息痛颗粒对犬脑血流量和血压的影响

目的观察息痛颗粒对犬脑血流量和血压的影响。方法将犬随机分为5组,每组4只。分别为:空白对照组,尼莫地平组(6.2 mg.kg-1),镇脑宁组(37.26 mg.kg-1),息痛颗粒高剂量组(1.29 g.kg-1),息痛颗粒低剂量组(0.25 g.kg-1)。经十二指肠给药,以尼莫地平和镇脑宁作阳性对照药,观察记录给药前后脑血流量和血压的变化。结果息痛颗粒高剂量显著增加犬脑血流量(P<0.05),显著降低血压(P<0.05);息痛颗粒低剂量显著减少脑血流量,对血压无明显影响。结论息痛颗粒低剂量减少犬脑血流量,对血压无明显影响,高剂量显著增加犬脑血流量,降低血压。     

Developmental neurotoxicity of endocrine disrupters: focus on estrogens

A number of different environmental compounds are proposed to interact with the endocrine system (i.e., endocrine disrupters). Many of these have estrogenic effects in vitro and/or in vivo. Recent reviews have focused attention on the need for assessing the neurotoxicity of these compounds following developmental exposure. This attention comes in part from the literature on the effects of developmental exposure to exogenous estrogen on later behavioral and neuropathological alterations. A review of the ongoing neurobehavioral and neuropathological studies at the National Center for Toxicological Research on four such estrogen mimics (genistein, methoxychlor, nonylphenol, and ethinyl estradiol) is presented with results indicating that intake of a sodium solution is sensitive to these estrogen mimics. Developmental dietary exposure in male and female rats resulted in increased consumption of the sodium solution. Volume of the sexually dimorphic nucleus of the medial preoptic area was reduced by genistein, nonylphenol, and ethinyl estradiol exposure in males. The regulatory impact of these data and the directions for future research are discussed.     

A Phase I study of combined modality (90)Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer.

PURPOSE: The purpose of this study was to determine the feasibility and maximum tolerated dose of (90)Yttrium-CC49 ((90)Y-CC49) as the radioimmunotherapy (RIT) component of an i.p. combined modality treatment for recurrent ovarian cancer. EXPERIMENTAL DESIGN: A Phase I trial of (90)Y-CC49 RIT was conducted in ovarian cancer patients who had persistent or recurrent intra-abdominal disease, had failed one or two prior chemotherapy regimens, and demonstrated TAG-72 expression. Patients were treated with a previously established combined modality treatment protocol of s.c. IFN alpha2b, i.p. paclitaxel, and increasing dosages of i.p. (90)Y-CC49. Patients were monitored for toxicity, generation of human antimouse antibody response, and clinical efficacy. RESULTS: Twenty eligible patients were treated per study specifications. All patients had been treated with debulking and paclitaxel/carboplatin-based chemotherapy at initial diagnosis. The patients included 11 patients with persistent disease at the time of second look laparotomy and 9 patients with delayed recurrence. Patients were treated with i.p. (90)Y-CC49 given in combination with s.c. IFN alpha2b (dose of 3 x 10(6) units for a total of four doses) and i.p. paclitaxel (dose of 100 mg/m(2)). RIT treatment was associated with primarily hematological toxicity. The maximum tolerated dose of i.p. (90)Y-CC49 was established at 24.2 mCi/m(2) in this combined regimen. Of nine patients with measurable disease, two had partial responses lasting 2 and 4 months. Of 11 patients with nonmeasurable disease, median time to progression was 6 months in 7 patients who recurred; 4 of these patients remain no evidence of disease at 9+, 18+, 19+, and 23+ months. CONCLUSIONS: (90)Yttrium-CC49-based RIT in combination with IFN alpha2b and i.p. paclitaxel is feasible and well tolerated at a dose of < or =24.2 mCi/m(2).     

Antipsychotics and the risk of sudden cardiac death

BACKGROUND: Case reports link antipsychotic drugs with sudden cardiac deaths, which is consistent with dose-related electrophysiologic effects. Because this association has not been confirmed in controlled studies, we conducted a retrospective cohort study in Tennessee Medicaid enrollees, which included many antipsychotic users; there were also computer files describing medication use and comorbidity. The study was conducted before the introduction of risperidone and, thus, did not include the newer atypical agents. METHODS: The cohort included 481,744 persons with 1,282,996 person-years of follow-up. This included 26,749 person-years for current moderate-dose antipsychotic use (>100-mg thioridazine equivalents), 31,864 person-years for current low-dose antipsychotic use, 37,881 person-years for use in the past year only, and 1 186,501 person-years for no use. The cohort had 1487 confirmed sudden cardiac deaths; from these, we calculated multivariate rate ratios adjusted for potential confounding factors. RESULTS: When current moderate-dose antipsychotic use was compared with nonuse, the multivariate rate ratio was 2.39 (95% confidence interval, 1.77-3.22; P<.001). This was greater than that for current low-dose (rate ratio, 1.30; 95% confidence interval, 0.98-1.72; P=.003) and former (rate ratio, 1.20; 95% confidence interval, 0.91-1.58; P<.001) use. Among cohort members with severe cardiovascular disease, current moderate-dose users had a 3.53-fold (95% confidence interval, 1.66-7.51) increased rate relative to comparable nonusers ( P<.001), resulting in 367 additional deaths per 10,000 person-years of follow-up. CONCLUSIONS: Patients prescribed moderate doses of antipsychotics had large relative and absolute increases in the risk of sudden cardiac death. Although the study data cannot demonstrate causality, they suggest that the potential adverse cardiac effects of antipsychotics should be considered in clinical practice, particularly for patients with cardiovascular disease.     

体温对急性脑卒中预后影响的临床研究

目的 探讨脑卒中急性期7d内的体温变化对预后的影响.方法 104例急性脑卒中患者,均在发病后24h入院,测量入院时72h及发病7d内每4h1次的腋温.同时评定一些可能影响预后的因素,利用Cox比例风险模犁及Logistic回归进行不同时间段体温对卒中预后(发病后1月的生存情况及ADL)影响的多因素分析.结果 入院时体温增高者,神经功能缺损更为严重.入院发热患者占15.4%,人院体温不是卒中预后的独立预测因素.但72h和7d的半均体温是发病后1月的生存情况的独立预测因素,体温每升高1℃,死亡的风险分别增加47.3%和46.1%(95%的可信区间分别为1.07～2.01,P=0.015和1.10～1.94,P=0.009),7d平均体温是发病后1月ADL预后不良的独立预测因素(OR=0.129,95%的可信区间0.022～0.755,P=0.023).结论 入院体温不是卒中1月时预后的独立预测因素,但随后数天的体温升高可能影响近期预后.72h和7d的平均体温是发病后1月的生存情况的独立预测因素,7d平均体温是发病后1月ADL预后不良的独立预测凶素.     

Post-marketing Surveillance for Combined Oral Contraceptive Containing Desogestrel(Marvelon~) in Chinese Rural Areas

Objective To assess the side effects and the continuation rate of combined oral contraceptive(COC) containing desogestrel(Marvelon) during 12 months. Methods This was a post-marketing surveillance study on Marvelon COC among 870 healthy rural women in 5 different counties of Jiangsu Province during 12 months. Results About 24.02% of the women who used Marvelon COC experienced side effects during 12 months. Gastrointestinal disorder,bleeding/spotting and chloasma were ranked the first three in the side ef...     

Loss of tumor-promoting activity of unleaded gasoline in N- nitrosodiethylamine-initiated ovariectomized B6C3F1 mouse liver

Unleaded gasoline (UG) vapor (2056 ppm) increased the incidence of liver tumors in a chronic bioassay and exhibited tumor-promoting activity in N-nitrosodiethylamine (DEN)-initiated female mouse liver. Estrogen inhibited mouse liver tumor development and the hepatocarcinogenic and tumor-promoting dose of UG produced uterine changes suggestive of estrogen antagonism. To directly test the hypothesis that UG-induced tumor-promoting ability is secondary to its interaction with the mouse liver tumor inhibitor, estrogen, we compared the tumor-promoting ability of UG in ovariectomized (Ovex) mice with the hepatic tumor-promoting ability of UG in intact mice. Ovaries were surgically removed at 4 weeks of age. Exposure to wholly vaporized UG (2018 ppm) under bioassay and tumor-promoting conditions began at 8 weeks of age. After 4 months of exposure, UG increased relative liver weight and hepatic microsomal cytochrome P450 pentoxyresourfin-O- dealkylase and ethoxyresorufin-O-deethylase activity to a similar extent in intact and Ovex mice. Non-focal hepatocyte proliferation, as measured by the incorporation of bromo-deoxyuridine, was not changed by UG exposure and was similar in all treatment groups. After 4 months of exposure to DEN-initiated mice, UG significantly increased the volume fraction of liver occupied by foci (three-fold) as compared to control intact mice. As expected, volume of foci was elevated in DEN/Ovex/control mice as compared to DEN/intact/control mice. In DEN/Ovex mice UG did not significantly increase the focal volume fraction. Thus, the tumor promoting activity of UG, as demonstrated by increased volume fraction of liver occupied by hepatic foci in intact mice, is greatly attenuated in Ovex mice. The volume fraction data in Ovex mice support the hypothesis that the tumor promoting activity of UG is dependent upon the interaction of UG with ovarian hormones. These data also indicate that hepatic microsomal cytochrome P450 PROD and EROD induction, hepatomegaly and non-focal hepatic LI are not specific markers of hepatic tumor promoting activity of UG.      

Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium

While tobacco smoke has been conclusively identified as a lung carcinogen, there is much debate over which smoke constituent(s) are primarily responsible for its carcinogenicity. Previous studies in our laboratory suggested that highly lipophilic carcinogens are slowly absorbed in the thicker epithelium of the conducting airways, potentially allowing for substantial local metabolism. The bioactivation of polycyclic aromatic hydrocarbons in airway epithelium may, hence, be important in tobacco smoke-induced carcinogenesis. In the present study, the hypothesis of slow absorption and substantial local metabolic activation of highly lipophilic carcinogen in airway epithelium was tested in dogs. A single dose of tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid suspension was instilled in the trachea, just anterior to the carina. At intervals of a few minutes up to 30 min over a 3-h period, blood samples were drawn from the azygous vein, which drains the area around the point of instillation, and from the systemic circulation. Tissue samples were taken at the end of the experiment. The concentration of BaP with depth into the tracheal mucosa was determined with autoradiography. BaP was slowly absorbed into the trachea with a half-time of approximately 73 min, which is consistent with diffusion-limited passage through the epithelium and lead to local doses in the tracheal epithelium that were more than a 1000-fold those of other tissues. The long retention of BaP in the epithelium provided the local metabolizing enzymes with high substrate levels over a long period, resulting in extensive metabolism. At 3 h after the exposure, 23% of the BaP-equivalent activity remained in the tracheal mucosa. Of this fraction, 13% was parent compound, 28% was organic extractable, 31% was water-soluble, and 28-7% of the instilled dose was bound to tracheal tissues. These results explain the tendency of highly lipophilic carcinogens, such as BaP, to induce tumors at the site of entry and, furthermore, indicate that the highly lipophilic components of tobacco smoke and polluted air may be the most important contributors to lung tumors of the conducting airways.