Pharmacokinetic and pharmacodynamic studies with mitoxantrone in the treatment of patients with nasopharyngeal carcinoma.

The pharmacokinetics and pharmacodynamics of mitoxantrone were studied in 15 patients with advanced nasopharyngeal carcinoma (NPC) after single intravenous rapid infusion (12 to 14 mg/m2). Mitoxantrone plasma concentrations and urinary excretion were measured specifically with the use of a high-performance liquid chromatographic method with ultraviolet detection at 242 and 658 nm. The pharmacokinetic parameters are described adequately by a three-compartment model with a terminal half-life of 71.5 +/- 40.1 hours and a volume of distribution of 5037 +/- 2377 l. The total plasma clearance was 743 +/- 462 ml/minute, and the renal clearance was 18.8 +/- 8.49 ml/minute. Within 72 hours, 1.8 +/- 0.6% of the administration dose was excreted in urine as mitoxantrone parent compound. From the urinary excretion rate data, glomerular filtration and possible tubular reabsorption were the mechanisms involved in the urinary excretion of mitoxantrone. The values for unbound fraction (%) in plasma at time 0 and 5 minutes were 2.88 +/- 0.91% and 3.25 +/- 1.19%, with an average of 3.04 +/- 1.01%. The degree of protein binding of mitoxantrone was not affected by concentration (P greater than 0.05) in Chinese patients with NPC. The response rate for mitoxantrone was poor in this study. Clinical studies have demonstrated that mitoxantrone was generally well tolerated. Only very low incidences of nausea, vomiting, and alopecia were observed. The mild and rapidly reversible dose-limiting hematologic toxic effects have proven leukopenia. Although the toxicities reported here were tolerated for most patients, other combination regimens including mitoxantrone or other administration routes may be considered and need to be evaluated carefully.     

稳定增殖神经干细胞的实验研究

目的探讨稳定、可靠建立神经干细胞体外增殖的方法,并对增殖培养的细胞进行鉴定。方法获取胚胎大鼠的脑组织,通过加入神经生长因子和采用保留细胞联系技术操作,使脑组织中的神经干细胞在体外克隆增殖并稳定传代。以免疫荧光方法对增殖克隆的神经干细胞球进行鉴定。结果神经干细胞不断增殖形成神经干细胞球且神经干细胞能快速稳定传代增殖。培养的细胞为神经干细胞特异性巢蛋白(nestin)染色阳性细胞。结论在神经生长因子的作用下,利用保留细胞联系技术操作,神经干细胞可以在体外快速、稳定克隆增殖并传代。     

MMP-2、TIMP-2在脑胶质瘤中的表达及其意义

目的 分析MMP-2、TIMP-2的表达与脑胶质瘤恶性程度和侵袭性之间的关系。方法 采用免疫组化和原位杂交的方法,检测42例人脑胶质瘤和8例正常脑组织中,MMP-2 mRNA、MMP-2和TIMP-2蛋白表达。结果 MMP-2蛋白表达水平(LI)与肿瘤的分级呈正相关(r=0.872,P<0.01);Ⅲ、Ⅳ级与正常脑组织、Ⅰ～Ⅱ级之间均有显著的差异(P<0.01)。MMP-2mRNA表达与肿瘤的分级同样呈正相关(P<0.01);Ⅲ、Ⅳ级与正常脑组织、Ⅰ～Ⅱ级之间均有显著的差异(P<0.01)。MMP-2蛋白表达增高时TIMP-2蛋白表达也增高;但随着肿瘤恶性程度的增加,TIMP-2表达强度增加的幅度较MMP-2明显减缓。结论 MMP-2的高表达与脑胶质瘤恶性程度呈正相关;TIMP-2与MMP-2间的平衡失调与脑胶质瘤的侵袭性和恶性程度密切相关。     

寒冷干燥地区平时火器伤的早期处理

目的　探讨寒冷干燥地区平时火器伤伤情特点与早期救治方法。方法　对 1991年 1月— 2 0 0 2年 12月间 40例火器伤病人的临床救治进行回顾分析。结果　 2 4例枪伤中 ,2 0例一期缝合伤口 ,均一期愈合 ,另外 4例只清创未一期缝合的伤口 ,3例愈合 ,1例感染 ;4例骨折内固定均愈合良好 ,无骨髓炎发生。 16例炸伤病人局部软组织损伤及污染比枪弹伤重 ,14例一期缝合伤口中 ,10例一期愈合 ,4例感染 ,骨折内固定 2例 ,均愈合良好 ,无骨髓炎发生。结论　寒冷干燥地区火器伤早期伤道清创时限可适当延长 ,在平时火器伤的救治中 ,对软组织条件较好的创面 ,早期清创后可一期闭合伤口和骨折内固定 ,这样可减少感染和伤残 ,促进康复     

Gender-specific response to isoflurane preconditioning in focal cerebral ischemia.

Inhalation anesthetics are effective chemical preconditioning agents in experimental cerebral ischemia. However, previous work has been performed exclusively in male animals. We determined if there is a gender difference in ischemic outcome after isoflurane preconditioning (IsoPC), and if this sex-specific response is linked to differences in Akt phosphorylation or expression of neuronal inducible cell-death putative kinase (NIPK), a negative modulator of Akt activation. Young and middle-aged male and female mice were preconditioned for 4 h with air (sham PC) or 1.0% IsoPC and recovered for 24 h. Cortices were subdissected from preconditioned young male and female mice for measurement of Akt phosphorylation (Western blot) and NIPK mRNA (quantitative polymerase chain reaction). Additional cohorts underwent 2 h of reversible middle cerebral artery occlusion. Lastly, male and female Akt1(+/+) and Akt1(-/-) mice were studied to determine if gender differences in ischemic outcome after IsoPC is Akt1-dependent. Infarction volume was determined at 22 h reperfusion (2,3,5-triphenyltetrazolium chloride). As expected, IsoPC decreased ischemic damage as compared with sham PC in young and middle-aged male mice. In contrast, IsoPC markedly increased infarction in young female mice and had no effect in middle-aged female mice. Cortical phospho-Akt was increased by IsoPC versus sham PC only in male mice. No increase was observed in IsoPC female mice. NIPK mRNA was higher in female mice than in male mice regardless of preconditioning status. Male IsoPC neuroprotection was lost in Akt1-deficient male mice. We conclude that IsoPC is beneficial only in ischemic male brain and that sex differences in IsoPC are mediated through Akt activation and basal NIPK expression.     

Anatomic and spiral computed tomographic study of the genial tubercles for genioglossus advancement.

OBJECTIVE: To measure and compare Chinese mandibular genial tubercles measured anatomically and with computed tomography (CT). STUDY DESIGN AND SETTING: Spiral CT scans were taken of 40 adult human skulls; the superior genial spines were measured using anatomic and CT methods. RESULTS: The height and width of the superior genial spines, mandible thickness, and distance from the menton to the inferior and superior margins of the superior genial spines were 5.82 +/- 0.71, 6.98 +/- 1.35, 11.95 +/- 1.59, 11.08 +/- 2.05, and 16.91 +/- 2.30 mm from anatomic measurements and 6.17 +/- 0.71, 7.01 +/- 1.13, 12.19 +/- 1.64, 10.41 +/- 1.55, and 15.73 +/- 2.12 mm using spiral CT, respectively. The anatomic and CT measurements were correlated. CONCLUSION: Spiral CT of the genial tubercles can help locate the osteotomy in genioglossus advancement. SIGNIFICANCE: This study acquired reference data on Chinese genial tubercles demonstrating that CT measurements of the genial tubercles reflect their anatomy, which should allow accurately locate the osteotomy.     

主动脉瓣机械瓣置换术后交替脉

报道４例因主动脉瓣关闭不全行主动脉瓣置换术后的患者在术后早期出现脉搏交替现象，此时心电图为整齐的窦性心律，所记录的脉搏图形高低交替，如扪诊桡动脉时则会发现桡动脉搏数为心电图示心率的一半。患者术后均顺利恢复，显示这一现象为一过性的、良性的过程。推测这一现象出现的原因可能是术后早期主动脉瓣不再有回流，因而巨大的左室腔充盈不足，加之左室收缩力尚低，不能在每次收缩时都能射出同等量的血流所致     

双歧杆菌对早产儿食道pH值的影响及临床意义

目的为探讨双歧杆菌对早产儿食道pH值的影响，及其对早产儿易发生的消化道疾病的防治意义。方法我们采用便携式24hpH值自动记录仪，对61例早产儿进行了食道pH值的动态监测。结果口服双歧杆菌活菌制剂组的30例早产儿，食道pH值明显高于未服药的对照组，t=2．4093，P＜0．05。总pH值＜4的时间占总观察时间的百分比显著小于对照组。并且治疗组发生消化道疾患的人数也较对照组少。结论早产儿口服双歧杆菌活菌制剂可以减少胃食道反流等消化道疾病的发生。     

Comparison of in vitro and in vivo alpha/beta ratios for prostate cancer

Parallel in vitro and in vivo studies provide insight into the relationship between clinical response and intrinsic cellular radiosensitivity and may aid in the development of predictive assays. Compilations of radiosensitivity parameters from in vitro experiments can also be used to examine the potential effectiveness of alternative or new treatment plan designs until enough clinical data become available to directly estimate the requisite radiosensitivity parameters. In this work, survival data for six prostate cancer cell lines (ten datasets total) have been extracted from the literature and re-analysed using the linear-quadratic (LQ) survival model. The paired bootstrap technique for regression is used to compute 95% confidence intervals for the estimated radiosensitivity parameters. LQ radiosensitivity parameters derived from the in vitro data are then compared to radiosensitivity parameters derived from clinical data for prostate cancer. Estimates of alpha range from 0.09 to 0.35 Gy(-1) (all cell lines), and the alpha/beta ratio ranges from 1.09 to 6.29 Gy (all cell lines). Point estimates of the repair half-time (PPC-1, TSU-Pr1, PC-3 and DU-145 cell lines) range from 5.7 to 8.9 h (95% confidence interval from 0.26 h to 10.7 h). Differences in the radiosensitivity parameters determined from the data reported by different laboratories are as large as or larger than the differences in radiosensitivity parameters observed among the various prostate cell lines. The reported studies demonstrate that even seemingly small corrections for dose rate effects, such as those expected in high dose rate (HDR) experiments, can sometimes have a significant impact on estimates of alpha and alpha/beta. By neglecting dose rate effects in the analysis of HDR experiments, estimates of the alpha/beta, ratio may be too high by factors as large as 1.3 to 6.2. The half-time for repair derived from the in vitro experiments appears significantly larger (slower repair rate) than estimates derived from the clinical data. However, the prostate radiosensitivity parameters alpha and alpha/beta may be approximately the same in vitro and in vivo. Most of the in vitro data are consistent with an alpha/beta ratio for prostate cancer less than 3 or 4 Gy.     

细菌对噬菌体感染的抵抗

噬菌体对其宿主菌具有特异性感染力,反之,宿主菌对噬菌体的感染具有抵抗现象.根据噬菌体侵入宿主的不同阶段,可以将宿主菌对噬菌体的天然抵抗机制分为4个主要的类别吸附抑制,流产感染,限制-修饰系统和穿入阻滞.此外,还有源于噬菌体的抗性作用以及通过人工插入突变获得的广谱噬菌体抗性菌株等.