Intelligent dialogue based on statistical models of clinical decision-making

The independence Bayesian model has been used widely in computer programs designed to support clinical decision-making. A reasoning strategy has been developed to enable these programs to conduct clinically pertinent dialogue and explain their reasoning. It has been implemented in a program for the diagnosis of acute abdominal pain based on the Bayesian model of de Dombal et al. Several features of the dialogue design have been adopted from artificial intelligence research, including shared initiative and critiquing. The program adopts a flexible goal-driven strategy, attempting to confirm the clinician's diagnosis or rule out the likeliest alternative. Symptoms and signs are selected in order of their expected weights of evidence in favour of the hypothesized disease.     

Pharmacodynamic Modeling for Change of Locomotor Activity by Methylphenidate in Rats

Purpose. The locomotive activity changes after intravenous (i.v.) administration of methylphenidate (MPD) in rats were pharmacodynamically analyzed. Methods. MPD concentration in plasma, MPD concentration and dopamine (DA) level in striatal dialysate collected by microdialysis method, and the locomotor activity after i.v. administration of MPD (2, 5 and 10 mg/kg doses) were used for the analysis. Results. The transport of MPD from plasma to the interstitial fluid in the brain could be expressed by the linear two-compartment model. The clockwise hysteresis between the MPD concentration and the DA level in the dialysate could be explained by the pharmacodynamic model considering Michaelis-Menten type reuptake process of the extracellular DA into the terminal of the dopaminergic nerve and its competitive inhibition by the extracellular MPD. The inhibition constant (K_i) of MPD for DA reuptake was estimated to be 41.3 ± 73.8 nM (mean ± SE), which was closely consistent with the in vitro value after correction with dialysis recovery. The relationship between DA level in dialysate and locomotor activity was expressed by the Emax model considering two contrary effects, hyperkinesia and stereotypy. The bi-phasic locomotor activity-time profiles after high dose of MPD could be represented by this model. Conclusions. The developed model made it possible to explain the tolerance in DA increase and the complicated locomotive change induced by MPD, and may be useful for other DA reuptake inhibitors, such as amphetamine and methamphetamine.     

Modulation of cytokine production from an EpiOcular corneal cell culture model in response to Staphylococcus aureus superantigen

The present study investigated the hypothesis that Staphylococcus aureus enterotoxin B (SEE) produces epithelial cell death and releases inflammatory cytokines that produce stromal infiltration during contact lens induced peripheral ulceration. Epithelial cells were incubated with different doses of SEB for various time periods. Culture supernatants were assayed for cytokines IL- lo, IL-6 and chemotactic agents IL-8 and LTB,. SEE induced the production of IL- I p and IL-8. Epithelial cells exposed for longer periods (48 h) with low concentrations of SEB produced significantly higher levels (N0.02) of IL-Ip and IL-8 (P<0.05) compared t o a 24 h exposure. SEB did not induce the production o f IL-6 and     

Implication of the systolic hump in systemic arterial pressure waves

The systolic hump in the aortic blood pressure wave is defined as the aorticresistance component proportional to the aortic blood flow superimposed on the windkessel component. An electrical analogue comprising a series resistance (aortic resistance) plus a resistance (peripheral resistance) and capacitance (aortic compliance) in parallel (i.e. windkessel component) is used for analysis. Curve fitting using the leastsquares method is performed on calculated and measured blood pressure waves from dogs under haemodynamical conditions induced by infusion of three drugs (noradrenaline, isoproterenol and acetylcholine). The curve fitting RMS (root mean square) errors are <3% for blood pressure waves and <30% for blood flow waves, with good agreement between measured and calculated blood flow waveforms. Infusion of noradrenaline and acetylcholine is found to induce a significant decrease and increase in the aortic resistance, respectively. Although only a small fraction of the blood pressure wave, the systolic hump has a marked effect on the systolic pressure waveform.     

Alteration of cytochrome P-450 by prolonged administration of imipramine and/or lithium to rats

Summary The aim of this study was to investigate imipramine-induced alterations of cytochrome P-450 and to determine whether prolonged concomitant administration of imipramine and lithium results in a pharmacokinetic interaction.Male Wistar rats received imipramine (10 mg/kg i. p.) at 12 h intervals or lithium chloride (100 mg/kg in drinking water) or they were treated with the combination of these drugs for 2 weeks. The long term treatment with imipramine produced a very complex alteration of cytochrome P-450: imipramine increased the level of the cytochrome, but it decreased the rate of its own aromatic hydroxylation in position 2. The rate of N-demethylation in the side chain was not changed. Consequently, in the case of both hydroxylation and demethylation, calculated molecular activities were decreased to 48% and 70% respectively. This differential change in activities corresponded well to the observed decrease of absorption in difference spectra (type I) produced in microsomes by imipramine. Carbamazepine-induced type I difference spectra were also decreased by imipramine pretreatment, but to a lesser extent. In contrast, hexobarbital type I binding was increased by imipramine treatment while type II difference spectra produced by metyrapone were not affected. The preliminary SDS-PAGE analysis of cytochrome P-450 isoenzymes of control and imipramine treated rats showed that the investigated antidepressant markedly intensified a protein band at 50.11 kD while bands at 51.28 kD, 56.20 kD and 56.88 kD were less intensive. These results indicate that the alteration of cytochrome P-450 by imipramine treatment is not only of quantitative but also of qualitative character. Lithium alone given to rats affected neither the concentration of cytochrome P-450 in microsomal protein nor the rate of imipramine metabolism in vitro. Lithium given jointly with imipramine reduced imipramine-induced elevation of cytochrome P-450. This, however, did not cause any change in the rate of imipramine metabolism in vitro and accordingly in imipramine pharmacokinetics in vivo. The concentration of lithium in the blood plasma tended to increase by concurrent administration of imipramine.Send offprint requests to K. J. Netter at the above address     

A preliminary statistical model for identifying repeaters of parasuicide

This paper presents a statistical model constructed using logisticregression to identify those at high-risk of repeating parasuicide. Thesubjects in the study are Cork city residents who exhibited parasuicidalbehaviour between 1 January and 30 June 1995. Repetition of the behaviourwithin six months of the index episode distinguishes repeaters fromnon-repeaters. The model was designed so that it could be used bynon-clinicians and hence does not require information relating topsychiatric diagnosis or use of psychiatric services. The proportion ofsubjects correctly classified remained stable across a range of cut-pointprobabilities (mean = 86%, range: 83.9–87.5%). Using acut-point of 0.2, 96% of repeaters and 81% of non-repeaters were correctly classified. Using 0.45 led to the correct identification of81% of repeaters and 90% of non-repeaters. If these highlevels of sensitivity and specificity are maintained in validation tests onfuture cohorts in Cork city then the model could form the basis of anintervention programme designed to prevent the repetition of parasuicide.     

指示肺通气不均匀性的熵变及其同其他指标的理论比较

熵代表无序的水平，作者使用通气的熵变（ＥＣＶ）指示肺通气的不均匀性，ＥＣＶ定义为当前泡潮气量趋近于零时每摩尔被吸入气体从不均匀通气到均匀通气的熵变的极限。本文从熵的基本公式民地出ＥＣＶ的计算方程。用几个数学模型肺将ＥＣＶ同其他７个洗出指标进行了比较。８个指标中，只有ＥＣＶ仅取决于通气分布，其他７个指标不仅取决于通气分布，还同潮气量和死腔的大小有关。这影响了它们评价肺通气不均匀性的效果，ＥＣＶ的另一     

Elevation of carbamazepine plasma levels by diltiazem in rabbits: a potentially important drug interaction

The effect of diltiazem on the plasma level of carbamazepine (CBZ) was investigated in rabbits. The animals were given either CBZ alone or in combination with diltiazem and plasma samples were collected at different time intervals. The concentration of CBZ was detected using an HPLC method. Diltiazem significantly increased the area under the curve (AUC), the maximum plasma concentration (Cmax), and the elimination half-life (t1/2) of CBZ (p less than 0.05). These results suggest that a potentially harmful drug-drug interaction may occur if CBZ and diltiazem are administered concurrently.     

Transactional models of early education effectiveness - What is the message for policy?

There is now a substantial body of American research evidence demonstrating that early education programmes can have major long term effects right through into adult life. Cost-benefit analysis has enabled the data to be transformed into a compelling case for public financial investment. But insufficient attention has been paid to explaining how a short term preschool programme could have such enduring effects. The effects are best understood by applying a transactional model which shows how processes in the school and community transformed and amplified short term effects into long term outcomes. Adopting a transactional model modifies the messages for policy. The results of evaluations carried out in one society may not apply in another. In some school systems there may be more effective strategies than early education for improving educational prospects.     

Ethanol regulated preference in rats

A series of experiments evaluated the determinants of preference for mixtures of ethanol plus sucrose relative to sucrose in rats. One dipper served 10% ethanol mixed with 10% sucrose, and the second dipper served 10% sucrose. Lever presses operated each dipper according to a variable-interval 5-s schedule. In three experiments the subjects were given pre-session meals of sucrose (2.5–20 ml) or sucrose (20 ml) plus chow (5 or 10 g). Pre-session meals decreased responding maintained by sucrose but not responding maintained by ethanol mixture. In two experiments body weight was varied from 85% to 125% of the initial free-feeding values. Increases in body weight, like pre-session meals, decreased responding reinforced by sucrose, but typically did not decrease responding reinforced by ethanol mixture. Throughout most of the study, ethanol consumption remained at about 1.25 ml per half hour session (3–4 g/kg per 30 min). For example, pre-session access to ethanol mixture decreased within-session ethanol consumption, but total consumption, counting both sources, remained about 1.25 ml/session. The within-session patterns of responding also differed. Responding reinforced by ethanol mix decreased as a function of ethanol consumption, whereas responding reinforced by sucrose was relatively constant throughout the session. The simplest explanation of the results is that ethanol's pharmacological consequences regulated preference.