普拉西坦在动物体内的药物代谢动力学

为研究普拉西坦在犬和大鼠体内药代动力学规律,给犬灌服普拉西坦后,抽取不同时间的血液,分离血浆,用ＨＰＬＣ测定血浆中药物浓度,采用３ｐ８７ 程序计算药代参数;应用ＨＰＬＣ测定大鼠灌服普拉西坦后各组织和胆汁、尿、粪中药物浓度。结果显示：血药浓度－时间曲线符合一室开放模型,其体内的Ｔ１／２为２．３～３．９ 小时;大鼠灌服普拉西坦后３ 小时各组织中有较高的浓度,以肾脏为最高,肝脏次之,依序为肠、肺、肌、心、生殖腺、脾、脂肪;脑组织也能测到一定的量。２４小时从胆汁排泄原形药物占给药量的０．７％ ,７２小时从尿和粪中排出原形药物量分别占给药量的２８．２６％ 和６．３５％ 。用平衡透析法测定普拉西坦的血浆蛋白结合率约为２０．１％ ～２２．２％ 。以上结果表明,普拉西坦吸收快,分布广,消除也快。     

医院固定资产管理存在的问题及对策

目前,医院的固定资产管理中存在着：一是责权问题,即账物不清,产权不清,移交不清。二是工作制度问题,即账反映不真实、残值不入账、盘盈盘亏处理不当、盲目购置等。解决上述问题的策略：①做好产权的界定和登记;②建立有效的管理机构;③完善和实施各项固定资产管理的制度。     

Influence of age and of desmotropic drugs on the step phenomenon observed in rat skin

Summary Comprehensive analysis of the mechanical properties of rat skin revealed the step phenomenon. This particular observation was made after constant strain rate (analysis of stress strain curves) as well as after constant load (creep experiments). Relative low extensions or low loads were necessary to provoke the steps. In most cases two, sometimes three steps were observed. The step phenomenon was found mainly in skin strips punched out perpendicularly to the body axis. Probably some bonds in the fibrous network are broken giving way to additional elongation whereafter stronger links take over the stress. Since earlier studies demonstrated a pronounced influence of age and of desmotropic drugs on mechanical properties at ultimate load, e.g., tensile strength, ultimate modulus of elasticity, and ultimate strain, also the step phenomenon was studied under these conditions. In stress-strain experiments most of the steps were found at the ages of 2 and 4 months. Total stress loss and total work loss due to the steps were the highest at the age of 4 months. If, however, these values were calculated as percentage of ultimate values, the highest figures were found in young animals. Elongation gain due to the steps also showed a maximum at time of maturation, e.g., 4 months. Similar findings were achieved in creep experiments at medium load (200 g). After treatment with prednisolone acetate more steps and after treatment with d-penicillamine fewer steps were observed. In stress-strain experiments total stress loss and total work loss due to steps were more than twice as high than controls after prednisolone treatment and only one half after d-penicillamine. If calculated as percentage of ultimate stress or percentage of work input, these changes disappeared because of similar changes at ultimate load. However, elongation gain due to steps, which was not significantly influenced by prednisolone acetate but significantly decreased by d-penicillamine, showed the same changes when calculated as percentage of ultimate strain. Under all conditions the step phenomenon mainly influenced the extension parameters. The data presented here confirm earlier observations that mechanical properties at low loads or low and medium extensions show at least to some extent a different pattern under the influence of maturation and age and after treatment with desmotropic drugs compared to the mechanical parameters at ultimate load.     

Effect ofβ-adrenergic blockade on haemodynamic responses to dynamic and isometric exercise in angina pectoris

Summary The effect of treatment for 1–4 weeks with metoprolol, a ₁-selective blocking agent, or alprenolol, on the heart rate and blood pressure response to isometric exercise was studied in two groups of 12 patients with angina. Measurements were made during the peak effect of metoprolol 10, 40 or 50 mg, and alprenolol 200 mg as Aptin^® Durules^®. After 1 min of sustained handgrip at 50% of maximal voluntary contraction, systolic (6–15%) and diastolic (8–12%) blood pressure after both drugs was significantly lower than without any -blockade; Heart rate was decreased by 19–22% by metoprolol but not by alprenolol. The blood pressurerise during handgrip was not attenuated by either drug. The rise in heart rate was significantly reduced (by 36–50%) by metoprolol 40 and 50 mg and alprenolol 200 mg. No patient experienced angina during handgrip. In contrast, all but one were restricted by angina during bicycle exercise without treatment, at a level that produced the same increase in heart rate as the handgrip test, viz. 3 min at a load of 33 W). The cardiovascular response to sustained handgrip is too small to provide a useful challenge for determination of the anti-anginal efficacy of drugs. However, slight ECG changes of ischaemia did occur during handgrip, which were reversed by -blockade.     

非线性混合效应模型法估算癫(间)患者苯妥英群体药物动力学参数

目的 应用非线性混合效应模型法(NONMEM),估算癫癇患者苯妥英群体药物动力学参数,考察各因素对最大消除速率常数Vm(mg·d-1)及米氏常数Km(mg·L-1)的影响。方法 回顾性搜集56例门诊及住院癫癇患者服用苯妥英钠日剂量和血药浓度数据96对,并运行SAS程序进行计算。结果 患者的性别、年龄、体重、合并用药等对药物动力学参数均无显著性影响,Vm=(522.40±10.25)mg·d-1(513.14～630.63 mg·d-1),Km=(11.05±9.62)mg·L-1(1.90～34.83 mg·L-1)。血药浓度预测值与实测值相关性良好。结论 用非线性混合效应模型法估算癫癇患者苯妥英群体药物动力学参数方法可靠,值得推广。     

肱骨外髁的生物力学实验研究及其临床应用

目的 :从生物力学角度探讨肱骨外髁骨折的发生机制和固定方法。方法 :通过电测实验法、三维光弹实验法 ,空间有限元分析法 ,研究肱骨外髁在各种体位下的受力情况和复位固定方法 ,三种实验方法互为验证 ,并应用于临床。结果 :66例肱骨外髁翻转骨折病人 ,经治疗优良率达 90 .9%。结论 :肱骨外髁骨折好发于肘关节半屈曲位跌倒 ,和肘关节伸直内翻位跌倒。骨折复位后固定在屈肘 60°～ 90°前臂旋后位最为稳定。本实验结论具有推广应用价值。     

抗菌药物的药动学及药效学相关研究的临床意义

通过对抗菌药物的药动学(PK)、药效学(PD)的相关研究，发现了抗菌药物不同的PK/PD特性；提出了预测抗菌药物疗效的重要PD参数为AUC0-24/MIC，Cmax/MIC，t＞MIC和抗生素后效应(PAE)等；而且对评价药物有效性。指导合理用药，提高药物疗效，避免产生耐药性都有指导性的作用。因此，PK/PD研究是抗菌药合理应用的基础，在研究、设计和制定抗菌药物治疗方案、制定敏感性临界值以及推荐用药指南等方面都具有重要价值。     

卵巢上皮性癌BRCA1和p53基因表达的临床意义及相互关系研究

目的：探讨BRCA1、p53基因蛋白在卵巢上皮性癌中的表达情况及相互关系。方法：应用S-P免疫组织化学法检测50例卵巢上皮性癌组织中BRCA1和p53蛋白的表达。采用Kaplan—Meier法分析两种蛋白表达情况与患者预后的关系。结果：1)BRCA1蛋白在卵巢癌组织中的阳性表达率仅为30％，明显低于正常卵巢组织(100％)和良性肿瘤组织(90％)(P＜0．01)；BRCA1在低分化癌、有淋巴结转移的卵巢癌组织中表达减少甚至缺失。2)p53蛋白在卵巢癌组织中的表达率为64％，而在正常卵巢及良性肿瘤组织中无表达；其表达仅与病理学分级有关。3)两种基因蛋白表达比较呈显著负相关(P＜0．01)。4)患者生存随访表明，有BRCA1表达的患者平均生存期长于无表达者；而p53对生存时间无影响。结论：BRCA1基因在转录后水平的下调对卵巢上皮性癌的发生发展有重要的作用．同时BRCA1基因与p53基因协同促进肿瘤的演进恶化。     

糖尿病酮症酸中毒患儿氧化应激状况及影响因素分析

Objective To investigate the oxidative stress state in children with diabetic ketoacidosis (DKA),and analyze whether any observed abnormalities were related to metabolic disturbances.Methods Four groups of subjects were studied,comprising with 22 patients with DKA(group 1),18 diabetic children with medium metabolic control,whose glycated hemoglobin(HbAlc) below 9%(group 2),22 children with poorly controlled diabetes,whose Hbal c above 9%(group 3),and 36 healthy control children(group 4).Malondialdehyde(MDA),nitrate oxidase(NO),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and metabolic parameters such as fasting blood glucose,HbAlc,blood gas analysis,serum ion,renal function of the subjects were measured.Results Mean serum MDA value was significantly higher in group 1 than in group 2(P ＜0.01) and group 4(P ＜0.01),but was not different from that in group 3 (P ＞0.05).Serum levels of NO were significantly higher in group 1,2 and 3 compared with group 4(P＜0.01).Serum levels of GSH-Px were significantly lower in group 1,2 and 3 than in group 4(P＜0.01).There were no significant differences of serum SOD value among the four groups(P＞0.05).Both serum MDA and NO values in the diabetic patients(groups 1 +2 +3) were positively related to HbAlc(r=0.375,P ＜0.01;r=0.250,P ＜0.05),and serum SOD values in the DKA patients were negatively related to HbAlc(r= -0.507,P＜0.05),there were not any significant relationship between the other oxidative markers and metabolic parameters.Conclusion There is an increase of oxidative stress and decrease of antioxygenic ability in DKA children,and these changes tend to correlate more with markers of diabetic imbalance than with parameters of acute metabolic disturbances of DKA.