咪唑立宾在肾移植术后的应用

目的 探讨咪唑立宾（MZR）在肾移植术后的临床应用效果。方法 选取2003年8月至2004年4月间肾移植术后采用环孢素A（CsA）或他克莫司（FK506）＋MZR＋激素三联免疫抑制方案的患者112例，定期检查患者用药后的血常规、肝肾功能、尿酸、血糖、血脂等生化指标；对乙型肝炎病毒、丙型肝炎病毒、艾滋病病毒、巨细胞病毒、EB病毒、腺病毒及带状疱疹病毒进行抗原学或者抗体监测；疑有排斥反应时，行移植肾穿刺病理检查。统计病毒感染发生情况，评价该治疗方案的安全性。结果 肾移植术后随访12～20个月，患者的人／肾存活率均为96％；急性排斥发生率为11．6％，经冲击治疗后全部逆转；患者主要不良反应是高尿酸血症，但可以控制而不需要停药；巨细胞病毒感染率为11．6％，未发生巨细胞病毒病；有1例感染腺病毒。结论 MZR是一种安全有效的免疫抑制剂，病毒感染的发生率相对较低。由于肾移植术后应用MZR患者主要不良反应是高尿酸血症，因此要注意对患者的尿酸进行控制。     

胸腹水组织因子及组织因子途径抑制物的检测及其意义

目的研究三组疾病胸腹水组织因子(Tissue factor,TF)及组织因子途径抑制物(Tissue factor pathway inhibitor,TFPI)的表达及其鉴别诊断意义。方法TF和TFPI采用ELISA法测定抗原表达。结果胸腹水TF水平和TFPI水平,恶性肿瘤组(570.04±627.53)ng/L,(28.60±15.57)μg/L和结核病组(283.82±143.16)ng/L,(31.16±12.26)μg/L明显高于肝硬化组(60.83±66.87)ng/L,(7.84±5.45)μg/L,P<0.01。TF/TFPI比值则为恶性肿瘤组(32.17±44.19)明显高于结核病组(13.55±13.15)和肝硬化组(11.22±9.05,P<0.05)。在恶性肿瘤组中,胸腹水癌细胞阳性组的TF表达(1106.92±1244.28)ng/L高于阴性组(331.08±295.84)ng/L,P<0.05。而阳性组的TFPI水平(27.35±17.75)μg/L与阴性组(30.34±13.20)μg/L无明显差异(P>0.05)。TF/TFPI比值则为阳性组(59.59±65.10)明显高于阴性组(11.54±8.37,P<0.01)。结论检测胸腹水TF和TFPI并分析TF/TFPI比值可以作为临床实验室有鉴别诊断意义的辅助指标,同时还可了解疾病的某些病理机制,尤其是肿瘤的某些生物学行为。     

Aspartylglucosaminuria in the United States

Aspartylglucosaminuria (AGU) was diagnosed in two unrelated males with progressive mental retardation, coarse facies and skeletal abnormalities. Until now, this disorder has been described in predominantly Finnish populations with only one previous case reported in the U.S. We conclude that AGU may be more common in nowFinnish populations than the number of reported cases would indicate and should be included in the differential diagnosis in patients with suspected lysosomal storage disorders regardless of their geographical or ethnic backgrounds.     

Comparison of the acute cardiotoxicity of the antimalarial drug halofantrine in vitro and in vivo in anaesthetized guinea-pigs

1. Several unrelated drugs have pro-arrhythmic activity associated with an ability to prolong the QT interval of the ECG. The aim of this work was to examine the effects of the antimalarial drug halofantrine in vivo and in vitro.
2. In anaesthetized guinea-pigs consecutive bolus doses of halofantrine (0.3, 1, 3, 10 and 30 mg kg⁻¹, i.v.) at 25 min intervals caused dose-dependent prolongation of the rate corrected QTc interval and bradycardia. The change in heart rate became significant after administration of 10 mg kg⁻¹ halofantrine (−23±9 beats min⁻¹) whereas the increase in QTc was significant with only 1 mg kg⁻¹ halofantrine (22±10 ms). It was only with the highest dose of halofantrine that the PR interval was increased (from 52±3 to 67±4 ms) and second degree atrioventricular (AV) block (type 1 Mobitz) occurred in all animals. No changes were observed in any parameters in a separate group of guinea-pigs which received vehicle (dimethylacetamide 60% propylene glycol 40%) at equivalent time points.
3. The blood concentrations of halofantrine ranged from 0.26±0.17 μM after administration of 0.3 mg kg⁻¹ to 2.79±0.87 μM after 30 mg kg⁻¹, i.v. There was a significant correlation between the blood concentrations of halofantrine and the changes in QTc interval.
4. In guinea-pig left papillary muscles the effective refractory period was increased significantly 60 min after addition of halofantrine; from 161±4 to 173±6 ms with 10 μM, 156±8 to 174±6 ms with 30 μM and 165±6 to 179±5 ms with 100 μM halofantrine. However, the vehicle (0.1% Tween 80 in DMSO; final concentration of vehicle in Krebs, 1%) also increased the effective refractory period from 164±5 to 173±6 ms. Similar results were obtained in right ventricular strips but left atrial effective refractory periods were not altered by either the vehicle or halofantrine.
5. The results of these experiments suggest that any direct effects that halofantrine may have had on the effective refractory period of cardiac muscle cannot be separated from those of the vehicle. The prolongation of QTc and consistent observation of AV block with halofantrine in anaesthetized guinea-pigs suggest that in vivo models may be more useful for further studies investigating the mechanisms underlying the cardiotoxicity of halofantrine.

     

Macular disease and optical coherence tomography

Optical coherence tomography (OCT) is a new diagnostic tool for high-resolution cross-sectional imaging of the retina. By measuring the "echo" delay time of light as it reflects from tissue at different ranges and by performing multiple axial scans in the transverse direction, OCT generates two-dimensional images detailing retinal architecture. OCT is a powerful new modality because it has a longitudinal resolution of 10 microns in the retina, which is superior to other currently available imaging techniques. Examinations are exceptionally tolerable for patients because OCT is noninvasive, the probe beam is near-infrared and thus not very bright, and scan acquisition time is only 2.5 seconds. OCT appears to be a useful device for evaluating a variety of retinal diseases, including macular holes, macular edema, and central serous chorioretinopathy.     

散发内淋巴囊瘤VHL基因位点微卫星标志杂合性丢失的研究

目的 探讨散发内淋巴囊瘤发病与VHL基因异常之间的关系。方法 采用组织微切割技术和多聚酶链式反应等方法对3例散发内淋巴囊瘤肿瘤细胞VHL基因位点染色体微卫星标志的杂合性丢失进行分析。结果 3例散发内淋巴囊瘤中有2例发生VHL基因位点微卫星标志的杂合性丢失,进一步的研究证实,该两例肿瘤细胞中分别存在着VHL基因第二外显子的异常。结论 VHL基因的异常导致其功能改变不但是VHL的致病原因,而且是散发性内淋巴囊瘤发病的重要的基因遗传学基础。     

对甲磺酰基苯乙烯环酮类衍生物的合成及抗炎活性

目的寻找新型高效低毒的非甾体抗炎药。方法合成对甲磺酰基苯乙烯环酮类衍生物，用二甲苯致小鼠耳肿胀模型和角叉菜胶致大鼠足跖肿胀模型评价其抗炎活性，并考察连续经口给药对大鼠胃肠道（GI）的影响。结果合成了9个新化合物（ZA_1-9），结构经IR，¹HNMR，MS和元素分析确证。小鼠试验表明ZA_3,5-9的抗炎活性与双氯芬酸钠(DC)和罗非昔布(RC)相当(P>0.05)，大鼠试验显示ZA_3,7,8的抗炎活性与DC和RC相当(P>0.05)， ZA₆的抗炎作用显著强于DC和RC(P<0.05)，ZA_3,5-9对GI损伤显著小于DC (P<0.05，P<0.01)，与RC相当(P>0.05)。结论对甲磺酰基苯乙烯环酮类衍生物的抗炎作用较强，GI不良反应小，值得进一步研究。     

自发性高血压大鼠血、尿III型前胶原水平变化及氯沙坦的干预作用

目的　探讨自发性高血压大鼠 (spontaneouslyhypertensiverat ,SHR)血、尿Ⅲ型前胶原 (ProcollagenⅢ ,PCⅢ )与早期肾脏损害的关系。方法　检测SHR及氯沙坦干预后血、尿PCⅢ水平。 14周龄雄性SHR16只随机分为高血压组和氯沙坦治疗组 (氯沙坦灌胃 3 0mg·kg-1·d-1)各 8只 ,14周龄雄性Wistar -kyoto大鼠 (WKY) 8只为正常对照组 ,16周后 ,放免法检测血、尿PCⅢ、尿微量白蛋白 (microalbumin ,ALB)及血、尿 β2 -微球蛋白 ( β2 -microglobin ,β2 -MG)。结果　SHR组尿PCⅢ、尿ALB及血、尿 β2 -MG水平明显高于WKY组 (P <0 0 5 ) ,三组血PCⅢ水平无显著差异 (P >0 0 5 )。氯沙坦可显著降低SHR组尿PCⅢ、尿 β2 -MG及尿ALB水平 ( P<0 0 5 )。血、尿PCⅢ无相关性 (r =0 2 2 6,P <0 0 5 )。尿PCⅢ与尿 β2 -MG(r =0 813 ,P <0 0 1)、尿ALB(r =0 5 60 ,P <0 0 1)、收缩压 (r =0 694,P <0 0 1)呈正相关。结论　SHR组尿PCⅢ、尿 β2 -MG、尿ALB水平升高 ,可一定程度反映高血压早期肾脏损害。氯沙坦可降低SHR血压、尿PCⅢ、尿 β2 -MG、尿ALB水平 ,对高血压肾脏有保护作用