复方黄黛片诱导治疗急性早幼粒细胞白血病193例疗效分析

目的 总结复方黄黛片诱导治疗193例急性早幼粒细胞白血病(APL)患者的疗效与不良反应.方法 复方黄黛片1.25 g,每日3次,饭后服;3 d后逐渐增量至7.5 g/d.结果 193例患者均获完全缓解(CR),其中78.8%的患者在用药44.3(31～60)d后获CR;疗程中未出现严重的感染、出血,不诱发与加重DIC.治疗中的主要不良反应是胃肠道症状.110例患者治疗前后的丙氨酸转氨酶、尿素、肌酐、心电图的QTc间期等指标变化不大.结论 复方黄黛片治疗APL具有CR率高,不抑制骨髓,不诱发与加重DIC,使用安全,患者耐受性好等特点.     

含碘清洗消毒剂的研究

试验表明，以有效碘浓度为２５０ｍｇ／Ｌ的含碘清洗消毒剂溶液作用１０分钟，可将大肠杆菌与金黄色葡萄球菌杀灭９９．９％以上。该清洗消毒剂无毒，无刺激，对铝有轻度腐蚀，除油效果与洗洁精相似．     

L-ASP治疗儿童急性淋巴细胞白血病副作用观察（附171例临床报告）

目的:探讨左旋门冬酰胺酶(L-asparaginase,L-ASP)在儿童急性淋巴细胞白血病联合化疗时的严重毒副作用及与临床分型和各化疗阶段的关系,以便针对性地进行预防。方法:对171例儿童急性淋巴细胞白血病(AcuteLymphoblasticLeukemia,ALL)应用左旋门冬酰胺酶后的临床表现、血液生化检查进行分析。结果:171例中发生副作用26例(15·2%),其中凝血功能异常9例(5·3%),急性过敏反应6例(3·5%),胰腺损害5例(2·3%),低蛋白血症3例(1·8%),肝功能损害3例(1·8%)。用确切概率法及X2检验对这几种副作用发生率与临床分型关系进行统计,结果P均大于0·05,无统计学意义。化疗不同阶段副作用的发生率比较,早期强化阶段占优势。结论:L-ASP引起的副作用与临床分型无关,可能与化疗不同阶段有关,主要发生在早期强化阶段。用药前及期间、之后要定期测血糖、尿糖、血尿淀粉酶、肝功和及时对症治疗,并加强饮食控制,能有效控制副作用严重程度,并防止糖尿病等某些毒副作用的发生。     

二氧化氯消毒剂的亚急性毒性试验

目的研究二氧化氯消毒剂亚急性毒性,作出生物安全性评价。方法采用动物试验法进行了实验室试验观察。结果该二氧化氯消毒剂给药量在117 mg/kg(体重)条件下,对大鼠的体重、血常规及血液生物化学等指标无异常变化,与阴性对照组比较均无显著差异(P>0.05)。病理检查发现,高剂量组个别动物肺脏切片可观察到少数组织轻度充血改变,但无组间特异性分布,同样的变化在对照组动物中也能观察到,其它脏器均无异常变化。结论二氧化氯消毒剂亚急性毒性试验组动物观察指标基本正常,少部分组织有异常变化,主要考虑为动物质量问题。因此,该消毒剂在本次实验条件下,未显示有亚急性毒性作用。     

Dose-dependent Hemodynamic Effect of Digoxin Therapy in Severe Verapamil Toxicity

Calcium chloride (CaCl(2)) alone is an ineffective antidote in severe calcium channel antagonist overdoses. Digoxin has been evaluated as a therapy to increase the effectiveness of calcium in severe calcium channel antagonist overdoses. OBJECTIVE: To determine if there is a dose-dependent hemodynamic effect of digoxin in the setting of severe verapamil toxicity treated with high-dose CaCl(2). METHODS: Eight dogs were instrumented to measure systolic and diastolic blood pressure, cardiac output, pulmonary artery pressures, and left ventricular pressures. Verapamil toxicity (50% decrease in mean arterial pressure) was induced with verapamil 6 mg/kg/hr and maintained for 30 minutes by titrating the verapamil rate. Following verapamil toxicity, each dog received one dose of digoxin equivalent to 0, 1, 1.5, 2, 3, 4, 6, or 8 times the loading dose of digoxin (0.009 mg/kg). The verapamil rate was changed to 4 mg/kg/hr and continued for the next five hours. CaCl(2) boluses were given (0.5 g immediately following verapamil toxicity and 1 g at one, two, and three hours). Measurements were compared with the loading dose of digoxin using linear regression analysis. RESULTS: Digoxin resulted in a dose-dependent increase in systolic blood pressure at 4 hours (10.23 mm Hg/loading dose of digoxin, 95% CI = 2.74 to 17.73), 4 hours, 15 minutes (13.9 mm Hg/loading dose of digoxin, 95% CI = 8.75 to 19.01), and 5 hours (17.04 mm Hg/loading dose of digoxin, 95% CI = 1.76 to 32.32). Digoxin resulted in a dose-dependent increase in maximal ventricular pressure at the end of hour 3 (8.55 mm Hg/loading dose of digoxin, 95% CI = 3.41 to 13.69), 3 hours, 15 minutes (11.81 mm Hg/loading dose of digoxin, 95% CI = 4.89 to 18.73), hour 4 (8.26 mm Hg/loading dose of digoxin, 95% CI = 1.03 to 15.48), and 4 hours, 15 minutes (9.74 mm Hg/loading dose of digoxin, 95% CI = 4.47 to 15.00). The authors were unable to detect a dose-dependent increase in other parameters, including diastolic relaxation (diastolic change in pressure over time) and time to onset of death. No ventricular arrhythmias developed in any dogs. CONCLUSIONS: There is a dose-dependent effect of digoxin on systolic blood pressure and maximal ventricular pressure in the setting of severe verapamil toxicity treated with high-dose CaCl(2).     

苯对尾悬吊大鼠血细胞及脂质过氧化的影响

目的:探讨苯吸入染毒对尾吊模拟失重大鼠血液系统、脂质过氧化水平及抗氧化酶的影响.方法:将20只雄性SD大鼠随机分为2组:对照组和染毒组.对照组吸入新鲜空气,染毒组吸入10 mg/m3的苯气体,每天24 h,连续7 d.结果:与对照组相比,染毒组中白细胞(WBC)显著低于对照组(P＜0.05);血红蛋白(HGB)显著低于对照组(P＜0.05);淋巴细胞(LYM)极显著低于对照组(P＜0.01);嗜碱性粒细胞(BAS)显著高于对照组(P＜0.05);T淋巴细胞亚群分类:CD4极显著降低(P＜0.01)、CD8极显著升高(P＜0.01).染毒组中血清超氧化物歧化酶SOD活力极显著低于对照组(P＜0.01);血清谷胱甘肽过氧化酶GSH-PX活力极显著高于对照组(P＜0.01).结论:苯吸入染毒7 d可导致尾吊SD大鼠血液学指标的改变,表现为WBC降低,HGB降低,淋巴细胞(LYM)降低,BAS升高;HGB明显降低,RDW明显升高.脂质过氧化及抗氧化酶指标的改变,表现为SOD活力降低和GSH-PX活力升高.     

Effects of 4-Methylpyrazole on Ethanol Neurobehavioral Toxicity in CD-1 Mice

OBJECTIVES: 4-Methylpyrazole (4-MP), an alcohol dehydrogenase (ADH) antagonist, is used for the treatment of ethylene glycol and methanol ingestions. However, ethanol is frequently co-ingested by those who ingest these more toxic alcohols. Several in vitro and in vivo studies have shown a decrease in the elimination rate of ethanol after the administration of 4-MP, but none has evaluated the effects of 4-MP administration on the neurobehavioral toxicity of ethanol. This was a study to determine whether ADH blockade with 4-MP prolongs ethanol neurobehavioral toxicity in a murine model. METHODS: D-1 mice were pretreated with 4-MP, with observation of its effect on ethanol dose-response curves. 4-MP (25 mg/kg) or an equal volume of saline was administered intraperitoneally. Ten minutes later, incremental ethanol doses of 1-5 g/kg were administered intraperitoneally. Pretreated and control groups were composed of ten mice each for each dose of ethanol tested. Outcomes for assessing ethanol neurobehavioral toxicity were successful performance on the rotarod test and presence of the righting reflex, two established and validated outcome measures for ethanol-induced neurobehavioral toxicity in mice. RESULTS: The dose of ethanol at which 50% of the animals failed a particular outcome test (toxic dose 50 [TD(50)]) was decreased with 4-MP administration for both the rotarod test and the righting reflex. The TD(50) intergroup differences (control vs. 4-MP) were statistically significant at 60, 120, and 180 minutes (p < 0.05). CONCLUSIONS: Pretreatment with 4-MP significantly prolonged ethanol neurobehavioral toxicity in CD-1 mice, presumably by inhibiting its metabolism by ADH. Further investigation is warranted to evaluate this interaction.     

生血胶囊的毒理学研究

目的本研究观察小鼠和大鼠口服生血胶囊的急性毒性和长期毒性反应,为临床用药提供参考。方法取健康小鼠和大鼠各30只,灌胃给药,2次/d,每次剂量分别为24和16 g/kg,给药后观察14 d,记录动物死亡及不良反应症状,取健康SD大鼠160只,随机分为低、中、高(0.5、2.5、5.0 g/kg)3个剂量组和一个对照组。灌胃,2次/d,每次10 ml/kg,连续26周。用药13周、26周和停药4周后分别取样进行血液学、血液生化学、脏器重量及重量指数,病理组织学检查。结果生血胶囊对小鼠和大鼠的口服最大给药量分别大于24和16 g/kg,该剂量是临床成人拟推荐用药剂量(0.08 g/kg)的240和160倍;长期毒性实验中各组大鼠的一般状况、体质量、血液学指标、血液生化学指标及主要脏器系数与对照组比较未见显著差异和异常改变;肉眼观察服药组心、肝、脾、肺、肾等脏器外观形态、颜色均无异常改变,光镜检查也未见各脏器组织结构和细胞形态异常。结论在推荐临床剂量下服用生血胶囊是安全可靠的。     

Risk Factors for Voriconazole Hepatotoxicity at 12 Weeks in Lung Transplant Recipients

Voriconazole is commonly used for prophylaxis and treatment of invasive aspergillosis in lung transplant recipients. However, the use of voriconazole may at times be limited by the development of hepatotoxicity. Our goal is to determine predictors of voriconazole‐associated hepatotoxicity in lung transplant recipients. We conducted a single center retrospective cohort study of lung transplant recipients from 2006 to 2010 who received voriconazole therapy. We compared characteristics of patients who developed hepatotoxicity and those who did not. One hundred five lung transplant recipients received voriconazole. Hepatotoxicity occurred in 51% (54/105) of patients and lead to discontinuation in 34% (36/105). In univariate analysis, age less than 40 years, cystic fibrosis, use of azathioprine, history of liver disease and early initiation of voriconazole were associated with hepatotoxicity. In multivariable logistic regression analysis, perioperative initiation of voriconazole (within 30 days of transplantation) was independently associated with hepatotoxicity (OR 4.37, 95% CI: 1.53–12.43, p = 0.006). The five risk factors identified in the univariate analysis were used to build a K‐nearest neighbor algorithm predictive model for hepatotoxicity. This model predicted hepatotoxicity with an accuracy of 70%. Voriconazole therapy initiated within the first 30 days of transplantation is associated with a greater risk of developing hepatotoxicity.     

Resuscitation strategies from bupivacaine-induced cardiac arrest

Objectives: Local anesthetic (LA) intoxication with cardiovascular arrest is a potential fatal complication of regional anesthesia. Lipid resuscitation has been recommended for the treatment of LA‐induced cardiac arrest. Aim of the study was to compare four different rescue regimens using epinephrine and/or lipid emulsion and vasopressin to treat cardiac arrest caused by bupivacaine intoxication. Methods: Twenty‐eight piglets were randomized into four groups (4 × 7), anesthetized with sevoflurane, intubated, and ventilated. Bupivacaine was infused with a syringe driver via central venous catheter at a rate of 1 mg·kg^?1·min^?1 until circulatory arrest. Bupivacaine infusion and sevoflurane were then stopped, chest compression was started, and the pigs were ventilated with 100% oxygen. After 1 min, epinephrine 10 μg·kg^?1 (group 1), Intralipid^® 20% 4 ml·kg^?1 (group 2), epinephrine 10 μg·kg^?1 + Intralipid^® 4 ml·kg^?1 (group 3) or 2 IU vasopressin + Intralipid^® 4 ml·kg^?1 (group 4) were administered. Secondary epinephrine doses were given after 5 min if required. Results: Survival was 71%, 29%, 86%, and 57% in groups 1, 2, 3, and 4. Return of spontaneous circulation was regained only by initial administration of epinephrine alone or in combination with Intralipid^®. Piglets receiving the combination therapy survived without further epinephrine support. In contrast, in groups 2 and 4, return of spontaneous circulation was only achieved after secondary epinephrine rescue. Conclusions: In cardiac arrest caused by bupivacaine intoxication, first‐line rescue with epinephrine and epinephrine + Intralipid^® was more effective with regard to survival than Intralipid^® alone and vasopressin + Intralipid^® in this pig model.