Influence of menstrual cycle on cytochrome P450 2A6 activity and cardiovascular effects of nicotine

BACKGROUND AND OBJECTIVES: The phase of the menstrual cycle has been reported to affect frequency of smoking, withdrawal symptoms, and the likelihood of smoking cessation in women. Cytochrome P450 (CYP) 2A6 is primarily responsible for the metabolism of nicotine. Our objective was to evaluate the effect of the phase of the menstrual cycle on the activity of CYP2A6 and the cardiovascular effects of nicotine. METHOD: Eleven healthy, nonsmoking women received a 30-minute combined infusion of deuterium-labeled nicotine and cotinine (0.5 microg . kg(-1) . min(-1) of each compound) during the midfollicular and midluteal phases of the menstrual cycle. Nicotine and cotinine pharmacokinetic parameters and plasma adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine responses were measured over time. RESULTS: There were no biologically or statistically significant differences in the comparison of menstrual cycle phases with regard to the pharmacokinetics of nicotine and cotinine. Nicotine clearance was 1000 +/- 315 mL/min and 1047 +/- 271 mL/min in the follicular and luteal phases, respectively (geometric mean ratio, 1.06; 90% confidence interval, 0.87-1.29). Cotinine clearance was 44 +/- 20 mL/min and 55 +/- 42 mL/min in the follicular and luteal phases, respectively (geometric mean ratio, 1.13; 90% confidence interval, 0.90-1.41). Nicotine infusion increased blood pressure, heart rate, and epinephrine concentrations. There were no differences in catecholamine, ACTH, or hemodynamic responses to nicotine infusion between menstrual cycle phases, although norepinephrine concentrations were constantly higher in the luteal phase compared with the follicular phase. CONCLUSIONS: CYP2A6 activity is not affected by menstrual cycle phase, and it is unlikely that menstrual cycle-related smoking habits of women are determined by changes in nicotine pharmacokinetics. The effects of nicotine on plasma ACTH and catecholamine levels and hemodynamic parameters are not altered by menstrual cycle phase in healthy, nonsmoking women.     

Management of chronic intractable angina - spinal opioids offer an alternative therapy

The successful treatment of chronic intractable angina by spinally administered opioids via an Algomed drug delivery device (hereinafter called the pump) is reported in seven patients. All patients had at least two prior cardiac surgeries and the duration of minimally controlled chronic intractable angina varied from 5 to 19 years prior to spinally administered opioids. The duration of effective spinally administered analgesia to either the epidural (two cases) or intrathecal (five cases) spaces varied from 2 to 7 years. The opioid used was either morphine or fentanyl and the dose increase (either mg/year or microg/year, respectively) varied from 1.2 to 16. We suggest that bolus spinal morphine or fentanyl administered via the pump is a viable alternative for the effective control of angina when more established therapies have been found to provide insufficient pain relief.     

机器人辅助腹腔镜下根治性膀胱切除加尿流改道术的临床分析

目的 探讨采用da Vinci S机器人系统完成机器人辅助腹腔镜下根治性膀胱切除(robotic-assisted laparoscopic radical cystectomy,RARC)加尿流改道术的临床可行性,并总结技术特点和临床效果. 方法 2007年12月至2012年3月膀胱尿路上皮癌患者22例,男20例,女2例.年龄37～ 72岁,平均62岁.体质指数22.5 ～ 30.1 kg/m2,平均26.1 kg/m2.麻醉评分1～2分.术前肿瘤活检病理诊断为浸润性或高危的非肌层浸润性膀胱尿路上皮痛,术前检查均未发现有其他邻近脏器浸润、盆腔淋巴结转移或远处转移,临床分期均低于T2N0M0.全麻下行RARC加尿流改道术,其中行体外尿流改道术15例(原位新膀胱2例,回肠膀胱术13例),行完全腹腔镜下尿流改道术7例(回肠膀胱术2例,原位新膀胱5例). 结果 本组22例手术均获得成功.手术时间300 ～ 667 min,平均480 min;出血量100 ～ 1200 ml,平均550 ml;淋巴结清扫数目6～ 25枚,平均15枚.术后2～3d下地活动,3～4d肠功能恢复,术后住院时间8～35 d,平均16d.行原位新膀胱的患者术后1个月行膀胱造影确定无吻合口漏后拔除尿管和双侧输尿管支架管.术后随访4 ～ 49个月,平均32个月,复发2例,死亡1例,出现肾积水2例,其余病例肾功能均正常,尿控较满意. 结论 根据初期的手术操作过程和随访结果,RARC加尿流改道术在临床上是可行的.更多的操作经验、长期和随机的对照研究将有助于对这一技术进行评估和推广.     

Amifostine (WR-2721) shortens the engraftment period of 4- hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty- three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high- dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

社会主义核心价值体系融入医学生医德教育的伦理诉求

医德修养和医德品质是医务人员必备的思想品质,是和谐医患关系的道德前提。以社会主义核心价值体系为指导,把社会主义核心价值体系融入医德教育中,是帮助医学生树立崇高的医德理想、明确医德追求、继承医德传统、锤炼医德品质和提升医德修养的重要途径和方法。     

Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model

BackgroundPreviously, we have shown that supplementation of intestinal alkaline phosphatase (IAP) decreased severity of necrotizing enterocolitis (NEC)–associated intestinal injury. We hypothesized that IAP administration is protective of intestinal epithelial barrier function in a dose-dependent manner.MethodsControl rat pups were vaginally delivered and breast-fed. Premature rats were divided into 4 groups: formula fed with lipopolysaccharide and hypoxia (NEC) or additional daily bovine IAP 40, 4, or 0.4 U/kg (NEC + IAP 40 U, IAP 4U, or IAP 0.4 U).ResultsNecrotizing enterocolitis is associated with decreased IAP protein expression and activity. Supplemental IAP increases IAP activity in intestinal homogenates and decreased NEC injury score in a dose-dependent manner. Intestinal injury as measured by fluorescein isothiocyanate–dextran flux from ileal loops showed increased permeability vs control, but supplemental IAP reversed this. Tight junction proteins claudin-1, claudin-3, occludin, and zonula occludin 1 were elevated in the NEC and IAP-treated groups with differences in expression patterns. No differences in messenger RNA levels were observed on postinjury day 3. Intestinal alkaline phosphatase administration decreases intestinal NEC injury in a dose-dependent manner.ConclusionEarly enteral supplemental IAP may reduce NEC-related injury and may be useful for preserving the intestinal epithelial barrier function.     

颅底外面枕骨基底部及周边骨性结构的测量和临床意义

目的为斜坡区肿瘤手术提供解剖资料。方法20例整颅,10例行水平切面,10例行正中矢状切面。测量切牙孔、前鼻棘、后鼻棘、枕骨大孔前端、枕髁前端、卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至咽结节的距离;测量卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至正中线的距离;测量枕骨基底部颅底外面的长径、枕骨大孔纵径(FML)、枕骨大孔前正中点与枕髁后缘连线垂直距离(AOCP)、枕髁轴径(OCA)、枕髁间距。结果切牙孔后缘、前鼻棘、后鼻棘、枕骨大孔前端、枕髁前端、卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至咽结节的距离分别为(mm):72.12±4.25、77.77±3.89、33.73±2.07、13.14±1.91、15.71±1.74、27.51±2.12、15.98±1.98、25.93±2.23、19.15±1.49。卵圆孔、破裂孔、颈动脉管及舌下神经管外口的内侧缘至中线的距离分别为:25.55±1.63、11.72±1.70、25.75±1.98、17.41±1.41。枕骨基底部颅底外面长径、FML、AOCP、OCA、枕髁间距分别为(mm):28.80±2.67、35.84±2.59、17.10±1.13、24.55±2.35、21.07±1.92。结论经口咽至斜坡区的手术入路中,开骨窗时安全范围是以咽结节为中心,以15mm为半径做斜坡磨除;也可以做矩形骨窗,即以咽结节为中心开一长(高)25mm×宽20mm的骨窗。     

慢性低氧时小鼠肺组织低氧诱导因子-1α的表达

目的：研究低氧时小鼠肺组织中低氧诱导因子-1α(HIF-k)表达的变化。方法：实验用雄性小鼠,低氧仓浓度分别为10％、7％、5％。用免疫荧光组织化学技术及共聚焦显微术,检测小鼠在低氧条件下肺组织中HIF-1α表达的变化。结果：正常组小鼠肺组织HIF-1α无表达,低氧组HIF-1α表达增加,且随低氧时间的延长及低氧强度的增加而增强。结论：低氧可诱导小鼠肺组织中HIF-1α的表达增强,(HIF-k)可能参与肺组织细胞凋亡的发生。