多源耐药基因表达水平的检测在儿童白血病中的临床意义

应用逆转录ＰＣＲ结合同位素定量分析，对３２例儿童白血病患者的多源耐药基因表达水平进行了研究。结果显示，初发病人的表达均较低，复发病人表达较高，缓解期病人表达程度介于两者之间，为探讨多源耐药基因表达水平与临床化疗之间的相关性及逆转克服多源耐药性药物的应用，提供了一定的理论依据。     

泌尿系感染病原菌的变迁及耐药性分析

目的了解近年来泌尿系感染病原菌的变迁及耐药现状. 方法应用回顾性调查分析方法,对我院1997至2000年间泌尿系感染检测的1 026株病原菌的分布及耐药性进行统计分析. 结果在泌尿系感染的病原菌中,G+球菌上升,G-杆菌下降,真菌上升,其中粪肠球菌上升和变形菌属下降差异有显著性(P<0.05),药敏实验结果对以往常用的抗菌药物青霉素类、复方新诺明、红霉素、诺氟沙星及一代头孢显示较高的耐药性,2000年耐药率>81.6%,对三代头孢、环丙沙星、庆大霉素呈中度耐药,耐药率在42.9%～78.3%,对阿米卡星及头孢哌酮/舒巴坦呈轻度耐药,耐药率<36.7%. 结论随着抗生素的更新换代、人口老龄化及医院感染等因素的变化,泌尿系感染病原菌的分布及耐药性均发生了变迁.     

甲状腺功能亢进症患儿合并糖代谢紊乱10例临床分析

目的：探讨儿童甲亢患者糖代谢紊乱的特点。方法：用SUPER GLUCOCARD^TM血糖仪和放射免疫方法检测29例甲亢患儿餐前、餐后60min、120min血糖和餐前、餐后60min胰岛素、C肽、胰高糖素、皮质醇及T3、T4、TSH、TGA、TMA（其中10例糖耐量减低为甲亢1组，另19例糖耐量正常为甲亢2组），并与20例健康儿童进行比较。结果：（1）34．5％甲亢患儿出现糖代谢紊乱，病程大于1年和小于1年糖代谢紊乱发生率为50％，9％（P＜0．05）。（2）甲亢1组餐后60min胰岛素、胰岛素／血糖、胰岛素／胰高糖素显著升高（P＜0．05）。结论：甲亢儿童存在糖代谢紊乱现象，表现为葡萄糖耐量减低和胰岛素拮抗，其发生与病程有关，病程较长，发生率较高。糖代谢紊乱可能与自身免疫、胰岛β细胞功能受损及胰岛素拮抗有关。     

Cough and converting enzyme inhibitors

Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3–7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents.     

Hyperglycaemia compensates for the defects in insulin-mediated glucose metabolism and in the activation of glycogen synthase in the skeletal muscle of patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Insulin resistance and a defective insulin activation of the enzyme glycogen synthase in skeletal muscle during euglycaemia may have important pathophysiological implications in Type 2 (non-insulin-dependent) diabetes mellitus. Hyperglycaemia may serve to compensate for these defects in Type 2 diabetes by increasing glucose disposal through a mass action effect. In the present study, rates of whole-body glucose oxidation and glucose storage were measured during fasting hyperglycaemia and isoglycaemic insulin infusion (40 mU·m^–2min^–1, 3 h) in 12 patients with Type 2 diabetes. Eleven control subjects were studied during euglycaemia. Biopsies were taken from the vastus lateralis muscle. Fasting and insulin-stimulated glucose oxidation, glucose storage and muscle glycogen synthase activation were all fully compensated (normalized) during hyperglycaemia in the diabetic patients. The insulin-stimulated increase in muscle glycogen content was the same in the diabetic patients and in the control subjects. Besides hyperglycaemia, the diabetic patients had elevated muscle free glucose and glucose 6-phosphate concentrations. A positive correlation was demonstrated between intracellular free glucose concentration and muscle glycogen synthase fractional velocity insulin activation (0.1 mmol/l glucose 6-phosphate: r=0.65, p<0.02 and 0.0 mmol/l glucose 6-phosphate: r= 0.91, p<0.0001). In conclusion, this study indicates an important role for hyperglycaemia and elevated muscle free glucose and glucose 6-phosphate concentrations in compensating (normalizing) intracellular glucose metabolism and skeletal muscle glycogen synthase activation in Type 2 diabetes.     

甲氟哌酸体外抗菌活性及对耐药感染者的治疗

对天津市新近临床分离的414株细菌进行了甲氟哌酸(Pflx)和氟哌酸(Nflx)体外抗菌活性研究。结果显示Pflx对绝大多数肠杆菌和细菌、不动杆菌有良好抗菌活性,抑菌率>90％。对绿脓杆菌、MSSA及凝固酶阴性葡萄球菌有中度抗菌作用,抑菌率分别为85％、87.5％、87.5％。对MRSA和链球菌抗菌活性稍差,抑菌率在40％～68.42％之间。Nflx体外抗菌活性和Pflx相似。此外,18例药敏试验耐Pflx和Nflx细菌感染患者,经Pflx治疗,肺化脓症1例显效,余17例难治性尿路感染者1例痊愈、9例显效、5例进步、2例无效。     

Olfactory Absorption of Insulin to the Brain

A vast number of potent neuropharmaceuticals, many of which are peptides, are excluded from entry into the brain because of the highly selective blood-brain barrier. The fact that a number of drugs have been shown to be transported directly to the central nervous system following application to the olfactory region of the nose is therefore of major interest. In the present study, the feasibility of delivering peptides to the brain via the olfactory route was assessed using insulin as a model peptide. Systemic hyperinsulinemia induced by subcutaneous injection did not significantly reduce the amount of ¹²⁵I-insulin transported from the nose to the brain in vivo, which suggests that the impact of systemic absorption on drug transport is minimal. A linear relationship was seen between insulin accumulation in the brain and the dose applied, without any relevant saturation. Contrary to what was expected, both systemic and olfactory absorption of insulin was enhanced when the pH of the medium was near the isoelectric point. The amount absorbed to the brain was found to be linearly related to the net charge of the molecule (r = -0.61; n = 20). It was concluded that insulin gains access to the central nervous system from the olfactory region of the nose by a nonspecific pathway. The olfactory route may therefore become an important means to deliver peptides to the brain.     

Preparation and evaluation of temperature sensitive liposomes containing adriamycin and cytarabine

Temperature sensitive liposomes (TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drugs. Lipid compositions of TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition temperature (T_c) of TSL was dependent on the lipid compositions of TSL.ADM broadened thermogram of TSL but Ara-C did not. However, T_c of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near T_c and observed at 39–41°C for DPPC (Dipalmitoylphosphatidylcholine) only, 52–54°C for DSPC (Distearoylphosphatidylcholine) only, 41–43°C for DPPC and DSPC (3∶1), and 43–45°C for DPPC and DSPC (1∶1), respectively. Effect of human serum albumin (HSA) on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below T_c. However, ADM release from TSL was increased at the near and above T_c. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near T_c. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at 4°C was not changed, the TSL was considered to be stable for at least 1 week at 4°C. Based on these findings, TSL may be useful to deliver drugs to preheated target sites due to its thermal behaviors.     

血管内皮功能障碍对肥胖伴高血糖患者胰岛分泌功能的影响

目的　探讨血管内皮功能障碍对胰岛 β细胞分泌功能的影响。 　方法　正常体重(NW )组 81例 ,单纯肥胖 (Ob)组 14 0例 ,肥胖伴高血糖 (Ob HG)组 97例。测定体质指数 (BMI)、腰臀围比 (WHR)、血压、血脂、空腹血糖和胰岛素 (FBG和FIns)及餐后血糖和胰岛素 (2hBG和 2hIns)。采用稳态模式法评价胰岛素抵抗 (HOMA IR)和 β细胞功能 (HOMA β)。用高分辨率血管外超声测定肱动脉对血流介导的内皮依赖性血管扩张 (EDD)及硝酸甘油的扩张反应。　结果　与Ob组比较 ,Ob HG组WHR、血压、甘油三酯 (TG)、FIns、2hIns和HOMA IR等显著升高 ,HOMA β明显降低 ,并伴有EDD所标志的血管内皮功能显著下降。相关分析显示 ,β细胞功能与EDD在Ob HG组呈显著正相关 (r=0 2 5 9,P <0 0 5 ) ,在Ob组和NW组无显著相关。在对Ob HG组影响EDD的因素进行控制后 ,EDD仍与 β细胞功能显著相关 (r =0 4 5 8,P <0 0 1)。多元逐步回归分析表明影响 β细胞功能的主要因素在Ob HG组为FBG、FIns和EDD ,在Ob组为FBG和HOMA IR。　结论　内皮依赖性舒张功能障碍可能是导致肥胖者 β细胞功能衰退 ,引发 2型糖尿病 (T2DM )的重要危险因素。