Site-specific biotinylation

We have developed an expeditious method for the incorporation of the biotinylaminocaproyl moiety on the ε-amino group of a lysine residue within a peptide chain in a site-specific manner. Using t-Boc chemistry for the solid phase synthesis approach and a base labile, acid stable protecting group (Fmoc-) for the ε-amino group of the target lysine, we prepared fully protected resin bound peptides which are site-specifically biotinylated. Following HF cleavage, the uniquely biotinylated peptides were obtained in a high degree of purity. Using this approach, a number of biotinylaminocaproyllysyl derivatives of a monocyclic Endothelin-1 analog were prepared. Synthesis of selected bicyclic analogs of high affinity monocycles led to the preparation of the bicyclic [Nle⁷]ET-1 analog containing ε-biotinylaminocaproyllysine at position-9. This peptide, with K_d= 0.08 nM, has 1000-fold higher affinity for the ET_A receptor than the commercially available N_α-biotinylated Endothelin-1. The general utility of this biotinylation methodology was demonstrated by the synthesis of a site-specifically biotinylated PTH analog which contained several side chain functionalized amino acid residues in its sequence. The synthetic method reported here is convergent in that it allows the facile variation of the length of the spacer and also offers the potential to introduce in a site specific manner other groups such as affinity labels and fluorescent tags.     

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.     

双相情感障碍混合相临床特征对照研究

目的:了解双相情感障碍混合相的临床特征。方法:收集42例双相情感障碍混合相患者(混合组)与93例无混合发作的双相情感障碍躁狂相的患者(躁狂组)住院治疗的临床资料进行对比。结果:混合组年龄稍低,多见于女性和独身者,性格多为外向型或中间型,首次发作多为抑郁,多伴有精神病性症状及自杀意念和企图。多元逐步回归分析提示,混合发作与自杀意念和企图、性格、性别、首次发作形式有显著的相关性。混合组具有易被误诊、住院时间长、疗效较差的特点。结论:双相情感障碍混合相临床表现具有特殊性、严重性及相应的难治性,应加强重视。     

科素亚与洛汀新治疗Ⅳ期糖尿病肾病蛋白尿的疗效比较

目的比较ARB类与ACEI类减少Ⅳ期糖尿病肾病尿蛋白的疗效。方法100例糖尿病肾病Ⅳ期患者随机分为2组,分别应用科素亚、洛汀新治疗8周,检测并对比实验前后24 h尿蛋白总量。结果科素亚与洛汀新对降低Ⅳ期糖尿病肾病患者尿蛋白量的效果相似。结论ARB与ACEI类药物减少Ⅳ期糖尿病肾病患者尿蛋白量的疗效无差异。     

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.     

二至天癸颗粒对黄体功能不健性不孕症患者子宫内膜容受性的影响

目的 探讨二至天癸颗粒对黄体功能不健所致不孕症患者的治疗作用及机理.方法 将60例黄体功能不健性不孕症患者随机分为二至天癸颗粒组(试验组)30例和六味地黄颗粒组(对照组)30例,观察两组治疗后中医证候改善情况,黄体中期血清雌二醇(E2)、孕酮(P)水平,黄体中期子宫内膜白血病抑制因子(LIF)表达,以及两组患者的妊娠率.结果 治疗后试验组患者中医证候改善程度优于对照组(P<0.05).试验组黄体中期血清P水平及子宫内膜LIF表达量均明显高于对照组(P<0.05);两组血清E2虽较治疗前有所降低,但差异均无统计学意义(P>0.05).试验组妊娠率亦高于对照组(P<0.05).结论 二至天癸颗粒治疗黄体功能不健性不孕症可能与其提高子宫内膜LIF的表达从而影响子宫内膜容受性有关.     

加味五味消毒饮对鼻窦炎手术后疗效观察

目的:观察加味五味消毒饮冲洗液鼻腔冲洗对慢性鼻窦炎鼻内镜手术(FESS)术后的临床疗效及黏膜修复的影响.方法:对60例Ⅱ型慢性鼻窦炎患者,在鼻内镜手术后,治疗组用自拟加味五味消毒饮冲洗液冲洗术腔,对照组以常规的西药冲洗液冲洗术腔,随访6个月,比较两组的疗效.结果:治疗组的治愈率、总有效率分别与对照组比较,差异均有统计学意义(P＜0.05).且治疗组鼻腔修复时间明显短于对照组,提前结束治疗病例数有明显差异(P＜0.05).结论:中药配方加味五味消毒饮冲洗液进行鼻腔冲洗,能缩短鼻黏膜修复时间,提高临床疗效.     

氟比洛芬酯用于抑制神经外科气管拔管期不良反应的观察

目的探讨氟比洛芬酯用于抑制神经外科术后气管拔管期不良反应的有效性和可行性。方法ASAⅠ～Ⅱ级神经外科手术患者56例,随机分为观察组（氟比洛芬酯组）和对照组,2组分别在停用麻醉药前30min静注氟比洛芬酯注射液1.5mg/kg和加生理盐水5ml。在围拔管期观察并记录血压、心率、血氧饱和度、拔管时间、呼唤睁眼时间、躁动呛咳发生情况以及Ramsay镇静评分、VAS疼痛程度评分。结果围拔管期观察组的血压、心率均明显低于对照组,躁动和呛咳发生例数少,清醒度镇痛度明显优于对照组（P〈0.05）。结论氟比洛芬酯用于神经外科围拔管期可减轻气管拔管期不良反应,同时可产生良好的镇痛作用并维持满意的镇静度。