Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy)

Rufinamide, a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs (AEDs), is in development for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in children and adults. Rufinamide is well absorbed after oral administration, demonstrates low protein binding, and is metabolized by enzymatic hydrolysis without involvement of cytochrome P450 enzymes, conferring a low drug interaction potential. In a randomized, double-blind trial involving 138 adult and pediatric patients with LGS, compared with placebo, rufinamide 45 mg/kg/day resulted in significantly superior reductions in drop attacks (median change −42.5% vs +1.4% with placebo) and total seizures (−32.1% vs −11.7% with placebo), accompanied by significantly higher responder rates. These results are comparable with findings reported for other AEDs in randomized, controlled clinical trials in patients with LGS. Rufinamide produced statistically significant seizure reduction which was maintained during long-term therapy and accompanied by good tolerability. The most frequently reported adverse events from a pooled safety database evaluating short- and long-term therapy were headache (22.9% and 29.5%), dizziness (15.5% and 22.5%) and fatigue (13.6% and 17.7%). Rufinamide therefore presents a favorable efficacy and tolerability profile and is a promising candidate for the adjunctive therapy of LGS.     

[Ca^2＋]i change in hippocampal neurons influenced by preconditioning of etomidate fat emulsion following cerebral ischemia in rats

BACKGROUND: It is known that intravenous anesthetic etomidate fat emulsion has cerebral protection. Now many scholars focus on the research of its cerebral protection from molecular biology, but the mechanism of cerebral protection is still fully unclear. OBJECTIVE: To observe the influence of etomidate fat emulsion on the [Ca2+]i in hippocampal neurons during the transient cerebral ischemia injury in rats. DESIGN: Randomized controlled observation. SETTING: Weifang Medical College. MATERIALS: This study was carried out in the functional laboratory of Weifang Medical College between October 2005 and March 2006. Twenty-four male healthy Wistar rats, aged 3 to 4 months, were involved. Etomidate fat emulsion was provided by the limited company of En-hua Medical Bloc in Jiangsu Province (code of H20020511) and the other agents and materials were provided by Laboratory Center of Weifang Medical College. METHODS: The 24 Wistar rats were randomized into 3 groups: sham-operation group, model group and etomidate preconditioning group, with 8 rats in each. Rat models of transient cerebral ischemia injury were made by the ligation of bilateral carotid arteries combined with descending blood pressure in the latter two groups. Before ischemia (ligation of bilateral common carotid artery), rats in the etomidate preconditioning group were intraperitoneally injected with 12 mg/kg etomidate fat emulsion and then persistently intraperitoneally injected with etomidate fat emulsion at 1.0 mg/kg per minute. Rats in the model group were not administrated. Rats in the sham-operation group were only performed bilateral common carotid artery isolation. When rats were modeled, their brain tissues were quickly taken out and detected. MAIN OUTCOME MEASURES: Change of the fluorescence pixel value of the [Ca2+]i in each group by the laser scanning confocal microscope. RESULTS: Twenty-four rats were involved in the final analysis. Fluorescence pixel value in the sham-operation group was in the low level. Fluorescence pixel value in the model group was significantly higher than that in the sham-operation group (P < 0.01). Fluorescence pixel value in the etomidate preconditioning group was significantly lower than that in the model group (P < 0.01). CONCLUSION: The protection of etomidate fat emulsion to the transient cerebral ischemic injury in rats is associated with the inhibition to the increase of [Ca2+]i to some extent.     

不同充填材料应用于山羊经皮椎体成形术的组织学研究

目的:研究聚甲基丙烯酸甲酯(PMMA)、磷酸钙人工骨(CPC)和复合重组人骨形态发生蛋白-2的磷酸钙人工骨(rhBMP-2/CPC)在山羊骨质疏松症模型上行经皮椎体成形术(PVP)后的组织学表现。方法:6～8岁雌性山羊8只,均行双侧卵巢切除术,术后4个月建立骨质疏松症模型。在C形臂X线机监视下,随机选取8只山羊的L2-L6的两节椎体行PVP,分别充填PMMA、CPC和rhBMP-2/CPC,保证每只山羊的两节穿刺椎体的充填材料各不相同,术后4个月处死所有动物,取出椎体,组织学观察。结果:8只山羊16个椎体的PVP均成功,共出现4个椎体的渗漏。肉眼观察:PMMA与松质骨界限清晰,一个椎体取材时交界面出现破碎和脱落现象;而CPC和rhBMP-2/CPC与椎体内松质骨界限不清,互相融合生长。HE染色光镜观察:PMMA与骨小梁松散结合,界限明显,未见PMMA吸收和新生骨形成;CPC均匀分布于骨小梁和骨髓组织内,有CPC吸收现象,同时可见有新生软骨样团块形成,并有新生骨组织形成向其中心长入;rhBMP-2/CPC除了CPC的表现外,可见成骨活动活跃。结论:在组织学上,rhBMP-2/CPC和CPC均具有降解活性和骨传导活性,优于PMMA。rhBMP-2/CPC还具有诱导成骨活性,可能成为PVP中强化骨质疏松性椎体的首选充填材料。     

后程三维适形放疗治疗Ⅲ期非小细胞肺癌临床研究

OBJECTIVE: To evaluate the therapeutic efficacy and radiation complications of late course three-dimensional conformal radiotherapy (3DCRT) in patients with stage III non-small cell lung cancer (NSCLC). METHODS: Eighty-six patients with stage III NSCLC were randomly divided into group A (n=42) receiving conventional radiotherapy at the total dose of 66 to 70 Gy in 33 to 35 fractions completed in 6 to 7 weeks and group B (n=44) with late course 3DCRT at the dose of 24-30 Gy in 6 fractions (400-500 cGy per fraction every other day) after 40 Gy conventional radiotherapy, completed in 5 to 6 weeks. RESULTS: The efficacy rates in groups A and B were 55.0% and 82.9%, and the complete remission rates were 7.5% and 31.7% respectively, showing significant difference between the two groups (P<0.05). The 1- and 2-year survival rates of the patients in group A and B were 62.5% vs 78.0%, and 40.0% vs 53.7% respectively, without significant difference (P>0.05). The median survival time in groups A and B were 11.4 months and 19.8 months respectively. The major radiation complications observed in the two groups were grade I to II acute radiation esophagitis and hematopoietic toxicity. The later stage radiation complications in the two groups were grade I to II radiation lung fibrosis, occurring at a similar rate between the two groups. CONCLUSION: Late course 3DCRT produces better therapeutic effects than conventional radiotherapy in patients with stage III NSCLC.     

云南省600例0~5岁儿童维生素A缺乏调查

目的:了解云南省城乡0~5岁儿童维生素A营养状况及影响因素。方法:省、地、县随机整群抽取600例儿童,采用微量荧光光度法检测VitA含量。结果:VitA缺乏发生率16·17%,地、县明显高于省会城市;0岁儿童明显高于其他年龄组;腹泻儿童明显高于正常儿童;VitA缺乏的影响因素:近1周内进食鸡蛋、奶类制品、鱼虾类、肝类、黄绿色蔬菜、鱼肝油等食物有利于维生素A的吸收,急性呼吸道感染、发烧与维生素A缺乏发生率差异不明显。结论:维生素A缺乏发生率城市明显低于农村地、县两级,说明维生素A缺乏防治工作重点在农村,特别是0岁儿童,防治的主要措施是采取合理膳食,均衡营养,控制腹泻流行。