Neuromuscular transmission and its pharmacological blockade. Part 3: Continuous infusion of relaxants and reversal and monitoring of relaxation

The use of seclusion or seclusion and restraints (S/SR) may affect patients negatively, even if controlling their behavior in the short run, by placing them in the "victim" role and fostering a corrosive atmosphere of patient-caregiver mistrust and alienation. This project's goal was to reduce the use of the most restrictive measures by increasing the use of the less restrictive removal from stimuli (RFS). Verbally and even physically threatening patients in a psychiatric intensive care unit were removed from stimuli if their behaviors were not sustained and they ultimately cooperated with staff. RFS was deemed successful when a patient did not need more restrictive measures following its use. The data for this study were obtained by tabulating RFS and S/SR utilization rates for a year. Frequencies, measures of variance, ratios, and t ratios were used to analyze the data. The use of RFS and other nonrestrictive measures to reduce patient stress and frustration resulted in decreased utilization of seclusion and restraints. The frequency and severity of negativistic, aggressive behaviors of patients were also observed to have diminished.     

Differences in the liability to self-administer intravenous cocaine between C57BL/6 x SJL and BALB/cByJ mice

Application of animal models of psychostimulant abuse for experimentation in mice is becoming increasingly important for studying the contribution of genetic differences, as well as the roles of selected (targeted) genes, in specific behaviors. The purpose of this study was to investigate strain differences in cocaine self-administration behavior between C57BL/6 x SJL hybrid mice and BALB/cByJ mice. These two strains were chosen because BALB/cByJ mice have a well-developed behavioral pharmacological profile, and hybrid strains on a C57BL/6 background are commonly used for generating transgenic expressing and knockout mutant mice. C57BL/6 x SJL mice dose-dependently acquired cocaine self-administration (1.0 mg/kg/injection but not 0.25 mg/kg/injection) by responding selectively in the active nose-poke hole and maintaining stable levels of daily drug intake; they also exhibited a characteristic inverted-U-shaped cocaine dose-effect function. BALB/cByJ mice failed to acquire cocaine self-administration at either dose under the same test conditions. The strain differences observed in self-administration did not seem to be attributed to other behavioral differences because the two strains exhibited similar amounts of spontaneous nose-poking in the absence of reinforcers, and BALB/cByJ mice responded more than C57BL/6 x SJL mice in a food-reinforced nose-poke operant task. Importantly, the dose-effect function for the motor stimulating effects of cocaine (3.8-30 mg/kg intraperitoneally) suggests enhanced sensitivity but reduced efficacy of cocaine in stimulating motor activity in BALB/cByJ mice relative to the C57BL/6 x SJL hybrid mice. These results indicate that the decreased liability of BALB/cByJ mice to acquire cocaine self-administration is not the result of differences in spontaneous activity or performance, but may reflect different sensitivities to the reinforcing, or rate-disrupting, properties of cocaine. The data support an influence of genetic background in the liability to self-administer cocaine. Thus, a hypothesis is proposed that the decreased liability of BALB/cByJ mice to acquire cocaine self-administration is related to differences in brain monoamine systems linked to the high "emotionality" profile of BALB/c mice in novel or fearful situations, including perhaps cocaine administration.     

Neuromodulatory control of hippocampal function: towards a model of Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of cognitive function whose cellular pathology and molecular etiology have been increasingly and dramatically unraveled over the last several years. Despite this substantial knowledge base, the disease remains poorly understood due to a basic lack of understanding of how memories are stored and recalled in the brain. We describe a preliminary attempt at constructing a detailed model of these basic neural mechanisms; in particular, the natural dynamics of neuronal activity in hippocampal region CA3 and the modulation and control of these dynamics by subcortical cholinergic and GABAergic input to the hippocampus. We view the construction of such a model, with sufficient detail at the cellular and subcellular level, to be a necessary first step in understanding the effect of AD pathology on the functional behavior of the underlying neural circuitry. The network is based on the 66-compartment hippocampal pyramidal cell model of Traub and colleagues and their 51-compartment interneuron interconnected with realistic AMPA-, NMDA-, and GABA(A)-mediated synapses. Traub and others have shown that a network composed of these modeled cells is capable of synchronization in the gamma frequency range. We demonstrate here that this synchronization mechanism can implement an attractor-based autoassociative memory. A new input pattern arrives at the beginning of each theta cycle (comprised of 5-10 gamma cycles), and the pattern of activity across the network converges, over several gamma cycles, to a stable attractor that represents the stored memory. In this model, cholinergic deprivation, one of the hallmarks of AD, leads to a slowing of the gamma frequency which reduces the number of "cycles" available to reach an attractor state. We suggest that this may be one mechanism underlying the memory loss and cognitive slowing seen in AD. Our results also support the idea that acetylcholine acts on individual neurons to induce and maintain a transition from intrinsic bursting to spiking in pyramidal cells. These results are consistent with the hypothesis that spiking and bursting in CA3 pyramidal cells mediate separate behavioral functions, and that cholinergic input is required for the transition to and support of behavioral states associated with the online processing and recall of information.     

WATER RE-USE - CAPTURING A WASTE RESOURCE

The east and south-east of England has the lowest rainfall in the UK, water resources are limited and under pressure through increased demand and population growth. In the late 1990's AW Innovation (the AW R&D group) developed a process that could produce high purity water from sewage effluent using membrane technology. In late 1999 Texas Utilities (TXU) signed a contract with Alpheus Environmental for the supply of high purity water for Peterborough Power Station. The novel treatment plant was built in 1999 - 2000 and opened in July 2000 by the Mayor of Peterborough. This paper is a review of the plant design, the technology used for the treatment process and a summary of the first four years of operation.
Changing from potable water to high purity water produced from sewage effluent has brought significant benefits for the power station resulting in higher purity steam generation while reducing chemical, power and effluent discharge costs. In addition Anglian Water is now saving 1,000 m³/day of potable water.     

Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions

BACKGROUND: Previous work from our laboratory demonstrated that interleukin (IL)-6 plays a potentially critical role in postreperfusion myocardial injury and is the major cytokine responsible for induction of intracellular adhesion molecule (ICAM)-1 on cardiac myocytes during reperfusion. Myocyte ICAM-1 induction is necessary for neutrophil-associated myocyte injury. We have previously demonstrated the induction of IL-6 in the ischemic myocardium, and the current study addresses the cells of origin of IL-6. METHODS AND RESULTS: In the present study, we combined Northern blot analysis and in situ hybridization to demonstrate IL-6 gene expression in cardiac myocytes. Isolated ventricular myocytes were stimulated with tumor necrosis factor-alpha, IL-1beta, lipopolysaccharide, preischemic lymph, and postischemic lymph. Unstimulated myocytes showed no significant IL-6 mRNA expression. Myocytes stimulated with preischemic lymph showed minimal or no IL-6 mRNA expression, whereas myocytes stimulated with tumor necrosis factor-alpha, IL-1beta, lipopolysaccharide, or postischemic lymph showed a strong IL-6 mRNA induction. Northern blot with ICAM-1 probe revealed ICAM-1 expression under every condition that demonstrated IL-6 induction. We then investigated the expression of IL-6 mRNA in our canine model of ischemia and reperfusion. Cardiac myocytes in the viable border zone of a myocardial infarction exhibited reperfusion-dependent expression of IL-6 mRNA within 1 hour after reperfusion. Mononuclear cells infiltrate the border zone and express IL-6 mRNA. CONCLUSIONS: Isolated cardiac myocytes produce IL-6 mRNA in response to several cytokines as well as postischemic cardiac lymph. In addition to its production by inflammatory cells, we demonstrate that IL-6 mRNA is induced in myocytes in the viable border zone of a myocardial infarct. The potential roles of IL-6 in cardiac myocytes in an infarct border are discussed.     

Review of patients with infective endocarditis of native valves over a five-year period

The clinical characteristics, echocardiographic features, bacteriologic data, morbidity and mortality of patients who were admitted to our hospital with infective endocarditis of their native valves over a five-year period were reviewed. There were 32 patients with a mean age of 38.2 +/- 16.2 years (range: 17 to 71 years) in our study population; 24 patients had underlying valvular abnormalities, six patients had congenital heart disease and two patients had no structural cardiac abnormality. Echocardiography was performed for all patients. Vegetations were absent in three (9.4%) patients, single in 19 (59.4%) patients and multiple in ten (31.3%) patients. Of the 24 (75%) patients who had left-sided endocarditis, mitral valve disease was the commonest valvular abnormality (16 patients). Ventricular septal defect was the commonest underlying abnormality in patients with right-sided endocarditis. Blood cultures were positive in 26 (81.3%) patients; the commonest organism was streptococcal (16 or 50% patients). Complications were present in 13 (40.6%) patients, of which eight patients had evidence of embolism, four patients had cardiac failure and one patient had a paravalvular abscess. Four (12.5%) patients died, two as a result of refractory heart failure and two as a consequence of septic embolism. Advances in medicine have resulted in a better outcome for patients with infective endocarditis, however, it remains an important disease with significant morbidity and mortality.