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We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
目的 探讨晕可宁颗粒的主要药效学 ,为临床提供药效学资料及治疗学基础。方法 采用三氯甲烷破坏豚鼠一侧膜迷路感受器模型 ,探讨受试药对眼震颤、摆头及旋转的影响 ;采用内淋巴囊和内淋巴管阻塞手术复制豚鼠膜迷路实验性膜迷路积水模型 ,研究内耳组织平均中阶面积 (SMA)增加率及形态学的变化。结果 抑眩宁阳性对照组、晕可宁颗粒 (8、16g/kg)模型给药组豚鼠眼球震颤次数减少 ,差异有显著意义 (P <0 .0 5 )。成功复制了不同程度膜迷路积水豚鼠模型 ,表现为前庭膜重度膨出 ,前庭阶缩小 ,膜蜗管增大 ,SMA增加率变大 ,差异有显著意义 (P <0 .0 1) ;晕可宁颗粒灌胃后可减轻豚鼠实验性膜迷路积水的程度 ,差异有显著意义 (P <0 .0 1) ;但与空白对照组比较SMA增加率差异无显著意义 (P >0 .0 5 )。结论 晕可宁颗粒可以减轻内淋巴囊积水程度 ,对梅尼埃病症状有对抗治疗作用。 相似文献
4.
毛细管电泳测定肝癌肝硬化患者血清氨基酸的临床意义 总被引:4,自引:0,他引:4
目的 用毛细管电泳的方法测定肝癌肝硬化患者血清氨基酸变化,并探讨其临床意义。方法 用P/ACEMDQ毛细管电泳仪对2 0例正常人、2 0例肝癌患者及2 0例肝硬化患者的血浆游离氨基酸进行测定。结果 在9min内分离12种氨基酸,线性在2 0~10 0 0 μmol/L范围,回收率为77. 5 %~113 .3% ,批内精密度2 . 6 %~11. 4 % ,批间精密度5 . 8%~19. 7%。对结果进行统计学分析,发现肝硬化组酪氨酸、丝氨酸、色氨酸明显升高,丙氨酸明显下降;肝癌组酪氨酸、半胱氨酸、缬氨酸明显升高,脯氨酸明显下降。结论 毛细管电泳测定血浆游离氨基酸对肝癌肝硬化的诊断和治疗有指导意义。 相似文献
5.
ADM对LNNA诱导的高血压心肌肥大的作用及机制探讨 总被引:1,自引:0,他引:1
本工作在LNNA经慢性NO封闭诱导的大鼠高血压心肌肥大模型上研究了ADM对其心肌肥大和M5LV钠一钙交换功能损伤的作用。结果:一、较之对照组,LNNA组MAO和LVI分别增加57.4%和18。0%(P<0.01).其MSLV经钠-钙交换蛋白的钙摄取则明显降低(P<0.01或0.05):二.ADM组的MAP和LVI则分别较LNNA组降低19.6%和11.3%,而其MSLV的钙摄取则高于LNNA组(P<0.05);三、对照组、LNNA组和ADM组钠-钙交换蛋白摄取钙的Km值分别为7.51.7.04和7.57uM,而Vmax则分别为6.38,4.32和5.45nmol/。mgpr/min。表明:ADM能拮抗LNNA诱导的高血压心肌肥大和减轻其MSllV钠-钙交换功能的损伤,并且后者可能是ADM拮抗心肌肥大的机制之一。揭示内源性ADM的诱导和外源性给予ADM可能有预防和/或延缓高血压心肌肥大发生发展的作用。 相似文献
6.
桂永浩 《中国超声医学杂志》1995,(12)
对20个16三体染色体异常小鼠胚胎进行了多普勒超声心动图研究。胎龄从10天至15天。9例发现流入道返流波型,6例发现流出道返流波型。120例染色体正常胚胎无一例发现返流波型。16三体小鼠模型作为先天性心脏病研究的理想模型,本文首次提供了对此类模型胚胎血液动力学研究的非创伤性监测方法。 相似文献
7.
Ching-Yuang Lin 《Pediatric nephrology (Berlin, Germany)》1988,2(2):224-228
Secondary IgG response to a tetanus toxoid booster and in vitro measurement of immunoglobulin synthesis, antibody-dependent cellular cytotoxicity (ADCC) and -interferon (IFN-) production were evaluated in 20 healthy controls and in 17 children with minimal change nephrotic syndrome (MCNS), during the acute nephrotic phase and 6 months after remission. Defective responses were observed in all but IFN- production during the acute nephrotic phase; these improved with disease remission. There was a significant correlation between decreases in vitro IgG production and ADCC reaction. These data indicate that defective antibody production is associated with decreased ADCC during the acute nephrotic phase of MCNS. 相似文献
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9.
N. Limberger E. A. Singer K. Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1988,338(1):62-67
Summary Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic 2-autoreceptors of effects mediated by presynaptic opioid - and adenosine A1-receptors requires activation of the 2-receptors. The slices were preincubated with 3H-noradrenaline and then superfused with medium containing desipramine 1 mol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz.The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca2+-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 mol/l or yohimbine 0.3 mol/l. Ethylketocyclazocine (EK; 0.1–10 nmol/l) and R-(–)-N6-phenylisopropyladenosine (PIA; 1–1,000 nmol/1) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. — The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 mol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca2+ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine.The results demonstrate that there is no 2-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic 2-adrenoceptor does not interfere with presynaptic opioid - and adenosine A1-receptor mechanisms. It is only when the autoreceptor is activated by released noradrenaline that it attenuates neighbouring presynaptic receptor mechanisms, and this attenuation is removed by 2-adrenoceptor antagonists.Send offprint requests to N. Limberger at the above address 相似文献
10.
The ability of thiols to reduce 3-azidothymidine (AZT) to 3-aminothymidine has been investigated. Incubation with glutathione, dithiothreitol (DTT), or mercaptoethanol at pH 7.2 and 37°C leads to quantitative reduction of the azido moiety to an amine. The reaction is first order in AZT and first order in reducing agent (mono- or dithiol). The second-order rate constants are 2.77 × 10–3, 6.55 × 10–5, and 6.35 × 10–6
M
–l sec–1 for the dithiothreitol, glutathione, and mercaptoethanol reductions, respectively. The thiol reduction of alkyl azide to amine under mild conditions is a synthetic method particularly suitable for water-soluble azido compounds that are sensitive to catalytic hydrogenation. The potential for the mono- or dithiol-mediated reduction of alkyl azides under biological conditions must be considered when conducting studies of azido drugs. 相似文献