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131.
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Primary biliary cirrhosis (PBC) is an immunologically mediated disease in which activated T lymphocytes attack and destroy epithelial cells in the small intralobular bile ducts of genetically susceptible patients. This article reviews the results of treatment of PBC with immunomodulatory agents. Results with drugs such as glucocorticoids, azathioprine, and chlorambucil have been disappointing because of either limited efficacy (azathioprine), toxicity (chlorambucil), or both (glucocorticoids). Colchicine improved tests of liver function in three prospective studies and was associated with improved survival for up to 4 years. However, survival benefits were lost at 8 years. Colchicine appears to slow the rate of progression of PBC but not to stop it. Preliminary results suggest that colchicine may have synergistic effects if used together with ursodeoxycholic acid, particularly in patients who are only partially responsive to ursodeoxycholic acid. Results with cyclosporine have been disappointing because of limited efficacy and predictable toxicity. The modest improvement in tests of liver function and survival are counterbalanced by the development of hypertension in some and worsening renal function in most. There is little beneficial effect on symptoms or histology. Results with methotrexate are promising. There are improvements in symptoms and tests of liver function that are equal to those seen with ursodeoxycholic acid and significant improvement in liver histology. Some patients, particularly those with striking inflammation and granulomas in portal triads, appear to have achieved sustained remission while on methotrexate. The effects of methotrexate are additive to those of ursodeoxycholic acid in patients whose blood tests have responded only partially to ursodeoxycholic acid. The most effective treatment of PBC will most likely use a combination of drugs such as ursodeoxycholic acid, colchicine, and methotrexate.  相似文献   
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134.
Using the fear-potentiated startle paradigm in rats, 4 experiments examined whether the inhibitory effect of a feature is evident after its offset following serial feature-negative discrimination training (A+ and X-->A-). When startle probes were presented shortly after the offset of X on X-->A test trials, the inhibitory properties of X were observed immediately after its offset. Furthermore, trace reinforcement of X (X-->+), but not delay reinforcement (X+), disrupted the ability of X to inhibit fear-potentiated startle on X-->A trials. Trace conditioning to X was also retarded after A+ and X-->A- training. These results suggest that the inhibitory properties of the serially trained feature are present after its offset and raise the possibility that either temporal information regarding nonreinforcement or poststimulus attributes of X acquire inhibitory properties.  相似文献   
135.
This paper is concerned with partially observed stochastic optimal control problems when nonlinearities enter the dynamics of the unobservable state and the observations as gradients of potential functions. Explicit representations for the information state are derived in terms of a finite number of sufficient statistics. Consequently, the partially observed problem is recast as one of complete information with a new state generated by a modified version of the Kalman filter. When the terminal cost is quadratic in the unobservable state and includes the integral of the nonlinearities, the optimal control laws are explicitly computed, similar to linear-exponential-quadratic-Gaussian (LEQG) and linear-quadratic-Gaussian (LQG) tracking problems. The results are applicable to filtering and control of Hamiltonian systems  相似文献   
136.
Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.  相似文献   
137.
The ability voluntarily to stabilize the head in space during lateral rhythmic oscillations (0.59+/-0.09 Hz) of the trunk has been investigated during microgravity (microG) and normal gravity (nG) conditions (parabolic flights). Five healthy young subjects, who gave informed consent, were examined. The movements were performed with eyes open or eyes closed, during phases of either microG or nG. The main result was that head orientation with respect to vertical may be stabilized about the roll axis under microG with, as well as without vision, despite the reduction in vestibular afferent and muscle proprioceptive inputs. Moreover, the absence of head stabilization about the yaw axis confirms that the degrees of freedom of the neck can be independently controlled, as was previously reported. These results seem to indicate that voluntary head stabilization does not depend crucially upon static vestibular afferents. Head stabilization in space may in fact be organized on the basis of either dynamic vestibular afferents or a short-term memorized postural body schema.  相似文献   
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139.
Imprudent linking weaves a tangled Web   总被引:1,自引:0,他引:1  
Lynch  P.J. Horton  S. 《Computer》1997,30(7):115-117
Hypertext linking is often embraced uncritically by Web authors eager to explore the power of hypertext without first considering its effects on their readers' comprehension. Hypertext linking is not a substitute for thought-we think with ideas, not with dissociated snippets of raw information. Even the most germane bits of information cannot become ideas, regardless of how cleverly they are stacked, listed or linked. Ideas define relevance, provide context and establish patterns. With patterns, most concepts become intelligible, and we need continuity and stability of theme and context to recognize patterns. So, like most powerful technologies, hypertext links are a mixed blessing. Used improperly, they can be detrimental to Web sites. “Loose links” can drive away an audience, dilute the site's message, confuse the reader with irrelevant digressions and become a continuing maintenance headache for site authors and Webmasters  相似文献   
140.
A comprehensive survey of photosensitivity in silica glasses and optical fiber is reviewed. Recent work on understanding the mechanisms contributing to germanium or aluminum doped fiber photosensitivity is discussed within the framework of photoelastic densification models  相似文献   
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