老年性痴呆危险因素的Logistic回归分析

目的 :探讨老年性痴呆的危险因素 ,为制订防范对策提供依据。方法 :抽样调查南京市 15 8名老年人健康状况及其影响因素 ,填写自我健康评估表、心理创伤量表、精神健康量表、幸福度量表、生活照料情况表、无望量表、老年性痴呆筛查量表等。资料用EPI和SAS系统作一元与多元分析。结果 :一元分析结果显示 ,年龄、性别、职业、婚姻、教育、中风史6个因子与老年性痴呆发生率均有密切关系 ;多元分析结果显示 ,年龄越高 ,老年性痴呆发生率越高 ,女性发生率高于男性 ,体力劳动者发生率高于脑力劳动者。结论 :老年性痴呆与社会心理因素有一定关系     

胸腺因子D对实验性大鼠肝纤维化防治作用的研究

目的　研究胸腺因子D(TFD)的体内抗肝纤维化作用。方法　用四氯化碳 (CCL4 )复制大鼠肝纤维化模型 ;造模开始或造模 30d后予TFD ;实验结束后分别测定肝功能、纤维化指标 (Ⅲ型前胶原、透明质酸和层粘连素 )、肝组织中谷胱甘肽、超氧化物岐化酶及丙二醛含量 ,并作肝病理检查。结果　TFD可显著减轻CCl4 肝纤维化程度 ,能明显降低血清Ⅲ型前胶原、透明质酸、层粘连素和肝组织中丙二醛含量 ;显著提高谷胱甘肽和超氧化物岐化酶活性 ,改善肝功能 ,组织学检查亦显示具有抗肝纤维化作用。结论　TFD在体内具有抗肝纤维化的作用 ,可望用于肝纤维化的防治。     

实验性自身免疫性内耳病耳蜗热休克蛋白70的表达

目的　探讨自身免疫性内耳病模型动物耳蜗热休克蛋白的表达。方法　利用同种异体内耳抗原免疫豚鼠 ,以建立自身免疫性内耳病 (autoimmuneinnereardisease ,AIED)动物模型 ,并应用免疫组织化学及原位杂位技术 ,研究热休克蛋白 (heatshockprotein ,hsp) 70在正常对照组及AIED模型动物实验组耳蜗中的表达情况。结果　对照组豚鼠螺旋神经节细胞中存在hsp70样蛋白基础表达 ;实验组 2 8耳中 10耳 (35 7% )听阈提高≥ 10dB ;此组动物螺旋神经节细胞和血管纹、螺旋韧带hsp70及其mRNA表达明显增强。结论　以粗制膜迷路抗原免疫豚鼠 ,听阈提高动物hsp70在螺旋神经节细胞和血管纹、螺旋韧带合成增加。     

被动吸烟孕兔胎盘形态学改变与孕兔血及脐血中一氧化氮的关系

目的 探讨被动吸烟与血中一氧化氮的关系,方法 在采用被动吸烟建立孕兔胎儿生长迟缓动物模型的基础上,对孕兔胎盘组织进行计量分析,以了解其与孕兔血及脐血中一氧化氮（ＮＯ）水平的关系。结果 吸烟可使胎盘绒毛面积百分比及绒毛毛细血管百分比降低,而且孕兔脐血ＮＯ水平高于母血ＮＯ水平（Ｐ〈０．０５）而吸烟组母及脐血中ＮＯ水平明显低于无被动吸烟组,结论 孕期吸烟可使胎盘组织形态学改变,导致母血及脐血中ＮＯ的水平     

吗啡依赖动物戒断后的焦虑情绪变化

本文采用高架十字迷宫模型和Vogel's饮水冲突模型观察吗啡依赖动物自然戒断后18、24、48、72、96、120h的焦虑情绪 ,结果表明吗啡依赖动物自然戒断后48h时的焦虑症状在两种模型上都最为明显 ,丁螺环酮可明显缓解吗啡所致的焦虑情绪。提示高架十字迷宫模型和Vogel's饮水冲突模型可较为客观和准确地反映吗啡所致焦虑情绪。     

The chemopreventive properties of soy isoflavonoids in animal models of breast cancer

Genistein (5,7,4-trihydroxyisoflavone), one of two major isoflavonoids in soy, has anti-proliferative effects on mitogen-stimulated cell growth of human breast cancer cells in culture and is a candidate for use in the prevention of breast cancer. Soy protein preparations containing isoflavonoid conjugates have chemopreventive activity in carcinogen-induced rat models of breast cancer. Recent experiments in these models with purified genistein have revealed that the timing of the exposure of rats to this isoflavonoid is critical. Rats treated neonatally or prepuberally with genistein have a longer latency before the appearance of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and a marked reduction in tumor number. The mechanism of genistein's preventive action is in part dependent on its estrogenic activity, which causes a more rapid differentiation of the cells of the mammary gland, analogous to the effects of an early pregnancy. Rats administered genistein after 35 days of age have smaller alterations in breast cancer risk, with a maximum reduction in mammary tumor number of 27%. In ovariectomized nude mice, dietary genistein increases cell proliferation of human breast cancer MCF-7 cell xenografts compared with a control diet. This estrogen-like effect of genistein is not observed in non-ovariectomized rats. Future studies on the anticancer potential of soy isoflavonoids should examine their interaction with other phytochemical components of soybeans and exploit newly developed animal models of breast cancer in which specific genes have been activated or inactivated.     

Basic Science in Medical Reasoning: An Artificial Intelligence Approach

A new generation of intelligent systems is growing up in the community of Artificial Intelligence in Medicine. The main goal of these systems is the representation and use of real theory of diseases, as they are represented in medical textbooks or in scientific articles, rather than the heuristic shortcuts of human experts. In this paper, we will argue that the difficulties in the integration of basic science and clinical knowledge in intelligent systems arise from ontological differences between these kinds of knowledge and that the solution can be found in their dynamic integration during the reasoning process. In order to illustrate this point, we will first describe an epistemological analysis of the interplay between basic science knowledge and clinical knowledge, and then we will provide the example of a computational architecture implementing this view. This revised version was published online in June 2006 with corrections to the Cover Date.     

Is proximal airway pressure a good reflection of peripheral airspace pressure in infants and children models under HFJV?

This expriimental study was carried out to determine if an alveolar positive end-expiratory pressure (PEEP) could occur during high frequency jet ventilation (HFJV) in infants, and if tracheal pressure is a good estimation of alveolar pressure.We used physical models simulating a 1.5 kg premature (P), a 3 kg newborn (N) and a 6 kg child (C) with normal compliance and normal resistance. Moreover, in the N model, we used two different resistances and lung compliance heterogeneity was studied in the P model. Pressure was measured simultaneously in the tube simulating trachea (Paw) and in the bottle simulating the lung (Palv). HFJV was performed either via an endotracheal tube (ETT) or via a long catheter as in laryngoscopy. The ratio of injection time upon cycle duration (Ti/Ttot) was 20% or 30%, jet frequency was altered from 150 to 300 min^–1 and the driving pressure was set as in clinical practice (0.5 and 0.6 bar).PEEP occurred mainly in N (1.1 to 3.2 cm H2O) and C models (0 to 3.5 cm H2O). It was inversely related to expiratory time (Te). The end-expiratory pressure drop between Palv and Paw (EEP) was higher in N and increased from 0.5 to 2 cm H2O with the shortening of Te and with airway resistances, i.e. the presence of ETT. In the heterogeneous model, PEEP and EEP were greater in the higher compliance alveolus.This study shows that the end-expiratory Palv is underestimated by end-expiratory Paw. This is particularly important in the presence of an heterogeneity of distribution in lung compliance. In this case the airway PEEP overestimates the PEEP in the lower compliance alveolus and underestimates the PEEP in the higher compliance alveolus.     

The pharmacology of VA21B7: an atypical 5-HT3 receptor antagonist with anxiolytic-like properties in animal models

VA21B7 (3-[2-(4-piperonylpiperazinyl) indolyl] carboxaldehyde) was synthesized as a potential 5-HT₃ receptor antagonist. Even though VA21B7 showed a higher affinity towards 5-HT₃ receptors as compared to other receptors studied, it was not a potent 5-HT₃ receptor antagonist either in the periphery or in the brain. In a simple animal model of anxiety such as the two-compartment box in mice, a remarkable anxiolytic-like effect was found at doses of 2–500 µg/kg IP and also at low oral doses, in the microgram range. These drug doses did not produce any significant effect on spontaneous motor activity of mice. The anxiolytic profile of VA21B7 was further explored using other models of anxiety in rats such as the elevated plus-maze and punished-drinking. VA21B7 was compared with standard 5-HT₃ receptor antagonists such as ondansetron, tropisetron and granisetron, with the 5-HT_1A agent buspirone and with diazepam. In the plus-maze, VA21B7 showed an anxiolytic-like profile after doses of 0.25–0.5 mg/kg IP or 2–4 mg/kg PO which did not modify the number of total entries into the open and closed arms of the maze. Diazepam, granisetron and tropisetron were also effective in this test but not ondansetron and buspirone. VA21B7 was also able to release suppressed behaviour in the punished-drinking test. The dose-response curve was bell-shaped with a peak at 2–4 mg/kg. At variance with other studies, 5-HT₃ receptor antagonists also increased the number of shocks taken in this test and the dose-response curve was also bell-shaped. VA21B7 was not anticonvulsant like diazepam, its anxiolytic action in the light/dark test was not flumazenil-sensitive and there was no rebound anxiogenic effect on withdrawal from chronic VA21B7 treatment for 15 consecutive days. Moreover, VA21B7 was not amnesic like the benzodiazepines but low doses of 2–4 mg/kg reduced the memory deficits induced in rats by scopolamine. Much higher doses were necessary to decrease spontaneous motor activity in rats. Since VA21B7 appears to be well tolerated in rodents at high doses, we think that it is of potential interest as an anxiolytic in humans.     

Pharmacodynamic Analysis of Analgesic Clinical Trials Using Empirical Methods

Data from analgesic clinical trials have characteristics such as ordered categorical longitudinal responses with repeated measures, delay of effect with respect to analgesic plasma concentration, and right-hand censoring of response due to remedication. In order to determine the concentration-effect relationship of such data, we propose convolving an empirical function for plasma concentration, in the form of broken lines which connect each pair of neighboring observations, with a monoexponential function, to generate effect site concentration Effect site concentration and time are used, simultaneously, as independent variables in the fit of the model for the logit of the probability of having a specific pain relief (PR) score at each time point pre-remedication, via maximum likelihood. Using corresponding effect site concentration, the probabilities of having specific PR scores post-remedication are predicted via the concentration-response relationship established. The overall (pre- and post-remedication) predictions and corresponding standard errors for the responses are then estimated. Inference of the PR scoring, using a posterior method, is proposed. An illustration using real data is used to demonstrate these methods.