number of AFP pulses used in the traditional approach. It is shown that octagonal volume selection in the human brain provides excellent suppression of extracranial lipids, and thus allows multislice (1)H MRSI at 4 Tesla to be performed within the guidelines for RF power deposition.     

Clinical influence of vagotomy on postoperative acute phase response

BACKGROUND: Although there is increasing evidence suggesting that the vagus nerve functions as a connector between the nervous and immune systems in animals, little is known about the role of the vagus nerve in postoperative acute phase response in humans. MATERIALS AND METHODS: The extent of fever and acute phase protein response and the production of inflammatory cytokine during the early postoperative period were compared among the patients who had undergone total gastrectomy including truncal vagotomy (n = 13), those having distal gastrectomy with division of vagal branches (n = 14), and the patients with vagal nerve preserving gastrectomy (n = 12). RESULTS: There was no significant difference in serum levels of C-reactive protein, alpha-1-antirypsin, and interleukin-6 among the three groups. Also, postoperative maximum body temperature was similar. CONCLUSIONS: Vagotomy did not influence acute phase response after gastric cancer surgery. A multipathway mechanism for acute phase response including the induction of fever is suggested.