Identification of residues linked to the slow-->fast transition of thrombin.

Residues energetically linked to the allosteric transition of thrombin from its anticoagulant slow form to the procoagulant fast form have been identified by site-directed mutagenesis. The energetics of recognition by the two forms of the enzyme were probed by using a synthetic chromogenic substrate, fibrinogen, and hirudin. The thrombin residues E39, W60d, E192, D221, and D222 are linked to the slow-->fast transition and are part of an "allosteric core" through which events originating at the Na+ binding loop propagate to other regions of the enzyme. The thrombin residues Y76, W96, W148, and R173 lie at the periphery of the allosteric core, affect recognition of fibrinogen and hirudin to the same extent in both forms, and are not linked to the slow-->fast transition.     

n-Hexane neuropathy caused by addictive inhalation: clinical and electrophysiological features

To assess the clinical and electrophysiological features of n-hexane neuropathy caused by addictive inhalation, 4 patients were studied in the progressive phase. The neurological manifestations were characterized by subacute predominantly motor polyneuropathy and disease progression despite discontinuance of the chemicals, which were similar to those reported in industrial exposure, although with a severer degree associated with anorexia and body weight loss. Electrophysiological studies showed that all showed multifocal conduction block and profound conduction slowing, as well as features of axonal degeneration. Sural nerve biopsy showed axonal loss, axonal swelling, and thin myelin probably due to retraction by axonal swelling. n-Hexane abuse causes severe subacute polyneuropathy. The mixed axonal and demyelinating electrophysiological features were consistent with peculiar pathological findings. Conduction block, probably due to paranodal myelin retraction or ongoing wallerian degeneration, is very frequent and could be responsible for the clinical deficits, especially in the early phase of illness.     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

The effect of megestrol acetate on growth of HepG2 cells in vitro and in vivo.

PURPOSE: Hepatocellular carcinoma (HCC) is generally considered as a sex hormone-dependent tumor, and hormonal therapy has been proposed as a strategy for the treatment of HCC. The aim of the study is to investigate the effect of megestrol acetate, a synthetic progesteronal agent, on growth of HepG2 cells in vitro and in vivo. EXPERIMENTAL DESIGN: Cell growth in vitro was assessed by a colormetric method, and cell growth in vivo was assessed by tumor volumetrics. RESULTS: Megestrol acetate was shown to inhibit the growth of HepG2 cells in vitro in dose- and time-dependent manners with an IC (50) of 260 microm (24-h incubation). The growth of HepG2 cell-transplanted tumors in nude mice was also inhibited by i.p. injection of megestrol acetate (10 mg/kg/day). The tumor volumes of the megestrol acetate-treated group regressed to 59% of controls by week 6 and to 41% of controls by week 13. Apoptosis following G(1) arrest was observed in megestrol acetate-treated cells and may be a mechanism through which megestrol acetate inhibits HepG2 cells. Megestrol acetate was also demonstrated to have a beneficial effect on the weight gain of tumor-bearing nude mice, and the mean weight of the megestrol acetate-treated animals was higher than that of controls from week 4 of the treatment period, and the differences were statistically significant in week 5 and 6 (P < 0.05, compared with controls). No significant survival advantage was, however, demonstrated in the treatment group. CONCLUSIONS: This study showed that megestrol acetate inhibited the growth of HepG2 cells grown in vitro and in vivo. These data provide useful information for clinical study of megestrol acetate for the treatment of HCC.     

国际海员疾病发生与治疗的社会因素浅析

从３０００例国际海员疾病发生率原因着手,结合国际海员群体工作游动性和成员多国性的特点,从社会医学和心理医学角度,分析国际海员健康工作中存在的问题,并对如何实现国第员“人人享有卫生保健”提出初步见解。国际海员群体的特殊性及他们的健康问题值得中国及国际航海医学界和社会医学界的关注。     

Coronary artery bypass surgery in a patient with myasthenia gravis

A 73-year-old man with myasthenia gravis required quadruple coronary artery bypass grafting due to triple-vessel disease. Anesthetic management was performed with general anesthesia using a reduced dose of muscle relaxant with the aid of a neuromuscular transmission monitor. He was extubated 14 hrs after surgery without difficulty under this monitor. His postoperative course was uneventful. A patient with myasthenia gravis who required coronary artery bypass surgery was successfully performed by the deliberate preoperative evaluation of patient's myasthenic and cardiac status, and by the careful perioperative management.     

Expression of Daxx sensitizes Jurkat T-cells to the apoptosis-inducing effect of chemotherapeutic agents.

BACKGROUND: The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector. RESULTS: Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents. CONCLUSIONS: We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents.     

后矢状位肛门直肠成形术后便秘原因初探

目的　研究无肛畸形胎鼠直肠盲端神经元细胞分布情况 ,探讨后矢状位肛门直肠成形术 (PSARP)后便秘发生原因。方法　选用 2～ 3个月龄 ,体重 2 5 0～ 30 0g健康Wistar大白鼠 12只 ,其中雌鼠 8只 ,雄鼠 4只。实验组雌鼠为 5只 ,对照组为 3只。雌雄交配后第 11d对实验组 5只雌鼠使用乙烯硫脲 (ethylenethiourea ,ETU)灌胃 (1%乙烯硫脲溶液 ,12 5mg/kg) ,对照组孕鼠在同一天使用等量蒸馏水灌胃。第 2 2d对两组孕鼠剖宫取胎 ,形态学研究取实验组及对照组各一只孕鼠 ,获实验组无肛胎鼠 6只 ,正常 5只 ,对照组胎鼠 10只。对胎鼠盆腔进行正中矢状切片 ,HE染色后在光镜下观察其形态。免疫组化研究将两组剩余孕鼠 (实验组 4只 ,对照组 2只 ) ,获胎鼠实验组无肛、正常和对照组各 2 7只、16只和 2 1只 ,取胎鼠直肠盲端 ,利用神经元特异性烯醇化酶 (neuronspecificenolaseNSE)和S 10 0蛋白标记肠壁内源性神经元细胞及胶质细胞 (SP)法 ,分别对肌间神经元、粘膜下神经元及胶质细胞进行计数并与对照组对比 ,进行统计学分析。结果　实验组无肛胎鼠盆腔正中矢状切面可显示直肠盲端的形态。直肠盲端与对照组直肠肌间神经元细胞数分别为 2 .0 9± 0 .5 0 ,2 .74±0 .5 1;直肠盲端与对照组直肠粘膜下神经元细胞数分别为 0 .72     

静脉全麻复合骶管阻滞在婴幼儿先天性心脏病介人封堵治疗的研究

目的比较静脉全麻复合单次骶管阻滞麻醉与单纯静脉全麻用于婴幼儿先天性心脏病介入封堵治疗的效果。方法616例婴幼儿先天性心脏病介入封堵治疗患者随机分成两组:骶管阻滞加静脉全麻(I组);另一组用全凭静脉麻醉(II组)。结果全麻药的用量,II组比I组明显增多(P<0.05);I组苏醒时间短,分泌物少,手术后呕吐发生率少(P<0.05)。结论静脉全麻复合小儿单次骶管阻滞麻醉比全凭静脉麻醉用于婴幼儿先天性心脏病介入封堵治疗麻醉费用少,生命体征平稳,麻醉并发症少,值得推广。     

基于ODS构建医院即时联机分析处理系统的研究

面向医院管理者在日常管理全过程中对信息服务的需求,基于HIS数据资源,研究了应用ODS技术进行数据集成整合的技术方法,提出了在医院HIS数据库基础上建立ODS的策略。