Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine

Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc.     

Marine biodiversity as a source of chemical diversity

Total global biodiversity is estimated at between 3 and 500 × 10⁶ species of prokaryote and eukaryote organisms spread across 70 or more phyla. The marine macrofauna alone are estimated between 0.5 and 30 × 10⁶ species and represents a broader range of taxonomic diversity than that found in the terrestrial environment, which has been the traditional source of natural products. With a typical eukaryote possessing 50,000 genes, the global marine macrofauna are the source of 2.5 × 10¹⁰ to 1.5 × 10¹² primary products and an associated extensive range of secondary products. However, only a few thousand novel compounds from marine organisms have been described. These compounds have proven unique in chemical and pharmacological terms but, as yet, no therapeutic agents have resulted. Given a broader drug discovery strategy, and facilitated by technological advances, it is predicted that the characterisation of marine chemical diversity will be accelerated. Strategies for drug discovery from the virtually untapped chemical diversity of marine organisms are discussed. © 1994 Wiley-Less, Inc.     

A decomposition approach to suboptimal control of discrete-time systems

A suboptimal controller for a class of discrete-time systems is presented. The controller is derived by first solving ‘off-line’ a simplified optimal control problem obtained by neglecting part of the system state and by considering a larger time step, then by solving ‘on-line’ at each time step an optimization problem based on the results of the previously solved ‘off-line’ problem. A simple numerical example is presented to illustrate the control scheme.     

Mixed h2 and h∞ optimal robust control design

This paper introduces a design methodology for a dynamic compensator that simultaneously minimizes the upper bound of a quadratic performance index and the H_∞-norm of a disturbance transfer function matrix of a multiple-input/multiple-output system whose model contains parameter uncertainty in the state and input matrices. The real parameter uncertainty is modelled as additional measurement outputs and as additional weights on the existing noise inputs and measurement outputs of the system. The compensator equations are derived by taking the dual of a system with parameter variation in the state and output matrices, for which the compensator equations have previously been derived, and then taking the dual of the compensator equations. An algorithm for applying this theory is given and an example is shown.     

海生多糖肽对亚急性辐射损伤小鼠的防护作用

目的 研究海生多糖肽对小鼠亚急性辐射损伤的防护作用。方法 给小鼠饲以海生多糖肽制剂，用^60Coγ射线进行全身性亚急性照射，检测外周血白细胞、脾淋巴细胞转化率、红细胞超氧化物歧化酶、丙二醛和过氧化酶含量、精子畸形率、睾丸精母细胞染色体畸变率和肝细胞半胱氨酸蛋白酶-3等指标。结果 海生多糖肽高、低剂量组小鼠的血白细胞数量、脾淋巴细胞转化率、红细胞超氧化物歧化酶值和过氧化酶值均高于照射对照组，红细胞丙二醛值、精子畸形率、睾丸精母细胞染色体畸变率和肝细胞半胱氨酸蛋白酶-3阳性表达率则低于照射对照组，差异有显著性。结论 海生多糖肽对亚急性辐射损伤有良好的防护作用。     

Introducing expert systems to medical students using esta, Expert System Teaching Aid

Medical students are allocated little curriculum time for exposure to expert systems. ESTA, a computer model of an expert system, was developed to make best use of this time. The nature of the students' interaction with ESTA is described, and their reactions to the expert system concepts and the place of expert systems in medicine are presented. A discussion of these reactions draws some conclusions about teaching expert systems in particular, and computers in general, in the basic medical course.     

Prognostic Factors in Elderly Patients with Acute Myeloid Leukaemia

Acute myeloid leukaemia (AML) is predominantly a disease of the elderly; the median age of incidence is 64 years, and 60% of all cases are over 60. With improved chemotherapy regimens and maximal supportive care, remission rates of up to 60% may be achieved in selected elderly patients. Whilst intensive chemotherapy is the treatment of choice for fit patients, it may be inappropriate for debilitated patients with poor prognosis disease in whom supportive care or palliative chemotherapy may be more suitable. AML in the elderly exhibits biological differences from AML in younger patients, and elderly patients may be unable to withstand the rigors of the intensive treatment regimens given to younger patients.     

Experience with the Berlin Heart Assist Device

Abstract: Different mechanical circulatory support systems (MCSS) have been in clinical use since 1987 to keep patients alive by assisting the heart during cardiac recovery after open heart surgery, myocardial infarction, acute graft failure after heart transplantation, or as a bridge to transplantation in heart transplant candidates. Four different hospitals in Germany used the Berlin Heart Assist Device. Up until 1993, there were 22 patients in the "recovery" group; 4 patients were weaned from the system, and only 1 patient was discharged from the hospital. In 112 patients the Berlin Heart Assist Device was implanted for the purpose of a bridge to transplantation, 68 were transplanted and 46 patients left the hospital. It was concluded that patients may be kept alive with this system for weeks and months after any kind of cardiogenic shock. Complete cardiac recovery may be achieved in patients with early posttransplant graft failure. Reliable prediction of outcome in bridge–to–transplantation patients requires further experience and improvement of system components.