Influence of low proximal aortic pressure on spinal cord oxygenation in experimental thoracic aortic occlusion

BACKGROUND: To evaluate the effect of low proximal aortic pressure on cerebrospinal fluid (CSF) oxygenation in an experimental thoracic occlusion model. METHODS: In nine pigs, continuous intrathecal pO(2), pCO(2) and pH monitoring was used during double descending thoracic aortic clamping following insertion of an aorto-aortic shunt. In five pigs, the shunt was connected to a citrated bag adjusted at approximately 40-45 cm above the heart for partial exsanguination in order to decrease mean proximal aortic pressure (MPAP) to below 50 mmHg. In four animals, sodium nitroprusside infusion was used for this purpose. RESULTS: Intrathecal pO(2) demonstrated a significant decrease from 4.9+/-2.1 to 2.9+/-2.4 kPa after 10 minutes of aortic cross-clamping. Lowering proximal aortic pressure caused a further significant decrease to 1.2+/-1.7 kPa (p<0.05). In seven pigs (5 in the exsanguination and 2 in the vasodilator group), restoration of mean proximal aortic pressure to 94.0+/-27.7 caused a recovery of CSF pO(2) from 1.2+/-1.9 to 2.8+/-3.0 (p<0.05). CONCLUSIONS: The results of this study demonstrate that MPAP which provides spinal cord perfusion through subclavian-vertebral arteries are crucial for maintenance of spinal cord oxygenation during thoracic aortic occlusion in this pig model.     

胃癌前病变中DNA甲基化状态与叶酸

DNA甲基化异常是胃癌发生的重要机制之一,为了能尽早发现并纠正DNA甲基化异常,阻止胃癌的发生,胃黏膜癌前病变中DNA甲基化状态的研究日益受到重视．众多研究表明,胃黏膜癌前病变中多种基因中存在甲基化异常,而且基因的甲基化异常程度与年龄、性别有关,还与胃黏膜上皮细胞是否存在活动性炎症、肠化及幽门螺杆菌感染有关．叶酸缺乏可导致DNA甲基化的紊乱和DNA修复机制效率的减弱, 叶酸摄入量不足患胃癌的相对危险度增高;胃黏膜癌前病变患者体内叶酸不足,黏膜细胞总基因组DNA甲基化水平下降;经叶酸治疗后,体内叶酸升高,黏膜细胞总基因组DNA 甲基化水平上升,异型增生、肠上皮化生明显改善．因此,叶酸缺乏与胃黏膜癌前病变的发生、发展有关,及时纠正叶酸不足,可逆转胃黏膜的病理改变,减少胃癌的发生．     

Human recombinant luteinizing hormone is as effective as, but safer than, urinary human chorionic gonadotropin in inducing final follicular maturation and ovulation in in vitro fertilization procedures: results of a multicenter double-blind study

In a prospective, comparative, dose-finding study, the minimal effective dose of recombinant human LH (rhLH) required to induce final follicular maturation and early luteinization in patients undergoing in vitro fertilization and embryo transfer was determined. In addition, the efficacy and safety of rhLH were compared with urinary human CG (u-hCG). A total of 259 infertile women, aged 18-39 yr, were enrolled in the study. After pituitary desensitization using a GnRH agonist, rhFSH was administered for ovarian stimulation. Patients then received either rhLH or u-hCG to achieve final follicular maturation. The doses of rhLH administered were 5,000, 15,000, 30,000, or 15,000 + 10,000 IU (second injection administered 3 days after the first injection; 129 patients), and those of u-hCG were consistently 5,000 IU (121 patients). Ovum pick-up was performed 34--38 h after rhLH or u-hCG injection. After fertilization in vitro, up to three embryos were replaced in the uterine cavity. The numbers of oocytes retrieved after u-hCG or rhLH administration were not significantly different between the four different doses of rhLH, when compared with each corresponding u-hCG group, nor when compared with the pool of all u-hCG groups. Similarly, there were no statistically significant differences in: the number of oocytes retrieved per follicle with a diameter of over 10 mm on the day of u-hCG or rhLH administration; the number of patients with at least one oocyte retrieved; oocyte nuclear maturity; oocyte potential for fertilization; the number of embryos; the number of total, biochemical, and clinical pregnancies; and the embryo implantation rate. However, in many of these parameters, the lowest dose of rhLH seemed suboptimal when compared with the higher dose. In terms of safety, rhLH was well tolerated at a dose of up to 30,000 IU. Moderate ovarian hyperstimulation syndrome (OHSS) was reported in 12.4% of patients who received u-hCG and 12.0% of patients who received two injections of rhLH. No moderate or severe OHSS was reported in patients who received a single dose of rhLH up to 30,000 IU. The results show that a single dose of rhLH is effective in inducing final follicular maturation and early luteinization in in vitro fertilization and embryo transfer patients and is comparable with 5,000 IU u-hCG. A single dose of rhLH results in a highly significant reduction in OHSS compared with hCG. The dose of rhLH giving the highest efficacy to safety ratio was between 15,000 and 30,000 IU.     

Outcomes of extended versus limited indications for patients undergoing a liver resection for colorectal cancer liver metastases

Background

Currently, resection criteria for colorectal cancer liver metastases (CRCLM) are only limited by remnant liver function. Morbidity and survival after a partial hepatectomy with limited or extended indication criteria were compared.

Methods/Design

Between 1991 and 2010, patients undergoing a liver resection for CRCLM with limited (n = 169) or extended indication criteria (n = 129) were retrospectively identified in a prospectively collected single-centre database. Limited indication criteria were defined as less than three unilateral, not centrally located liver metastases in the absence of extra hepatic metastases. The extended criteria were only limited by predicted remnant liver volume and patients fitness. Data on co-morbidity, resection margin, short- and long-term morbidity, disease-free (DFS) and overall survival were compared.

Results

Patients with limited indications had less major complications (19.5% vs. 33.1%, P < 0.01), longer overall survival of 68.8 months [confidence interval (CI) 46.5–91.1] vs. 41.4 months (CI 33.4–49.0, P ≤ 0.001) and longer median DFS of 22.0 months [confidence interval (CI) 15.8–28.2] vs 10.2 months (CI 8.4–11.9, P < 0.001) compared with the extended indication group. Cure rates, defined as 10-year DFS, were 35.5% and 15.8%, respectively. Fewer patients in the extended indication group underwent an R0 resection (92.9% vs. 77.5%, P < 0.001). Only 17% of all R1 resected patients had recurrences at the transection plane.

Conclusion

A partial hepatectomy for CRCLM with extended indications seems justified but is associated with higher complication rates, earlier recurrence and lower overall survival compared with limited indications. However, the median 5-year survival was substantial and a cure was achieved in 15.8% of patients.     

中华大蟾蜍皮化学成分的研究

从中华大蟾蜍(Bufo bufo gargarizans Cantor)皮水溶性部分应用制备型反相HPLC分离得到一个新蟾蜍毒素,根据光谱(UV,IR,¹HNMR,¹³CNMR,EIMS,FDMS)、氨基酸分析及化学性质,确定其结构为Ⅰ所示,命名为蟾毒它灵3-丁二酰精氨酸酯,同时还分到三个已和蟾蜍毒素;蟾毒灵3-丁二酰精氨酸酯(Ⅱ),华蟾毒精3-丁二酰精氨酸酯(Ⅲ),脂蟾毒配基3-丁二酰精氨酸酯(Ⅳ)。     

化学合成法确证柄果花椒酰胺的结构

柄果花椒酰胺(podocarpamide)是从柄果花椒干树皮中分离得到的一结晶化合物。经药理筛选,体外有抗血小板凝聚作用和降转氨酶活性。该天然产物的结构从光谱推断有如下两种可能的组合方式:     

(Sp)-8-氯腺苷-3',5'-环磷酸辛酯对人白血病HL-60细胞的诱导分化作用

(Sp)-8-氯腺苷-3',5'-环磷酸辛酯(Sp-octyl8-chloroadenosine3',5'-cyclophosphate,OCC)对人白血病HL-60细胞有生长抑制和分化诱导作用,该作用与OCC浓度和处理时间呈正相关,为不可逆性。流式细胞光度术发现,OCC阻断HL-60细胞周期于G1期。参入实验证实,OCC对HL-60细胞DNA合成有显著抑制作用,但不影响RNA和蛋白质合成。OCC能直接激活HL-60细胞浆中提取的蛋白激酶A(PKA),并抑制它与cAMP的结合。经OCC处理的HL-60细胞浆中PKA活性明显升高,说明OCC能与cAMP竞争PKA的结合并激活PKA。     

Transfusion therapy: improved patient care and resource utilization

Improving the quality of medical care while reducing costs is one of the major challenges facing the health care system in the United States. At a 1020-bed, tertiary-care, teaching hospital, the Transfusion Committee modified transfusion practice by establishing new transfusion guidelines based upon national standards rather than local practices and by implementing educational and monitoring systems. Over a 3-year period, the number of transfusions decreased, the types of transfused components changed, and the waste due to unused components decreased. From the baseline of Fiscal Year (FY) 1989 (89), the number of exposures to components from allogeneic blood donors for the patient population decreased by 11,015 in FY 90, 14,067 in FY 91, and 16,990 in FY 92, thereby decreasing the risk of transfusion-transmitted disease, transfusion reaction, and alloimmunization. As compared to costs in FY 89, the altered transfusion practices resulted in cost savings of $376,269 in FY 90, $566,375 in FY 91, and $684,704 in FY 92. Over the 3- year period, exposures to components from allogeneic blood donors for the patient population were reduced by 42,072, and the total cost savings was $1,627,348. The methodology and results should be reproducible at other hospitals.