Scrapie infection of transgenic mice leads to network and intrinsic dysfunction of cortical and hippocampal neurones

The human prion encephalopathy Creutzfeldt-Jakob disease often is manifest as rapidly progressing dementia with myoclonus and synchronous, periodic discharges. To investigate the electrophysiology of prion disease we used intra- and extra-cellular recordings from brain slices from Tg(SHaPrP+/+) 81 mice, which express Syrian hamster prion protein and which are susceptible to hamster-passaged scrapie isolates. Forty days after intracerebral inoculation with scrapie isolate Sc237, we recorded prolonged, epileptiform discharges in cortex and hippocampus. Neurological signs were subtle and histopathology was minimal. Central nervous system (CNS) dysfunction progressed; by 57 days the mice were ataxic, had spongiform histopathology and they died in <63 days. During the terminal phase, intrinsic neuronal properties changed dramatically and action potentials broadened from <4 to 20-100 ms in 30% of cortical cells. We conclude that brain dysfunction in experimental scrapie precedes clinical signs and spongiform histopathology, and is preserved in slices maintained in vitro, making it accessible to electrophysiological analysis.     

Long-term prognosis for women with chronic pelvic pain without laparoscopically demonstrable cause

With the object of assessing the long-term prognosis and the frequencies of recurrence and remission in women chronic low abdominal pain without laparoscopically visible cause, questionnaire were sent in 1985 and 1991 to 55 women who had been submitted to laparoscopy in 1982-1984 for this reason. These women had been told that there was no demonstrable explanation of the pain experienced and were then discharged. 65% and 55% respectively had experienced and unfavourable course with considerable and continued symptoms. Only 22% stated in both investigations that they had experienced a favourable course and that they were, by and large, free from pain. 36% changed from an unfavourable to a favourable course or the reverse. The assessment made by the women was confirmed by a series of subordinate questions and this demonstrated a marked difference between the favourable and unfavourable courses of the condition. It is concluded that laparoscopy with exclusion of significant pathology is not, in itself, satisfactory as treatment of this patient group and that no improvement occurs in the course of time. The condition varies greatly with many recurrences and remissions and, for this reason, uncontrolled reports of the therapeutic effects are of no significance. When compared with the literature, it is suggested that this patient group should be referred early in the course of the condition to a therapist with specialist psychological/sexological insight and/or to a physiotherapist with interest in this patient group.     

Reduction and uptake of methylene blue from rat air spaces

The use of methylene blue (MB) to estimate dilution of epithelial lining fluid, which occurs during bronchoalveolar lavage (BAL), is complicated by loss of this redox dye from the air spaces. The rate of MB uptake from the air spaces of isolated rat lungs and the effects of oxidation and reduction on this process were investigated in this study. Movement of MB from the air spaces to perfusate was compared with the corresponding transport of 125I-labeled albumin, [14C]-dextran, 99mTc-labeled diethylenetriaminepentaacetate, [3H]-sucrose, and 3H2O. By the end of 2 min, MB concentrations in the BAL had fallen by 58 +/- 4% (SE; n = 11) and 3H2O by 78 +/- 2% (n = 13), whereas concentrations of the other indicators decreased by approximately 6%. All but 10% of the 3H2O lost from the air spaces was found in the perfusate, whereas 19% of the lost MB was not recovered in the perfusate, suggesting retention of MB in the pulmonary tissues. Absorption of MB from the air spaces was slowed by 20% when the lungs were left unperfused, and absorption was accelerated threefold by reduction of MB to leukomethylene blue with Na2S2O4. In contrast, MB losses from the air space were slowed by the oxidizing agent K3Fe(CN)6 and by addition of superoxide dismutase or ascorbic oxidase. It is therefore possible that ascorbic acid and O2- entering the air spaces reduce MB to the uncharged leuko form. Lowering the pH of the BAL fluid to 3.5 also slowed MB reabsorption. This suggests that acid aspiration may stimulate release of oxidants into the air spaces.     

Adaptive two-loop Voltage-mode control of DC-DC switching converters

A new two-loop control scheme for voltage-mode control (VMC) of dc-dc switching converters is presented. The proposed method adds a high-gain robust loop with two controllers to the conventional VMC loop, achieving an analog "adaptive" loop in which the "equivalent voltage regulator" varies with the changing power stage parameters given as follows: 1) input voltage; 2) load; and 3) component tolerances. The loop significantly improves the disturbance rejection of the control system, i.e., closed-loop output impedance and audiosusceptibility while preserving the stability and the loop gain crossover frequency to a significant extent. Both the small-signal analysis and the experimental results carried out on a buck converter demonstrate the superiority of the proposed scheme with respect to the conventional single loop.     

Outcome of treatment for bilateral congenital cataracts

The outcome of treatment for bilateral congenital cataracts was studied retrospectively in a group of 51 patients. Two major categories of lens opacities were identified. In the first category, the opacities were extensive and visual impairment was evident early in the first year. These cataracts often occurred in eyes with small corneal diameters and poorly dilating pupils. Postoperative strabismus was nearly universal; nystagmus developed in over 50%; and late onset open-angle glaucoma developed in 8 of the 29 patients studied. Early surgery did not seem to abort the development of nystagmus in this group of patients. In the second category, the lens opacities were partial, often lamellar in configuration, and visual impairment was less severe. Surgery was usually performed after 3 years of age, with good visual results if the opacities were symmetrical and there was no nystagmus. No deprivation amblyopia developed in this group, even when surgery was delayed into the second decade. Strabismus developed postoperatively in about a third, but so far, no delayed open-angle glaucoma has been identified.     

Dynamic Policy-Based Network Management for a Secure Coalition Environment

This article reports the latest results of an R&D effort to develop a prototype implementation of a dynamic policy-based network management (PBNM) system that can be used to configure and manage a secure network for a coalition environment across an unsecured wide area network. The prototype, based on a distributed architecture, includes capabilities for policy creation and management, dynamic policy negotiation, and dynamic policy provisioning. The policy negotiation facilitates the rapid deployment of a coalition network while the dynamic policy provisioning automates the configuration and management of network services including firewalls, virtual private network connections, routing, quality of service (QoS), and domain name services. Such a PBNM system enhances an organization's ability to react to network incidents identified by a network situational awareness assessment. Although the focus of the current research is a military coalition environment, the system can be used in any distributed enterprise or collaborative environment     

A new curvature technique calculation for surface tension contribution in PLIC-VOF method

The volume of fluid (VOF) methods have been used for numerous numerical simulations. Among these techniques used to define the moving interface, the piecewise linear interface reconstruction (PLIC-VOF) is one of the most accurate. A study of the superficial tension impact on two-phase flow with free surface is presented. A new method based on direct staggered grid is developped to include surface tension in PLIC-VOF. The new numerical curvature calculation method doesn't need smoothed colour function and leads to less “spurious current”. This technique is applied to the calculus of surface tension force in the case of the rise of air bubble in viscous liquid and the fall of liquid drop in the same liquid on free surface. Droplets, thin layer and capillarity waves are observed after the free surface rupture for different Bond number. The influence of surface tension calculus is then obvioused and when the drop hit the free surface, wavelets propagate toward the virtual boundaries imposed.     

Differential response of arteries and vein grafts to blood flow reduction

BACKGROUND: Because the relative efficacy of antiarrhythmic agents on halothane-epinephrine arrhythmias has not been well characterized, this study was undertaken to comparatively evaluate the antiarrhythmic action of Na(+)-, K(+)- and Ca(2+)-channel blockers on epinephrine-induced ventricular arrhythmias during halothane anesthesia in rats. METHODS: Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs were mechanically ventilated with oxygen. The rats were studied in three consecutive protocols. Protocol I determined the arrhythmogenic thresholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine during halothane anesthesia in 64 rats receiving saline (control) or one of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rats receiving saline (control) or one of five antiarrhythmic agents. RESULTS: In protocol I, the arrhythmogenic doses of epinephrine during halothane, isoflurane, or pentobarbital anesthesia were 1.7 +/- 3.2, 11.1 +/- 0.6, and 39.0 +/- 3.9 micrograms/kg, respectively, and the corresponding plasma concentrations were 4.3 +/- 0.8, 103.7 +/- 9.2, and 246.7 +/- 28.9 ng/ml, respectively. In protocol II, the arrhythmogenic doses were similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na(+)- and K(+)-channel blocker), E-4031 (K(+)-channel blocker), or amiodarone(K(+)-channel blocker with Na(+)-, Ca(2+)-, and beta-blocking activity) increased significantly, i.e., 4.2, 4.2, 5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arrhythmias. Flecainide, E-4031, and verapamil markedly reduced the duration of arrhythmias induced by epinephrine, 8 micrograms/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhythmias induced by epinephrine, 16 micrograms/kg intravenously (P < 0.01). CONCLUSIONS: It was concluded that agents with K(+)-channel blocking properties were the most effective in preventing halothane-epinephrine arrhythmias in rats.