Intra-arterial administration of carboplatin and the blood brain barrier permeabilizing agent,RMP-7: A toxicologic evaluation in swine

RMP-7 is a bradykinin B2 receptor agonist shown to permeabilize the blood-brain barrier, especially that associated with brain tumors, when administered via both intracarotid and intravenous routes. Both routes of administration are currently being tested in human trials in combination with the chemotherapeutic agent carboplatin as therapy for gliomas. As an essential prerequisite to the initial intracarotid clinical trials, the potential neurotoxicity of intra-arterial administration of RMP-7 (at a high or low dose), alone and in combination with carboplatin, was assessed in anesthetized Red Duroc swine. Five treatment groups were evaluated with each pig receiving a series of alternating, intra-arterial infusions of RMP-7 (or saline) followed by carboplatin (or saline), as follows: (1) vehicle control: saline/saline; (2) carboplatin only control: saline/carboplatin (50 mg total); (3) RMP-7 only control: RMP-7 (750 ng/kg)/saline; (4) low dose combination: RMP-7 (75 ng/kg)/carboplatin (50 mg total); and (5) high dose combination: RMP-7 (750 ng/kg)/carboplatin (50 mg total). For each subject, one of the alternating dosing sequences (above) was repeated four times during a single dosing session which lasted approximately 40 minutes. Assessments during the in-life phase of the study in the pre- and post-treatment periods consisted of heart rate, arterial blood pressure (systolic, diastolic, and mean), blood gases, body weight, general clinical observations (including evaluation for neurological deficit) and clinical pathology (including a comprehensive battery of standard blood coagulation, hematological and serum chemistry tests). In addition, during the time of treatment, heart rate and arterial blood pressure were monitored. The animals were terminated two weeks after dosing and the brain and rete mirabile (distal to site of infusion) were evaluated for gross and histopathological abnormalities. The histopathology analysis included a reader-blinded analysis using low and high power light microscopic examination of both H&E and Kluver-Berrera stained sections through several key cortical and subcortical brain regions. Transient decreases in arterial blood pressure (mean of 10–25 mmHg) were observed in both groups receiving the high dose of RMP-7 (i.e., 750 ng/kg). No other side effects attributable to RMP-7 and/or carboplatin were observed, and clinical observations revealed no evidence of neurologic deficits. Post-mortem examination revealed no evidence of CNS or cerebral vascular pathology attributable to carboplatin and RMP-7. This study demonstrates that intracarotid administration of the maximum tolerated dose of RMP-7 (750 ng/kg) alone, or in combination with carboplatin (50 mg) is not accompanied by any serious adverse effect, apparent cerebrovascular abnormality or neuropathologic consequence and offers further evidence for the safety of this novel therapeutic approach for enhancing delivery of chemotherapeutics to brain tumors.     

Success Rate with Repeated Cycles of In Vitro Fertilization–Embryo Transfer

Objective: To analyze data from a large multicenter study to determine whether pregnancy and delivery rates decrease with repeated IVF-ET cycles.

Design: Multicenter retrospective study.

Setting: Participating centers from the Society of Assisted Reproductive Technology.

Patient(s): Fifty-four centers contributed 4,043 cycles of oocyte retrieval for uterine transfer.

Intervention(s): Oocyte retrieval for uterine transfer.

Main Outcome Measure(s): Pregnancy and delivery rates, analyzed according to age, program success rate, and whether the program was doing assisted hatching.

Result(s): Pregnancy and delivery rates for cycles 1, 2, 3, 4, and >4 were 33.7% and 27.0%, 33.9% and 27.4%, 28.9% and 23.4%, 25.9% and 16.1%, and 21.0% and 15.4%, respectively. The pregnancy rate decreased significantly for >4 cycle; delivery rate decreased significantly for cycles 4 and >4. Assisted hatching was strongly related to better odds of pregnancy (OR, 1.50) and delivery (OR, 1.44) in women under age 40, and for pregnancy (1.64) in women age 40–42 years.

Conclusion(s): Success rates do not decrease markedly with repeated IVF attempts, and the decrease did not change with program success rate, suggesting the IVF population is not markedly heterogeneous. Uncontrolled studies of new treatments for cycle repeaters cannot assume that success rate is poor without a treatment change.     

剖宫产后再次妊娠的分娩方式探讨

目的 :探讨剖宫产后再次妊娠的最佳分娩方式。方法 :对 15 6例剖宫产后再次妊娠孕妇的分娩方式进行回顾性分析。结果 :88例孕妇阴道试产 ,试产成功率者 88 6 %。选择再次剖宫产 6 8例。结论 :剖宫产史作为再次妊娠剖宫产的指征是不合理的 ,如无剖宫产指征 ,应给予试产 ,因为阴道分娩可减少再次开腹手术给患者带来的各种危险和并发症 ,减少患者手术痛苦和经济负担。     

Human chorionic gonadotropin assay in cervical secretions for accurate diagnosis of preterm labor.

OBJECTIVES: We planned to determine whether the concentration of human chorionic gonadotropin (hCG) in cervical secretions could be a useful marker for accurate diagnosis of preterm labor, and whether the use of cervical hCG assay in combination with the Bishop score would improve the prediction of delivery within 7 days, and to determine the cut-off values for hCG in prediction of delivery within 100 h, 7 and 14 days, as well as before 35 and 37 weeks of gestation in a group of women at high risk for preterm delivery. METHODS: The study was conducted in the perinatology department of Zeynep Kamil Women and Children Diseases Education and Research Hospital between February 2002 and February 2003. One hundred and two subjects with a diagnosis of threatened preterm labor with intact membranes were included in the study. For hCG measurements, a cotton swab was rolled intracervically for 10 s to absorb fluid. Bishop scores were assessed. The correlation test was employed for the variables influencing hCG values. The ROC curve analysis was used to establish an optimal cut-off concentration for cervical hCG and an optimal cut-off level for Bishop score. The continuous variables were analyzed by the unpaired, independent, two-tailed t-test and categorical data were analyzed by the chi-square test. RESULTS: A significant positive correlation was present between the cervical hCG concentrations and Bishop scores (r=0.72, P<0.0001), and a highly negative correlation between the cervical hCG concentrations and the time interval from sampling time until delivery (r=-0.80, P<0.0001) was detected. The cut-off value for cervical hCG concentration and its sensitivity, specificity, positive and negative predictive values, accuracy, relative risk and likelihood ratio for accurate determination of delivery within 100 h were > or =32 mIU/ml, 98%, 55%, 70%, 96%, 77%, 19.68 and 2.18, respectively. However, these values were > or =32 mIU/ml, 97%, 84%, 89%, 95%, 92%, 17.37 and 6.06, respectively, for prediction of delivery within 7 days; > or =30 mIU/ml, 97%, 79%, 87%, 94%, 89%, 15.15 and 4.62, respectively, for prediction of delivery within 14 days; > or =33 mIU/ml, 89%, 92%, 94%, 83%, 90%, 5.83 and, 11.55, respectively, for prediction of delivery before 35 weeks; and finally > or =27 mIU/ml, 76%, 50%, 85%, 37%, 71%, 1.34 and 1.52, respectively, for prediction of delivery before 37 weeks. CONCLUSIONS: Cervical hCG expression seems to be rewarding in accurate diagnosis of preterm labor. This test has the advantage of low cost and wide availability.     

竞争情报与医院战略管理整合研究新视角:应用模式

在深化医院改革的过程中,当今医院处在体制转轨的特殊时期,医院为求生存走向市场,走向竞争也是必然,如何把医院办好、做强是摆在每个医院管理人员面前不容忽视的问题。怎样打破制约医院发展不科学的管理模式,打破瓶颈,走出新路。提出竞争情报与战略管理整合的新思路,即应用模式的研究,为推进医院现代化管理的理论研究提供参考。     

构建医院协会"四位一体"创新模式

介绍了广东省医院协会构建“四位一体”的组织创新模式:医院协会、广东现代医院管理研究所、广东《现代医院》杂志社、广东现代医院管理顾问有限公司的形成、发展成为协会做强做大的载体和基础的体会。     

Mode of delivery in the early preterm infant (<28 weeks)

Elective caesarean section for women in labour with an immature baby might reduce the chances of fetal or neonatal death, but might also increase the risk of maternal morbidity. A review (updated in February 2004) of randomised trials comparing a policy of elective caesarean section versus expectant management with recourse to caesarean section produced six studies involving only 122 women. Differences in fetal outcome did not reach significance, but mothers undergoing elective caesarean section were more likely to have serious morbidity. Scientifically, the evidence remains inadequate. Clinically, the recommendation is that prematurity is not, in itself, an indication for caesarean section. In a survey from Israel, published in December 2004, of 2955 very low birthweight infants born at 24–34 weeks of gestation, the overall caesarean section rate was 51.7%, and the mortality rate among babies prior to discharge was lower after caesarean section (13.2 versus 21.8%). After adjustment using multiple logistic regression, caesarean section had no effect on survival except in a subgroup with amnionitis, and it was again concluded that caesarean section cannot be routinely recommended unless there are other indications. A decision model developed in the USA has compared costs and health outcomes of two options for managing labour at 24 weeks of gestation. The probabilities of both intact survival (16.8 versus 12.9%) and survival with major morbidity (39.2 versus 19.4%) are higher with willingness to perform caesarean section, but less aggressive management is the more cost-effective strategy. Large studies are few and recruitment to such studies is perceived as a major problem. For clinicians, the decision will be influenced by local circumstances.     

多种工作模式的踝关节活动器的研制

各种原因导致患者长期卧床后将引起严重的并发症:踝关节跖屈畸形。新型踝关节活动器以大扭矩、超低速电机为动力,结合定时控制电路,具有多种工作模式,能使踝关节在被动的情况下背伸20～30°,跖屈40～50°,并能根据患者的个体情况设置不同的运用角度与时间,且能根据需要进行缓慢、连续、往返式运动,这对那些踝关节不能或较难进行主动活动的病人防止踝关节跖屈畸形、踝关节僵硬的及下肢肌肉萎缩有良好的作用。     

通气模式名称与临床应用

呼吸机通气模式名称的不统一或说混乱,给临床使用呼吸机带来了很大困难,严重影响了紧急情况下的抢救工作。     

中医正骨学认知学徒模式与传统教学模式比较研究

目的探索适合模拟医院环境下的教学模式.方法选择中医系骨伤专业2000级学生为研究对象,分为实验组和对照组,分别采用认知学徒模式和传统教学模式教学,组织专家听课.课后对学生进行基础理论、临床技能测试和操作考核,并通过向学生及专家发放调查问卷听取专家和学生对认知学徒教学模式的评价.结果实验组学生的基础理论、临床技能测试、考核成绩均高于对照组,结果有统计学意义.调查问卷反映认知学徒模式具有营造合适的学习环境,激发学生的学习兴趣,加快学生对知识和技能的掌握速度的作用.结论认知学徒模式能最大限度发挥模拟医院在医学临床教学中的作用,是适合于模拟医院教学环境的教学模式.